RESUMEN
Our sensory adaptation to cold and chemically induced coolness is mediated by the intrinsic property of TRPM8 channels to desensitize. TRPM8 is also implicated in cold-evoked pain disorders and migraine, highlighting its inhibitors as an avenue for pain relief. Despite the importance, the mechanisms of TRPM8 desensitization and inhibition remained unclear. We found, using cryo-electron microscopy, electrophysiology, and molecular dynamics simulations, that TRPM8 inhibitors bind selectively to the desensitized state of the channel. These inhibitors were used to reveal the overlapping mechanisms of desensitization and inhibition and that cold and cooling agonists share a common desensitization pathway. Furthermore, we identified the structural determinants crucial for the conformational change in TRPM8 desensitization. Our study illustrates how receptor-level conformational changes alter cold sensation, providing insights into therapeutic development.
Asunto(s)
Frío , Mentol , Canales Catiónicos TRPM , Canales Catiónicos TRPM/metabolismo , Canales Catiónicos TRPM/antagonistas & inhibidores , Humanos , Mentol/farmacología , Simulación de Dinámica Molecular , Adaptación Fisiológica , Microscopía por Crioelectrón , Células HEK293 , Conformación Proteica , AnimalesRESUMEN
Plantar fasciitis is the most common cause of heel pain in adults with an overall prevalence of 0.85% in the adult population of the US, affecting over 2 million adults annually. Most current treatment modalities are not supported by sufficient evidence to recommend one particular strategy over another. Topical application of analgesics for soft tissue pain is well established, however the plantar fascia presents challenges in this regard due to thick skin, fibrotic tissue, and an often thickened fat pad. Sixty-two patients with plantar fasciitis were randomized to a placebo controlled trial testing the efficacy of a topical solution of plant terpenes containing camphor, menthol, eugenol, eucalyptol, and vanillin. Skin permeation of the mixture was enhanced with 15% dimethylsulfoxide (DMSO), 1% limonene, and rosemary oil. One ml of solution was applied topically twice daily, and pain scores evaluated on Day 0, Day 1, Day 3, and Day 10. Using the validated foot function index 78.1% of patients reported an 85% or greater decrease in their total pain score by day 10 while placebo treatment was without effect (One Way ANOVA, P < 0.01). This study adapts the treatment modality of topical analgesia for soft tissue pain to a problematic area of the body and shows therapeutic promise.ClinicalTrials.gov Identifier: NCT05467631.
Asunto(s)
Dimetilsulfóxido , Fascitis Plantar , Humanos , Femenino , Masculino , Fascitis Plantar/tratamiento farmacológico , Persona de Mediana Edad , Adulto , Dimetilsulfóxido/uso terapéutico , Dimetilsulfóxido/administración & dosificación , Dimetilsulfóxido/química , Terpenos/uso terapéutico , Resultado del Tratamiento , Anciano , Mentol/administración & dosificación , Mentol/uso terapéutico , Benzaldehídos/administración & dosificación , Benzaldehídos/uso terapéutico , Benzaldehídos/química , Eugenol/uso terapéutico , Eugenol/administración & dosificación , Eugenol/farmacología , Alcanfor/uso terapéutico , Alcanfor/administración & dosificación , Dimensión del Dolor , Aceites VolátilesRESUMEN
Low temperatures and cooling agents like menthol induce cold sensation by activating the peripheral cold receptors TRPM8 and TRPA1, cation channels belonging to the TRP channel family, while the reduction of potassium currents provides an additional and/or synergistic mechanism of cold sensation. Despite extensive studies over the past decades to identify the molecular receptors that mediate thermosensation, cold sensation is still not fully understood and many cold-sensitive peripheral neurons do not express the well-established cold sensor TRPM8. We found that the voltage-gated potassium channel KCNQ1 (Kv7.1), which is defective in cardiac LQT1 syndrome, is, in addition to its known function in the heart, a highly relevant and sex-specific sensor of moderately cold temperatures. We found that KCNQ1 is expressed in skin and dorsal root ganglion neurons, is sensitive to menthol and cooling agents, and is highly sensitive to moderately cold temperatures, in a temperature range at which TRPM8 is not thermosensitive. C-fiber recordings from KCNQ1-/- mice displayed altered action potential firing properties. Strikingly, only male KCNQ1-/- mice showed substantial deficits in cold avoidance at moderately cold temperatures, with a strength of the phenotype similar to that observed in TRPM8-/- animals. While sex-dependent differences in thermal sensitivity have been well documented in humans and mice, KCNQ1 is the first gene reported to play a role in sex-specific temperature sensation. Moreover, we propose that KCNQ1, together with TRPM8, is a key instrumentalist that orchestrates the range and intensity of cold sensation.
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Frío , Canal de Potasio KCNQ1 , Animales , Masculino , Femenino , Ratones , Canal de Potasio KCNQ1/metabolismo , Canal de Potasio KCNQ1/genética , Ratones Noqueados , Ganglios Espinales/metabolismo , Sensación Térmica/fisiología , Canales Catiónicos TRPM/metabolismo , Canales Catiónicos TRPM/genética , Ratones Endogámicos C57BL , Potenciales de Acción/fisiología , Caracteres Sexuales , Mentol/farmacologíaRESUMEN
A Pickering emulsion was synergistically stabilised with zein nanoparticles (ZNPs) and starch nanocrystals (SNCs) to prepare it for menthol loading. After response surface optimisation of the emulsion preparation conditions, a Pickering emulsion prepared with a ZNPs:SNCs ratio of 1:1, a particle concentration of 2 wt% and a water:oil ratio of 1:1 provided the highest menthol encapsulation rate of the emulsions tested (83%) with good storage stability within 30 days. We examined the bilayer interface structure of the emulsion by optical microscopy, scanning electron microscopy, and confocal laser scanning microscopy. The results of simulated digestion experiments showed that the release rate of free fatty acid was 75.06 ± 1.23%, which ensured bioavailability. At the same time, the emulsions facilitated the slow release of menthol. Bacteriostatic studies revealed that the Pickering emulsion had a protective effect on menthol, with the most significant inhibitory effects on Escherichia coli and Staphylococcus aureus under the same conditions. Overall, this study proposes a novel approach for the application and development of l-menthol by combining it with Pickering emulsion.
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Emulsiones , Escherichia coli , Mentol , Nanopartículas , Staphylococcus aureus , Almidón , Zeína , Mentol/química , Mentol/farmacología , Emulsiones/química , Nanopartículas/química , Zeína/química , Almidón/química , Staphylococcus aureus/efectos de los fármacos , Escherichia coli/efectos de los fármacos , Antibacterianos/farmacología , Antibacterianos/química , Tamaño de la PartículaRESUMEN
BACKGROUND: This study examines the impact of titanium dioxide nanoparticles (TiO2NPs) on gene expression associated with menthol biosynthesis and selected biochemical parameters in peppermint plants (Mentha piperita L.). Menthol, the active ingredient in peppermint, is synthesized through various pathways involving key genes like geranyl diphosphate synthase, menthone reductase, and menthofuran synthase. Seedlings were treated with different concentrations of TiO2NPs (50, 100, 200, and 300 ppm) via foliar spray. After three weeks of treatment, leaf samples were gathered and kept at -70 °C for analysis. RESULTS: According to our findings, there was a significant elevation (P ≤ 0.05) in proline content at concentrations of 200 and 300 ppm in comparison with the control. Specifically, the highest proline level was registered at 200 ppm, reaching 259.64 ± 33.33 µg/g FW. Additionally, hydrogen peroxide and malondialdehyde content exhibited a decreasing trend following nanoparticle treatments. Catalase activity was notably affected by varying TiO2NP concentrations, with a significant decrease observed at 200 and 300 ppm compared to the control (P ≤ 0.05). Conversely, at 100 ppm, catalase activity significantly increased (11.035 ± 1.12 units/mg of protein/min). Guaiacol peroxidase activity decreased across all nanoparticle concentrations. Furthermore, RT-qPCR analysis indicated increased expression of the studied genes at 300 ppm concentration. CONCLUSIONS: Hence, it can be inferred that at the transcript level, this nanoparticle exhibited efficacy in influencing the biosynthetic pathway of menthol.
Asunto(s)
Regulación de la Expresión Génica de las Plantas , Mentha piperita , Mentol , Nanopartículas , Titanio , Titanio/farmacología , Mentha piperita/efectos de los fármacos , Mentha piperita/metabolismo , Mentha piperita/genética , Mentol/metabolismo , Regulación de la Expresión Génica de las Plantas/efectos de los fármacos , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Hojas de la Planta/metabolismo , Hojas de la Planta/efectos de los fármacos , Hojas de la Planta/genética , Nanopartículas del Metal , Genes de Plantas , Peróxido de Hidrógeno/metabolismoRESUMEN
Transient receptor potential melastatin 8 (TRPM8) is a temperature- and menthol-sensitive ion channel that contributes to diverse physiological roles, including cold sensing and pain perception. Clinical trials targeting TRPM8 have faced repeated setbacks predominantly due to the knowledge gap in unraveling the molecular underpinnings governing polymodal activation. A better understanding of the molecular foundations between the TRPM8 activation modes may aid the development of mode-specific, thermal-neutral therapies. Ancestral sequence reconstruction was used to explore the origins of TRPM8 activation modes. By resurrecting key TRPM8 nodes along the human evolutionary trajectory, we gained valuable insights into the trafficking, stability, and function of these ancestral forms. Notably, this approach unveiled the differential emergence of cold and menthol sensitivity over evolutionary time, providing a fresh perspective on complex polymodal behavior. These studies provide a paradigm for understanding polymodal behavior in TRPM8 and other proteins with the potential to enhance our understanding of sensory receptor biology and pave the way for innovative therapeutic interventions.
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Frío , Mentol , Canales Catiónicos TRPM , Canales Catiónicos TRPM/metabolismo , Canales Catiónicos TRPM/genética , Humanos , Mentol/farmacología , Evolución Molecular , Filogenia , Sensación TérmicaRESUMEN
INTRODUCTION: In addition to imparting flavor, menthol in menthol-flavored cigarettes enhances nicotine addiction and increases experimentation, initiation, and progression to regular smoking. Menthol can be added to cigarettes at perceptible levels (so-called flavored cigarettes or characterized flavored cigarettes) or non-perceptible levels (subliminal). Our objective was to understand the reasons that tobacco companies use subliminal menthol. METHODS: We identified previously secret internal tobacco company documents dated 1955-2012 in the Truth Tobacco Industry Documents archive on menthol at subliminal levels. RESULTS: Beginning in at least the 1950s, tobacco companies used subliminal menthol to compensate the flavor loss caused by filters, reduce smoke harshness, reduce dryness, and increase smoke coolness. Varying menthol concentrations were considered to help convert people who smoke non-menthol to menthol brands, possibly because people who use menthol cigarettes have more harship quitting than people who use non-menthol cigarettes. CONCLUSIONS: Menthol is an important additive beyond its function as a "characterizing flavor." Tobacco companies use menthol in "non-menthol" cigarettes at subliminal (non-perceptible by the people who smoke cigarettes) levels to improve taste, make them easier to smoke and facilitate initiation, and possibly convert people who smoke non-menthol cigarettes to menthol cigarettes.
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Aromatizantes , Mentol , Productos de Tabaco , Humanos , Industria del TabacoRESUMEN
This present study aims to characterize the essential oil compositions of the aerial parts of M. spicata L. and endemic M. longifolia ssp. cyprica (Heinr. Braun) Harley by using GC-FID and GC/MS analyses simultaneously. In addition, it aims to perform multivariate statistical analysis by comparing with the existing literature, emphasizing the literature published within the last two decades, conducted on both species growing within the Mediterranean Basin. The major essential oil components of M. spicata were determined as carvone (67.8%) and limonene (10.6%), while the major compounds of M. longifolia ssp. cyprica essential oil were pulegone (64.8%) and 1,8-cineole (10.0%). As a result of statistical analysis, three clades were determined for M. spicata: a carvone-rich chemotype, a carvone/trans-carveol chemotype, and a pulegone/menthone chemotype, with the present study result belonging to the carvone-rich chemotype. Carvone was a primary determinant of chemotype, along with menthone, pulegone, and trans-carveol. In M. longifolia, the primary determinants of chemotype were identified as pulegone and menthone, with three chemotype clades being pulegone-rich, combined menthone/pulegone, and combined menthone/pulegone with caryophyllene enrichment. The primary determinants of chemotype were menthone, pulegone, and caryophyllene. The present study result belongs to pulegone-rich chemotype.
Asunto(s)
Cromatografía de Gases y Espectrometría de Masas , Mentha spicata , Mentha , Aceites Volátiles , Aceites Volátiles/química , Mentha/química , Mentha spicata/química , Análisis Multivariante , Región Mediterránea , Monoterpenos Ciclohexánicos/química , Monoterpenos Ciclohexánicos/análisis , Monoterpenos/química , Monoterpenos/análisis , Limoneno/química , Terpenos/química , Terpenos/análisis , MentolRESUMEN
INTRODUCTION: This study examined menthol cigarette use among youth who smoked, after menthol cigarette bans were implemented in England (May 2020) and Canada (October 2017). AIMS AND METHODS: Cross-sectional data come from 2021 ITC Youth Tobacco and Vaping Survey respondents aged 16-19 who smoked in the past 30 d in England (N = 715) and Canada (N = 419). Adjusted logistic regression models, estimated separately for each country, examined sociodemographic correlates of usually smoking menthol cigarettes (reporting currently most often smoking menthol cigarettes) overall, and by past 30-d use of any menthol accessories (e.g., filters, capsules). Youth reported the cigarette variety they smoked most often, coded as menthol or nonmenthol. RESULTS: Almost no youth who smoked in the past 30 d reported most often smoking a cigarette variety coded as menthol. However, 34.5% (95% CI: 30.4% to 38.9%) of youth who smoke in England and 30.9% (26.0%-36.3%) in Canada reported usually smoking menthol cigarettes, with greater odds of use among those identifying as black, or other race/ethnicity, respectively, compared to white in England (60.0%, aOR = 3.08, p = .001; 47.4%, aOR = 2.27, p = .011) and Canada (43.6%, aOR = 2.44, p = .046; 51.2%, aOR = 2.92, p = .001). Among those who reported usually smoking menthol cigarettes in England (N = 223) and Canada (N = 108), 71.7% (64.0%-78.2%) and 51.5% (41.1%-61.7%) reported using menthol accessories. CONCLUSIONS: After menthol cigarette bans in England and Canada, approximately one-third of youth who smoked reported usually smoking menthol cigarettes, with disproportionately higher use among those identifying as black and other race/ethnicity. Menthol accessories accounted for most menthol cigarette use. Closing regulatory loopholes is critical to advancing public health equity. IMPLICATIONS: Use of menthol cigarette accessories (eg, filters, cards, capsules) among youth who smoked was prevalent after implementation of menthol cigarette bans in England and Canada, and there was disproportionately higher use among those who identified as black and any other race/ethnicity. Efforts are therefore required to close regulatory loopholes of menthol cigarette bans. Findings further support countries, such as the United States, proposing menthol cigarette bans which extend coverage to accessories. More comprehensive menthol bans that also restrict accessories are likely to be more effective in reducing flavored tobacco use among young people and in advancing health equity.
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Mentol , Productos de Tabaco , Humanos , Adolescente , Inglaterra/epidemiología , Canadá/epidemiología , Masculino , Femenino , Productos de Tabaco/legislación & jurisprudencia , Productos de Tabaco/estadística & datos numéricos , Adulto Joven , Estudios Transversales , Fumar Cigarrillos/epidemiología , Fumar Cigarrillos/tendencias , Vapeo/epidemiología , Vapeo/legislación & jurisprudenciaRESUMEN
Effective removal of organic UV filters from aquatic environmental compartments and swimming waters is very important because these substances are hazardous to humans and wildlife at low concentrations and act as endocrine disruptors. Therefore, the aim of the present article is to determine the extraction efficiencies of hydrophobic deep eutectic solvents (HDES) for the selected UV filters based on benzophenone structure (benzophenone, 2,4-dihydroxybenzophenone, 2,2´,4,4´-tetrahydroxybenzophenone, 2-hydroxy-4-methoxybenzophenone, 2,2´-dihydroxy-4-methoxybenzophenone, 4-methacryloxy-2-hydroxybenzophenone) from aqueous matrices. For this purpose, six HDESs based on dl-menthol in combination with caprylic, decanoic and lauric acid are prepared and compared with referent terpene solvents such as terpineol and linalool. The effect of various parameters such as HDES composition, volume ratio, frequency and shaking time are studied. The highest extraction efficiency is shown by HDES of menthol:caprylic acid (1:1) composition at the aqueous:organic phase volume ratio of 1:1, shaking frequency of 1500â¯rpm and shaking time of 15â¯min. The achieved extraction efficiencies are higher than 99.6â¯% for all benzophenones studied in the purification of stagnant pond water, swimming pool water and river water samples. After a simple and fast sample treatment, the residual levels of benzophenones in the waters are controlled by a newly developed sensitive HPLC-MS/MS method with LOQs in the range of 0.7 - 5.0â¯ng/mL.
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Benzofenonas , Disolventes Eutécticos Profundos , Interacciones Hidrofóbicas e Hidrofílicas , Protectores Solares , Contaminantes Químicos del Agua , Purificación del Agua , Benzofenonas/química , Contaminantes Químicos del Agua/análisis , Contaminantes Químicos del Agua/química , Protectores Solares/química , Protectores Solares/toxicidad , Purificación del Agua/métodos , Disolventes Eutécticos Profundos/química , Mentol/química , Caprilatos/químicaRESUMEN
Introduction: Menthol cigarettes have been associated with increased smoking initiation. Although numerous studies have focused on correlates of menthol cigarette smoking among youths, fewer studies have assessed the prevalence and correlates of overall menthol-flavored tobacco product use among middle and high school students. Methods: We analyzed 2022 National Youth Tobacco Survey data to estimate the prevalence of menthol-flavored tobacco product use among US middle and high school students who used tobacco products within the past 30 days. Characteristics associated with menthol-flavored tobacco product use were also examined. Results: Use of menthol-flavored tobacco products was reported by 23.8% of students who currently used any tobacco product and by 39.5% of students who currently used any flavored tobacco product. Among students who reported past 30-day use of a flavored tobacco product, characteristics associated with a higher prevalence of menthol-flavored tobacco product use included non-Hispanic White race and ethnicity, frequent tobacco product use, use of multiple tobacco products, wanting to use a tobacco product within the first 30 minutes of awakening, and craving tobacco products within the past 30 days. Conclusion: Unlike results of prior research focused on cigarette smoking among young people, prevalence of use of any menthol-flavored tobacco product was highest among non-Hispanic White youths. Any use of menthol-flavored tobacco products of any type (alone or in combination with other flavors) among young people may be associated with continued product use and symptoms of dependence.
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Aromatizantes , Mentol , Estudiantes , Productos de Tabaco , Humanos , Adolescente , Masculino , Femenino , Productos de Tabaco/estadística & datos numéricos , Estados Unidos/epidemiología , Estudiantes/estadística & datos numéricos , Prevalencia , Niño , Encuestas y CuestionariosRESUMEN
INTRODUCTION: Menthol cigarettes are disproportionately marketed and advertised in the commercial tobacco retail environment in Black communities across the United States, contributing to menthol cigarette-related disparities and lower likelihood of successful quitting among Black people who smoke. Policies restricting retail sales of menthol cigarettes are aimed at preventing initiation, promoting quitting, and reducing related disparities. METHODS: Structured phone interview surveys were conducted from January to July 2021 with commercial tobacco retailers in Los Angeles County, California, unincorporated communities with a high percentage of Black residents, eight months after a local policy restricting retail sales of menthol cigarettes and other flavored nicotine and commercial tobacco products became effective on May 20, 2020. Interviews examined menthol cigarette sales restrictions-related knowledge, attitudes, and practices. RESULTS: Among 22 retailers interviewed, most (86.4%) reported having knowledge of the local ban on menthol cigarettes, and more than half (54.5%) reported offering price promotions for menthol cigarettes. Additionally, more than half (54.5%) reported believing customers who buy menthol cigarettes would stop smoking altogether following the ban. CONCLUSIONS: Most retailers reported having knowledge of the menthol ban, yet half reported offering price promotions for menthol cigarettes. Findings suggest retail availability of menthol cigarettes in Los Angeles County unincorporated communities with a high percentage of Black residents, post ban. Public health and policy implications are discussed.
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Comercio , Mentol , Productos de Tabaco , Humanos , Productos de Tabaco/economía , Productos de Tabaco/legislación & jurisprudencia , Comercio/legislación & jurisprudencia , Comercio/estadística & datos numéricos , Femenino , Masculino , Adulto , Negro o Afroamericano/estadística & datos numéricos , California , Conocimientos, Actitudes y Práctica en Salud , Persona de Mediana Edad , Cese del Hábito de Fumar/métodos , Cese del Hábito de Fumar/legislación & jurisprudencia , Los Angeles , Encuestas y CuestionariosRESUMEN
INTRODUCTION: The commercial tobacco industry has long targeted Black communities by making menthol cigarettes not only appealing but affordable through marketing, advertising, and pricing strategies, particularly in the retail environment. Policies that focus on restricting the sale of menthol cigarettes have the potential to significantly reduce the death toll from smoking while also mitigating health inequities and advancing racial equity. However, limited qualitative research exists on the perceptions of menthol cigarette sales restrictions, including local policies, among Black adults who smoke menthol cigarettes. AIMS AND METHODS: In-depth semi-structured interviews were conducted between January and September 2021 with self-identified non-Hispanic Black adults who reported current menthol cigarette use (nâ =â 26). Participants were asked open-ended questions about awareness and perceptions of the Los Angeles County law banning the retail sale of menthol cigarettes in unincorporated communities, including how it influences their smoking and purchasing behaviors. RESULTS: We used three thematic categories to structure the results: (1) Are People Aware of Local Menthol Cigarette Sales Restrictions? Levels of Awareness and Strategies to Increase Awareness, (2) Why Ban Menthol? Concerns About Equity and Fairness, and (3) Will Menthol Cigarette Bans Decrease Smoking? Mixed Perceptions About Potential Impact. Most participants (88.5%) had heard about the menthol ban in their communities. Participants described ambivalence towards the ban and identified several factors that hinder support, participation, and well-being, including uncertainty regarding the rationale for banning menthol cigarettes; perceptions that the ban specifically targets Black communities; and concerns regarding government overreach and constraining individual choice. Participants had differing views on whether the ban would likely help them and others who smoke menthol cigarettes reduce or quit smoking. Participants also described situations in which they would purchase menthol cigarettes in another state, country, online, or in the illicit market. Furthermore, participants often viewed the ban as perpetuating criminalization and over-policing of Black communities-arguments used by the commercial tobacco industry to oppose menthol bans. CONCLUSIONS: Our community-based sample of Black adults who smoke menthol cigarettes face challenges and concerns about local menthol bans. Community-centered interventions, messages, and materials about racial equity in menthol bans, access to free cessation services, and countering commercial tobacco industry interference, in addition to measurable steps toward rectifying injustice from the commercial tobacco industry and repeated exemptions of menthol cigarettes from federal legislation through tangible reparations, would be helpful to this community. IMPLICATIONS: We sought to add to the literature on flavored nicotine and commercial tobacco policies in the United States by centering the voices of Black adults who smoke menthol cigarettes regarding their awareness, perceptions, and opinions of local laws restricting menthol cigarette retail sales and how such polices influence their smoking and purchasing behaviors. Our findings suggest that Black adults who smoke menthol cigarettes are aware of local laws restricting menthol cigarette retail sales and are ambivalent about the rationale. Our findings have implications for the development and delivery of equity-focused strategies and resources to increase awareness of and rationale for the ban; counter commercial tobacco industry interference; and facilitate smoking cessation among Black adults who experience more combustible tobacco-related morbidity and mortality than their racial/ethnic counterparts. By understanding this relevance, we can also recognize how individual awareness and perceptions are moored within and contextualized by broader social structures and systemic inequities that warrant policy considerations.
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Negro o Afroamericano , Comercio , Mentol , Investigación Cualitativa , Productos de Tabaco , Humanos , Masculino , Femenino , Adulto , Negro o Afroamericano/psicología , Negro o Afroamericano/estadística & datos numéricos , Productos de Tabaco/legislación & jurisprudencia , Productos de Tabaco/economía , Persona de Mediana Edad , Los Angeles , Comercio/legislación & jurisprudencia , Industria del Tabaco/legislación & jurisprudencia , Adulto Joven , Fumadores/psicología , Fumadores/estadística & datos numéricosRESUMEN
Transdermal drug delivery is a formulation in which the drug is absorbed through the skin for systemic action. Its advantages include avoidance of first-pass effects, sustained drug supply, and ease of administration and discontinuation. Drugs administered transdermally transfer into the blood circulation through the stratum corneum, epidermis, and dermis. The stratum corneum on the skin surface plays a barrier function in skin absorption. Therefore, developing of transdermal drug delivery systems requires innovations that overcome the barrier function of the stratum corneum and improve skin permeation. This review examines the usefulness of transdermal formulations based on solid nanoparticles using raloxifene. Milled raloxifene was gelled with (mRal-NPs) or without menthol (Ral-NPs) using Carbopol. The drug release and transdermal penetration were measured using a Franz diffusion cell, and the therapeutic evaluation of osteoporosis was determined in an ovariectomized rat model. Although the raloxifene released from Ral-NPs remained in the nanoparticle state, the skin penetration of raloxifene nanoparticles was prevented by the stratum corneum in rat. The inclusion of menthol in the formulation attenuated the barrier function of the stratum corneum and permitted raloxifene nanoparticles to penetrate through the skin. Moreover, macropinocytosis relates to the formulation's skin penetration, including menthol (mRal-NPs). Applying mRal-NPs attenuated the decreases in calcium level and stiffness of bones of ovariectomized rats. This information can support future studies aimed at designing novel transdermal formulations.
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Administración Cutánea , Sistemas de Liberación de Medicamentos , Mentol , Nanopartículas , Clorhidrato de Raloxifeno , Absorción Cutánea , Animales , Clorhidrato de Raloxifeno/administración & dosificación , Clorhidrato de Raloxifeno/farmacocinética , Mentol/administración & dosificación , Nanopartículas/administración & dosificación , Ratas , Humanos , Piel/metabolismo , Nanotecnología , Liberación de Fármacos , Osteoporosis/tratamiento farmacológico , Femenino , Desarrollo de MedicamentosRESUMEN
INTRODUCTION: The Food and Drug Administration (FDA) has proposed banning cigarettes and cigars with characterizing flavors-products used disproportionately by African American/black (AA/B) individuals. Little is known about how AA/B individuals who smoke menthol cigarettes will respond to flavor bans or how to amplify the intended benefits. This study explored predictors of quit intentions following a hypothetical flavor ban and further probed anticipated ban-related responses. AIMS AND METHODS: We recruited 213 AA/B individuals who use menthol cigarettes from Richmond, VA (September 2021-August 2022) for a mixed-methods study. Participants rated seven motivations for quitting and six barriers to quitting (Not a motivation or challenge[1]-Major motivation or challenge[4]), then reported how likely they were to quit smoking if characterizing flavors were banned in cigarettes and cigars. A subsample of 31 participants completed semi-structured interviews to further explore reactions to flavor restriction policies. RESULTS: Multivariable linear regressions suggested that participants who were more motivated to quit smoking because of "information about health hazards" and the "cost of cigarettes" reported higher quit intentions following a hypothetical menthol ban (pâ <â .05). Additionally, those with cessation-related weight concerns reported lower post-ban quit intentions (pâ <â .05). Interview themes highlighted smoking for stress reduction, harm/addiction perceptions of flavored tobacco products, trusted sources of tobacco-related information (including testimonials from people who formerly smoked), potential ban responses, and varying experiences with cessation strategies. CONCLUSIONS: Culturally specific cessation strategies that emphasize the health-related benefits of quitting, particularly those featuring the experiences of people who formerly smoked, may help AA/B individuals who smoke menthol cigarettes quit following a menthol ban. IMPLICATIONS: For the FDA's proposed bans on characterizing flavors in cigarettes and cigars to advance racial health equity, they must maximize cessation among African American/black (AA/B) individuals who use menthol cigarettes. This work suggests information on the health hazards and costs of smoking, as well as concerns over gaining weight, were predictors of quit intentions in a hypothetical flavor ban. Qualitative data suggest messaging highlighting the experiences of individuals who successfully quit may constitute an effective communication strategy. These insights can be used in the development of culturally specific cessation strategies for AA/B individuals who smoke menthol cigarettes.
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Negro o Afroamericano , Aromatizantes , Intención , Mentol , Motivación , Cese del Hábito de Fumar , Productos de Tabaco , Humanos , Cese del Hábito de Fumar/psicología , Cese del Hábito de Fumar/métodos , Femenino , Masculino , Negro o Afroamericano/psicología , Negro o Afroamericano/estadística & datos numéricos , Adulto , Persona de Mediana Edad , Estados Unidos , Adulto JovenRESUMEN
INTRODUCTION: People's reaction to the FDA's ban on flavored cigarettes and cigars may be modified by a concurrent ban on flavored e-cigarettes. We aim to estimate the prevalence of smoking and e-cigarette use among U.S. adults under various ban scenarios. METHODS: We collected the reactions of people who used cigarettes, cigars, and e-cigarettes reactions to three hypothetical ban scenarios, (1) restricting menthol cigarettes and flavored cigars only, or (2) further restricting e-cigarettes with any flavors except menthol or tobacco, or (3) further restricting e-cigarettes with all flavors. The above data were analyzed to identify determinants of reactions and to estimate and calibrate the probabilities of quitting and switching to non-flavored cigarettes and cigars. Afterward, the probabilities were applied to 2018-2019 TUS-CPS respondents to estimate the prevalence of smoking and e-cigarette use. RESULTS: Compared with the baseline, the prevalence of smoking decreased from 12.6% to 10.5%, and e-cigarette use increased from 2.6% to 3.8% in Scenario No.1. In Scenario No.2 and No.3, the prevalence of smoking was 10.5% and 10.7%, and the prevalence of e-cigarette use were 3.1% and 2.4%, respectively. For black people, the prevalence of smoking decreased from 14.2% in baseline to 8.1%-8.8% in three scenarios. CONCLUSIONS: The result indicated that for a ban on menthol cigarettes and flavored cigars, a concurrent ban on flavored e-cigarettes with an exemption of menthol flavor could be more effective in encouraging people to quit smoking. Black people may see a disproportionate benefit from all ban scenarios compared with other race/ethics groups.
What is already known on this topic: ban menthol in cigarettes and flavored cigars increases quitting among people who currently smoke.What this study adds: For a ban on menthol cigarettes and flavored cigars, a concurrent ban on flavored e-cigarettes could be complementary if menthol flavor was exempted.How this study might affect research, practice or policy: For flavor bans, inventions to mitigate the increasing use of e-cigarettes and alternative tobacco products are needed, also the interventions should be tailored to various population segments.
Asunto(s)
Sistemas Electrónicos de Liberación de Nicotina , Aromatizantes , Mentol , Productos de Tabaco , Vapeo , Humanos , Adulto , Estados Unidos/epidemiología , Femenino , Masculino , Prevalencia , Sistemas Electrónicos de Liberación de Nicotina/estadística & datos numéricos , Adulto Joven , Productos de Tabaco/estadística & datos numéricos , Persona de Mediana Edad , Vapeo/epidemiología , Adolescente , Fumar/epidemiologíaRESUMEN
Bosentan is a drug used to treat pulmonary hypertension via dual endothelial receptor antagonism. Bosentan has a restricted oral bioavailability, a problem that's mostly due to poor solubility and hepatic metabolism. It is extensively used for the elderly and children who require a friendly dosage form like orodispersible tablets. So, the goal of this research work was to hasten the dissolution rate of bosentan to produce an orodispersible tablet with immediate drug release. Bosentan was exposed to ethanol-assisted kneading with a rise of xylitol or menthol concentrations (1:1 and 1:2 molar ratio of bosentan with excipient). In addition to observing the dissolution behavior, the resulting dry products were investigated using Fourier transform infrared spectroscopy (FTIR), differential thermal analysis (DTA), and X-ray diffraction (XRD). The FTIR reflected possible hydrogen bonding with xylitol and menthol. DSC studies reflected a reduction in the enthalpy and Tm. These results with XRD data reflected partial co-amorphization in the case of xylitol and eutaxia in the case of menthol. These modifications were related to an accelerated dissolving rate. The developed systems were fabricated as orodispersible tablets which exhibited immediate release of bosentan. Thus, the current study offered simple co-processing for the preparation of orodispersible bosentan tablets.
Asunto(s)
Bosentán , Mentol , Solubilidad , Comprimidos , Xilitol , Bosentán/química , Xilitol/química , Mentol/química , Administración Oral , Espectroscopía Infrarroja por Transformada de Fourier , Liberación de Fármacos , Difracción de Rayos X , Excipientes/química , Humanos , Composición de Medicamentos/métodos , Rastreo Diferencial de CalorimetríaRESUMEN
Oxidative stress and neuroinflammation in the aging brain are correlated with the development of neurodegenerative diseases, such as Alzheimer's disease (AD). The blood-brain barrier (BBB) poses a significant challenge to the effective delivery of therapeutics for AD. Prior research has demonstrated that menthol (Men) can augment the permeability of the BBB. Consequently, in the current study, we modified Men on the surface of liposomes to construct menthol-modified quercetin liposomes (Men-Qu-Lips), designed to cross the BBB and enhance quercetin (Qu) concentration in the brain for improved therapeutic efficacy. The experimental findings indicate that Men-Qu-Lips exhibited good encapsulation efficiency and stability, successfully crossed the BBB, improved oxidative stress and neuroinflammation in the brains of aged mice, protected neurons, and enhanced their learning and memory abilities.