Elisabete Castelon Konkiewitz

Antihyperalgesic and antidepressive actions of (R)-(+)-limonene, α-phellandrene, and essential oil from Schinus terebinthifolius fruits in a neuropathic pain model

Abstract Objectives Previous studies have shown that essential oil containing (R)-(+)-limonene and α-phellandrene, extracted from fruits of Schinus terebinthifolius Raddi, exhibit anti-inflammatory activity. This work aimed to verify the antihyperalgesic and antidepressive actions of (R)-(+)-limonene, α-phellandrene, and essential oil from S. terebinthifolius fruits in spared nerve injury (SNI) model of neuropathic pain in rats. Methods In the present work, essential oil from fruits of S. terebinthifolius, as well as the pure (R)-(+)-limonene and α-phellandrene compounds, were assayed for their effects on SNI-induced mechanical and cold hyperalgesia, and depressive-like behavior (immobility in forced swim test) in rats. The locomotor activity was evaluated in open-field test. Results Oral administration for up to 15 days of essential oil of S. terebinthifolius (100 mg/kg), (R)-(+)-limonene (10 mg/kg), α-phellandrene (10 mg/kg), and also subcutaneous 10 mg/kg dose of ketamine (positive control) significantly inhibited SNI-induced mechanical hyperalgesia and increased immobility in the forced swim test. On the 15th day of oral treatment, α-phellandrene, but neither the essential oil from S. terebinthifolius nor (R)-(+)-limonene, prevented the SNI-induced increase in sensitivity to a cold stimulus. The oral treatment with essential oil (100 mg/kg) or with compounds (10 mg/kg) did not interfere on locomotor activity. Discussion Together, the results of the present work show that essential oil of S. terebinthifolius and compounds present in this oil, including (R)-(+)-limonene and α-phellandrene, exhibit antihyperalgesic effects against mechanical hyperalgesia, and are antidepressive, while only α-phellandrene inhibited cold hyperalgesia in SNI rats.

Socioeconomic disadvantage increasing risk for depression among recently diagnosed HIV patients in an urban area in Brazil: cross-sectional study

Depression is the most common psychiatric co-morbidity among people living with HIV (PLHIV), with prevalence rates ranging from 25% to 36%. Depression impacts negatively upon adherence and response to combined antiretroviral therapy (CART) and the transmission of HIV infection through increased sexually risky behavior. This cross-sectional study presents data from a reference HIV-outpatient service in Dourados (Brazil) that evaluated the association between depressive symptoms, health-related quality of life, and clinical, socioeconomic, and demographic factors in newly diagnosed HIV/AIDS patients. Using the Beck Depression Inventory (BDI), the prevalence of depressive symptoms was 61% with a predominance of self-deprecating and cognitive-affective factors. Depressive symptoms were associated with lower income (p = 0.019) and disadvantaged social class (p = 0.005). Poorer quality of life was related to depressive symptoms (p < 0.0001), low educational level (p = 0.05), and lower income (p = 0.03). These data suggest that socioeconomic factors, including level of income and education, are mediating the risk of depression and poor quality of life of PLHIV. Possible explanations for this effect are discussed, including the possible role of stigma.

Animal Models for Depression Associated with HIV-1 Infection

Antiretroviral therapy has greatly extended the lifespan of people living with human immunodeficiency virus (PLHIV). As a result, the long-term effects of HIV infection, in particular those originating in the central nervous system (CNS), such as HIV associated depression, have gained importance. Animal models for HIV infection have proved very useful for understanding the disease and developing treatment strategies. However, HIV associated depression remains poorly understood and so far there is neither a fully satisfactory animal model, nor a pathophysiologically guided treatment for this condition. Here we review the neuroimmunological, neuroendocrine, neurotoxic and neurodegenerative basis for HIV depression and discuss strategies for employing HIV animal models, in particular humanized mice which are susceptible to HIV infection, for the study of HIV depression.

Limonene reduces hyperalgesia induced by gp120 and cytokines by modulation of IL-1 β and protein expression in spinal cord of mice

Aims: We have investigated the antihyperalgesic effects of limonene in mice that received intrathecal injection of gp120. Main methods: Male Swiss mice received gp120, IL‐1&bgr; or TNF‐&agr; intrathecally or sterile saline as a control. A mechanical sensitivity test was performed at 2 and 3 h after the injection. Spinal cord and blood samples were isolated for protein quantification. Key findings: Intrathecal administration of gp120 increased mechanical sensitivity measured with an electronic Von Frey apparatus, at 2 and 3 h after the injections. Limonene administered orally prior to gp120 administration significantly decreased this mechanical sensitivity at 3 h after the gp120 injection. In addition, intrathecal injection of gp120 increased IL‐1&bgr; and IL‐10 in serum, and limonene prevented the ability of gp120 to increase these cytokines. Limonene also inhibited TNF‐&agr; and IL‐1&bgr;‐induced mechanical hyperalgesia. Western blot assay demonstrated limonene was capable of increasing SOD expression in the cytoplasm of cells from spinal cord at 4 h after intrathecal IL‐1&bgr; injection. Significance: These results demonstrate that gp120 causes mechanical hyperalgesia and a peripheral increase in IL‐1&bgr; and IL‐10, and that prior administration of limonene inhibits these changes. Also limonene modulates the activation of SOD expression in the spinal cord after spinal IL‐1&bgr; application. The ability of limonene to inhibit the mechanical hyperalgesia induced by gp120, TNF‐&agr; and IL‐1&bgr; emphasizes the anti‐inflammatory action of limonene, specifically its ability to inhibit cytokine production and its consequences.

Dissociation, Delusion and the Splitting of the Self in The Trial by Franz Kafka: Phenomenology and Neurobiology of Schizophrenia

In this essay, we propose an association between Franz Kafkas novel, The Trial, and phenomenological and neurobiological processes in schizophrenia. We begin by presenting a summary of the plot, pointing to some of its remarkable literary aspects. We next compare the mental processes of dissociation, disorientation and delusion as represented in the novel with phenomenological processes that take place in the prodromal states of schizophrenia. We discuss how such disorders of the self and disorders of thought, both crucial aspects of the schizophrenic experience, appear in The Trial and in other literary and private writings by Franz Kafka. We relate how these disorders may arise from the false attribution of salience and false associative learning caused by hyperactivity of dopaminergic function associated with chaotic firing of dopaminergic neurons. Finally, we show how Kafka leads not just the protagonist of The Trial, but even more the reader to experience a quasi-delusional state. We discuss the relationship between the perturbation of thought and disorientation of mind evoked by the novel in the reader and the need of our brains for empathy and predictability.

Letter to His Father by Franz Kafka: Literary Reconstruction of a Traumatic Childhood?

Franz Kafkas Letter to His Father is one of the greatest examples in world literature of memory of a traumatic childhood. In it, the author takes a retrospective journey through his life, recollecting and analyzing the reasons for the estrangement and hostility between a father and a son. This essay considers Letter to His Father in the light of current knowledge about autobiographical memory. The essay first sets forth basic aspects of Kafkas life in order to place Letter to His Father in the context of Kafkas biography, and then presents Kafkas relevance to the literature and thought of the twentieth and twenty-first centuries. The essay then considers the different forms of childhood abuse and their consequences in light of evidence from neurodevelopmental psychology. We present evidence about the relationship between trauma and the construction of self-image. Furthermore, we discuss the subjectivity of Kafkas recollections from the perspective of recent advances in neurobiology. Memory is shown to be dynamic, selective, inherently malleable and dependent on perception, which is a subjective construction, in which the brain interprets and gives coherence to experienced stimuli. We consider the inaccuracy of memory, which is related to neuroplastic changes in the brain that take place over time: consolidation, reconsolidation and transformation. Finally, the relationship between literature and autobiography in the Kafkaesque universe is considered.