Sandra Peternel

Immunopathogenesis of psoriasis: focus on natural killer T cells

Psoriasis is a common inflammatory skin disease triggered by dysregulated immune response and characterized by hyperproliferation and altered differentiation of keratinocytes. Formation of psoriatic lesions is thought to be elicited by the complex cellular and cytokine network arising from the pathogenic interactions between keratinocytes and components of innate and acquired immune system. Natural killer T (NKT) cells are a heterogenous T‐cell lineage that has been implicated in the pathogenesis of various autoimmune diseases including psoriasis. Due to the numerous functions of NKT cells that link innate and adaptive immunity, their role in psoriasis is complex and still elusive. We summarize the currently available literature data on this issue and discuss the possible role of NKT cells in the immunopathogenesis of this autoimmune disease.

Seizure susceptibility and the brain regional sensitivity to oxidative stress in male and female rats in the lithium-pilocarpine model of temporal lobe epilepsy ☆

Several studies have shown the existence of sex differences in the sensitivity to various convulsants in animals and to the development of some epilepsy types in humans. The purpose of this study was to investigate whether there are sex differences in seizure susceptibility and sensitivity of different brain regions to oxidative stress in rats with status epilepticus (SE) induced by lithium-pilocarpine administration, that provides a common experimental model of temporal lobe epilepsy (TLE) in humans. Latencies to isolated full limbic seizures or SE onset as well as the number of the animals presenting full limbic seizures, SE or full limbic seizures that progressed to SE were recorded for 2 h after pilocarpine administration. Number of animals which survived 24 h after SE onset was also monitored. Levels of lipid peroxidation as well as the superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) activities in the piriform and entorhinal cortices, temporal neocortex, thalamus, and hippocampus in rats of both sexes, at 24 h after SE onset were determined. Results of our study showed that males developed full limbic seizures and SE more rapidly and in greater number than females. Levels of lipid peroxidation in all brain regions examined, the SOD activities in the piriform and entorhinal cortices, and temporal neocortex as well as the GSH-Px activities in the piriform and entorhinal cortices, and thalamus were significantly higher in rats with SE in comparison to the values of mentioned biochemical parameters in rats of the control groups. Lipid peroxidation level in the temporal neocortex as well as the GSH-Px activity in the hippocampus in male rats were significantly higher in comparison to the values registered in females. With the exception of the thalamus, where SOD activity in male rats with SE was significantly higher in relation to the respective control group and also to females with SE, sex differences in the response of other brain regions investigated to oxidative stress were not obtained, at 24 h after SE.

Childhood and adulthood traumatic experiences in patients with psoriasis

It is well known that several psychiatric disorders may be related to childhood psychological trauma. Recent studies have associated childhood exposure to trauma to some skin diseases. Our study aimed at exploring whether psoriasis is related to the reported positive and negative traumatic life events in different age intervals beginning from early childhood to adulthood. Furthermore, we investigated differences between psoriatics with early and late onset according to traumatic experiences in different age intervals. Also, we investigated the possible correlation of traumatic experiences with the disease severity. One hundred patients with psoriasis and 101 controls (patients with skin conditions considered to be “non‐psychosomatic”) were enrolled in the study. All participants completed a specific questionnaire measuring traumatic life experiences (Traumatic Antecedents Questionnaire, TAQ). The TAQ assesses positive personal experiences (competence and safety) and negative personal experiences (neglect, separation, secrets, emotional, physical and sexual abuse, trauma witnessing, other traumas and exposure to alcohol/drugs) from early childhood to adulthood. The severity of psoriasis was estimated according to the Psoriasis Area and Severity Index (PASI), a standardized measuring instrument. The amount of positive experiences did not differ significantly among groups, except for safety scores that were higher in controls compared with both psoriatic groups (early and late onset). On the other side, negative traumatic experiences appeared more frequently in patients with psoriasis during all developmental periods. We found no correlation between severity of psoriasis and traumatic experiences. The present study demonstrates an increased history of childhood and adulthood negative traumatic experiences in patients with psoriasis compared to the control group. Our findings suggest a relationship between retrospectively reported negative traumatic experiences and psoriasis.

Expression of TWEAK in normal human skin, dermatitis and epidermal neoplasms: association with proliferation and differentiation of keratinocytes.

Background: Tumor necrosis factor‐like weak inducer of apoptosis (TWEAK) has been implicated in the pathogenesis of various inflammatory pathologies and cancer. We aimed to investigate its expression in normal human skin, inflammatory skin diseases and epidermal neoplasms.

Oxidative stress parameters in different rat brain structures after electroconvulsive shock-induced seizures

Electroconvulsive therapy has been used in the treatment of psychiatric disorders since the 1930s, but little progress has been made in understanding the cellular mechanisms underlying its therapeutic and adverse effects. Electroconvulsive shock (ECS) in animals provides a common experimental model for studying the effects of electroconvulsive therapy in humans. In order to examine the changes of the brain oxidative stress parameters in several brain structures in the early time period after ECS-induced seizures, the levels of lipid peroxidation as well as superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) activities in the rat hippocampus, cerebellum, frontal cortex and the pons/medulla region were determined at different time points during the first 24 h after single ECS-induced seizures. In the hippocampus and cerebellum the levels of lipid peroxidation were unchanged, while the SOD and GSH-Px activities were significantly increased. Levels of lipid peroxidation and the activities of SOD and GSH-Px were not statistically changed in the pons/medulla region. Levels of lipid peroxidation in the frontal cortex were significantly higher in comparison to the control group at all time points examined while the SOD and GSH-Px activities were not statistically changed. In conclusion, the results of the present study indicate that single ECS causes the rat brain structure-specific alterations in the levels of lipid peroxidation as well as in the SOD and GSH-Px activities at different time points within the first 24 h after the seizures induction. Oxidative lipid damage was evident only in the frontal cortex, while the hippocampus, cerebellum and the pons/medulla region remained oxidatively unaffected in our experimental conditions.

Negative and positive life experiences in patients with psoriatic arthritis

Recent data suggest that childhood and adulthood stressors may play a significant role in the development of an autoimmune disease. The present study explores the relationship between psoriatic arthritis (PsA) and positive and negative life events during childhood and adulthood in psoriatic patients. Forty-five patients with psoriatic arthritis and 101 controls (patients with skin conditions considered to be “non-psychosomatic”) were enrolled in the study. All participants completed a specific questionnaire measuring traumatic life experiences [Traumatic Antecedents Questionnaire (TAQ)]. The TAQ assesses positive personal experiences (competence and safety) and negative personal experiences (neglect, separation, secrets, emotional, physical and sexual abuse, trauma witnessing, other traumas and exposure to alcohol/drugs) from early childhood to adulthood. The patients with psoriatic arthritis exhibited lower mean scores of total positive experiences during late childhood (latency) as compared to the control group. Negative experiences during four developmental periods appeared more frequently in patients with psoriatic arthritis than in the controls. The most frequently reported negative experiences were neglect, emotional abuse, physical abuse, sexual abuse, alcohol/drug abuse and other traumas. The present findings add evidence to the relationship between retrospectively reported childhood experiences and psoriatic arthritis. Furthermore, a high amount of reported emotional and physical abuse occurs in patients with psoriatic arthritis during latency and adolescence.

Pityriasis rubra pilaris in association with laryngeal carcinoma

Pityriasis rubra pilaris (PRP) is a rare group of hyperkeratotic, papulosquamous diseases that can be acquired or inherited. Cases of PRP associated with malignancy have been rarely reported. We report a case of 46‐year‐old man who presented with rapidly progressing PRP as a possible initial cutaneous symptom of a previously undiagnosed laryngeal carcinoma. Microlaryngoscopy was performed because of the patient’s hoarseness, and this revealed leucoplakia on the left vocal cord. Histopathological examination led to the diagnosis of squamous cell carcinoma in situ. After surgical treatment, the clinical signs of PRP began to resolve, and the patient was free of skin lesions at follow‐up. This case represents a rare coexistence of PRP with malignancy, and indicates that PRP can occur as paraneoplastic dermatosis associated with laryngeal cancer.

Cytotoxic T lymphocytes as a potential brake of keratinocyte proliferation in psoriasis

Psoriasis is a chronic papulosquamous skin disease, histologically characterized by epidermal hyperproliferation and dermal infiltration of inflammatory cells. The majority of T lymphocytes infiltrating dermis are CD4+ T lymphocytes secreting type 1 and type 17 cytokines. These cytokines are responsible for triggering keratinocyte proliferation as well as chemokine secretion and subsequent migration of other inflammatory cells in the skin. Contrarily, lymphocytes that accumulate in epidermis are mainly CD8+ T lymphocytes. According to the recent findings, these cells can also secrete type 1 and type 17 cytokines. However, it is demonstrated so far that epidermal CD8+ T lymphocytes contain higher amounts of cytolytic molecules, such as perforin, granzyme B and granulysin whose role in psoriasis pathogenesis is still unknown. Therefore, in this article we hypothesize the active involvement of cell mediated cytotoxicity in killing the proliferating keratinocytes as a mechanism of potential self-defense and possible brake in psoriatic plaque formation, maintaining skin homeostasis.

Erratum to: Negative and positive life experiences in patients with psoriatic arthritis

The corresponding author of the manuscript was inadvertently omitted the author name Marija Kaštelan from the author group of the published article. The revised author group is given below.