Behavioral and brain oscillatory correlates of affective processing in subclinical depression

Named among the most dangerous diseases of the modern era, depression is characterized primarily by distortions in the affective sphere. Despite extensive investigations of underlying the neural background, mechanisms of the distortion still remain unknown. The current study analyzed brain oscillatory dynamics in different frequencies during resting state and presentation of affective stimuli in nonclinical individuals with high Beck Depression Inventory–II (BDI–II) scores (HB) versus controls. Both behavioral and electrocortical “markers” of clinical depression were apparent at subclinical level. A resting-state electroencephalogram (EEG) of HB revealed increased power in low frequencies, predominantly in the frontal cortical areas, that is in accordance with a “spatio-temporal dysfunction” model of depression. Related to that, transition from an eyes-closed to eyes-open condition was associated with diminished alpha blockade in HB, suggesting difficulties with the relocation of attention focus from inner processes toward environmental stimuli. Subsequently, independently of a sign of emotion, five out of six discrete emotions were evaluated as less valenced and four out of six as less intense by HB than by controls, corroborating the view of emotion context insensitivity (ECI) associated with depression. Underlying brain oscillatory dynamics revealed that depression was associated with deficits in the early, implicit, processing stages of emotional stimuli. Later processing stages were characterized by prominent power surges in low and alpha frequencies, presumably indicating emotion upregulation processes and increased engagement of cognitive mechanisms in affective tasks. The study provides brain oscillatory-based mechanisms of emotion processing distortions associated with depression.     

The DeBakey classification exactly reflects late outcome and re-intervention probability in acute aortic dissection with a slightly modified type II definition

Objective: The DeBakey classification was used to discriminate the extent of acute aortic dissection (AD) and was correlated to long-term outcome and re-intervention rate. A slight modification of type II subgroup definition was applied by incorporating the aortic arch, when full resectability of the dissection process was given. Methods: Between January 2001 and March 2010, 118 patients (64% male, mean age 59 years) underwent surgery for acute AD. As many as 74 were operated on for type I and 44 for type II AD. Complete resection of all entry sites was performed, including antegrade stent grafting for proximal descending lesions. Results: Patients were comparable with respect to demographics and preoperative hemodynamic status. They underwent isolated ascending replacement, hemiarch, or total arch replacement in 7%, 26%, and 67% in type I, versus 27%, 37%, and 36% in type II, respectively. Additional descending stent grafting was performed in 33/74 (45%) type I patients. In-hospital mortality was 14%, 16% (12/74) in type I versus 9% (4/44, type II), p = 0.405. After 5 years, the estimated survival rate was 63% in type I versus 80% in type II, p = 0.135. In type II, no distal aortic re-intervention was required. In type I, the freedom of distal re-interventions was 82% in patients with additional stent grafting versus 53% in patients without, p = 0.022. Conclusions: The slightly modified DeBakey classification exactly reflects late outcome and aortic re-intervention probability. Thus, in type II patients, the aorta seems to be healed without any probability of later re-operation or re-intervention.     

Clinical determinants of primary and secondary fatigue in patients with Parkinson’s disease

Clinical and psychosocial factors associated separately with primary and secondary fatigue in Parkinson’s disease (PD) patients have not been thoroughly studied before. The aim of our study was to assess factors associated with different fatigue domains in groups with primary and secondary fatigue in PD separately. We divided 165 non-demented PD patients according to the absence/presence of depression, anxiety and excessive somnolence into groups with primary fatigue (N = 63) and with secondary fatigue (N = 102). Fatigue domains examined using the multidimensional fatigue inventory were associated through multiple linear regression analyses for each group separately with sociodemographic data, disease duration, functional status as assessed by the Unified Parkinson’s Disease Rating Scale, treatment, depression, anxiety, excessive somnolence and sleep quality. Out of the assessed non-motor symptoms, fatigue was the most frequent (77.6 %). The prevalence of fatigue in the secondary fatigue group was significantly higher than in the primary fatigue group. Both fatigue groups differed significantly in factors associated with different fatigue domains. Functional status or other disease-related factors were not associated with primary fatigue. In the secondary fatigue group, we found associations between some fatigue domains and functional status, older age, male gender and higher anxiety scores. To our knowledge, this is the first study to separately describe clinical determinants and psychosocial factors associated with different fatigue domains in primary and secondary fatigue in PD, underlining the importance of distinguishing primary and secondary fatigue in future PD studies and clinical practice.     

Age-related DNA methylation changes in normal human prostate tissues.

PURPOSE: Prostate cancer is a leading cause of cancer death among the aging male population but the mechanism underlying this association is unclear. Aberrant methylation of promoter CpG islands is associated with silencing of genes and age-dependent methylation of several genes has been proposed as a risk factor for sporadic cancer. We examined the extent of gene methylation in pathologically normal human prostate as a function of age. EXPERIMENTAL DESIGN: We used pyrosequencing to quantitatively analyze the methylation status of nine CpG islands in normal prostate tissue DNA from 45 organ donors and 45 patients who had undergone cystoprostatectomy for bladder cancer. We also analyzed 12 pairs of matched benign and prostate cancer tissue DNA from patients with prostate cancer. RESULTS: Linear regression analysis revealed a significant increase in promoter methylation levels correlating with age for CpG islands at RARbeta2 (r = 0.4; P < 0.0001), RASSF1A (r = 0.27; P = 0.01), GSTP1 (r = 0.59; P < 0.0001), NKX2-5 (r = 0.27; P = 0.008), and ESR1 (r = 0.244; P = 0.023) in the normal prostate tissue samples studied. A calculated average methylation (z score) at all nine CpG loci analyzed in the normal prostate tissues showed a strong correlation with age (r = 0.6; P < 0.001). Comparison of the methylation level for the matched benign and prostate cancer tissues from individual patients with prostate cancer showed significantly higher methylation in the prostate cancer tissue samples for RARbeta2 (P < 0.001), RASSF1A (P = 0.005), GSTP1 (P < 0.001), NKX2-5 (P = 0.003), ESR1 (P = 0.016), and CLSTN1 (P = 0.01). CONCLUSIONS: Our findings show aberrant hypermethylation as a function of age in the normal prostate tissues. Such age-related methylation may precede and predispose to full-blown malignancy.     

A study of the conditions of the supercritical fluid extraction in the analysis of selected anti-inflammatory drugs in plasma

Supercritical fluid extraction (SFE) was employed to analyze selected anti-inflammatory drugs in plasma. Evaluation of selected drugs (ibuprofen, indomethacin, and flufenamic acid) was performed using the HPLC method on columns with the reverse phase C-18 and detection in the UV region of the spectrum. A study of the conditions of SFE carried out for 30 min at 50 degrees C investigated the magnitude of the pressure of carbon dioxide suitable for drug extraction, the selection of the collecting solvent, and the modification of CO2 with an organic solvent. The results of the study made it possible to determine the optimal procedure for SFE of ibuprofen, indomethacin, and flufenamic acid from plasma, which renders their HPLC quantification possible.     

Renal ischemia-reperfusion injury in the rat is prevented by a novel immune modulation therapy

BACKGROUND: Vasogen Inc.'s (Mississauga, Ontario, Canada) immune modulation therapy (IMT) is a therapy in which cells from the patient's own blood are modified by ex vivo exposure to specific physicochemical stressors, including oxidation, ultraviolet (UV) light, and an elevated temperature. The therapy has been shown to have a beneficial effect in models of inflammation and vascular diseases. This study tested the hypothesis that IMT can prevent renal ischemia-reperfusion (I/R) injury in rats. METHODS: Whole blood was collected from syngeneic age-matched donors by cardiac puncture. It was treated with a combination of controlled physiochemical stressors consisting of elevated temperature, a gas mixture of medical oxygen containing ozone, and UV light. The treated blood (150 microL) was injected in the gluteal muscle. Control animals received the same volume of untreated blood or physiological saline. Transient (45 or 60 minutes) left-renal ischemia was produced with simultaneous contralateral nephrectomy in treated and control spontaneously hypertensive rats (SHR). Young and old male and female rats were studied. Plasma creatinine, diuresis, and the survival rates of each group were compared. Renal apoptosis-necrosis was estimated by DNA laddering, histology, and in situ terminal deoxynucleotidyl transferase assay. mRNA levels of several regulators of apoptosis-regeneration were determined in control and postischemic kidneys by Northern blotting. RESULTS: IMT pretreatment of SHR significantly reduced renal I/R injury compared with equivalent placebo treatments consisting of untreated blood- or saline-injected SHR, as evidenced by a significant increase of the survival rate curves in young and old male SHR, which correlated with 24-hour postischemic diuresis. The increases in plasma creatinine following renal I/R were significantly lower in IMT-treated young male and old female SHR compared with saline or untreated blood-injected controls. Dilution analysis showed that the protective effect of treated blood was lost by dilution. Loss of epithelial cells was reduced in IMT-treated rats, with a significant decline in the peak of apoptosis 12 hours after acute ischemic renal injury. IMT did not modify the pattern of mRNA levels of several genes involved in the inflammation and regeneration processes. CONCLUSION: Our data demonstrate that IMT prevents the destruction of kidney tissue and the resulting animal death caused by renal I/R injury.     

Microsatellite instability in hematological malignancies

The replication error (RER+) phenotype, characterized by microsatellite instability (MSI) has been recently related to mutations of genes involved in DNA mismatch repair pathway. These genetic alterations were first described in hereditary non polyposis colorectal cancer (HNPCC). We examined 44 patients with hematological malignancies (27 AML, 9 MDS, 2 CML-BP and 6 T-ALL) for evidence of MSI. Twenty seven percent of our patients showed differences for only one marker. In four cases (9.1%) MSI was observed in multiple markers and these cases were described as RER+ phenotype. Presented data suggest that this phenomenon may play a role in at least a subset of patients with hematological malignancies.     

Evaluation of geometric and dosimetric inaccuracies of stereotactic irradiation in the rat brain

OBJECTIVE: To evaluate geometric and dosimetric inaccuracies in the irradiation of the rat brain with the Leksell Gamma Knife. MATERIALS AND METHODS: Altogether three types of dosimeters were employed for these measurements: (a) a thermoluminescent dosimeter, (b) a semiconductor detector and (c) a polymer gel dosimeter. The thermoluminescent dosimeter and the semiconductor detector were calibrated using an ion chamber and then implanted in the brain of a rat cadaver and used for absolute dose determination. A special glass phantom mimicking exactly the shape of the rat body filled with the polymer gel was used for measurements of the relative dose distribution and evaluation of geometric inaccuracies during the stereotactic irradiation in the rat brain. RESULTS: Both thermoluminescent and semiconductor detectors, due to their size, measured mean doses. The observed results demonstrated that the Leksell GammaPlan can be employed for the calculation of absorbed doses in irradiation of experimental animals. In our case, it was necessary to apply a correction factor of 1.078 for the absolute absorbed dose to obtain reliable results. A comparison of calculated dose profiles using the treatment planning system in all three axes with those measured by the polymer gel dosimeter demonstrated a very good geometric agreement with the mean deviation in profile position of 0.5 mm. CONCLUSION: The results indicate that this technique can effectively check the geometric and dosimetric accuracy of stereotactic irradiation in the rat brain. The Leksell GammaPlan can be employed for the calculation of absorbed doses, but the correction factor of 1.078 had to be applied for the absolute dose calculations in our irradiation geometry.     

Über Versuche zur Normalisierung einer gestörten Darmflora beim Säugling

Ohne Zusammenfassung     

Polymerization of lactams, 58. Nonactivated polymerization of 2-pyrrolidone in the presence of higher lactams

Addition of a higher lactam (ε-caprolactam or 8-octanelactam) to the nonactivated polymerization of 2-pyrrolidone, initiated with potassium tert-butoxide or the isolated potassium salt of 2-pyrrolidone, does not lead to the formation of a copolyamide. Only a marked decrease of polymerization rate is observed and the maximum rate of 2-pyrrolidone homopolymerization shifts to a lower temperature. The possible causes of this interesting phenomenon are discussed.