Ciencias Biosanitarias

The Successful and Safe Real-Time TDM-Guided Treatment of Invasive Pulmonary Aspergillosis Using Isavuconazole Administered by Enteral Tube

2026-07-20T07:21:25Z

Background: Invasive aspergillosis (IA) is an opportunistic infection that affects immuno compromised patients. While voriconazole is commonly used for IA treatment, it presents the risk of drug interactions, particularly in patients on polytherapy. Isavuconazole may serve as a safer alternative with fewer interactions. However, the use of isavuconazole is typically limited to the parenteral route for patients without access to the enteral route, due to recommendations against tablet handling for enteral administration. The objective of this study was to evaluate the suitability of isavuconazole administration via an enteral tube, by therapeutic drug monitoring of isavuconazole plasma concentrations. Methods: This case study examines a patient with diffuse large B-cell lym phoma who was diagnosed with IA and treated with isavuconazole via an enteral tube. Therapeutic pharmacokinetic monitoring of isavuconazole plasma concentrations was performed to assess the feasibility and safety of enteral administration.The results show that isavuconazole concentrations were maintained within the therapeutic range when administered via an enteral tube. No significant deviations in plasma concentration were noted during the monitoring period. Conclusions: Administering isavuconazole through an enteral tube is a safe and viable alternative for patients that are unable to receive the drug via the oral route. Therapeutic monitoring of plasma concentrations is recommended to ensure proper dosing and efficacy.

Population pharmacokinetics of isavuconazole in hematologic patients: implications for model-informed precision dosing

2026-07-20T07:21:05Z

Background: Isavuconazole is a broad-spectrum antifungal agent used for treating invasive fungal infections (IFIs). Its pharmacokinetics may be impacted in hematologic patients due to concomitant clinical and therapeutic factors potentially affecting drug exposure. The aim of this study was to develop a population pharmacokinetic (popPK) model of isavuconazole in adult hematologic patients to support model-informed precision dosing. Materials and method: Prospective, non-controlled study performed in adult hematologic patients receiving isa vuconazole for IFIs and followed up by a therapeutic drug monitoring (TDM) program. Isavuconazole plasma concentrations were quantified using an ultra-high-performance liquid chromatography (UPLC) with UV de tector. A popPK model was developed using NONMEM v.7.5.0. Simulations were based on the final model to evaluate the differences across physiological variables with impact on drug exposure. Results: A one-compartment model with first-order absorption and elimination described adequately 121 isa vuconazole concentrations from 52 patients. Body surface area (BSA) and serum albumin (ALB) significantly influenced drug clearance. The final popPK model showed good precision, robustness, and predictive perfor mance, supporting its use for individualized isavuconazole dosing in this population. Conclusions: BSA and serum ALB were identified as covariates influencing isavuconazole clearance in adult he matologic patients. Further studies are needed to better characterize the absorption of isavuconazole and im plications on dosage recommendations, especially for higher proposed doses.

Optimization of Isavuconazole Dosing in Patients with Invasive Fungal Infections Through Therapeutic Drug Monitoring: Real-World Clinical Practice Experience

2026-07-20T07:20:49Z

Therapeutic drug monitoring (TDM) is routinely recommended for most antifungal triazoles to ensure efficacy and safety. Isavuconazole, however, was initially approved without this recommendation due to its predictable pharmacokinetic profile. Later clinical data have raised concerns about subtherapeutic exposures in certain populations. This prospective, single-center study aimed to assess the need for TDM of isavuconazole in critically ill and hematologic patients with invasive fungal infections. Between March 2022 and November 2023, patients receiving standard dosing of isavuconazole were enrolled, and plasma concentrations were measured to determine the proportion of patients with values outside the therapeutic range (1–4 µg/mL), particularly focusing on subtherapeutic levels. A total of 65 isavuconazole plasma concentrations from 24 patients (9 critically ill and 15 hematologic) were analyzed. Critically ill patients had lower initial concentrations than hematologic patients (median [range]: 0.75 [not detectable (ND)–5.18] vs. 3.03 [1.03–6.65] µg/mL), with 66.7% showing levels outside the therapeutic range and 55.5% having subtherapeutic concentrations. The coefficient of variation (CV%) of concentrations values at the first TDM was 124.7% in critically ill patients and 57.3% in hematologic patients. After dose adjustment in critically ill patients, the proportion with levels outside the therapeutic range decreased to 28.6%. These findings suggest that, despite initial assumptions, isavuconazole exhibits considerable pharmacokinetic variability in specific populations, particularly in critically ill patients, and the findings support the implementation of TDM to optimize antifungal therapy and improve patient outcomes in real-world clinical settings.

Drug Recalls in Spain: A 14-year Retrospective Regulatory Analysis in Spain

2026-07-20T07:20:35Z

Purpose Drug (or medicine) recalls represent a public health risk and may contribute to shortages, potentially affecting sup ply continuity and, consequently, patient care. This study analyzed drug recalls issued by the Spanish Agency of Medicines and Medical Devices (AEMPS) and conducted an additional descriptive recall-related shortage assessment to estimate their potential impact on supply continuity in Spain. Methods A descriptive retrospective regulatory analysis was conducted on drug recalls in Spain over a 14-year period (2010–2023). Data from the AEMPS website were analyzed, and drug recalls recorded during the last 4 years of the study period (2020–2023) were cross‑referenced with national shortage records to assess their supply impact. Results A total of 1,120 drug recalls were identified, 87.86% (n = 984) involved prescriptions and 57.32% (n = 642) were classified as Class 2, recalls with a moderate risk of temporary or medically reversible adverse health consequences. The presence of nitrosamines (22.50%, n = 252) was the leading cause of recalls, driven by a phase-specific crisis (2018–2019), with the highest number of issued recalls (19.19%, n = 215) observed in 2018. Five manufacturers of active substances and finished products accounted for 27.32% (n = 306) of all recalls. Drug recalls issued between 2020 and 2023 (n = 195) resulted in a total of 55 drug shortages. Of these shortages, 10.91% (n = 6) were considered to have a high clinical impact on supply continuity. Conclusion Nitrosamines emerged as the leading cause of recalls in Spain during the study period. A subset of recalls was linked to shortages affecting supply continuity, posing a potential risk to patients’ health. These findings underscore the importance of monitoring recalls and addressing supply chain vulnerabilities to mitigate negative effects on patients’ health and access to essential medications

Comparison of Essential Oil Extraction Techniques and Their Therapeutic Applications in Dentistry: Focus on Candida albicans Inhibition

2026-07-20T07:20:16Z

Background In this study, the efficacy of three essential oil extraction techniques steam entrainment, Soxhlet extraction, and supercritical fluid extraction (SCF) was evaluated. Aim Determine the most effective method for obtaining bioactive compounds from Cymbopogon citratus, Origanum vulgare, and Coriandrum sativum, plant species recognized for their antimicrobial and anti-inflammatory properties with potential applications in dentistry. The selected plants, identified based on scientific evidence, were certified and lyophilized prior to extraction. The efficiency of each technique was assessed in terms of essential oil yield, purity, and biological activity. Methodology The plant species were selected for their therapeutic properties based on scientific reports, certified, and lyophilized before proceeding with the different extraction methods. The efficacy of each technique was compared in terms of the purity and yield of the essential oils obtained. The statistical analysis was performed using SPSS version 25. Results It was shown that FSC extraction is the method that allows obtaining essential oils with the highest purity and yield, followed by steam entrainment, with the Soxhlet method being the least efficient. However, in the microbiological analysis, the essential oil obtained by steam entrainment showed a greater inhibitory effect against Candida albicans ATCC 90028. Conclusion In this study, the FSC and steam entrainment techniques are the most suitable for obtaining essential oils for therapeutic applications in dentistry, since they allow better preservation of the bioactive components and reduce the environmental impact. These results position FSC and vapor entrainment extraction as promising options for the development of therapeutic products in dentistry.

Guía para cuidadores de personas con daño cerebral adquirido (DCA)

2026-07-16T00:02:14Z

Guía informativa dirigida a cuidadores de personas con daño cerebral adquirido (DCA). Se explica de forma sencilla qué es el DCA, sus causas más frecuentes y las principales áreas afectadas. Incluye recomendaciones para el cuidado físico y emocional de la persona con DCA; así como, pautas para el autocuidado del cuidador y el acceso a recursos especializados. Su diseño visual facilita la comprensión y la difusión de información básica sobre el cuidado integral de las personas con DCA. Se ha desarrollado dentro del proyecto NeuroMotion-USAL.

Dietary adherence and disability evolution in multiple sclerosis: an exploratory 12-month prospective cohort study

2026-07-14T00:01:08Z

[EN]Lifestyle factors may influence disability trajectories in multiple sclerosis (MS), yet prospective data linking sustained dietary adherence to objective clinical outcomes remain limited. Homocysteine, a metabolite involved in one-carbon metabolism, represents a biologically plausible mediator between nutrition and neurodegeneration, although its longitudinal clinical relevance in MS is uncertain. This study aimed to investigate whether adherence to a structured dietary intervention is associated with longitudinal changes in plasma homocysteine levels and disability progression in patients with MS over 12 months. In this prospective cohort study, 41 patients with MS were followed for 12 months. Dietary adherence was quantified using a structured follow-up scale (range 2-6). Plasma homocysteine levels and Expanded Disability Status Scale (EDSS) scores were assessed at baseline, 6 months, and 12 months. Associations between adherence, metabolic changes, and EDSS evolution were evaluated using correlation analyses and multivariate linear regression adjusting for age, sex, BMI, baseline EDSS, and treatment line. Baseline mean homocysteine was 10.91 ± 6.94 μmol/L and decreased to 8.24 ± 3.33 μmol/L at 6 months, remaining stable at 8.27 ± 2.42 μmol/L at 12 months. Between-group differences in homocysteine showed a trend toward significance at 12 months (ANOVA p = 0.059). Mean EDSS increased slightly from 1.14 to 1.23 in the overall cohort (p > 0.05). However, EDSS evolution differed according to dietary adherence (ANOVA p = 0.009): low-adherence patients showed a mean EDSS increase (+0.53 ± 0.72), whereas high-adherence patients showed a mean EDSS decrease (-0.56 ± 1.08). Given the low baseline EDSS, short follow-up, and small high-adherence subgroup, these changes should be interpreted as exploratory differences in short-term EDSS trajectory rather than confirmed clinical improvement and do not establish causality. Adherence score was inversely correlated with EDSS change (r = -0.57, p = 0.0006) and remained independently associated in multivariate analysis (β = -0.45, 95% CI -0.68 to -0.22, p = 0.0005). Higher adherence to the dietary counselling programme was associated with a more favourable short-term disability trajectory over 12 months. However, causality cannot be inferred, and the clinical significance of these modest changes remains uncertain. Because the adherence score was not formally validated and may partly reflect broader health-related behaviours or engagement with care, and because the dietary intervention was individualized, the study cannot identify specific dietary components or dietary patterns associated with disability trajectories. These exploratory findings require confirmation in larger controlled studies using validated dietary assessment instruments.

Assessment of muscle function decline and cachexia-related biomarkers in hospitalized oncology patients: study protocol

2026-07-11T00:01:50Z

[ENG]Background: Cancer cachexia and sarcopenia are highly prevalent complications affecting up to 50% of patients with cancer and are associated with increased treatment toxicity, poorer functional outcomes, and reduced survival. Early identification of muscle deterioration during hospitalization remains challenging. Objective: To evaluate the change in dominant-hand handgrip strength between hospital admission and discharge in hospitalized oncology patients. Methods: This prospective longitudinal study will evaluate hospitalized adults with confirmed malignancy and an expected hospital stay of ≥5 days. Daily handgrip strength and sEMG assessments will be performed as exploratory secondary measures to characterize temporal patterns of muscle function during hospitalization. Baseline and discharge evaluations will additionally include bioelectrical impedance analysis, validated patient-reported outcome measures (SARC-F, EORTC QLQ-C30, PSQI), and serum biomarkers related to inflammatory and nutritional status. Linear mixed models will be used to evaluate longitudinal changes and associations between functional, electrophysiological, and biochemical parameters. Expected results: The study aims to characterize trajectories of muscle function decline during hospitalization, identify candidate biomarker signatures for cachexia detection, and evaluate neuromuscular fatigue patterns using sEMG. Conclusions: This protocol proposes a feasible multimodal framework for monitoring skeletal muscle deterioration during acute oncology hospitalization and may inform future interventional strategies targeting cancer-related cachexia and sarcopenia.

Massage-Related changes in cortical activity and cerebral oxygenation in healthy term infants: an exploratory EEG-fNIRS study with sex-specific observations

2026-07-11T00:01:47Z

[ENG]Background: Central nervous system development is a rapid and highly plastic process during the first years of life. Tactile stimuli have been shown to induce cortical changes, but potential sex-related differences remain unexplored. This study aimed to investigate sex-specific differences in cortical activity and cerebral oxygenation in response to tactile stimulation via body massage. Methods: Four healthy full-term infants (two females and two males), all aged 11 weeks, were included in this prospective exploratory study. Each infant received a standardized 5 min massage protocol. Cortical activity and cerebral oxygenation were assessed using an 8-channel electroencephalogram (EEG) and functional near-infrared spectroscopy (fNIRS) before, during, and after the intervention, with a 5 min pre-intervention resting period used as the baseline. Results: EEG analysis focused on a single spectral band (4 Hz–30 Hz). This range was selected to capture the main cortical oscillations in infants, including theta, alpha, and beta activity, while delta activity below 4 Hz was partially excluded to reduce movement and physiological artifacts. Standard infant EEG bands were considered when defining this range. Data shows for the female subject an average PSD of −6.726 (± −4.075), and for the male subject, −12.594 (± −10.741). Although babies are of the same gestational age, they exhibited distinct basal cortical activity, which prevented comparisons from being made. Nevertheless, massage induced similar activity patterns in all subjects with increased cortical electrical activity in the left parietal region relative to baseline. fNIRS data showed that comparable HbO concentration patterns between participants were observed only during the second minute of recording. Relative to baseline, pre-intervention HbO responses displayed an opposite distribution, and the effects of the intervention differed by sex. The female participant exhibited a slight reduction in activation in the right hemisphere accompanied by a modest increase in the most ventral region of the left hemisphere. Conversely, the male participant showed an inverse response pattern, characterized by a marked increase in right hemispheric activation and a pronounced decrease in the left hemisphere during the intervention period. Conclusions: These preliminary observations suggest the presence of early variations in cortical processing that warrant further investigation in larger samples, although they cannot be considered conclusive. While baseline response patterns differed between participants, both showed increased left parietal activity during tactile stimulation. The inversion of HbO responses between the pre-intervention and intervention phases points to potential sex-related differences in hemodynamic trajectories. Nevertheless, these results remain preliminary, and larger, well-powered studies are required to determine whether these patterns reflect stable, sex-dependent developmental changes.

Prevalence and predictors of kinesiophobia in psoriatic arthritis: the role of central sensitization and comorbidities

2026-07-11T00:01:44Z

[ENG]Background – Kinesiophobia (excessive fear of movement due to belief of injury) is highly prevalent in rheumatologic diseases, yet its prevalence and associations in psoriatic arthritis (PsA) remain unexplored. Objective – To determine the prevalence of kinesiophobia in PsA and examine its associations with central sensitization (CS), demographic characteristics, disease activity, physical function, and patient-reported outcomes. Methods – Cross-sectional study of 246 consecutive PsA patients. Kinesiophobia was assessed using the Tampa Scale of Kinesiophobia-11. CS was measured by Central Sensitization Inventory (CSI). Disease activity, functional status, physical activity, sleep quality, anxiety, depression, and fatigue were systematically evaluated. Univariate and multivariable analyses (logistic and linear regression) were performed. Results – Kinesiophobia was present in 45.5% (112/246) of patients. Patients with kinesiophobia demonstrated significantly higher CSI scores (41.5 vs. 29; p < 0.001), reduced physical activity (1619.5 vs. 2, 970 MET-minutes/week; p = 0.01), greater disease activity (cDAPSA: 13 vs. 11; p = 0.001), functional impairment (HAQ-DI; p = 0.001), and increased comorbid anxiety and depression (p = 0.001). A significant correlation existed between kinesiophobia and CSI (r = 0.39; p < 0.001). In multivariable logistic regression, central sensitization (OR: 1.03; 95% CI: 1.00–1.05; p = 0.02) and sleep quality (PSQI; OR: 1.09; 95% CI: 1.00–1.1; p = 0.03) emerged as independent predictors, explaining 20% of kinesiophobia variance. In linear regression, these variables accounted for 12% of variance (R2 = 0.12). Conclusion – Kinesiophobia functions as an amplifier of pain perception and functional disability, particularly in patients with symptom-inflammation discordance. A bidirectional pathophysiologic relationship between kinesiophobia and CS likely perpetuates chronic pain and disability. Multidimensional interventions may enhance clinical outcomes in kinesiophobic PsA patients, especially those with high perceived impact despite adequate inflammatory control.

Obstructive sleep apnea in psoriatic arthritis: clinical characteristics and comorbidities

2026-07-11T00:01:41Z

[ENG]Background: Obstructive sleep apnea (OSA) is increasingly recognized in chronic inflammatory diseases, yet its prevalence and clinical correlates in psoriatic arthritis (PsA) remain poorly characterized. Objective: The objective of this study was to evaluate OSA prevalence and its relationship with disease activity, functional impairment, and comorbidities in PsA patients. Methods: A cross-sectional analysis of 247 consecutive PsA patients was conducted. OSA diagnosis was determined through medical record review. Disease activity was assessed using cDAPSA and ASDAS-CRP. Functional disability was measured using HAQ-DI and BASFI. Sleep quality (PSQI) and psychological symptoms (HADS) were evaluated. Inflammatory markers included CRP, IL-6, and TNF-α. Multivariable logistic regression identified independent predictors of OSA. Results: OSA prevalence was found to be 8.9% (22/247). OSA+ patients had significantly higher median age (58.0 vs. 54.0 years, p = 0.02), tender joint count (2.0 vs. 1.0, p = 0.002), functional disability (1.1 vs. 0.3, p = 0.001), fatigue (30.5 vs. 38.0, p = 0.04), anxiety (7.5 vs. 5.0, p = 0.03), depression (7.0 vs. 3.0, p = 0.004), and worse sleep quality (11.5 vs. 7.0, p = 0.001). Notably, no significant differences in inflammatory markers (CRP, swollen joints) were found between groups despite substantially higher pain burden in OSA+ patients. Female sex and greater tender joint count emerged as independent predictors of OSA. Conclusions: OSA occurs in ~9% of unselected PsA patients and is independently associated with functional disability, psychological distress, and elevated tender joint counts despite comparable inflammatory markers. This dissociation suggests that OSA drives pain amplification through non-inflammatory mechanisms. These findings support the use of systematic OSA screening in PsA patients with pain or disability disproportionate to inflammatory burden, particularly in those with psychological comorbidities.

Traumatic symptoms among syrian refugees in host countries: a comparative study of Jordan and Spain

2026-07-11T00:01:37Z

Background: Displaced individuals endure challenges, including conflict, forced migration, family separation, human rights violations, limited access to essential services, and increased exposure to violence and abuse. These hardships significantly impact their mental health, often leading to heightened trauma-related symptoms. Methods: We used a cross-sectional correlational design in refugee camps, homes, and centers across Jordan and Spain. 200 refugees with confirmed status in the past ten years were recruited. Demographic data were collected via a demographic form, the PTSD-8 Inventory assessed traumatic symptoms, and data analysis included descriptive statistics, independent t-tests, one-way ANOVA, and Chi-square tests. Results: Most participants had a secondary education, were unemployed, and had low incomes. PTSD symptoms were prevalent, with rates of recurrent thoughts (63.5%), re-experiencing events (57.5%), nightmares (50.5%), sudden reactions (56.5%), activity avoidance (53.5%), avoidance of specific thoughts or feelings (56.5%), jumpiness (53.5%), hypervigilance (53.5%), feeling on guard (41.5%), and general avoidance (43.5%) rated from rarely to most of the time. All symptoms were significantly more frequent among refugees in Jordan than in Spain. Conclusions and Recommendations: Intrusive thoughts were more frequent among females, urban residents, and unemployed individuals. Avoidance behaviors were higher in married and unemployed individuals. Hypervigilance was more prevalent among females, married individuals, and those with lower incomes. Regionally, females and married individuals in Jordan exhibited more intrusive thoughts and avoidance. In Spain, intrusive thoughts and hypervigilance were more common among females and the unemployed. The findings highlight the urgent need for targeted mental health interventions, particularly in refugee camps like those in Jordan, where PTSD symptom rates were significantly higher. Programs should prioritize trauma-focused therapies, such as Cognitive Behavioral Therapy, while adopting gender-sensitive approaches to address the heightened vulnerability of women and unemployed individuals. Given the strong link between unemployment and symptom severity, livelihood support and vocational training should be integrated into psychosocial care. Policymakers in host countries like Jordan could benefit from adopting integration strategies similar to Spain’s, which may contribute to lower PTSD prevalence. Additionally, community-based awareness initiatives could improve early symptom recognition and access to care. Future research should explore longitudinal outcomes to assess the long-term impact of displacement and resettlement conditions on mental health.

Potentiation of mitochondrial function by mitoDREADD-Gs reverses pharmacological and neurodegenerative cognitive impairment in mice

2026-07-02T00:01:51Z

[EN]Many brain disorders involve mitochondrial alterations, but owing to the lack of suitable tools, the causal role of mitochondrial dysfunction in pathophysiological processes is difficult to establish. Heterotrimeric guanine nucleotide-binding (G) proteins are key regulators of cell functions, and they can be found within mitochondria. Therefore, we reasoned that the activation of stimulatory mitochondrial G proteins (Gs) could rapidly promote the activity of the organelle and possibly compensate for bioenergetic dysfunction. Here, we show that a mitochondria-targeted recombinant designer receptor exclusively activated by designer drugs (mitoDREADD-Gs) can acutely trigger intramitochondrial signaling to increase mitochondrial membrane potential and oxygen consumption. In vivo activation of mitoDREADD-Gs abolished memory alterations in cannabinoid-treated mice and in two mouse models of Alzheimer’s disease and frontotemporal dementia. Thus, mitoDREADD-Gs enables the establishment of causal relationships between mitochondria and biological or disease-related processes and represents an innovative potential therapeutic approach for disorders associated with mitochondrial impairment.

Tratamiento de la muerte súbita

2026-06-25T00:00:25Z

[ES]Se describe el manejo inmediato y tratamiento de la muerte súbita en el deportista.

Oxidative eustress regulates insulin signaling and promotes GLUT4-mediated glucose uptake in insulin-resistant skeletal muscle fibres

2026-06-24T00:01:31Z

[EN]The document focuses on how oxidative eustress (a moderate and beneficial level of reactive species) acts as an alternative regulatory mechanism to trigger GLUT4 trafficking and restore glucose uptake within insulin-resistant skeletal muscle.

Influencia sexual en la modulación cardiovascular ejercida por el sistema serotonérgico periférico en rata

2026-06-26T01:05:02Z

[ES] La serotonina (5-HT) es una neurohormona que regula el tono vascular por mecanismos directos e indirectos, a través del sistema nervioso autónomo y sensorial, mediante una amplia familia de receptores serotonérgicos. Los mecanismos serotonérgicos implicados en la modulación de la neurotransmisión simpática y sensorial CGRPérgica en la vasculatura sistémica han sido caracterizados por nuestro grupo y otros autores en ratas macho. Sin embargo, el sexo biológico influye tanto en el metabolismo de la 5-HT y la expresión de sus receptores, como en la neurotransmisión simpática y sensorial CGRPérgica, lo que limita la comprensión y el desarrollo de dianas farmacológicas eficaces para el sexo femenino en patologías cardiovasculares y neurovasculares. La presente Tesis Doctoral tiene como objetivo determinar si los mecanismos serotonérgicos involucrados en la regulación cardiovascular presentan diferencias dependientes del sexo biológico en ratas. Para ello, en ratas hembra pithed, se ha estudiado el papel diferencial de los distintos receptores de 5-HT sobre las respuestas vasculares obtenidas por liberación endógena de noradrenalina y del péptido relacionado con el gen de la calcitonina (CGRP), así como la posible implicación de mediadores dependientes de endotelio en la respuesta noradrenérgica. Los resultados obtenidos muestran que el sexo biológico influye en el tono vascular basal y en los mecanismos serotonérgicos que regulan tanto la neurotransmisión simpática vascular como la inervación sensorial CGRPérgica perivascular, modificando el tipo y subtipo de receptores de 5-HT implicados, su localización en la unión neuroefectora, y las vías indirectas involucradas. Estos hallazgos podrían abrir nuevas estrategias terapéuticas dependientes del sexo en el tratamiento de enfermedades cardiovasculares y neurovasculares.; [EN] Serotonin (5-HT) is a neurohormone that regulates vascular tone by direct and indirect mechanisms via the autonomic and sensory nervous systems, acting through a large family of serotonergic receptors. The serotonergic mechanisms involved in the modulation of sympathetic and sensory CGRPergic neurotransmission in the systemic vasculature have been characterised by our group and others in male rats. However, biological sex influences 5-HT metabolism and receptor expression, as well as sympathetic and sensory CGRPergic neurotransmission, which limits the understanding and development of effective pharmacological targets for the female sex in cardiovascular and neurovascular disorders. The aim of the present Doctoral Thesis was to determine whether the serotonergic mechanisms involved in cardiovascular regulation display sex-dependent differences in rats. To do so, female pithed rats were used to study the role of different 5-HT receptors on vascular responses elicited by the endogenous release of noradrenaline and calcitonin generelated peptide (CGRP), along with the possible involvement of endothelium-dependent mediators in the noradrenergic response. The results show that biological sex influences basal vascular tone and the serotonergic mechanisms regulating both vascular sympathetic neurotransmission and perivascular sensory CGRPergic outflow, modifying the 5-HT receptor types and subtypes involved, their localisation at the neuroeffector junction, and the indirect pathways implicated. Altogether, these findings may contribute to the development of novel sex-dependent therapeutic strategies for cardiovascular and neurovascular diseases.