Obsessive compulsive symptoms are associated with better functioning independently of cognition in schizophrenia.

OBJECTIVES: Although the relationship of obsessive-compulsive symptoms (OCSs) with both cognition and social functioning (SF) has already been the focus of research in schizophrenia, the moderation of the relationship of OCSs with SF by cognition has not been explored to date. We investigated the association of OCSs with SF and its interaction with cognition in schizophrenia. METHODS: We recruited 110 schizophrenia patients and assessed OCSs (Yale-Brown Scale), schizophrenia symptoms (Positive and Negative Syndrome Scale), SF (Strauss-Carpenter Scale) and cognition. 51 patients had one obsessive-compulsive symptom or more, whereas 59 patients had no obsessive compulsive-symptom, according to the Yale-Brown Scale. We mainly investigated: a) the predictive effect of OCSs on SF, controlling for cognition, illness duration and symptoms' severity and b) the moderating effect of cognition on the OCSs-SF relationship. RESULTS: The mean score of OCSs for patients having at least one symptom was 13.43 (SD=8.32). Higher OCSs predicted increased SF (B=0.98, t=2.41, df=88, p=0.018). This relationship was driven by the association of compulsions with job functioning (B=0.074, t=2.029, df=88, p=0.046). Patients without OCSs demonstrated worse functioning compared with those having at least one obsessive-compulsive symptom (mean difference=2.496, t=3.732, df=88, p<0.001). We failed to find evidence that cognition moderates the effect of OCSs on SF. CONCLUSION: There may be a beneficial effect of OCSs on SF in patients with schizophrenia which is independent of their cognitive performance.

Investigation on Toxicity and Teratogenicity in Rats of a Retinoid-Polyamine Conjugate with Potent Anti-Inflammatory Properties.

Previous studies have shown that N(1),N(12)-bis(all-trans-retinoyl)spermine (RASP), a retinoid analog, inhibits RNase P activity and angiogenesis in the chicken embryo chorioallantoic membrane, demonstrates anti-tumor activity on prostate cancer cells, and acts as anti-inflammatory agent, being more effective and less toxic than all-trans retinoic acid. In an attempt to further characterize the biological profile of RASP, we tested its effects on organ toxicity and teratogenicity by daily oral gavage of RASP at a level of 50 mg/Kg of body weight in two generations of rats. We found that this compound does not induce changes to the body growth, the appearance of physical features, and the animal's reflexes. Additionally, no substantial histopathological lesions were found in brain, heart, lung, thymus, liver, thyroid gland, adrenal gland, pituitary gland, kidneys, spleen, skin, femora, prostate, testis, epididymis, vagina, uterus, and ovaries of RASP-treated animals. These results suggest RASP, as a promising lead compound for the treatment of several dermatological disorders and certain cancer types, has apparently minimal toxic side-effects as revealed in this two-generation reproduction study in rats.

Hepatitis C in patients with ß-thalassemia major. A single-centre experience.

Chronic hepatitis C (CHC) and iron overload are the main causes of liver disease in ß-thalassemia major (ßTM). There is limited data regarding the course of CHC in this population. All patients (n=144) from the thalassemia centre of the University Hospital of Patras were evaluated (January 1981 to June 2012). Patients were classified into group A (n=57), which consisted of patients with CHC, who either had received antiviral treatment (n=49) or not (n=8), and group B which included 87 patients without CHC. Nineteen patients died during follow-up (median: 257.5 months (1-355)). Survival rates were 84.2 % and 88.5 % for group A and B, respectively. The causes of death were heart failure (63.2 %), accident (10.5 %), sepsis (5.3 %), liver failure (5.3 %), hepatocellular carcinoma (HCC) (5.3 %), non-Hodgkin lymphoma (5.3 %) and multiorgan failure (5.3 %). There were no differences in total survival between the two groups (p=0.524). In the multivariate analysis, survival was neither correlated with CHC (p=ns), nor with anti-HCV treatment (p=ns), whereas independent negative predictors were presence of heart failure (p<0.001), presence of malignancy other than HCC (p=0.001) and non-adherence to chelation treatment (p=0.013). Predictive factors for the development of cirrhosis were: CHC (p<0.001), age>35 years (p=0.007), siderosis grade 3/4 (p=0.029) and splenectomy (p=0.001); however, multivariately, only siderosis grade 3/4 was found to be significant (p=0.049). In this study, survival of patients with ßTM was mainly associated with heart failure, presence of malignancy other than HCC and non-adherence to chelation treatment, rather than with liver disease. Multicentre studies need to be designed to define more accurately the indications of antiviral treatment in this population.

Ectopic expression of TrKA in the adult rat basal ganglia induces both nerve growth factor-dependent and -independent neuronal responses.

Ectopic expression of tropomyosin-related kinase A (TrkA), the high-affinity receptor of nerve growth factor (NGF), has been widely used in cell culture systems to uncover its role in cell survival or death events. In contrast, little is known about the consequences of its expression in vivo. To address this question, adeno-associated virus (AAV) vectors were used to express TrkA in the substantia nigra (SN) and striatum of adult rats. Nine weeks after transfer, tyrosine hydroxylase (TH) and dopamine transporter (DAT) mRNAs were slightly decreased in the ipsilateral SN. This decrease was no longer significant when NGF was delivered into the striatum. There was no change of DAT binding sites or D1 or D2 receptor mRNAs and binding sites in the striatum, suggesting that ectopic TrkA exerts a limited effect on the pool of TH and DAT transcripts, without affecting overall dopamine signaling. When transferred into the striatum, TrkA transgene had no effect on the size of the cholinergic interneurons, but it exerted typical neurotrophic effects, as shown by an enlargement of the projection neurons and nitric oxide synthase (nNOS)-expressing interneurons. This trophic action was amplified by a delivery of NGF. No toxic effect of the transgene was noted. These data indicate that ectopic expression of TrkA may result in the promotion of neurotrophic effects or can influence neuronal plasticity in the absence of exogenous NGF in neuronal populations that naturally fail to respond to this factor.

Critical illness-related corticosteroid insufficiency in patients with cirrhosis and variceal bleeding.

BACKGROUND & AIMS: Relative adrenal insufficiency (AI) occurs in patients with cirrhosis with sepsis, but not with variceal bleeding. We evaluated adrenal function in cirrhotic patients with and without bleeding. METHODS: Twenty cirrhotic patients with variceal bleeding were evaluated using the short synacthen test (SST) and 10 using the low-dose synacthen test (LDSST) followed by SST. The control group included 60 stable cirrhotic patients, assessed by LDSST (n = 50) or SST (n = 10), and 14 healthy volunteers. AI was diagnosed using SST, based on peak cortisol levels ≤ 18 µg/dL in nonstressed patients or Δmax <9 µg/dL or a total cortisol level <10 µg/dL in stressed patients with variceal bleeding-the current criteria for critical illness-related corticosteroid insufficiency. Using LDSST, diagnosis was based on peak concentrations of cortisol ≤ 18 µg/dL in nonstressed patients and <25 µg/dL (or Δmax <9 µg/dL) in patients with variceal bleeding. We evaluated patients with levels of serum albumin >2.5 g/dL, to indirectly assess cortisol binding. RESULTS: All healthy volunteers had normal results from LDSSTs and SSTs. Patients with variceal bleeding had higher median baseline concentrations of cortisol (15.4 µg/dL) than stable cirrhotic patients (8.7 µg/dL, P = .001) or healthy volunteers (10.1 µg/dL, P = .01). Patients with variceal bleeding had higher median peak concentrations of cortisol than stable cirrhotic patients (SST results of 32.7 vs 21 µg/dL, P = .001; LDSST results of 9.3 vs 8.1 µg/dL; nonsignificant), with no differences in Δmax in either test. These differences were greater with variceal bleeding than in stable cirrhotic patients with AI. Subanalysis of patients with albumin levels >2.5 g/dL did not change these differences. CONCLUSIONS: Cirrhotic patients with variceal bleeding have AI. Despite higher baseline concentrations of serum cortisol and subnormal Δmax values, they did not have adequate responses to stress, and therefore had critical illness-related corticosteroid insufficiency.

Modulation of the basal ganglia dopaminergic system in a transgenic mouse exhibiting dystonia-like features.

Dystonia is a movement disorder characterized by involuntary excessive muscle activity and abnormal postures. There are data supporting the hypothesis that basal ganglia dysfunction, and specifically dopaminergic system dysfunction, plays a role in dystonia. In the present study, we used hyperkinetic transgenic mice generated as a model of DYT1 dystonia and compared the basal ganglia dopaminergic system between transgenic mice exhibiting hyperkinesia (affected), transgenic mice not showing movement abnormalities (unaffected), and non-transgenic littermates. A decrease in the density of striatal D2 binding sites, measured by [³H]raclopride binding, and D2 mRNA expression in substantia nigra pars compacta (SNpc) was revealed in affected and unaffected transgenic mice when compared with non-transgenic. No difference in D1 receptor binding and DAT binding, measured by [³H]SCH23390 and [³H]WIN35428 binding, respectively, was found in striatum of transgenic animals. In SNpc, increased levels of DAT binding sites were observed in affected and unaffected animals compared to non-transgenic, whereas no change in DAT mRNA expression was found. Our results show selective neurochemical changes in the basal ganglia dopaminergic system, suggesting a possible involvement in the pathophysiology of dystonia-like motor hyperactivity.

Response to novelty, social and self-control behaviors, in rats exposed to neonatal anoxia: modulatory effects of an enriched environment.

Perinatal asphyxia is a concern for public health and may promote subtle and long-lasting neuropsychiatric disorders. In the present study, newborn Wistar rat pups underwent a repeated 20-min exposure to a 100% N2 atmosphere (or air) on postnatal days (pnd) 1, 3, 5, and 7. Half of the animals were housed during adolescence (pnd 21-35) in an enriched environment. The consequences on behavior were assessed throughout adolescence to adulthood. When scored for social performance, adolescent rats exposed to neonatal asphyxia exhibited exaggerated levels of anogenital sniffing behavior, which was normalized by enriched living. In air-exposed controls, enriched living increased the expression of affiliative and novelty-seeking behaviors, as compared to standard housing. However, this enrichment-induced behavioral plasticity was not found in rats neonatally exposed to asphyxia. At adulthood, levels of impulsivity and 5-HT2A receptors in the striatum were markedly increased in neonatal-asphyxia rats kept in standard-housing conditions. Interestingly, impulsivity and receptor density were normalized by enriched rearing during adolescence. These findings indicate profound long-lasting behavioral alterations as a consequence of repeated neonatal asphyxia in rats. Beneficial effects of stimulation by an enriched environment during the still-plastic window of adolescence are suggested in these animals.

Effect of adult onset hypothyroidism on behavioral parameters and acetylcholinesterase isoforms activity in specific brain regions of male mice.

Thyroid hormones (TH) are essential for normal development and function of mammalian central nervous system (CNS); TH dysregulation has been implicated in several cognitive and behavioral deficits related to dysfunctions of neurotransmitter systems. In the present study, we investigated the effects of adult onset hypothyroidism on the activity of acetylcholinesterase (AChE) and on related behavioral parameters. For this purpose we used adult male Balb/cJ mice that were divided randomly into euthyroid and hypothyroid animal groups. Animals were rendered hypothyroid through administration of 1% w/v KClO4 in their drinking water for 8weeks. At the end of the treatment, learning/memory procedures were examined through step-through passive avoidance task while fear/anxiety was assessed using elevated plus-maze (EPM) and open-field (OF) tests. AChE activity was determined colorimetrically in two different fractions, salt-soluble fraction (SS) (containing mainly the G1 isoform) and detergent-soluble fraction (DS) (containing mainly the G4 isoform) in cerebral cortex, cerebellum, midbrain, hippocampus and striatum. Our results indicate that adult onset hypothyroidism caused significant memory impairment and increased fear/anxiety. Moreover, the activity of both isoforms of AChE was reduced in all brain regions examined in a brain region- and isoform-specific manner.

Health-related quality of life in patients with inflammatory bowel disease: a single-center experience.

BACKGROUND: Inflammatory bowel disease (IBD) has a negative impact on health-related quality of life (HRQoL). The aim of the study was to assess HRQoL of IBD patients in South-Western Greece. METHODS: 89 IBD patients [38 (42.7%) Crohn's disease (CD), 51 (57.3%) ulcerative colitis (UC)] were included. HRQoL was assessed using IBD questionnaire (IBDQ), which tests four health domains: bowel symptoms (BS), systemic symptoms (SS), emotional function (EF) and social function (SF). Total score (TS) ranges from 32 to 224. Disease activity was measured using Crohn's Disease Activity Index (CDAI) (CD), and Truelove and Witts classification (UC). The impact of epidemiological and disease-specific characteristics on IBDQ was studied. RESULTS: No statistically significant difference was found in all IBDQ scores between UC and CD patients. No correlation was found regarding age, sex, smoking, anemia, disease duration and use of corticosteroids, 5-aminosalicylates or immunosuppressives with HRQoL. The factors found to have a major negative impact on all IBDQ scores was disease severity both in CD and UC, and education on bowel symptoms in CD. On multivariate analysis, only high disease activity had significant effects on total and dimensional scores of IBDQ in UC (TS, P=0.005; BS, P<0.001; SS, P=0.004; EF, P=0.05; SF, P=0.001), whereas in CD, only CDAI (TS, P=0.001; BS, P=0.004; SS, P=0.001; EF, P=0.003; SF, P=0.003) and education (TS, P=0.047; BS, P=0.004; SS, P=0.03) had significant effects. CONCLUSIONS: IBD patients in remission experience better HRQoL than patients with active disease. Induction of remission should become the mainstay of care regarding improvement in HRQoL.

Translation and standardization of the HoNOSCA (Health of the Nation Outcome Scales for Children and Adolescents) scale in a Greek sample.

The Health of the Nation Outcome Scales for Children and Adolescents (HoNOSCA) is a brief measure of outcomes. Evidence for the effectiveness of patient treatments conducted in mental health services is limited in Greece. Thus, in an attempt to employ an easily administered and valid outcome measure, to assess outcomes in clinical practice for children and adolescents, but also to be able to compare the results across countries, the HoNOSCA was the measure of choice. In this study we have translated and validated it in a Greek sample. We have investigated the inter-rater reliability, intraclass correlation, concurrent validity, and clinical change across time, of the HoNOSCA Greek translation. The results show that the Greek translation of HoNOSCA is a reliable and valid instrument. It can be used for clinical, managerial, research and audit purposes, but, most importantly, to facilitate multinational clinical research and comparison of data with other countries.