Brain‐based treatment—A new approach or a well‐forgotten old one?

For a relatively long period of time, mental functioning was mainly associated with personal profile while brain functioning went by the wayside. After the 90s of the 20th century, or the so called “Decade of the Brain”, today, contemporary specialists work on the boundary between fundamental science and medicine. This brings neuroscience, neuropsychology, psychiatry, and psychotherapy closer to each other. Today, we definitely know that brain structures are being built and altered thanks to experience. Psychotherapy can be more effective when based on a neuropsychological approach—this implies identification of the neural foundations of various disorders and will lead to specific psychotherapeutic conclusions. The knowledge about the brain is continually enriched, which leads to periodic rethinking and updating of the therapeutic approaches to various diseases of the nervous system and brain dysfunctions. The aim of translational studies is to match and combine scientific areas, resources, experience and techniques to improve prevention, diagnosis and therapies, and “transformation” of scientific discoveries into potential treatments of various diseases done in laboratory conditions. Neuropsychological studies prove that cognition is a key element that links together brain functioning and behaviour. According to Dr. Kandel, all experimental events, including psychotherapeutic interventions, affect the structure and function of neuronal synapses. The story of why psychotherapy works is a story of understanding the brain mechanisms of psychic processes, a story of how the brain has been evolving to ensure learning, forgetting, and the mechanisms of permanent psychological change. The new evidence on brain functioning necessitates the integration of neuropsychological achievements in the psychotherapeutic process. An integrative approach is needed to take into account the dynamic interaction between brain functioning, psyche, soul, spirit, and social interaction, ie, development of a model of psychotherapeutic work based on cerebral plasticity! Brain‐based psychotherapy aims at changing brain functioning not directly, but through experiences. This is neuro‐psychologically informed psychotherapy.     

Mannan-binding lectin deficiency modulates the humoral immune response dependent on the genetic environment

Mannan-binding lectin (MBL) is a plasma protein implicated in innate immune defence against a broad range of microorganisms, including viruses. It is also thought that MBL plays a role in the recruitment of the specific clonal immune response. This was studied by injecting soluble hepatitis B surface antigen (HBsAg) intravenously into mice deficient in both MBL-A and MBL-C (MBL DKO mice). The MBL DKO animals on mixed genetic background (SV129EvSv × C57BL/6) produced higher antibody titres than the wild-type littermates. After primary challenge with the antigen the immunoglobulin M anti-HBsAg antibody titres were threefold higher in the MBL DKO mice than in the wild-type mice. Following the boost, the immunoglobulin G anti-HBsAg antibody titres were 10-fold higher in the MBL DKO mice, suggesting that MBL plays a role in a negative feedback regulation of adaptive immunity. However, the modulating effect of MBL was dependent on the genetic environment. The MBL DKO mice backcrossed on a C57BL/6 background showed the opposite response with the MBL DKO mice now producing fewer antibodies than the wild-type animals, whereas MBL deficiency in mice with the SV129EvSv background did not show any effect in antibody production. These findings indicate that the modifying effect of MBL on the humoral immune response is influenced by the genetic environment.     

Lactate Dehydrogenase-5 (LDH-5) Expression in Human Gastric Cancer: Association with Hypoxia-Inducible Factor (HIF-1α) Pathway,Angiogenic Factors Production and Poor Prognosis

Background  Lactate-dehydrogenase-5 (LDH-5) is an important isoenzyme converting pyruvate to lactate under hypoxic conditions and might play an important role in the development and progression of malignancies. However, the role of LDH-5 in gastric cancer is still unclear. In this study, we investigated the clinical significance of LDH-5 expression in gastric carcinoma. Methods  LDH-5 expression in 152 patients with different grade and stage gastric carcinoma was analyzed by immunohistochemistry. In addition, hypoxia-inducible factor 1α (HIF-1α) as a marker of tumor hypoxia, as well as vascular endothelial growth factor (VEGF) and cyclooxygenase-2 (COX-2) as angiogenesis parameters were also assessed in this study. Correlations between the expression of investigated proteins and various clinicopathological factors including survival were determined. Results  There were 94 cases (61.8%) showing high LDH-5 expression, and 95 patients (62.5%) had high HIF-1α expression. Positive correlation was found between LDH-5 expression and HIF-1α, VEGF, and COX-2. The overexpression of LDH-5 was more prevalent in advanced tumors having positive vessel invasion. Patients with overexpression of LDH-5 showed far lower disease-free (63.5% vs 82.7%) and overall (56.3% vs 78.4%) survival rates compared with patients with low LDH-5 expression. HIF-1α expression was shown to have no significance on survival. In multivariate analysis, high LDH-5 expression kept its independence as a negative prognostic indicator. Conclusion  The results of the current study show that LDH-5 expression may be a useful prognostic factor for patients with gastric carcinoma.     

Delta responses and cognitive processing: single-trial evaluations of human visual P300.

Visual P300 responses were recorded by using checkerboard-type stimuli. (1) High amplitude P300-delta responses were visible even in single trial ERPs. (2) An algorithm for efficient selection of P300 single trials (based on evaluation of delta responses) is introduced. (3) The 'universal' character of the P300-delta response demonstrated in this report may open new avenues for the understanding of functional ERP components.     

Evaluation of contractile state of the left ventricle from the peak of the first derivative of the apexcardiogram

Simultaneous records of the electrocardiogram, phonocardiogram, apexcardiogram (ACG), and the first derivative of the apexcardiogram ($\text{dA}\text{dt}$) were obtained in 50 normal subjects and in 38 patients with ischemic heart disease. This allowed us to measure the ratio of peak $\text{dA}\text{dt}$ to total amplitude of the first derivative in percent and the interval from electrical stimulation to peak $\text{dA}\text{dt}$ (R to peak $\text{dA}\text{dt}$). In 16 additional normal subjects the effects of pharmacological agents with positive and negative inotropic action were studied with the above parameters. During isoprenaline infusion the ratio of peak to total amplitude $\text{dA}\text{dt}$ was increased and the interval R to peak $\text{dA}\text{dt}$ was shortened, while after propranolol the ratio of peak $\text{dA}\text{dt}$ diminished and the interval R to peak $\text{dA}\text{dt}$ showed elongation.In normal subjects the ratio of peak $\text{dA}\text{dt}$ averaged 48 ± 14% and it is significantly lower in patients with ischemic heart disease (32 ± 13%, p < 0.001). In controls the interval R to peak $\text{dA}\text{dt}$ was 73 ± 15 msec., whereas in ischemic heart disease it showed elongation (121 ± 15 msec., p < 0.01).It is concluded that the ratio peak $\text{dA}\text{dt}$ and the interval R to peak $\text{dA}\text{dt}$, expressing noninvasively the rate of pressure changes and the duration of the development of maximum tension during isovolumic contraction, provide useful information on left ventricular function.     

Modulation of fibrinolysis by the combined action of phospholipids and immunoglobulins.

Because both immunoglobulin G (IgG) and phospholipids interfere with fibrinolysis, their combined modulating effects were investigated in experimental models of three consecutive steps of the fibrinolytic process [diffusion of tissue-type plasminogen activator (tPA) into the clot, plasminogen activation on fibrin surface and fibrin dissolution by plasmin] using IgGs isolated from healthy subjects and from patients with antiphospholipid syndrome in combination with mixtures of synthetic dipalmitoylphosphatidylcholine and dipalmitoylphosphatidylserine. In fibrin clots containing phospholipids the normal IgG enhanced the barrier function of the phospholipids with respect to the diffusion of tPA and plasminogen activation, but did not modify the lysis by plasmin. One of the examined antiphospholipid syndrome-IgGs also restricted the diffusion of tPA, but it accelerated the plasminogen activation on the fibrin surface and slowed down the lysis of fibrin by plasmin. Another antiphospholipid syndrome IgG, which did not affect significantly the tPA penetration into the fibrin gel, did not modify the plasminogen activation on its own, but it partially opposed the inhibiting effect of phospholipids on plasmin formation and accelerated the end-stage lysis of fibrin containing phospholipids. The IgGs from the two examined antiphospholipid syndrome patients did not show consistent deviation from the pattern of normal IgG effects on fibrinolysis in phospholipid environment. Thus, a high degree of heterogeneity with respect to the profibrinolytic or antifibrinolytic effects of the pathological IgGs can be expected in the antiphospholipid syndrome patient population, which may contribute to the variable thrombotic symptoms in this clinical syndrome.