The N363S and I559N single nucleotide polymorphisms of the h-GR/NR3C1 gene in patients with bronchial asthma

Bronchial asthma is a disease of multifactorial etiology. The natural variability of the DNA sequence within the h-GR/NR3C1 gene affects both the conformation and the activity of glucocorticoid receptors. There are 2 major types of resistance to glucocorticoids (GCS)-resistant asthma failing to respond to treatment with high doses of inhaled and oral glucocorticoids. Type I GCS-resistant asthma is cytokine-induced or acquired. Type II GCS resistance involves generalized primary cortisol resistance, which affects all tissues and is likely to be associated with a mutation in the glucocorticoid receptor (GCR) gene or in genes that modulate GCR function. There are clear examples of glucocorticoid gene h-GR/NR3C1 polymorphisms that can influence responses and sensitivity to glucocorticosteroids. Among the numerous polymorphisms observed within this gene, N363S and I559N single nucleotide polymorphisms (SNPs) may play an important role in the development of bronchial asthma and in the alteration of sensitivity to GCS in severe bronchial asthma. The aim of this research project was to study the correlation between the N363S and I559N polymorphisms of the h-GR/NR3C1 gene and the occurrence of asthma in a population of Polish asthmatics. Peripheral blood was obtained from 210 healthy volunteers and 234 asthma patients. Structuralized anamnesis, spirometry and allergy skin prick tests were performed in all participants. Genotyping was carried out using the polymerase chain reaction (PCR)-restriction fragment length polymorphism (RFLP) and PCR-HRM methods. In the healthy, non-atopic population, the GG variant of the N363S polymorphism was found with a 5.7% frequency. In asthma patients, GG SNP of N363S occurred with the frequency of 6.4%. In the groups of patients with uncontrolled moderate asthma and uncontrolled severe disease, the genotype distribution for the investigated polymorphisms were as follows: N363S, AA, AG, GG occurring with 0.8750/0.0834/0.0416 frequency and I559N, TT, TA, AA occurring with 1.000/0.000/0.000 frequency. The analysis demonstrated a significantly higher frequency of the A and G variants of the N363S polymorphisms in uncontrolled moderate asthma and uncontrolled severe disease than in the healthy population. No variant-related differences in the frequency of the studied I559N polymorphism were demonstrated in healthy controls and asthma patients. In conclusion, the N363S polymorphism of the h-GR/NR3C1 gene is significantly associated with an increased sensitivity to glucococorticoids in vivo and susceptibility to the development of a moderate to severe form of uncontrolled bronchial asthma in the Polish population. This observation needs to be confirmed in a larger group of subjects.     

Anti-NMDA receptor encephalitis - case report

We present a patient with multiple sclerosis, diagnosed at the age of 16.5, in whom mental and orientation disturbances, strange behaviour as well as bizarre dyskinesias of the face and extremities occurred at age 20. After several days, tonic-clonic status epilepticus developed. Head computed tomography showed no abnormalities. Lumbar puncture revealed a pleocytosis of 20/3, which became normal after treatment. Seizures were brought under control, but the psychiatric symptoms persisted; they subsided after a dozen or so weeks. Magnetic resonance of the head and cervical spinal cord did not show any new abnormalities. After another several months, all symptoms recurred. A wide range of laboratory tests, as well as positron emission tomography, did not reveal any abnormalities. Suspicion of autoimmune encephalitis led to a test for serum anti-NMDA-receptor antibodies that confirmed the diagnosis. After immunotherapy, our patient improved and was transferred for rehabilitation.     

Motor cortex stimulation in the treatment of neuropathic pain

Background and purposeDespite the rapid development of neuropharmacotherapy, medical treatment of neuropathic pain (NP) still constitutes a significant socioeconomic problem. The authors herein present a group of patients treated with motor cortex stimulation (MCS) for NP of various types and aetiologies.Material and methodsOur cohort included 12 female and 11 male NP patients aged 53 ± 16 treated with MCS. Eleven patients were diagnosed with neuropathic facial pain (NFP), 8 with hemi-body neuropathic pain (HNP), and 4 with deafferentation pain (DP). Prior to surgery, 16 out of 23 patients were treated with repetitive transcranial magnetic stimulation (rTMS), with a positive response in 10 cases. Pain intensity in our group was evaluated with the visual analogue scale (VAS) one month before and three months after MCS implantation.ResultsImprovement on the VAS was reported in the whole group of patients (p < 0.001). The best results were reported in the NFP group (p < 0.001) while the worst ones were noted in the DP group (p = 0.04). Anamnesis duration positively correlated with outcome. Infection forced the authors to permanently remove the system in one case. There were no other complications in the group.ConclusionsMinimally invasive, safe neuromodulative treatment with MCS permits neuropathic pain control with good efficacy. The type of neuropathic pain might be a prognostic factor.     

Impaired discrimination between imagined and performed actions in schizophrenia

The main aim of the present study was to investigate whether a specific type of source monitoring, namely self-monitoring for actions (differentiation between imagined and performed actions), is disrupted in schizophrenia. Persons diagnosed with schizophrenia (n=32) and healthy participants (n=32) were assessed with an action memory task. Simple actions were presented to the participants either verbally (short instructions) or nonverbally (icons). Some of the items required participants to physically perform the action whereas other actions had to be imagined. In the recognition phase of the study, participants were asked whether an action was previously displayed (verbally or nonverbally), whether it was a new action (not presented before), and if they had performed or imagined the action. In addition, participants were asked how confident they were in their decision. Participants in the group with schizophrenia significantly more often misattributed imagined actions as performed and vice versa and were more convinced about their wrong decision than participants in the control group. Patients revealed worse recognition for both verbal and nonverbal actions. In accordance with prior studies, we found that patients were less confident in their correct answers than healthy subjects. However, no enhanced confidence in incorrect answers was found. There was no observed significant relationship between source misattributions and the severity of psychopathological symptoms. Our findings suggest tentatively general source monitoring deficits in schizophrenia.     

Association of genetic polymorphisms with personality profile in individuals without psychiatric disorders

Objective

Population-based twin studies demonstrate that approximately 40–50% of the variability in personality dimensions results from genetic factors.This study assessed selected polymorphisms in the COMT Val158Met, MAOA 3′VNTR, 5HTTLPR, 102T/C 5-HT2A, DAT 3′VNTR and DRD2 exon 8 genes and evaluated their association with personality profiles, anxiety levels, and depressiveness in healthy subjects.

Methods

This study included 406 unrelated (mean age 38.51 years), mentally and somatically healthy Caucasian subjects of Polish origin. The prevalence of the gene variants mentioned above and their association with personality profiles, anxiety levels, and depressiveness was assessed using the Temperament and Character Inventory, NEO Five-Factor Inventory, Spielberger's State-Trait Anxiety Inventory and Beck's Depression Inventory.

Results

The effects of the 5HTTLPR gene on the s/s genotype and empathy (C2) were lowest in the entire group. The effects of gender, age and the HT2A gene for the T/T genotype and attachment (RD3) were highest in women.The effects of gender, age and the DAT gene on the 9/9 DAT genotype, compassion (C4) and cooperativeness (C) were lowest in women. The effects of gender, age and the COMT gene on the Met/Met genotype and neuroticism (NEU) NEO-FFI were also lowest in women.

Conclusions

Our results suggest considerable influence of individual genes on the formation of personality traits.     

Differential expression of calbindin D28k, calretinin and parvalbumin in the cerebellum of pups of ethanol-treated female rats

Three calcium-binding proteins (CaBPs), calbindin D28k, calretinin and parvalbumin, were immunohistochemically examined in the cerebellum of ten-day-old rat pups of ethanol-treated dams. Dams were treated with ethanol during pregnancy and/or lactation. In the cerebellar cortex of the pups from control groups, Purkinje cells with their processes and Golgi cells were positive for calbindin D28k, whereas interneurons (Lugaro, Golgi and unipolar brush cells) and sometimes Purkinje cells were positive for calretinin. Parvalbumin immunoreactivity was observed in Golgi and basket cells, stellate cells and in some Purkinje cells. The number of positive cells and staining intensity for calbindin D28k and parvalbumin decreased in all experimental groups, whereas the immunoreaction for calretinin was visible only in interneurons and was more intense in experimental than in control groups. Calbindin D28k immunoreactivity in experimental groups was detected in some Purkinje cells and rarely in Golgi cells. The localization of very intense calretinin expression was visible mainly in unipolar brush cells. A parvalbumin-positive reaction was detected in single Purkinje cells and sometimes in basket cells. The results of the present study showed that immunoreactivity of the three calcium-binding proteins was found in the cells of the cerebellum of the ten-day-old pups from the control groups. In experimental groups of females treated with ethanol during pregnancy and/or lactation, we observed the most significant decrease in both the intensity and the number of immunoreactions of calbindin D28k and parvalbumin, but the intensity of the immunoreaction for calretinin was increased for interneurons. Ischaemic damage to Purkinje cells and loss of interneurons and Purkinje cells were also noted in these groups. A possible correlation between the duration of ethanol intoxication, expression of calcium-binding proteins and pathological changes of cells in the cerebellar cortex of the pups of ethanol-treated dams is discussed.     

Acute inflammation of the true cecal diverticulum--case report

In this case report, we describe a rare event: acute inflammation of the true cecal diverticulum. Emergency surgery enabled proper diagnosis and management of this condition. Diagnostic approaches and the management of this disease are described in detail and based on literature review. In conclusion, pathologies of cecal diverticula should be considered in differential diagnosis of pain in the right iliac fossa.