RESUMO

Resumen La seguridad de los psicofármacos durante el embarazo es un tema crucial en la práctica clínica. En esta revisión, se hace un breve recorrido sobre los cambios en el embarazo que impactan en la farmacodinamia de los medicamentos, además, se analizan los principales grupos farmacológicos en psiquiatría y sus efectos durante el embarazo. Se identifican tres períodos críticos durante el embarazo. El período de las primeras dos semanas se asocia con un mayor riesgo de aborto espontáneo. El período de la segunda a la décima semana es el más riesgoso, ya que pueden ocurrir alteraciones teratogénicas que afectan el desarrollo fetal. El período posterior a la décima semana se caracteriza por alteraciones en el crecimiento y desarrollo funcional del feto, pero suelen ser menos graves. Los antidepresivos, especialmente los inhibidores selectivos de la receptación de serotonina (ISRS) y los antipsicóticos de segunda generación se consideran los más seguros, pero estos últimos pueden estar asociados con síndrome metabólico, cardiopatías congénitas y trastornos del neurodesarrollo. El litio se ha asociado con efectos teratogénicos y malformaciones cardíacas, mientras que el valproato está relacionado con defectos congénitos importantes. Las benzodiacepinas pueden tener efectos tóxicos y causar síndrome de abstinencia en el recién nacido. La seguridad de los psicofármacos durante el embarazo requiere una evaluación individualizada de los beneficios y riesgos. Aunque algunos grupos de psicofármacos se consideran relativamente seguros, es necesario tener precaución y considerar las posibles complicaciones asociadas con su uso durante el embarazo.

Abstract: The safety of psychoactive drugs during pregnancy is a crucial issue in clinical practice. In this review, a brief overview of the changes in pregnancy that impact the pharmacodynamics of drugs is made; in addition, the main pharmacological groups in psychiatry and their effects during pregnancy are analyzed. Three critical periods during pregnancy are identified. The period of the first two weeks is associated with an increased risk of miscarriage. The period from the second to the tenth week is the most at risk , since teratogenic effects that affect fetal development can take place. The period after the tenth week is characterized by alterations in fetal growth and functional development , however ,less severe defects. Antidepressants, especially selective serotonin reuptake inhibitors (SSRIs), and second-generation antipsychotics are considered the safest, but the latter may be associated with metabolic syndrome, congenital heart disease, and neurodevelopmental disorders. Lithium has been associated with teratogenic effects and cardiac malformations, while valproate is associated with major birth defects. Benzodiazepines can have toxic effects and cause Neonatal Withdrawal Syndrome . The safety of psychotropic drugs during pregnancy requires an individualized assesment of the benefits and risks. Although some groups of psychiatric drugs are considered relatively safe, caution is needed when considering the potential complications associated with their use during pregnancy.

RESUMO

Valproic acid (VA) is a widely used drug for the treatment of diseases affecting the central nervous system. Due to its epigenetic modulatory potential, it has been studied for possible therapeutic application in anticancer therapies. However, the VA exhibits different side effects in its application. Thus, synthetic coordination complexes with valproate can generate promising candidates for new active drugs with reduced toxicity. In this sense, we investigated the genotoxic and mutagenic potential of the sodium valproate and of the mixed ternary mononuclear Mg complex based on VA with 1,10-phenanthroline (Phen) ligand - [Mg (Valp)2Phen], in Saccharomyces cerevisiae and V79 cells. The MTT and clonal survival assays in V79 cells indicated that the Mg complex has higher cytotoxicity than sodium valproate. A similar cytotoxicity profile is observed in yeast. This fact is possibly due to the intercalation capacity of [Mg(Valp)2Phen], inducing DNA strand breaks, as observed in the comet assay and micronucleus test. In this sense, members of the NER, HR, NHEJ and TLS repair pathways are required for the repair of DNA lesions induced by [Mg(Valp)2Phen]. Interestingly, BER proteins apparently increase the cytotoxic potential of the drug. Furthermore, the [Mg(Valp)2Phen] showed higher cytotoxicity in V79 cells and yeast when compared to sodium valproate indicating applicability as a cytotoxic agent.

RESUMO

Cutaneous adverse drug reactions, or pharmacodermias, are the most common form of adverse drug reactions (ADR). It was our interest to know their epidemiological behavior in a tertiary hospital level in Mexico. We stablished the frequency of ADR in 61 infants and adults hospitalized patients and those seen in the outpatient Dermatology Clinic at the National Institute of Cardiology Ignacio Chávez in Mexico City (INCICh) over a period of 10 years. The most frequently diagnosed pharmacodermias were acneiform dermatitis, cutaneous hyperpigmentation and maculopapular exanthema mainly associated to prednisone, hydroxychloroquine, cephalothin, amiodarone and vitamin B-complex, although we registered less frequently more severe and hazardous reactions. These results were consistent with other reports in our country. Multiple drugs administered at a time was an important causative factor for the ADR. It is necessary for every practitioner to develop skills that permit the identification of these dermatoses in order to correctly manage each case and diminish the morbimortality associated.

Las reacciones adversas cutáneas a medicamentos o farmacodermias constituyen la forma más común de las reacciones adversas a medicamentos (RAM), por lo que fue nuestro interés conocer su comportamiento epidemiológico en un hospital de tercer nivel en México. Establecimos su frecuencia en 61 pacientes, infantes y adultos, hospitalizados y de la Consulta externa de Dermatología en el Instituto Nacional de Cardiología Ignacio Chávez (INCICh) en la Ciudad de México, en 10 años, y encontramos que la reacciones más frecuentes fueron la dermatitis acneiforme, la hiperpigmentación cutánea y el exantema maculopapular principalmente asociados a prednisona, hidroxicloroquina, cefalotina, amiodarona y complejo B, aunque con menos frecuencia registramos reacciones más graves, lo cual es consistente con otros reportes similares en nuestro país. La polifarmacia de la mayoría de los pacientes que presentaron estas RAM fue un factor determinante en su presentación. Es fundamental desarrollar habilidades para reconocer el cuadro clínico de estas dermatosis, con el fin de abordar correctamente cada caso y disminuir la morbimortalidad de las RAM.

RESUMO

To analyze stigma related to depression, beliefs about psychotropics, and associated factors in a population of Japanese ancestry in Brazil. This cross-sectional study was conducted between March and June, 2022. Beliefs about psychotropics (BMQ-specific) and depression-related stigma (The Stigma Scale) were collected through an online questionnaire. Multiple linear regression analysis was performed to identify the factors associated with these dependent variables. Ninety-three respondents of Japanese ancestry completed the questionnaire. Participants were more focused on the necessity of the prescribed psychotropics than on possible adverse effects. Married individuals (ß=-4.68 [95%CI -8.74, -0.63]; p = 0.024) were less concerned with their psychotropics than single individuals, while those undergoing treatment for longer years (ß = 6.23 [95%CI 1.35, 11.11]; p = 0.013) perceive a greater necessity for treatment than those who started it recently. In addition, older individuals perceived less necessity for treatment (ß=-5.83 [95%CI -10.76, -0.90]; p = 0.021) than younger individuals. Unemployed people (ß = 12.09 [95%CI 0.47, 23.70]; p = 0.042) perceived more depression-related stigma than those employed. Aspects of Japanese cultural heritage related to depression and its treatment are still prevalent among people of Japanese ancestry in Brazil. Factors such as age, treatment duration, and marital status affects the perception of beliefs about psychotropics, whereas occupation affects the perception of stigma.

RESUMO

The Target-Based Virtual Screening approach is widely employed in drug development, with docking or molecular dynamics techniques commonly utilized for this purpose. This systematic review (SR) aimed to identify in silico therapeutic targets for treating Diabetes mellitus (DM) and answer the question: What therapeutic targets have been used in in silico analyses for the treatment of DM? The SR was developed following the guidelines of the Preferred Reporting Items Checklist for Systematic Review and Meta-Analysis, in accordance with the protocol registered in PROSPERO (CRD42022353808). Studies that met the PECo strategy (Problem, Exposure, Context) were included using the following databases: Medline (PubMed), Web of Science, Scopus, Embase, ScienceDirect, and Virtual Health Library. A total of 20 articles were included, which not only identified therapeutic targets in silico but also conducted in vivo analyses to validate the obtained results. The therapeutic targets most frequently indicated in in silico studies were GLUT4, DPP-IV, and PPARγ. In conclusion, a diversity of targets for the treatment of DM was verified through both in silico and in vivo reassessment. This contributes to the discovery of potential new allies for the treatment of DM.

Assuntos

RESUMO

Dronedarone (DRN) is a clinically used drug to mitigate arrhythmias with multichannel block properties, including the sodium channel Nav1.5. Extracellular acidification is known to change the pharmacological properties of several antiarrhythmic drugs. Here, we explore how modification in extracellular pH (pHe) shapes the pharmacological profile of DRN upon Nav1.5 sodium current (INa) and in the ex vivo heart preparation. Embryonic human kidney cells (HEK293T/17) were used to transiently express the human isoform of Nav1.5 α-subunit. Patch-Clamp technique was employed to study INa. Neurotoxin-II (ATX-II) was used to induce the late sodium current (INaLate). Additionally, ex vivo Wistar male rat preparations in the Langendorff system were utilized to study electrocardiogram (ECG) waves. DRN preferentially binds to the closed state inactivation mode of Nav1.5 at pHe 7.0. The recovery from INa inactivation was delayed in the presence of DRN in both pHe 7.0 and 7.4, and the use-dependent properties were distinct at pHe 7.0 and 7.4. However, the potency of DRN upon the peak INa, the voltage dependence for activation, and the steady-state inactivation curves were not altered in both pHe tested. Also, the pHe did not change the ability of DRN to block INaLate. Lastly, DRN in a concentration and pH dependent manner modulated the QRS complex, QT and RR interval in clinically relevant concentration. Thus, the pharmacological properties of DRN upon Nav1.5 and ex vivo heart preparation partially depend on the pHe. The pHe changed the biological effect of DRN in the heart electrical function in relevant clinical concentration.

Assuntos

RESUMO

Approximately 30% of people with epilepsy will be refractory. This manuscript reviews current evidencebased non-surgical treatment modalities for pediatric refractory epilepsy, including pharmacological and dietary strategies.

Aproximadamente el 30% de las personas con epilepsia será refractaria. Este manuscrito revisa las modalidades actuales y basadas en la evidencia de tratamientos no quirúrgicos para la epilepsia refractaria pediátrica, incluyendo estrategias farmacológicas y dietéticas.

Assuntos

RESUMO

BACKGROUND: Algae-derived nutraceuticals, such as spirulina, have been reported to have biological activities that may minimize clinical consequences to COVID-19 infections. OBJECTIVES: This study aimed to determine whether spirulina is an effective treatment for high-risk patients with early COVID-19 in an outpatient setting. METHODS: The TOGETHER trial is a placebo-controlled, randomized, platform trial conducted in Brazil. Eligible participants were symptomatic adults with a positive rapid test for SARS-CoV-2 older than 50 y or with a known risk factor for disease severity. Patients were randomly assigned to receive placebo or spirulina (1 g twice daily for 14 d). The primary end point was hospitalization defined as either retention in a COVID-19 emergency setting for >6 h or transfer to tertiary hospital owing to COVID-19 at 28 d. Secondary outcomes included time-to-hospitalization, mortality, and adverse drug reactions. We used a Bayesian framework to compare spirulina with placebo. RESULTS: We recruited 1126 participants, 569 randomly assigned to spirulina and 557 to placebo. The median age was 49.0 y, and 65.3% were female. The primary outcome occurred in 11.2% in the spirulina group and 8.1% in the placebo group (odds ratio [OR]: 1.24; 95% credible interval: 0.84, 1.86). There were no differences in emergency department visit (OR: 1.21; 95% credible interval: 0.81, 1.83), nor time to symptom relief (hazard ratio: 0.90; 95% credible interval: 0.79, 1.03). Spirulina also not demonstrate important treatment effects in the prespecified subgroups defined by age, sex, BMI, days since symptom onset, or vaccination status. CONCLUSIONS: Spirulina has no any clinical benefits as an outpatient therapy for COVID-19 compared with placebo with respect to reducing the retention in an emergency setting or COVID-19-related hospitalization. There are no differences between spirulina and placebo for other secondary outcomes. This trial was registered at clinicaltrials.gov as NCT04727424.

Assuntos

RESUMO

This essay examines the combination of psychoanalytic therapy and psychedelic substances in mid-20th century Argentina. Through document analysis, it examines the intersection of psychedelics and psychoanalysis, drawing from historical texts and writings by local psychoanalysts to develop a comprehensive understanding of the distinctive clinical practices and therapeutic approaches in the Argentine context. It details the experimental use of these substances, the clinical practices developed, and the professional and societal challenges encountered. Notably, psychoanalysts Luisa de Álvarez de Toledo, Alberto Tallaferro, and Alberto Fontana conducted pioneering research, exploring the therapeutic potential of these substances and publishing their findings in academic papers and books. According to these psychoanalysts, the use of psychedelic drugs in therapy could enhance transference, catalyze catharsis, and circumvent unconscious defenses, allowing for a vivid exploration of the patient's psyche that necessitated interpretation. Despite the innovative nature of this work, resistance from within the Argentine Psychoanalytic Association led to the eventual cessation of psychedelic research in this country. The essay calls for a reconsideration of the psychoanalytic community's relationship with psychedelics, emphasizing the potential for renewed dialogue and incorporation of these substances in contemporary therapeutic practices. In conclusion, this article sheds light on an overlooked chapter of psychoanalysis in a local setting and serves as a call for future explorations in broader scenarios. The resurgence of interest in psychedelics for mental health treatment presents an opportunity for psychoanalysts to engage with emerging research, enriching both theory and practice.

RESUMO

Introduction: We conducted an extensive, sex-oriented real-world data analysis to explore the impact and safety of non-steroidal anti-inflammatory drugs (NSAIDs) and selective COX-2 inhibitors (coxibs) on cancer treatment outcomes. This is particularly relevant given the role of the COX-2/PGE2 pathway in tumor cell resistance to chemotherapy and radiotherapy. Methods: The study applied a retrospective cohort design utilizing the TriNetX research database consisting of patients receiving cancer treatment in 2008-2022. The treated cohorts included patients who were prescribed with coxibs, aspirin or ibuprofen, while individuals in the control cohort did not receive these medicines during their cancer treatment. A 1:1 propensity score matching technique was used to balance the baseline characteristics in the treated and control cohorts. Then, Cox proportional hazards regression and logistic regression were applied to assess the mortality and morbidity risks among patient cohorts in a 5-year follow-up period. Results: Use of coxibs (HR, 0.825; 95% CI 0.792-0.859 in females and HR, 0.884; 95% CI 0.848-0.921 in males) and ibuprofen (HR, 0.924; 95% CI 0.903-0.945 in females and HR, 0.940; 95% CI 0.917-0.963 in males) were associated with improved survival. Female cancer patients receiving aspirin presented increased mortality (HR, 1.078; 95% CI 1.060-1.097), while male cancer patients also had improved survival when receiving aspirin (HR, 0.966; 95% CI 0.951-0.980). Cancer subtype specific analysis suggests coxibs and ibuprofen correlated with survival, though ibuprofen and aspirin increased emergency department visits' risk. Secondary analyses, despite limited by small cohort sizes, suggest that COX inhibition post-cancer diagnosis may benefit patients with specific cancer subtypes. Discussion: Selective COX-2 inhibition significantly reduced mortality and emergency department visit rates. Further clinical trials are needed to determine the optimal conditions for indication of coxibs as anti-inflammatory adjuvants in cancer treatment.

RESUMO

A differential diet with royal jelly (RJ) during early larval development in honeybees shapes the phenotype, which is probably mediated by epigenetic regulation of gene expression. Evidence indicates that small molecules in RJ can modulate gene expression in mammalian cells, such as the fatty acid 10-hydroxy-2-decenoic acid (10-HDA), previously associated with the inhibition of histone deacetylase enzymes (HDACs). Therefore, we combined computational (molecular docking simulations) and experimental approaches for the screening of potential HDAC inhibitors (HDACi) among 32 RJ-derived fatty acids. Biochemical assays and gene expression analyses (Reverse Transcriptase - quantitative Polymerase Chain Reaction) were performed to evaluate the functional effects of the major RJ fatty acids, 10-HDA and 10-HDAA (10-hydroxy-decanoic acid), in two human cancer cell lines (HCT116 and MDA-MB-231). The molecular docking simulations indicate that these fatty acids might interact with class I HDACs, specifically with the catalytic domain of human HDAC2, likewise well-known HDAC inhibitors (HDACi) such as SAHA (suberoylanilide hydroxamic acid) and TSA (Trichostatin A). In addition, the combined treatment with 10-HDA and 10-HDAA inhibits the activity of human nuclear HDACs and leads to a slight increase in the expression of HDAC-coding genes in cancer cells. Our findings indicate that royal jelly fatty acids collectively contribute to HDAC inhibition and that 10-HDA and 10-HDAA are weak HDACi that facilitate the acetylation of lysine residues of chromatin, triggering an increase in gene expression levels in cancer cells.

Assuntos

RESUMO

Aim: Identifying drugs of abuse and their metabolites in plasma is vital in both forensic and clinical toxicology. While the QuEChERS (Quick, Easy, Cheap, Effective, Rugged and Safe) method offers an efficient approach to sample preparation, its application is complex due to the wide-ranging properties of target analytes and the challenges posed by biological matrix interferences. This study aims to develop a microQuEChERS approach for the quantification of 14 drugs of abuse and metabolites utilizing minimal sample and solvent volumes.Methods: The microQuEChERS method involved using 10 µl plasma samples, 25 mg of a salt mixture and 150 µl of acetonitrile. Extracts were analyzed by liquid chromatography-tandem mass spectrometry (LC-MS/MS), with a 7.5 min run. The assay was validated according to bioanalytical guidelines.Results: The accuracy was 96.8-112.4%. The within-assay precision was within 2.0-8.9% and the between-assay precision was within 3.2-8.2%. Matrix effects were found to range from -5.7 to 13.5%. The extraction yield was higher than 74.7%.Conclusion: This study described a microQuEChERS sample preparation approach for determining drugs of abuse and metabolites using plasma microsamples and LC-MS/MS. The approach is efficient, environmentally friendly and suitable for scenarios with limited amounts of biological samples.

[Box: see text].

RESUMO

This study assessed the occurrence and ecological potential risk of nine selected pharmaceuticals in water samples from the Juquehy River. The river flows continuously to Juquehy Beach, known as "the jewel of the north coast" of São Paulo, Brazil. Samples were collected during Christmas and the New Year (period of December 2023-January 2024), in addition to a previous baseline weekend, to compare the loads during "celebratory parties" versus "normal operational conditions." The findings indicated that the "mass gathering" during Christmas and New Year holidays contributed significantly to an increase of the mass load of the nine pharmaceuticals flowing along to the Juquehy River, i.e., caffeine (14.40-633.00 ng/L) > losartan ( furosemide (< LOQ to 9.16 ng/L) > diclofenac (0.61-4.55 ng/L) > carbamazepine (< LOQ to 0.73 ng/L) > orphenadrine (< LOQ to 0.11 ng/L) showed higher concentrations during the New Year holiday. Conversely, atenolol (< LOQ to 13.10 ng/L) > benzoylecgonine (0.33-7.23 ng/L) > cocaine (0.12-6.59 ng/L) showed higher concentrations during the Christmas day. The individual ecological risk assessment in the Juquehy River revealed a clear environmental concern for the aquatic ecosystem. The threat to the aquatic biota is significant, with caffeine and losartan presenting a moderate level of risk. Moreover, the mixture ecological risk assessment of nine compounds indicates acute moderate risks to algae, crustaceans, and fishes, as well as chronic low risks to fishes.

RESUMO

Resumen Introducción : Las consecuencias económicas de la cobertura obligatoria, vía judicial, de medicamentos de alto precio constituye un problema creciente, que amerita conocer sus características locales para aportar posibles soluciones. Objetivo : Identificar medicamentos, enfermedades, impacto económico y factores contextuales de la ju dicialización de medicamentos de alto precio (MEP) Argentina. Métodos : Estudio descriptivo cuali-cuantitativo que analizó retrospectivamente recursos de amparos legales por MEP de tres bases de datos nacionales y provinciales durante 4 años, evaluando relación existente entre am paros con aprobación regulatoria, inclusión de los MEP al paquete de beneficios y relación con notas periodísticas. Resultados : Se incluyeron 405 amparos provenientes principalmente del Ministerio de Salud Nacional. Los tres medicamentos más judicializados fueron nusiner sen (21.7%), palbociclib (5.9%) y agalsidasa-alfa (4.7%). Solo el 69.4% de los medicamentos se encontraban aprobados para la comercialización en Argentina al momento del amparo; el 45.7% se encontraban incorpo rados al Sistema Único de Reintegros y el 16.8% contaban con informe de la Comisión Nacional de Evaluación de Tecnologías Sanitarias y Excelencia Clínica (CONETEC), negativa en el 87.1% de casos. El tiempo promedio des de la solicitud hasta la provisión del medicamento fue de 150 días. Se observó una correlación temporal entre la aparición del MEP en la prensa nacional gráfica y la presentación de amparos de dicho MEP. Conclusiones : La judicialización se concentró en medicamentos de altísimo precio para enfermedades poco frecuentes u oncológicas. Los fallos fueron mayo ritariamente a favor del demandante, siendo los tiempos de acceso al medicamento prolongados. Los medios de comunicación anticiparon los procesos judiciales.

Abstract Introduction : The economic consequences of manda tory coverage, through judicial means, of high-priced medications constitutes a growing problem, which mer its knowing its local characteristics to provide possible solutions. Objective : To identify medications, diseases involved, economic impact and contextual factors of the judi cialization of high-priced medications in the Argentine Health System(MEP). Methods : Quali-quantitative descriptive study that retrospectively analyzed legal protection resources by MEP from three national and provincial databases from January 2017 to December 2020, evaluating the exist ing relationship between lawsuits with regulatory ap proval, inclusion in benefit packages and relationship with journalistic articles for the three most frequently prosecuted drugs. Results : 405 lawsuits were included, mainly from the Ministry of National Health. The three most prosecuted medications were nusinersen (21.7%), palbociclib (5.9%) and agalsidase-alfa (4.7%). Only 69.4% of medications were approved for marketing in Argentina at the time of the protection; 45.7% were incorporated into the Single Reimbursement System, and 16.8% had a report from the National Commission for the Evaluation of Health Technologies and Clinical Excellence (CONETEC), which was negative in 87.1% of cases. The average time from request to provision of the medication was 150 days. A temporal correlation was observed between the appear ance of the MEP in the national graphic press and the appeals occurrence. Conclusions : Judicialization focused on very high-priced medications for rare or oncological diseases. The rulings were mostly in favor of the plaintiff, and access times to the medication took a long time. The mass media anticipated the judicial processes.

RESUMO

OBJECTIVE: Tumor hypoxia is associated with a poorer prognosis in cancer patients and can diminish the efficacy of radiation therapy (RT). This study investigates the potential of metformin to enhance radiosensitivity in hypoxic cancer cells. METHODS: Preliminary experiments were conducted to validate the impact of hypoxia on radiation response. Reactive oxygen species (ROS) levels, cell migration, and cell death were assessed in hypoxic, radiated cells treated with metformin. Proteomic and ontological analyses were employed to identify molecular targets associated with the radiosensitizing effect of metformin. Proteomic and ontological findings were validated through patient samples and in vitro studies. RESULTS: Metformin amplified cell death, induced DNA fragmentation, decreased cell migration, and elevated ROS levels in hypoxic, radiated cells. Proteomic analyses revealed that GAPDH and TAGLN2 were identified as pivotal targets linked to the radiosensitizing effect of metformin. Oral cancer patients exhibited elevated levels of TAGLN2 and reduced levels of GAPDH. Metformin downregulated TAGLN2 and upregulated GAPDH in hypoxic, radiated cells. Additionally, metformin reduced levels of mutated p53. CONCLUSIONS: This study suggests that metformin can enhance radiosensitivity in hypoxic cells, operating through modulation of GAPDH and TAGLN2. Furthermore, metformin effectively reduces mutated p53 levels in radiated cells under hypoxic conditions.

Assuntos

RESUMO

Rosacea is a chronic dermatological condition that currently lacks a clear treatment approach due to an uncomprehensive knowledge of its pathogenesis. The main obstacle lies in understanding its etiology and the mode of action of the different drugs used. This study aims to clarify these aspects by employing drug repositioning. Using an in silico approach, we performed a transcriptomic analysis comparing samples from individuals with diverse types of rosacea to those from healthy controls to identify genes deregulated in this disease. Subsequently, we realized molecular docking and molecular dynamics studies to assess the binding affinity of drugs currently used to treat rosacea and drugs that target proteins interacting with, and thus affecting, proteins deregulated in rosacea. Our findings revealed that the downregulation of SKAP2 and upregulation of S100A7A in rosacea, could be involved in the pathogenesis of the disease. Furthermore, considering the drugs currently used for rosacea management, we demonstrated stable interactions between isotretinoin and BFH772 with SKAP2, and permethrin and PAC-14028 with S100A7A. Similarly, considering drugs targeting SKAP2 and S100A7A interactome proteins, we found that pitavastatin and dasatinib exert stable interactions with SKAP2, and lovastatin and tirbanibulin with S100A7A. In addition, we determine that the types of bonds involved in the interactions were different in SKAP2 from S100A7A. The drug-SKAP2 interactions are hydrogen bonds, whereas the drug-S100A7A interactions are of the hydrophobic type. In conclusion, our study provides evidence for the possible contribution of SKAP2 and S100A7A to rosacea pathology. Furthermore, it provides significant information on the molecular interactions between drugs and these proteins, highlighting the importance of considering structural features and binding interactions in the design of targeted therapies for skin disorders such as rosacea.

Assuntos

RESUMO

In the pursuit of new lead compounds with fewer side effects than opioids, the novel synthetic phytochemical core, 3,3-dibromoflavanone (3,3-DBF), has emerged as a promising candidate for pain management. Acute assays demonstrated dose-dependent central and peripheral antinociceptive activity of 3,3-DBF through the µ-opioid receptor. This study aimed to explore repeated administration effects of 3,3-DBF in mice and compare them with morphine. Mice were treated with 3,3-DBF (30 mg/kg), morphine (6 mg/kg), or vehicle for 10 days, alongside single-treatment groups. Unlike morphine, 3,3-DBF demonstrated antinociceptive effects in the hot plate test without inducing tolerance. Locomotor activity and motor coordination tests (evaluated through the inverted screen and rotarod tests) revealed no significant differences between the 3,3-DBF-treated and control groups. The gastrointestinal transit assay indicated that 3,3-DBF did not induce constipation, in contrast to morphine. Furthermore, withdrawal signs assessed with the Gellert-Holtzman scale were not comparable to morphine. Additionally, 3,3-DBF exhibited antidepressant-like activity, reducing immobility time in the forced swimming and tail suspension tests, akin to imipramine. In summary, 3,3-DBF demonstrated antinociceptive effects without inducing tolerance or dependence and exhibited antidepressant properties. These findings highlight the potential of 3,3-DBF as a promising therapeutic agent for pain management and its comorbidities, offering advantages over morphine by minimizing side effects.

Assuntos

RESUMO

The development of new methods of identification of active pharmaceutical ingredients (API) is a subject of paramount importance for research centers, the pharmaceutical industry, and law enforcement agencies. Here, a system for identifying and classifying pharmaceutical tablets containing acetaminophen (AAP) by brand has been developed. In total, 15 tablets of 11 brands for a total of 165 samples were analyzed. Mid-infrared vibrational spectroscopy with multivariate analysis was employed. Quantum cascade lasers (QCLs) were used as mid-infrared sources. IR spectra in the spectral range 980-1600 cm-1 were recorded. Five different classification methods were used. First, a spectral search through correlation indices. Second, machine learning algorithms such as principal component analysis (PCA), support vector classification (SVC), decision tree classifier (DTC), and artificial neural network (ANN) were employed to classify tablets by brands. SNV and first derivative were used as preprocessing to improve the spectral information. Precision, recall, specificity, F1-score, and accuracy were used as criteria to evaluate the best SVC, DEE, and ANN classification models obtained. The IR spectra of the tablets show characteristic vibrational signals of AAP and other APIs present. Spectral classification by spectral search and PCA showed limitations in differentiating between brands, particularly for tablets containing AAP as the only API. Machine learning models, specifically SVC, achieved high accuracy in classifying AAP tablets according to their brand, even for brands containing only AAP.

Assuntos

RESUMO

Given the scarcity of studies addressing substance consumption and its relationship with attachment styles and early maladaptive schemas in adolescents, the present study is proposed. Aims of this study are to analyze the relationship among attachment styles, early maladaptive schemas, and substance use; test the predictive role of attachment styles on substance use; and observe the mediating role of early maladaptive schemas in the relationship between attachment and substance use. The sample consisted of 1533 adolescents from Ecuador (53.9% males) aged between 14 and 18 years (M = 15.76; SD = 1.25). The attachment styles of security, value to parental authority, parental permissiveness, parental interference, self-sufficiency and resentment against parents, childhood trauma, and family concern predict substance use (tobacco, alcohol, tranquilizers/sedatives or sleeping pills, hashish or marijuana, cocaine, GHB or liquid ecstasy, ecstasy, amphetamines/speed, hallucinogens, heroin, inhalants/volatiles), and the mediating role of early maladaptive schemas is confirmed (explained variance up to 33.33%). Identifying risk or vulnerability factors, such as attachment and early maladaptive schemas related to substance consumption, is especially relevant for designing and implementing preventive interventions in the adolescent population.

Assuntos

RESUMO

BACKGROUND: It has been documented that NSAIDs (nonsteroidal anti-inflammatory and antirheumatic drugs) reduce the effectiveness of some antihypertensive drugs. OBJECTIVE: Analyze the prescription of NSAID and the variables associated in outpatients with hypertension and explore some characteristics of the physicians. MATERIAL AND METHODS: Cross-sectional study, included patients with hypertension from the Family Medicine Unit No. 24 in Mante, Tamaulipas. From the patients, sociodemographic data, clinical history and pharmacological treatments were obtained. From the physicians, sociodemographic and academic information were collected. RESULTS: Mean age of the patients was 63 ± 11 years and 31.7% were prescribed NSAIDs. When compare exposed versus non-exposed to NSAIDs, being in uncontrolled high blood pressure, uncontrolled hypertension, multimorbidity and polypharmacy. The variables associated to the prescription of NSAIDs were: uncontrolled hypertension, multimorbidity and polypharmacy. The 56.7% of the physicians were women, 83.3% with experience >10 years and 33.3% with current certification by the Council in Family Medicine. CONCLUSIONS: The inappropriate prescription of NSAIDs revealed the need to implement actions to mitigate the potential risk for the hypertension patients to present a complication.

ANTECEDENTES: Los antiinflamatorios y los antirreumáticos no esteroideos (AINE) disminuyen la eficacia de algunos antihipertensivos. OBJETIVO: Analizar el patrón de prescripción de AINE y las variables asociadas en pacientes ambulatorios con diagnóstico de hipertensión arterial, así como explorar algunas características de los médicos prescriptores. MATERIAL Y MÉTODOS: Estudio transversal de pacientes con hipertensión de la Unidad de Medicina Familiar 24 en Ciudad Mante, Tamaulipas. De los pacientes se registraron datos sociodemográficos, antecedentes patológicos y tratamientos farmacológicos; y de los médicos, información sociodemográfica y académica. RESULTADOS: La edad promedio de los pacientes fue de 63 ± 11 años, 31.7 % recibía AINE y al contrastarlos con quienes no los recibían, se identificó mayor proporción de obesidad, presión arterial más elevada, más casos en descontrol de la hipertensión arterial, multimorbilidad y polimedicación. Las variables asociadas a la prescripción de AINE fueron estar en descontrol de la hipertensión arterial, multimorbilidad y polimedicación; 56.7 % de los médicos prescriptores fue del sexo femenino, 83.3 % con antigüedad superior a 10 años y 33.3 % con certificación vigente. CONCLUSIONES: La prescripción inapropiada de AINE reveló la necesidad de implementar acciones para mitigar el riesgo potencial de los pacientes hipertensos de presentar una complicación.

Assuntos