Executive dysfunction and memory impairment in schizoaffective disorder: a comparison with bipolar disorder, schizophrenia and healthy controls.

BACKGROUND: Deficits in memory and executive performance are well-established features of bipolar disorder and schizophrenia. By contrast, data on cognitive impairment in schizoaffective disorder are scarce and the findings are conflicting. METHOD: We used the Wechsler Memory Scale (WMS-III) and the Behavioural Assessment of the Dysexecutive Syndrome (BADS) to test memory and executive function in 45 schizophrenic patients, 26 schizomanic patients and 51 manic bipolar patients in comparison to 65 healthy controls. The patients were tested when acutely ill. RESULTS: All three patient groups performed significantly more poorly than the controls on global measures of memory and executive functioning, but there were no differences among the patient groups. There were few differences in memory and executive function subtest scores within the patient groups. There were no differences in any test scores between manic patients with and without psychotic symptoms. CONCLUSIONS: Schizophrenic, schizomanic and manic patients show a broadly similar degree of executive and memory deficits in the acute phase of illness. Our results do not support a categorical differentiation across different psychotic categories with regard to neuropsychological deficits.

Human Gene Expression in Uncomplicated Plasmodium falciparum Malaria.

To examine human gene expression during uncomplicated P. falciparum malaria, we obtained three samples (acute illness, treatment, and recovery) from 10 subjects and utilized each subject's recovery sample as their baseline. At the time of acute illness (day 1), subjects had upregulation of innate immune response, cytokine, and inflammation-related genes (IL-1β, IL-6, TNF, and IFN-γ), which was more frequent with parasitemias >100,000 per μL and body temperatures ≥39°C. Apoptosis-related genes (Fas, BAX, and TP53) were upregulated acutely and for several days thereafter (days 1-3). In contrast, the expression of immune-modulatory (transcription factor 7, HLV-DOA, and CD6) and apoptosis inhibitory (c-myc, caspase 8, and Fas Ligand G) genes was downregulated initially and returned to normal with clinical recovery (days 7-10). These results indicate that the innate immune response, cytokine, and apoptosis pathways are upregulated acutely in uncomplicated malaria with concomitant downregulation of immune-modulatory and apoptosis inhibitory genes.

CTP in Transient Global Amnesia: A Single-Center Experience of 30 Patients.

BACKGROUND AND PURPOSE: Medial temporal lobe abnormalities on DWI and functional imaging are occasionally observed in patients with transient global amnesia. We used CTP to study these patients during or briefly after resolution of their amnesic syndrome. MATERIALS AND METHODS: From 2002 onward, patients satisfying clinical criteria for transient global amnesia who underwent CTP were included. Patients with additional clinical features suggesting transient ischemic attack or stroke and those with an ischemic lesion on subsequent DWI were excluded. If deemed necessary by the clinician, DWI was performed within 10 days. RESULTS: Thirty patients with transient global amnesia underwent CTP at a median latency of 5.9 hours (interquartile range, 4.3-9.7 hours) after symptom onset. All findings, except for those in 1 patient, were normal, including those in the 14 patients with well-imaged hippocampi. In the patient with abnormal findings, CTP and PWI showed hypoperfusion in both lentiform nuclei extending into the insulae, with normalization on the repeat CTP 6 days later. In 10 patients, DWI was performed at a median latency of 2 days (interquartile range, 0-9 days). Of these, 2 showed punctate hippocampal lesions, often seen in transient global amnesia. In 2 patients excluded because of mildly atypical transient global amnesia and ischemic lesions on subsequent DWI, acute CTP findings were also normal. CONCLUSIONS: Patients with transient global amnesia had normal CTP findings in the acute phase with the exception of 1 patient with transient hypoperfusion in both basal ganglia. If imaging is performed for typical and atypical transient global amnesia, DWI should be the preferred method.

"Role of long non-coing RNAs in the stressed heart". Wisper : a novel cardiac fibroblast-enriched IncRNA that modulate fibrosis in the failing heart

LncRNAs are transcripts greater than 200 nucleotides in length with no apparent coding potential. They exert important regulatory functions in the genome. Their role in cardiac fibrosis is however unexplored. To identify IncRNAs that could modulate cardiac fibrosis, we profiled the long non-coding transcriptome in the infarcted mouse heart, and identified 1500 novel IncRNAs. These IncRNAs have unique characteristics such as high tissue and cell type specificity. Their expression is highly correlated with parameters of cardiac dimensions and function. The majority of these novel IncRNAs are conserved in human. Importantly, human IncRNAs appear to be differentially expressed in heart disease. Using a computational pipeline, we identified a super-enhancer-associated IncRNA, which is dynamically expressed after myocardial infarction. We named this particular transcript Wisper for «Wisp2 super-enhancer- derived IncRNA ». Interestingly, Wisper expression is overexpressed in cardiac fibroblasts as compared to cardiomyocytes or to fibroblasts isolated from other organs than the heart. The importance of Wisper in the biology of fibroblasts was demonstrated in knockdown experiments. Differentiation of cardiac fibroblast into myofibroblasts in vitro is significantly impaired upon Wisper knockdown. Wisper downregulation in cardiac fibroblasts results in a dramatic reduction of fibrotic gene expression, a diminished cell proliferation and an increase in apoptotic cell death. In vivo, depletion of Wisper during the acute phase of the response to infarction is detrimental via increasing the risk of cardiac rupture. On the other hand, Wisper knockdown following infarction in a prevention study reduces fibrosis and preserves cardiac function. Since WISPER is detectable in the human heart, where it is associated with severe cardiac fibrosis, these data suggest that Wisper could represent a novel therapeutic target for limiting the extent of the fibrotic response in the heart. -- Les long ARN non-codants (IncRNAs) sont des ARN de plus de 200 nucléotides qui ne codent pas pour des protéines. Ils exercent d'importantes fonctions dans le génome. Par contre, leur importance dans le développement de la fibrose cardiaque n'a pas été étudiée. Pour identifier des IncRNAs jouant un rôle dans ce processus, le transcriptome non-codant a été étudié dans le coeur de'souris après un infarctus du myocarde. Nous avons découverts 1500 nouveaux IncRNAs. Ces transcrits ont d'uniques caractéristiques. En particulier ils sont extrêmement spécifiques de sous-populations de cellules cardiaques. Par ailleurs, leur expression est remarquablement corrélée avec les paramètres définissant les dimensions du coeur et la fonction cardiaque. La majorité de ces IncRNAs sont conservés chez l'humain. Certains sont modulés dans des pathologies cardiaques. En utilisant une approche bioinformatique, nous avons identifié un IncRNA qui est associé à des séquences amplificatrices et qui est particulièrement enrichi dans les fibroblastes cardiaques. Ce transcrit a été nommé Wisper pour «Wisp2 super-enhancer-derived IncRNA ». L'importance de Wisper dans la biologie des fibroblastes cardiaques est démontrée dans des expériences de déplétion. En l'absence de Wisper, l'expression de protéines impliquées dans le développement de la fibrose est dramatiquement réduite dans les fibroblastes cardiaques. Ceux-ci montrent une prolifération réduite. Le niveau d'apoptose est largement augmenté. In vivo, la déplétion de Wisper pendant la phase aiguë de l'infarctus rehausse le risque de rupture cardiaque. Au contraire, la réduction de l'expression de Wisper pendant la phase chronique diminue la fibrose cardiaque et améliore la fonction du coeur. Puisque Wisper est exprimé dans le coeur humain, ce transcrit représente une nouvelle cible thérapeutique pour limiter la réponse fibrotique dans le coeur.

Ohjauksen ja neuvonnan vaikutukset sepelvaltimoiden ohitusleikkauspotilaiden terveyskäyttäytymiseen, terveyteen ja toimintakykyyn

Effects of counseling and guidance on health behavior, health, and functional abilities of coronary artery bypass (cab) patients Hospital periods of heart patients are brief and full of activity today, and for that reason, the meaning of counseling and guidance becomes emphasized. The present intervention study started based on observations of staff members at the heart organization. According to these observations, there were gaps in counseling and guidance intended for coronary artery bypass (CAB) patients. The purpose of the present intervention study was to describe and evaluate the program on counseling and guidance organized for patients who were referred to CAB operations. More specifically, the study was to assess its short-term (3-month), intermediate (6-month), and long-term (12-month) effects on health behavior, health, and functional abilities of CAB patients of any age on one hand and elderly on the other, as well as on their mortality. The data consisted of those individuals having coronary heart disease (CHD) and living in Uusimaa (n = 365) who went through their first CAB operation at the Helsinki University Hospital between May 7th, 1998 and December 31st, 2001. Based on the need of urgency, they were divided into two groups: 1) surgery with regular referral procedure (non-acute) or 2) surgery in the acute phase of CHD. Randomization into an intervention and a control group was separately carried out within these two groups. A subgroup was formed by including those 65 years or older who were operated on with regular referral procedure. Data on health behavior, health, and functional abilities were gathered with survey questionnaires. Times and causes of death were examined January 1st, 1998 through December 31st, 2004. Intervention included counseling and guidance in small groups. The intervention of the non-acutely operated patients was implemented prior to and following surgery, whereas the intervention of the acutely operated patients was implemented after surgery alone. The control group received regular health care services. Counseling and guidance contributed in positive terms to the frequency of alcohol use among non-acutely operated men and to the frequencies of exercise and functional ability among women. The intervention was also capable of having an effect on the exercise frequencies of elderly and acutely operated men. The present intervention did not have an effect on the body mass index, whereas it had barely a slight effect on the health status of the CAB patients. The findings of the intervention and generalizations resulting from them must be viewed critically because the data analysis utilized a multi-testing situation, many variables, and several subgroups. The study did not involve intention to treat analysis. Additionally, a loss of patients was great especially among the elderly and acutely operated patients.

Blood pressure levels and haematoma growth in patients with Intracerebral Haemorrhage (ICH) A retrospective observational study

Intracerebral haemorrhage (ICH) is a spontaneous extravasation of blood into brain parenchyma. Although ICH represents approximately only 15% of all strokes, it is one of the major causes of stroke-related death and disability. One of the causes of poor outcome is the haematoma growth. The association between elevated blood pressure (BP) and haematoma enlargement in acute ICH has not been clarified. Our objective is to try to identify this relationship that may suggest an immediate target for intervention to possibly improve outcomes in patients with spontaneous ICH and might settle the controversy surrounding the optimal management of blood pressure.We propose a retrospective revision using a sample present in our database of approximately 250 patients with primary ICH and less than 12h from symptoms onset. Systolic blood pressure levels (SBP) are assessed at baseline, at 6h, at 12h, at 24h and at 72h, being these last four the average levels of the different recordings during those time intervals. Haematoma growth will be defined as an increase in the volume of intraparenchymal haemorrhage of >33% as measured by image analysis on the 24-hour CT or 72-hour CT compared with the baseline CT scan. A qualified neuroradiologist not informed of the aim of the study, will review the CT images. The secondary objective will be to correlate the BP levels in the acute phase of ICH with clinical outcome. We will evaluate early neurologic deterioration at 72h by using the National Institutes of Health Stroke Scale (NIHSS); outcome at 90 days by using the modified Rankin scale and mortality at 72h and 90 days. The statistical analysis will be adjusted by possibly confounding variables

Anxiolytic-like effects of erythrinian alkaloids from erythrina suberosa

Two alkaloids, erysodine (1) and erysothrine (2) were isolated from the flowers of a Pakistani medicinal plant, Erythrina suberosa. These compounds were investigated for anxiolytic properties, and the results showed significant effect, in an acute oral treatment with 1-2, which were suspended in saline (NaCl 0.9%) plus DMSO 1%, and evaluated in 122 Swiss male mice exposed to two tests of anxiety - the elevated plus-maze (EPM) and the light/dark transition model (LDTM).

Impact of Roux-en-Y gastric bypass on lipid and inflammatory profiles

Objective: To evaluate the behavior of acute phase proteins and lipid profile in patients undergoing Roux-en-Y gastric bypass. Methods : We conducted a prospective study, consisting of three moments: M1 - preoperative (24 hours before surgery); M2 - 30 days after surgery; and M3 - 180 days after surgery. We carried measured height and BMI, as well as determined the concentrations of acute phase proteins (C-reactive protein (CRP), albumin and Alpha-1-acid glycoprotein) and total cholesterol, LDL-c, HDL-c and triacylglycerol. Results : participants comprised 25 individuals, with a mean age of 39.28 ± 8.07, 72% female. At all times of the study there was statistically significant difference as for weight loss and BMI. We found a significant decrease in CRP concentrations between the moments M1 and M3 (p = 0.041) and between M2 and M3 (p = 0.018). There was decrease in Alpha-1-GA concentrations between M1 and M2 (p = 0.023) and between M1 and M3 (p = 0.028). The albumin values increased, but did not differ between times. Total cholesterol and triacylglycerol decreased significantly ay all times. LDL-c concentrations decreased and differed between M1 and M2 (p = 0.001) and between M1 and M3 (p = 0.001). HDL-c values increased, however only differing between M1 and M2 (p = 0.050). Conclusion : Roux-en-Y gastric bypass promoted a decrease in plasma concentrations of CRP and Alpha-1-acid glycoprotein, improving lipid and inflammatory profiles.

Freund's adjuvant-induced inflammation: clinical findings and its effect on hepcidin mRNA expression in horses

Hypoferremia observed during systemic inflammatory disorders is regulated by hepcidin. Hepcidin up-regulation is particularly important during acute inflammation, as it restricts the availability of iron, which is necessary for pathogenic microorganism growth before adaptive immunity occurs. The aim of this study was to evaluate the clinical findings and hepatic hepcidin mRNA expression in horses using a Freund's complete adjuvant (FCA) model of inflammation. The expression of hepcidin mRNA in the liver was determined in healthy horses following two intramuscular injections of FCA at 0 h and 12 h. Plasma iron and fibrinogen concentrations were measured at multiple time points between 0 h and 240 h post-FCA injection (PI). Hepcidin mRNA expression was determined by RT-qPCR using liver biopsy samples performed at 0 h (control), 6 h and 18 h PI. The mean plasma fibrinogen level was significantly different from the control values only between 120 and 216 h PI. The mean plasma iron level was significantly lower than the control between 16 and 72 h PI, reaching the lowest levels at 30 h PI (33 % of the initial value), and returned to the reference value from 96 h PI to the end of the experiment. Hepcidin mRNA expression increased at 6 h PI and remained high at 18 h PI. The iron plasma concentration was an earlier indicator of inflammatory processes in horses when compared with fibrinogen and might be useful for the early detection of inflammation in the horse. FCA administration caused the rapid onset of hypoferremia, and this effect was likely the result of up-regulated hepatic hepcidin gene expression. This study emphasizes the importance of hepcidin and iron metabolism during inflammation in horses.

Babesia bovis: expression of adhesion molecules in bovine umbilical endothelial cells stimulated with plasma from infected cattle

Ten male, 12-month-old Jersey with intact spleens, serologically and parasitologically free from Babesia were housed individually in an arthropod-free isolation system from birth and throughout entire experiment. The animals were randomly divided into two groups. Five animals (group A) were intravenously inoculated with 6.6 X10(7) red blood cells parasitized with pathogenic sample of Babesia bovis (passage 7 BboUFV-1), for the subsequent "ex vivo" determination of the expression of adhesion molecules. Five non-inoculated animals (group B) were used as the negative control. The expression of the adhesion molecules ICAM-1, VCAM, PECAM-1 E-selectin and thrombospondin (TSP) was measured in bovine umbilical vein endothelial cells (BUVECs). The endothelial cells stimulated with a pool of plasma from animals infected with the BboUFV-1 7th passage sample had a much more intense immunostaining of ICAM-1, VCAM, PECAM-1 E-selectin and TSP, compared to the cells which did not received the stimulus. The results suggest that proinflammatory cytokines released in the acute phase of babesiosis may be involved in the expression of adhesion molecules thereby implicating them in the pathophysiology of babesiosis caused by B. bovis.

Effects of intramammary infection on whey proteinograms of sheep during lactation

The study aimed to identify potential biomarkers of mammary gland infection in Santa Inês sheep. Commercial flocks of sheep provided the same hygiene, sanitary, and nutritional management under semi-intensive production systems were monitored during the lactation stage-and assessed 15, 30, 60, and 90 days after delivery (through the end of lactation and weaning). The California Mastitis Test (CMT) was performed on the mammary glands. Milk was collected for bacterial examination and protein analysis. Bacterial culture and biochemical characterization of the samples were performed. Forty-two milk samples from healthy glands (negative CMT and bacterial testing) and 43 milk samples from infected glands (positive CMT and bacterial testing) taken at the predefined time points were assessed. A rennin solution was used to obtain the whey. The proteins analysis was performed using sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE), which allowed for the quantification of nine whey proteins produced in healthy glands: serum albumin, lactoferrin, IgA, IgG heavy-chain (IgG HC), IgG light-chain (IgG LC), total IgG (IgG HC + IgG LC), α-lactalbumin, β-lactoglobulin, protein with MW 15.000 Da, protein with MW 29.000 Da and eleven whey proteins secreted by infected glands, including haptoglobin and α-1-acid glycoprotein. A comparison of whey proteins between healthy and infected glands showed increases (P<0.05) in the secreted and total contents of all proteins, except for IgG LC and α-lactoalbumin. The most significant changes were observed in α-1-acid glycoprotein, lactoferrin and haptoglobin, which showed three-, five-, and seven-fold increases in secretion, respectively. This study showed that haptoglobin, α-1-acid glycoprotein, lactoferrin, albumin, and the IgA and IgG immunoglobulins may serve as potential biomarkers for mammary gland infection in sheep.

Accidental and experimental Closantel intoxication in Uruguayan sheep

Abstract An outbreak of Closantel intoxication in sheep in Uruguay is described. The outbreak occurred in a group of 1300 weaning lambs treated orally with a 10% solution of Closantel. One hundred forty eight lambs showed clinical signs of intoxication and 14 died. The clinical signs included mydriasis, nystagmus, and negative pupillary reflex, bilateral blindness, bump into objects, and lateral movement of the head. No macroscopic lesions were observed. The histological lesions of the retina were cytoplasmic vacuolization in ganglion cells and in cells of the inner and outer nuclear layers with different degrees of atrophy. Vacuolization and axonal degeneration were observed in the optic nerve, with multifocal areas of fibrosis and infiltration by lymphocytes and Gitter cells. To reproduce the intoxication, four sheep were given two, four and 10 times the therapeutic dose of Closantel (0.1g/kg of BW). Only the animals receiving 10 times the recommended dose showed clinical signs. The histological examination of the lesions in experimental sheep showed similar results to those described in the accidental outbreak, except for the absence of optic nerve fibrosis and inflammation, characterizing an acute phase. Axonal myelin sheaths loss, fibroblasts and collagen fibers were observed in the ultrastructural study of the optic nerve of accidental intoxicated animals. The optic nerve of experimentally intoxicated animals had vacuoles that separated the myelin sheaths of axons. To prevent outbreaks it is suggested to weigh the animals before Closantel administration to avoid errors in dose calculation.

Induction of cell-mediated immunity during early stages of infection with intracellular protozoa

Toxoplasma gondii and Trypanosoma cruzi are intracellular parasites which, as part of their life cycle, induce a potent cell-mediated immunity (CMI) maintained by Th1 lymphocytes and IFN-g. In both cases, induction of a strong CMI is thought to protect the host against rapid parasite multiplication and consequent pathology and lethality during the acute phase of infection. However, the parasitic infection is not eliminated by the immune system and the vertebrate host serves as a parasite reservoir. In contrast, Leishmania sp, which is a slow growing parasite, appears to evade induction of CMI during early stages of infection as a strategy for surviving in a hostile environment (i.e., inside the macrophages which are their obligatory niche in the vertebrate host). Recent reports show that the initiation of IL-12 synthesis by macrophages during these parasitic infections is a key event in regulating CMI and disease outcome. The studies reviewed here indicate that activation/inhibition of distinct signaling pathways and certain macrophage functions by intracellular protozoa are important events in inducing/modulating the immune response of their vertebrate hosts, allowing parasite and host survival and therefore maintaining parasite life cycles.

Cytokine profiles during experimental Chagas' disease

People infected with Trypanosoma cruzi remain so for life, yet only 30-40% of these individuals develop characteristic chagasic cardiomyopathies. Similarly, when infected with the Brazilian strain of T. cruzi, DBA/2 mice develop severe cardiac damage while B10.D2 mice do not. To better understand the immunological parameters that may be involved in the disease process, we have used this murine model (DBA/2 vs B10.D2) and compared the changes in cytokine production during the course of infection with T. cruzi. Concanavalin A (Con A) stimulation of spleen cells harvested during the acute phase (day 30) resulted in similarly high levels of IFN-g in both mouse strains. However, the amount of IFN-g in supernatants from cultures of B10.D2 spleen cells initiated during the chronic phase (day 72) was at subacute levels, whereas secretion by chronic DBA/2 spleen cells remained high. In addition, Con A-stimulated spleen cells from acute DBA/2 mice produced approximately twice as much IL-10 and significantly more IL-4 than cells from B10.D2 mice. IL-4 secretion remained low by cells from chronic B10.D2 mice, but when using cells from chronic DBA/2 mice, levels continued to increase beyond the already high levels secreted by cells harvested during the acute phase. Proliferative responses to Con A stimulation by spleen cells from DBA/2 mice were significantly higher than those from B10.D2 mice in both the acute and chronic phases. These data suggest that enhanced responses in DBA/2 mice, which may be related to a higher parasite burden, a lack of down-regulation, and/or the onset of autoimmune phenomena, correlate with the more severe cardiomyopathy seen in pathopermissive mice.

Baroreflex control of sympathetic activity in experimental hypertension

The arterial baroreceptor reflex system is one of the most powerful and rapidly acting mechanisms for controlling arterial pressure. The purpose of the present review is to discuss data relating sympathetic activity to the baroreflex control of arterial pressure in two different experimental models: neurogenic hypertension by sinoaortic denervation (SAD) and high-renin hypertension by total aortic ligation between the renal arteries in the rat. SAD depresses baroreflex regulation of renal sympathetic activity in both the acute and chronic phases. However, increased sympathetic activity (100%) was found only in the acute phase of sinoaortic denervation. In the chronic phase of SAD average discharge normalized but the pattern of discharges was different from that found in controls. High-renin hypertensive rats showed overactivity of the renin angiotensin system and a great depression of the baroreflexes, comparable to the depression observed in chronic sinoaortic denervated rats. However, there were no differences in the average tonic sympathetic activity or changes in the pattern of discharges in high-renin rats. We suggest that the difference in the pattern of discharges may contribute to the increase in arterial pressure lability observed in chronic sinoaortic denervated rats.