Time experience in patients with schizophrenia and affective disorders

BackgroundThe experience of time, or the temporal order of external and internal events, is essential for humans. In psychiatric disorders such as depression and schizophrenia, impairment of time processing has been discussed for a long time.AimsIn this explorative pilot study, therefore, the subjective time feeling as well as objective time perception were determined in patients with depression and schizophrenia, along with possible neurobiological correlates.MethodsDepressed (n = 34; 32.4 ± 9.8 years; 21 men) and schizophrenic patients (n = 31; 35.1 ± 10.7 years; 22 men) and healthy subjects (n = 33; 32.8 ± 14.3 years; 16 men) were tested using time feeling questionnaires, time perception tasks and critical flicker-fusion frequency (CFF) and loudness dependence of auditory evoked potentials (LDAEP) to determine serotonergic neurotransmission.ResultsThere were significant differences between the three groups regarding time feeling and also in time perception tasks (estimation of given time duration) and CFF (the “DOWN” condition). Regarding the LDAEP, patients with schizophrenia showed a significant negative correlation to time experience in terms of a pathologically increased serotonergic neurotransmission with disturbed time feeling.ConclusionsImpairment of time experience seems to play an important role in depression and schizophrenia, both subjectively and objectively, and novel neurobiological correlates have been uncovered. It is suggested, therefore, that alteration of experience of time should be increasingly included in the current psychopathological findings.     

Quality of life and mental health in hemodialysis and peritoneal dialysis patients: the role of health beliefs

Background and objective  

Patients’ beliefs regarding their health are important to understand responses to chronic disease. The present study aimed to determine (i) whether beliefs about health differ between different renal replacement therapies in end-stage renal disease (ESRD) patients and (ii) whether these beliefs are associated with health-related quality of life (HQoL), as well as with mental health.     

A modified ETDRS visual acuity chart for European-wide use.

PURPOSE: The log MAR visual acuity (VA) chart developed for use in the Early Treatment Diabetic Retinopathy Study (ETDRS) is composed of 10 Sloan letters, which are not used in the Greek, Cyrillic, and Central European alphabets. In this study we evaluate a modified ETDRS chart, the University of Crete (UoC) chart, which contains a set of letters readable by all European citizens. METHODS: In the UoC charts, the letters C, D, R, N, V, S, and Z were substituted with E, P, B, X, Y, A, and T, respectively. The similarity between the modified and the standard acuity charts was evaluated using two procedures. First, VA of 227 secondary school children (454 eyes) was evaluated using both sets of charts. Second, the relative difficulty for the identification of individual Sloan letters used in both charts, as well as letter M, was assessed from psychometric functions for five subjects. RESULTS: Bland-Altman plots revealed no statistical significant differences in the value of VA between the standard and the UoC set of charts. Although, estimates of identification log MAR threshold showed relatively significant interletter variability, in total, the new set of Sloan letters was equally identifiable with the original set. CONCLUSIONS: The overall pattern of results suggests that the modified log MAR UoC charts forms a valid alternative to the ETDRS for assessing VA in multinational clinical trials, offering the advantage of containing letters recognizable by a wider population basis, such as European citizens, as well as subjects from countries using the Cyrillic alphabet.     

Multiple liver abscesses associated with bacteremia due to Leuconostoc lactis

Leuconostoc species, which are members of the family Streptococcacae, have only recently been recognized as potential pathogens. We describe a patient with type II diabetes mellitus who had multiple liver abscesses associated with bacteremia due to Leuconostoc lactis. To our knowledge, this is the first case of this association to be reported in the literature.     

Enhanced microtubule-dependent trafficking and p53 nuclear accumulation by suppression of microtubule dynamics

The tumor suppressor protein p53 localizes to microtubules (MT) and, in response to DNA damage, is transported to the nucleus via the MT minus-end-directed motor protein dynein. Dynein is also responsible for MT-mediated nuclear targeting of adenovirus type 2 (Ad2). Here we show that treatment with low concentrations of MT-targeting compounds (MTCs) that do not disrupt the MT network but are known to suppress MT dynamics enhanced p53 nuclear accumulation, and the activation of the p53-downstream target genes. p53 nuclear accumulation required binding of MTCs to MTs and enhanced the induction of p53-up-regulated modulator of apoptosis (PUMA) mRNA and apoptosis on challenging cells with the DNA-damaging drug adriamycin. Low concentrations of MTCs enhanced the rate of movement of fluorescent Ad2 to the nucleus and increased the nuclear targeting efficiency of Ad2. We propose that suppression of MT dynamics by low concentrations of MTCs enhances MT-dependent trafficking toward the minus ends of MTs and facilitates nuclear targeting.     

Growth hormone deficiency in a child with Williams-Beuren syndrome. The response to growth hormone therapy

Pre- and postnatal growth retardation of unknown pathogenesis is a common clinical feature in patients with Williams-Beuren syndrome (WBS). However, growth hormone deficiency (GHD) has not been considered a major cause of growth retardation. There is only one patient in the literature with confirmed GHD who responded well to human growth hormone (hGH) therapy. We report a female infant with confirmed WBS who, through provocative testing, was found to have GHD and who responded satisfactorily to hGH therapy. Height SDS was -4.2 at the age of 12 months when hGH was initiated and increased to -0.8 at the age of 4.25 years. The pathogenesis of GHD in our patient is unclear. Nevertheless, the elevated levels of prolactin and the response of hGH to growth hormone releasing hormone (GHRH) administration are indicative of a hypothalamic rather than pituitary defect. In conclusion, GH deficiency might contribute to the growth failure in a number of patients with WBS and in such cases hGH therapy will most likely improve final height.     

Evidence that unsaturated fatty acids are potent inhibitors of renal UDP-glucuronosyltransferases (UGT): kinetic studies using human kidney cortical microsomes and recombinant UGT1A9 and UGT2B7

Renal ischaemia is associated with accumulation of fatty acids (FA) and mobilisation of arachidonic acid (AA). Given the capacity of UDP-glucuronosyltransferase (UGT) isoforms to metabolise both drugs and FA, we hypothesised that FA would inhibit renal drug glucuronidation. The effect of FA (C2:0-C20:5) on 4-methylumbelliferone (4-MU) glucuronidation was investigated using human kidney cortical microsomes (HKCM) and recombinant UGT1A9 and UGT2B7 as the enzyme sources. 4-MU glucuronidation exhibited Michaelis-Menten kinetics with HKCM (apparent K(m) (K(m)(app)) 20.3 microM), weak substrate inhibition with UGT1A9 (K(m)(app) 10.2 microM, K(si) 289.6 microM), and sigmoid kinetics with UGT2B7 (S(50)(app)440.6 microM) Similarly, biphasic UDP-glucuronic acid (UDPGA) kinetics were observed with HKCM (S(50) 354.3 microM) and UGT1A9 (S(50) 88.2 microM). In contrast, the Michaelis-Menten kinetics for UDPGA observed with UGT2B7 (K(m)(app) 493.2 microM) suggested that kinetic interactions with UGTs were specific to the xenobiotic substrate and the co-substrate (UDPGA). FA (C16:1-C20:5) significantly inhibited (25-93%) HKCM, UGT1A9 or UGT2B7 catalysed 4-MU glucuronidation. Although linoleic acid (LA) and AA were both competitive inhibitors of 4-MU glucuronidation by HKCM (K(i)(app) 6.34 and 0.15 microM, respectively), only LA was a competitive inhibitor of UGT1A9 (K(i)(app) 4.06 microM). In contrast, inhibition of UGT1A9 by AA exhibited atypical kinetics. These data indicate that LA and AA are potent inhibitors of 4-MU glucuronidation catalysed by human kidney UGTs and recombinant UGT1A9 and UGT2B7. It is conceivable therefore that during periods of renal ischaemia FA may impair renal drug glucuronidation thus compromising the protective capacity of the kidney against drug-induced nephrotoxicity.     

A novel E1A-E1B mutant adenovirus induces glioma regression in vivo

Malignant gliomas are the most frequently occurring primary brain tumors and are resistant to conventional therapy. Conditionally replicating adenoviruses are a novel strategy in glioma treatment. Clinical trials using E1B mutant adenoviruses have been reported recently and E1A mutant replication-competent adenoviruses are in advanced preclinical testing. Here we constructed a novel replication-selective adenovirus (CB1) incorporating a double deletion of a 24 bp Rb-binding region in the E1a gene, and a 903 bp deleted region in the E1b gene that abrogates the expression of a p53-binding E1B-55 kDa protein. CB1 exerted a potent anticancer effect in vitro in U-251 MG, U-373 MG, and D-54 MG human glioma cell lines, as assessed by qualitative and quantitative viability assays. Replication analyses demonstrated that CB1 replicates in vitro in human glioma cells. Importantly, CB1 acquired a highly attenuated replicative phenotype in both serum-starved and proliferating normal human astrocytes. In vivo experiments using intracranially implanted D-54 MG glioma xenografts in nude mice showed that a single dose of CB1 (1.5 x 10(8) PFU/tumor) significantly improved survival. Immunohistochemical analyses of expressed adenoviral proteins confirmed adenoviral replication within the tumors. The CB1 oncolytic adenovirus induces a potent antiglioma effect and could ultimately demonstrate clinical relevance and therapeutic utility.