Animal models of prenatal immune challenge and their contribution to the study of schizophrenia: a systematic review

Prenatal immune challenge (PIC) in pregnant rodents produces offspring with abnormalities in behavior, histology, and gene expression that are reminiscent of schizophrenia and autism. Based on this, the goal of this article was to review the main contributions of PIC models, especially the one using the viral-mimetic particle polyriboinosinic-polyribocytidylic acid (poly-I:C), to the understanding of the etiology, biological basis and treatment of schizophrenia. This systematic review consisted of a search of available web databases (PubMed, SciELO, LILACS, PsycINFO, and ISI Web of Knowledge) for original studies published in the last 10 years (May 2001 to October 2011) concerning animal models of PIC, focusing on those using poly-I:C. The results showed that the PIC model with poly-I:C is able to mimic the prodrome and both the positive and negative/cognitive dimensions of schizophrenia, depending on the specific gestation time window of the immune challenge. The model resembles the neurobiology and etiology of schizophrenia and has good predictive value. In conclusion, this model is a robust tool for the identification of novel molecular targets during prenatal life, adolescence and adulthood that might contribute to the development of preventive and/or treatment strategies (targeting specific symptoms, i.e., positive or negative/cognitive) for this devastating mental disorder, also presenting biosafety as compared to viral infection models. One limitation of this model is the incapacity to model the full spectrum of immune responses normally induced by viral exposure.     

The burden of HCV treatment in patients with inherited bleeding disorders

Summary. Many patients with inherited bleeding disorders are infected with hepatitis C virus (HCV). Antiviral treatment, consisting of pegylated interferon and ribavirin, has many side‐effects. The aim of the study was to prospectively assess the occurrence and course of side‐effects and changes in health‐related quality of life (HRQoL) during antiviral treatment in patients with inherited bleeding disorders and chronic HCV. Forty‐seven patients were followed during antiviral treatment. Side‐effects of treatment were recorded, and the Beck Depression Inventory and the RAND‐36 HRQoL questionnaire were administered at regular intervals. Frequently reported side‐effects were fatigue (100%), headache (94%), pruritus and skin rash (94%), concentration problems (89%), decreased appetite (89%), fever, irritability and hair loss (all 85%). Many side‐effects disappeared soon after end of treatment, but 4 weeks after cessation fatigue, concentration problems and sleeping problems were still present in more than 30% of patients. Dose reduction was necessary in 21 patients (45%), mostly because of decreasing weight or haemoglobin levels. Two patients stopped treatment prematurely because of side‐effects. Depression was present in 28 patients (60%). HRQoL decreased significantly during treatment in all RAND‐36 domains, and increased again within 4 weeks after treatment. Major side‐effects were similar in patients with successful (n = 31, 66%) and unsuccessful antiviral treatment. In patients with inherited bleeding disorders and chronic HCV, antiviral treatment has many, but mostly transient side‐effects and a significant impact on quality of life. Careful follow‐up and management of side‐effects will ensure optimal compliance and treatment results.     

In vivo measurement of apparent diffusion coefficients of hyperpolarized 13C‐labeled metabolites

The combination of hyperpolarized MRS with diffusion weighting (dw) allows for determination of the apparent diffusion coefficient (ADC), which is indicative of the intra‐ or extracellular localization of the metabolite. Here, a slice‐selective pulsed‐gradient spin echo sequence was implemented to acquire a series of dw spectra from rat muscle in vivo to determine the ADCs of multiple metabolites after a single injection of hyperpolarized [1‐¹³C]pyruvate. An optimal control optimized universal‐rotation pulse was used for refocusing to minimize signal loss caused by B₁ imperfections. Non‐dw spectra were acquired interleaved with the dw spectra and these were used to correct for signal decay during the acquisition as a result of T₁ decay, pulse imperfections, flow etc. The data showed that the ADC values for [1‐¹³C]lactate (0.4–0.7 µm²/ms) and [1‐¹³C]alanine (0.4–0.9 µm²/ms) were about a factor of two lower than the ADC of [1‐¹³C]pyruvate (1.1–1.5 µm²/ms). This indicates a more restricted diffusion space for the former two metabolites consistent with lactate and alanine being intracellular. The higher ADC for pyruvate (similar to the proton ADC) reflected that the injected substance was not confined inside the muscle cells but also present extracellular. Copyright © 2014 John Wiley & Sons, Ltd.     

Effect of Al–5Ti–C Master Alloy on the Microstructure and Mechanical Properties of Hypereutectic Al–20%Si Alloy

Al–5Ti–C master alloy was prepared and used to modify hypereutectic Al–20%Si alloy. The microstructure evolution and mechanical properties of hypereutectic Al–20%Si alloy with Al–5Ti–C master alloy additions (0, 0.4, 0.6, 1.0, 1.6 and 2.0 wt%) were investigated. The results show that, Al–5Ti–C master alloy (0.6 wt%, 10 min) can significantly refine both eutectic and primary Si of hypereutectic Al–20%Si alloy. The morphology of the primary Si crystals was significantly refined from a coarse polygonal and star-like shape to a fine polyhedral shape and the grain size of the primary Si was refined from roughly 90–120 μm to 20–50 μm. The eutectic Si phases were modified from a coarse platelet-like/needle-like structure to a fine fibrous structure with discrete particles. The Al–5Ti–C master alloy (0.6 wt%, 30 min) still has a good refinement effect. The ultimate tensile strength (UTS), elongation (El) and Brinell hardness (HB) of Al–20%Si alloy modified by the Al–5Ti–C master alloy (0.6 wt%, 10 min) increased by roughly 65%, 70% and 51%, respectively, due to decreasing the size and changing the morphology on the primary and eutectic Si crystals. The change in mechanical properties corresponds to evolution of the microstructure.     

Phospholipase C from Pseudomonas aeruginosa and Bacillus cereus:characterization of catalytic activity

Objective:To study characteristics of phospholipases C(PLCs),their importance for producing microorganisms us well us the potential of their use for industrial purposes.Methods:PLC from Bacillus cereus(B.cereus) D101 was selected as an example of Gram-positive PLCs and PLC from Pseudomanas aeruginosa(P.aeruginosa) D183 of Gram-negative ones.Enzymes were partially purified by ammonium sulfate precipitation followed by membrane dialysis.Partially purified preparations were used to study effect of different factors on activities as well as in substrate specificity tests which were conducted using a turbidimetric assay method.Results:Maximum activity was at pH 7 and 8 and 40 ℃ for P.aeruginosa PLC,and pH 8-10 and 37 ℃ for B.cereus PLC.Both PLCs were inhibited by Pi at 5 mM or higher,whereas,PLC from B.cereus only was inhibited by EDTA.Activity of P.aeruginosa PLC was not affected by removing Zn~(2+) ions from reaction mixture or their replacement with Ca~(2+),Ba~(2+),Mg~(2+) or Mn~(2+)ions.Vis-a-vis,activity of B.cereus PLC was found to be metal ion dependent PLCs from both isolates were relatively thermostable and showed maximum affinity toward phosphatidylcholine.Sphingomyelin and phosphatidylethanolamine were not good substrates and phosphatidylinositol,phosphatidylserine,phosphatidylglycerol and cardiolipin could be considered nonsubstrates.Conclusions:Human body physiological conditions could favor activity of P.aeruginosa and B.cereus PLCs.These enzymes may participate in phosphate scavenging and virulence of producing isolates but not in autolysis.PLCs from both isolates are potential candidates for industrial use.