RESUMO
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.
Assuntos
Transtorno da Personalidade Borderline , Humanos , Criança , Transtorno da Personalidade Borderline/epidemiologia , Transtorno da Personalidade Borderline/genética , Transtorno da Personalidade Borderline/psicologia , Fator Neurotrófico Derivado do Encéfalo/genética , Interleucina-6 , Fator de Necrose Tumoral alfaRESUMO
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.
RESUMO
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.
Assuntos
Disfunção Cognitiva , Demência , Bexiga Urinária Hiperativa , Idoso , Disfunção Cognitiva/induzido quimicamente , Demência/induzido quimicamente , Humanos , Succinato de Solifenacina/efeitos adversos , Bexiga Urinária , Bexiga Urinária Hiperativa/tratamento farmacológicoRESUMO
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.
RESUMO
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.
Assuntos
Ambiente Construído , Dípteros/fisiologia , Comportamento Alimentar , Mudanças Depois da Morte , Animais , Brasil , Cidades , Entomologia Forense , HumanosRESUMO
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.
Assuntos
Animais , Masculino , Coelhos , Encéfalo/efeitos dos fármacos , Encéfalo/enzimologia , Fator Neurotrófico Derivado do Encéfalo/metabolismo , Ketamina/farmacologia , Antidepressivos/farmacologia , Astrócitos , Quinase 3 da Glicogênio Sintase , Modelos Animais de Doenças , Proteína Glial Fibrilar Ácida , Histona DesacetilasesRESUMO
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.
Assuntos
Antidepressivos/farmacologia , Fator Neurotrófico Derivado do Encéfalo/metabolismo , Encéfalo/efeitos dos fármacos , Encéfalo/enzimologia , Ketamina , Animais , Astrócitos , Modelos Animais de Doenças , Proteína Glial Fibrilar Ácida , Quinase 3 da Glicogênio Sintase , Histona Desacetilases , Ketamina/farmacologia , Masculino , CamundongosRESUMO
Background Complex percutaneous coronary intervention (PCI) is associated with higher ischemic risk, which can be mitigated by long-term dual antiplatelet therapy (DAPT). However, concomitant high bleeding risk (HBR) may be present, making it unclear whether short- or long-term DAPT should be prioritized. Objectives This study investigated the effects of ischemic (by PCI complexity) and bleeding (by PRECISE-DAPT [PRE dicting bleeding Complications in patients undergoing stent Implantation and Sub sequent Dual Anti Platelet Therapy] score) risks on clinical outcomes and on the impact of DAPT duration after coronary stenting. Methods Complex PCI was defined as ≥3 stents implanted and/or ≥3 lesions treated, bifurcation stenting and/or stent length >60 mm, and/or chronic total occlusion revascularization. Ischemic and bleeding outcomes in high (≥25) or non-high (<25) PRECISE-DAPT strata were evaluated based on randomly allocated duration of DAPT. Results Among 14,963 patients from 8 randomized trials, 3,118 underwent complex PCI and experienced a higher rate of ischemic, but not bleeding, events. Long-term DAPT in non-HBR patients reduced ischemic events in both complex (absolute risk difference: −3.86%; 95% confidence interval: −7.71 to +0.06) and noncomplex PCI strata (absolute risk difference: −1.14%; 95% confidence interval: −2.26 to −0.02), but not among HBR patients, regardless of complex PCI features. The bleeding risk according to the Thrombolysis In Myocardial Infarction scale was increased by long-term DAPT only in HBR patients, regardless of PCI complexity. Conclusions Patients who underwent complex PCI had a higher risk of ischemic events, but benefitted from long-term DAPT only if HBR features were not present. These data suggested that when concordant, bleeding, more than ischemic risk, should inform decision-making on the duration of DAPT. (AU)
Assuntos
Humanos , Doenças Cardiovasculares/prevenção & controle , Avaliação Nutricional , Alimentos, Dieta e NutriçãoRESUMO
The harsh conditions of the Brazilian seasonally dry tropical forest known as Caatinga pose challenges to the insects specialized in the exploitation of ephemeral resources. We investigated the diversity and daily flight activity of dipterans associated with decomposing rat carcasses in a field experiment performed in the semi-arid region of Pernambuco State, Brazil. We also analyzed the temporal arrival of adult insects on the carcasses at three stages of decomposition: early, intermediate, and advanced. We collected 1173 individuals, of which Muscidae had the highest abundance (36.5%), followed by Sarcophagidae (28.1%), Calliphoridae (25.2%), and Fanniidae (10.2%). Chrysomya albiceps (Wiedemann, 1819) (Calliphoridae), Fannia pusio (Wiedemann, 1830) (Fanniidae), Atherigona orientalis (Schiner, 1868), and Musca domestica (Linnaeus, 1758) (Muscidae) were the most abundant species. The richness reached its maximum value on the second day of decomposition, with 18 species, decreasing to 8 species on the last day of decomposition (7 days). The ecological indices of diversity, dominance, and evenness varied little among the stages. There was an overlap of most species throughout the decomposition, although the overall abundance was higher at the intermediate stage for Calliphoridae, Muscidae, and Sarcophagidae. In accordance to previous studies, nocturnal flight was rare, as approximately 8% of insects were captured at night. Our results expand the knowledge on ecological and behavioral aspects of necrophagous flies under inhospitable environments, such as the dry season in the Caatinga. The dominance of the invasive species C. albiceps reinforced here illustrates its geographical expansion towards the countryside of Northeastern Brazil.
Assuntos
Dípteros/fisiologia , Voo Animal , Muscidae/fisiologia , Sarcofagídeos/fisiologia , Animais , Brasil , Cadáver , RatosRESUMO
Islands act as natural laboratories for ecological studies to explain bioinvasion processes and, in this scenario, necrophagous Diptera have never been used as model organisms. This study aimed to (i) describe assemblages of necrophagous Diptera (Calliphoridae and Sarcophagidae) in two insular environments of different origins and distances from mainland, (ii) investigate the effect of anthropogenic impact on the assemblage of carrion flies, (iii) to quantify the establishment of invasive species in the two islands, and (iv) to infer about the conservation status of the islands based on the ecological parameters. Sampling was performed in 2011-2012, in the dry and rainy season. Insects were collected by using traps with chicken liver or sardine baits. In each island, environments exposed to different degrees of human impact were sampled. Ecological analyses were carried out to characterize the assemblages of Calliphoridae and Sarcophagidae, with emphasis on the relation between native and invasive species. In total, 99,862 adults of 21 species of blow flies and flesh flies were collected. Overall abundance in the oceanic island was higher than in the continental island, although the richness of species was higher in the latter. The type of bait did not influence diversity of species sampled in either island. No difference was observed in total richness of both families according to the gradient of anthropogenic impact, in both islands. The invasive species Chrysomya megacephala (Fabricius) was classified as dominant in all environments, irrespective of the anthropogenic impact, which raises concern about the conservation status of each island.