Oxidative stress and inflammatory process in borderline personality disorder (BPD): a narrative review.

Borderline personality disorder (BPD) is a severe psychiatric condition that affects up to 2.7% of the population and is highly linked to functional impairment and suicide. Despite its severity, there is a lack of knowledge about its pathophysiology. Studies show genetic influence and childhood violence as factors that may contribute to the development of BPD; however, the involvement of neuroinflammation in BPD remains poorly investigated. This article aimed to explore the pathophysiology of BPD according to the levels of brain-derived neurotrophic factor (BDNF), inflammatory cytokines, and oxidative stress substances that exacerbate neuronal damage. Few articles have been published on this theme. They show that patients with BPD have a lower level of BDNF and a higher level of tumor necrosis factor (TNF)-α and interleukin (IL)-6 in peripheral blood, associated with increased plasma levels of oxidative stress markers, such as malondialdehyde and 8-hydroxy-2-deoxyguanosine. Therefore, more research on the topic is needed, mainly with a pre-clinical and clinical focus.

Oxidative stress and inflammatory process in borderline personality disorder (BPD): a narrative review

Borderline personality disorder (BPD) is a severe psychiatric condition that affects up to 2.7% of the population and is highly linked to functional impairment and suicide. Despite its severity, there is a lack of knowledge about its pathophysiology. Studies show genetic influence and childhood violence as factors that may contribute to the development of BPD; however, the involvement of neuroinflammation in BPD remains poorly investigated. This article aimed to explore the pathophysiology of BPD according to the levels of brain-derived neurotrophic factor (BDNF), inflammatory cytokines, and oxidative stress substances that exacerbate neuronal damage. Few articles have been published on this theme. They show that patients with BPD have a lower level of BDNF and a higher level of tumor necrosis factor (TNF)-α and interleukin (IL)-6 in peripheral blood, associated with increased plasma levels of oxidative stress markers, such as malondialdehyde and 8-hydroxy-2-deoxyguanosine. Therefore, more research on the topic is needed, mainly with a pre-clinical and clinical focus.

Papel de vortioxetina en el tratamiento del dolor neuropático / Role of vortioxetine in the treatment of neuropathic pain

El dolor neuropático es un problema clínico importante e incapacitante, su manejo constituye un reto para los profesionales sanitarios. Vortioxetina es un nuevo fármaco antidepresivo con acción multimodal, lo que le confiere un perfil único. Los antidepresivos tricíclicos, en particular amitriptilina, y los inhibidores de la recaptación de serotonina y noradrenalina venlafaxina y duloxetina constituyen fármacos de primera línea en el tratamiento del dolor neuropático. La interacción entre el binomio dolor y depresión es muy frecuente, siendo la complicación psicológica más frecuente en los pacientes con dolor crónico. Esta revisión exhaustiva y descriptiva resume los datos farmacológicos más relevantes de vortioxetina, así como la bibliografía específica de vortioxetina en dolor neuropático y dolor crónico.(AU)

Neuropathic pain is an important and disabling clinical problem, its management constitutes a challenge for healthcare professionals. Vortioxetine is a new antidepressant drug with multimodal action, which gives it a unique profile. Tricyclic antidepressants, in particular amitriptyline, and serotonin and norepinephrine reuptake inhibitors venlafaxine and duloxetine are first-line drugs in the treatment of neuropathic pain. The interaction between the pain and depression binomial is very frequent, being the most frequent psychological complication in patients with chronic pain. This comprehensive and descriptive review summarizes the most relevant pharmacological data on vortioxetine, as well as the specific literature on vortioxetine in neuropathic pain and chronic pain.(AU)

Role of vortioxetine in the treatment of neuropathic pain.

Neuropathic pain is an important and disabling clinical problem, its management constitutes a challenge for healthcare professionals. Vortioxetine is a new antidepressant drug with multimodal action, which gives it a unique profile. Tricyclic antidepressants, in particular amitriptyline, and serotonin and norepinephrine reuptake inhibitors venlafaxine and duloxetine are first-line drugs in the treatment of neuropathic pain. The interaction between the pain and depression binomial is very frequent, being the most frequent psychological complication in patients with chronic pain. This comprehensive and descriptive review summarizes the most relevant pharmacological data on vortioxetine, as well as the specific literature on vortioxetine in neuropathic pain and chronic pain.

[Is there scientific evidence for the use of perampanel in neuropathic pain?] / ¿Existe evidencia científica para el empleo de perampanel en el dolor neuropático?

TITLE: ¿Existe evidencia científica para el empleo de perampanel en el dolor neuropático?

[Pharmacological approach to neuropathic pain: past, present and future]. / Abordaje farmacológico del dolor neuropático: pasado, presente y futuro.

INTRODUCTION: Neuropathic pain (NP) is difficult to treat due to the heterogeneity of causes, symptoms and underlying mechanisms. It constitutes a great medical need that is not covered, and has a high number of therapeutic failures in recent randomized clinical trials. DEVELOPMENT: This narrative review presents an update on the pharmacological treatment of NP with emphasis on the new published clinical guidelines, new drugs in development, and the new challenges that arise in the therapeutic management of this entity. CONCLUSIONS: First-line drugs proposed include tricyclic antidepressants (particularly amitriptyline), serotonin and norepinephrine reuptake inhibitors (particularly duloxetine), pregabalin, and gabapentin. However, the latest recommendations are still relevant and the most recent clinical studies even question the role of pregabalin as a first-line treatment. Therefore, we consider that periodic updates of the clinical guidelines in NP are necessary to better guide our daily clinical practice and rationalize the use of all available therapeutic options. Furthermore, the expansion of knowledge in NP has generated a series of challenges, such as the development of new drugs based on pathophysiological mechanisms investigated in animals, and the development of optimal therapeutic approaches in clinical trials, based more on personalized than etiological approaches.

TITLE: Abordaje farmacológico del dolor neuropático: pasado, presente y futuro.Introducción. El dolor neuropático (DN) es difícil de tratar debido a la heterogeneidad de causas, síntomas y mecanismos subyacentes. Constituye una gran necesidad médica que no está cubierta y cuenta con un número elevado de fracasos terapéuticos en ensayos clínicos aleatorizados recientes. Desarrollo. En esta revisión narrativa se presenta una actualización sobre el tratamiento farmacológico del DN con énfasis en las nuevas guías clínicas publicadas, los nuevos fármacos en desarrollo y los nuevos retos que se presentan en el manejo terapéutico de esta entidad. Conclusiones. Los fármacos propuestos como primera línea incluyen antidepresivos tricíclicos (particularmente amitriptilina), inhibidores de la recaptación de la serotonina y la noradrenalina (particularmente duloxetina), pregabalina y gabapentina. Sin embargo, las últimas recomendaciones siguen siendo relevantes y los estudios clínicos más recientes incluso cuestionan el papel de la pregabalina como tratamiento de primera línea. Por tanto, consideramos necesarias las actualizaciones periódicas de las guías clínicas en DN para guiar mejor nuestra práctica clínica diaria y racionalizar el uso de todas las opciones terapéuticas disponibles. Por otro lado, la expansión del conocimiento en DN ha generado una serie de desafíos, como el desarrollo de nuevos fármacos basados en mecanismos fisiopatológicos investigados en animales y el desarrollo de planteamientos terapéuticos óptimos en ensayos clínicos, más basados en enfoques personalizados que etiológicos.

Abordaje farmacológico del dolor neuropático: pasado, presente y futuro / Pharmacological approach to neuropathic pain: past, present and future

Introducción: El dolor neuropático (DN) es difícil de tratar debido a la heterogeneidad de causas, síntomas y mecanismos subyacentes. Constituye una gran necesidad médica que no está cubierta y cuenta con un número elevado de fracasos terapéuticos en ensayos clínicos aleatorizados recientes. Desarrollo: En esta revisión narrativa se presenta una actualización sobre el tratamiento farmacológico del DN con énfasis en las nuevas guías clínicas publicadas, los nuevos fármacos en desarrollo y los nuevos retos que se presentan en el manejo terapéutico de esta entidad. Conclusiones: Los fármacos propuestos como primera línea incluyen antidepresivos tricíclicos (particularmente amitriptilina), inhibidores de la recaptación de la serotonina y la noradrenalina (particularmente duloxetina), pregabalina y gabapentina. Sin embargo, las últimas recomendaciones siguen siendo relevantes y los estudios clínicos más recientes incluso cuestionan el papel de la pregabalina como tratamiento de primera línea. Por tanto, consideramos necesarias las actualizaciones periódicas de las guías clínicas en DN para guiar mejor nuestra práctica clínica diaria y racionalizar el uso de todas las opciones terapéuticas disponibles. Por otro lado, la expansión del conocimiento en DN ha generado una serie de desafíos, como el desarrollo de nuevos fármacos basados en mecanismos fisiopatológicos investigados en animales y el desarrollo de planteamientos terapéuticos óptimos en ensayos clínicos, más basados en enfoques personalizados que etiológicos.(AU)

Introduction: Neuropathic pain (NP) is difficult to treat due to the heterogeneity of causes, symptoms and underlying mechanisms. It constitutes a great medical need that is not covered, and has a high number of therapeutic failures in recent randomized clinical trials. Development: This narrative review presents an update on the pharmacological treatment of NP with emphasis on the new published clinical guidelines, new drugs in development, and the new challenges that arise in the therapeutic management of this entity. Conclusions: First-line drugs proposed include tricyclic antidepressants (particularly amitriptyline), serotonin and norepinephrine reuptake inhibitors (particularly duloxetine), pregabalin, and gabapentin. However, the latest recommendations are still relevant and the most recent clinical studies even question the role of pregabalin as a first-line treatment. Therefore, we consider that periodic updates of the clinical guidelines in NP are necessary to better guide our daily clinical practice and rationalize the use of all available therapeutic options. Furthermore, the expansion of knowledge in NP has generated a series of challenges, such as the development of new drugs based on pathophysiological mechanisms investigated in animals, and the development of optimal therapeutic approaches in clinical trials, based more on personalized than etiological approaches.(AU)

Treatment of bladder dysfunction with solifenacin: is there a risk of dementia or cognitive impairment?

The use of bladder antimuscarinics is very common in the elderly. However, recent population-based studies that assessed the use of anticholinergics or bladder antimuscarinics showed an increased risk of dementia when these drugs were used for a prolonged period. Several of these population-based studies included patients who used solifenacin, which is a bladder antimuscarinic released in 2005 with the prospect of being a more selective antimuscarinic for M3 receptors (M3R), which could make it a safer drug when trying to avoid unwanted effects of older bladder antimuscarinics such as oxybutynin, especially with regard to changes in cognition. Since the various bladder antimuscarinics have distinct pharmacological characteristics, such as in the ability to penetrate the blood-brain barrier, in selectivity for muscarinic receptors, and in brain efflux mechanisms, their effects on the central nervous system (CNS) may vary. Solifenacin was the drug selected in this review, which aims to describe the results of several articles published in recent years reporting the effects of solifenacin on cognition or the risk of dementia development. Although preclinical studies show that solifenacin can also act on brain M1 receptors (M1R), short-term clinical studies have shown it to be safe for cognition. However, there are no long-term randomized studies that prove the safety of this drug for the CNS. Thus, until the safety of solifenacin has been established by long-term studies, it seems advisable to avoid prolonged use of this drug in elderly patients.

Treatment of bladder dysfunction with solifenacin: is there a risk of dementia or cognitive impairment?

The use of bladder antimuscarinics is very common in the elderly. However, recent population-based studies that assessed the use of anticholinergics or bladder antimuscarinics showed an increased risk of dementia when these drugs were used for a prolonged period. Several of these population-based studies included patients who used solifenacin, which is a bladder antimuscarinic released in 2005 with the prospect of being a more selective antimuscarinic for M3 receptors (M3R), which could make it a safer drug when trying to avoid unwanted effects of older bladder antimuscarinics such as oxybutynin, especially with regard to changes in cognition. Since the various bladder antimuscarinics have distinct pharmacological characteristics, such as in the ability to penetrate the blood-brain barrier, in selectivity for muscarinic receptors, and in brain efflux mechanisms, their effects on the central nervous system (CNS) may vary. Solifenacin was the drug selected in this review, which aims to describe the results of several articles published in recent years reporting the effects of solifenacin on cognition or the risk of dementia development. Although preclinical studies show that solifenacin can also act on brain M1 receptors (M1R), short-term clinical studies have shown it to be safe for cognition. However, there are no long-term randomized studies that prove the safety of this drug for the CNS. Thus, until the safety of solifenacin has been established by long-term studies, it seems advisable to avoid prolonged use of this drug in elderly patients.

Role of vortioxetine in the treatment of neuropathic pain. / Papel de vortioxetina en el tratamiento del dolor neuropático.

Neuropathic pain is an important and disabling clinical problem, its management constitutes a challenge for healthcare professionals. Vortioxetine is a new antidepressant drug with multimodal action, which gives it a unique profile. Tricyclic antidepressants, in particular amitriptyline, and serotonin and norepinephrine reuptake inhibitors venlafaxine and duloxetine are first-line drugs in the treatment of neuropathic pain. The interaction between the pain and depression binomial is very frequent, being the most frequent psychological complication in patients with chronic pain. This comprehensive and descriptive review summarizes the most relevant pharmacological data on vortioxetine, as well as the specific literature on vortioxetine in neuropathic pain and chronic pain.

Vertical location of ephemeral resources by adult Diptera: Implications for the colonization of cadavers in high-rise buildings.

Sarcosaprophagous flies (Diptera) rank among the most common insects associated with human-transformed environments all over the world. Synanthropic species of the families Calliphoridae, Muscidae, Sarcophagidae and Phoridae, in particular, have tremendous forensic importance due to their ability to colonize human cadavers and thus provide information on minimum post-mortem interval. Recently, cases of flies colonizing cadavers inside buildings of different heights drew attention to the vertical dispersal abilities of these flies, a subject that has received little attention. We investigated the vertical distribution of sarcosaprophagous flies in an urban environment, using uninhabited buildings as experimental models in Northeastern Brazil. To assess the vertical stratification of flies, one in every three floors of nine buildings was sampled using traps baited with bovine spleen, from the ground to the 27th floor. Calliphoridae was the most abundant family (52.9%), followed by Muscidae (41.2%), Sarcophagidae (3.2%) and Phoridae (2.7%). Most of the insects were collected at ground level (78.8%), with a decreasing abundance registered on the higher floors. Nevertheless, adults of the four families tested here were able to reach substrates as high as the 15th floor, which corresponds to approximately 48 m in height. Regarding calliphorids, seven species were identified, of which Chrysomya albiceps (30.4%) and C. megacephala (68.3%) were the most abundant. This is, to our knowledge, the first detailed, replicated study on vertical resource localization of sarcosaprophagous flies.

Rapid and long-lasting antidepressant-like effects of ketamine and their relationship with the expression of brain enzymes, BDNF, and astrocytes

Ketamine (KET) is an N-methyl-D-aspartate (NMDA) antagonist with rapid and long-lasting antidepressant effects, but how the drug shows its sustained effects is still a matter of controversy. The objectives were to evaluate the mechanisms for KET rapid (30 min) and long-lasting (15 and 30 days after) antidepressant effects in mice. A single dose of KET (2, 5, or 10 mg/kg, po) was administered to male Swiss mice and the forced swim test (FST) was performed 30 min, 15, or 30 days later. Imipramine (IMI, 30 mg/kg, ip), a tricyclic antidepressant drug, was used as reference. The mice were euthanized, separated into two time-point groups (D1, first day after KET injection; D30, 30 days later), and brain sections were processed for glycogen synthase kinase-3 (GSK-3), histone deacetylase (HDAC), brain-derived neurotrophic factor (BDNF), and glial fibrillary acidic protein (GFAP) immunohistochemical assays. KET (5 and 10 mg/kg) presented rapid and long-lasting antidepressant-like effects. As expected, the immunoreactivities for brain GSK-3 and HDAC decreased compared to control groups in all areas (striatum, DG, CA1, CA3, and mainly pre-frontal cortex, PFC) after KET injection. Increases in BDNF immunostaining were demonstrated in the PFC, DG, CA1, and CA3 areas at D1 and D30 time-points. GFAP immunoreactivity was also increased in the PFC and striatum at both time-points. In conclusion, KET changed brain BDNF and GFAP expressions 30 days after a single administration. Although neuroplasticity could be involved in the observed effects of KET, more studies are needed to explain the mechanisms for the drug's sustained antidepressant-like effects.