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The effect of heating methods (microwave and water bath, and combined microwave and water bath heating) on 6 nucleotides and related compounds (NRCs) in minced Pacific white shrimp and Antarctic krill was investigated at 25, 40, 55, 65, 75, 85, and 95 °C. In Pacific white shrimp, the main changes of NRCs were in adenosine monophosphate (AMP) and inosine monophosphate (IMP). High temperature (85 and 95 °C) can inhibit the ATP degradation by water bath heating. In Antarctic krill, the main change of NRCs was in inosine (HxR) that decreased in microwave heating treatment at 95 °C. The different methods were compared in terms of IMP content and flavor/bitter ratio, which are related to flavor of aquatic products. The best heating method was pre-heating at 75 °C in water bath followed by microwave heating at 95 °C (IMP content and relatively flavor/bitter ratio were 4.34 μmol/g and 3.00, respectively) for pacific white shrimp and pre-heating at 65 °C in microwave followed by water bath heating at 95 °C (IMP content and relatively flavor/bitter ratio were 0.18 μmol/g and 0.06, respectively) for Antarctic krill, respectively. Chemical analysis, microbiological analysis and sensory evaluation showed that the K value is not suitable for assessing the freshness of Antarctic krill. [ABSTRACT FROM AUTHOR]

Objective: Interferon-free therapy for hepatitis C virus (HCV) infection is costly, and therefore patients with advanced fibrosis are prioritized. Although coupled with considerable side effects, a large proportion of genotype 2/3 infected patients achieve a sustained virological response (SVR) following interferon-based therapy. The present study evaluates experimental clinical trial and verifying real-life data with the aim of identifying patients with a high likelihood of favorable outcome following short interferon-based treatment.Material and methods: The impact of established response predictors, e.g. age,ITPAandIL28Bgenetic variants, IP-10, liver histopathology and early viral kinetics on outcome was evaluated among HCV genotype 2/3 infected patients enrolled in the NORDynamIC trial. Similarly outcome was evaluated among Finnish and Swedish real-life genotype 2/3 infected patients treated for 12–16 weeks in accordance with national guidelines.Results: In the NORDynamIC trial, age <40 years or achieving HCV RNA <1000 IU/mL day 7 were highly predictive of favorable outcome following 12 weeks therapy. Among 255 Finnish real-life patients below the age of 40 years treated for 12 weeks with interferon and ribavirin, 87% of HCV genotype 2 and 79% of genotype 3 infected patients achieved SVR, and among 117 Swedish real-life patients treated for 12–16 weeks, 97% of HCV genotype 2 and 94% of genotype 3 infected achieved SVR.Conclusions: Short interferon-based therapy offers a high likelihood of achieving SVR for selected HCV genotype 2/3 infected patients, and is an acceptable option given that a thorough discussion of the side effects is provided prior to initiation. [ABSTRACT FROM PUBLISHER]

Inosine, a breakdown product of adenosine, has recently been shown to exert immunomodulatory and neuroprotective effects. We show here that the oral administration of inosine has antidepressant-like effects in two animal models. Inosine significantly enhanced neurite outgrowth and viability of primary cultured neocortical neurons, which was suppressed by adenosine A1 and A2A receptor agonists. Oral administration of inosine to mice transiently increased its concentration in the brain and enhanced neuronal proliferation in the dentate gyrus, accompanied by phosphorylation of mitogen-activated protein kinase and increase in transcript level of brain-derived neurotrophic factor. In stress models, oral inosine prevented an increase in immobility time in forced swim test after chronically unexpected stress and mitigated a reduction in sucrose preference after chronic social defeat stress. These results indicate that oral administration of inosine has the potential to prevent depressive disorder via adenosine receptors. [ABSTRACT FROM AUTHOR]

Abstract: Mitochondria vary in their number and function, but how these variations are associated with intestinal cell differentiation remains elusive. The object of this study was to investigate the underlying mechanisms of inosine-mediated intestinal cell maturation, analysing the effects of this nutrient on metabolic functionality, mitochondrial biogenesis and mitochondrial function in human colonic cells. The role of oxidative stress in the control of intestinal cell growth was also explored. We report the novel finding that inosine-mediated differentiation improves aerobic metabolism through an increase in mitochondrial bioenergetics and biogenesis in colonic cells, which probably confers them greater resistance to cytotoxic oxidative stress. [ABSTRACT FROM AUTHOR]

Adenosine-to-inosine (A-to-I) RNA editing is a post-transcriptional processing event involved in diversifying the transcriptome responsible for various biological processes. Although bioinformatic approaches have predicted a number of A-to-I editing sites in cDNAs, the human transcriptome is thought to still harbor large numbers of as-yet-unknown editing sites. Exploring new editing sites requires a biochemical method to accurately identify inosines on RNA strands. We here describe a chemical method to identify inosines, called inosine chemical erasing (ICE), that is based on cyanoethylation combined with reverse transcription. We carried out a large-scale verification of the ICE method focusing on 642 regions in human cDNA and identified 5,072 editing sites, including 4,395 new sites. Functional study revealed that A-to-I intronic editing in the SARS gene mediated by ADAR1 is involved in preventing aberrant exonization of Alu sequence into mature mRNA. [ABSTRACT FROM AUTHOR]

Chronic infection with the hepatitis C virus (HCV) affects 170 million people worldwide and is an important cause of liver-related morbidity and mortality. The standard of care therapy combines pegylated interferon (pegIFN) alpha and ribavirin (RBV), and is associated with a range of treatment-limiting adverse effects. One of the most important of these is RBV-induced haemolytic anaemia, which affects most patients and is severe enough to require dose modification in up to 15% of patients. Here we show that genetic variants leading to inosine triphosphatase deficiency, a condition not thought to be clinically important, protect against haemolytic anaemia in hepatitis-C-infected patients receiving RBV. [ABSTRACT FROM AUTHOR]

BSTRACT: The effect of 2 slaughter methods (immersion in ice-water slurry and electrical stunning followed by ice slurry asphyxiation) on the quality of grass carp ( Ctenopharyngodon idella) stored in ice for 20 d was evaluated using sensory and chemical analysis. Electricity immediately stunned the fish and did not induce blood spots in the flesh. Fish killed by electricity showed a faster initial rate of ATP degradation and entered into rigor mortis earlier, but did not show significant differences in the sensory score when compared with fish killed by immersion in ice-water slurry. Thus, no differences were observed in the shelf life of carps between the 2 slaughter methods evaluated. The limit for acceptability of grass carp stored in ice was around 13 to 16 d. Grass carp accumulated more inosine than hypoxanthine. K, Ki, P, Fr, and H values were highly correlated with storage time and with the TFRU sensory scores in both groups; these could be used to assess the freshness quality of grass carp. [ABSTRACT FROM AUTHOR]

Inosine triphosphate pyrophosphohydrolase (ITPase) deficiency is a common inherited condition characterized by the abnormal accumulation of inosine triphosphate (ITP) in erythrocytes. The genetic basis and pathological consequences of ITPase deficiency are unknown. We have characterized the genomic structure of the ITPA gene, showing that it has eight exons. Five single nucleotide polymorphisms were identified, three silent (138G→A, 561G→A, 708G→A) and two associated with ITPase deficiency (94C→A, IVS2+21A→C). Homozygotes for the 94C→A missense mutation (Pro32 to Thr) had zero erythrocyte ITPase activity, whereas 94C→A heterozygotes averaged 22.5% of the control mean, a level of activity consistent with impaired subunit association of a dimeric enzyme. ITPase activity of IVS2+21A→C homozygotes averaged 60% of the control mean. In order to explore further the relationship between mutations and enzyme activity, we examined the association between genotype and ITPase activity in 100 healthy controls. Ten subjects were heterozygous for 94C→A (allele frequency: 0.06), 24 were heterozygotes for IVS2+21A→C (allele frequency: 0.13) and two were compound heterozygous for these mutations. The activities of IVS2+21A→C heterozygotes and 94C→A/IVS2+21A→C compound heterozygotes were 60% and 10%, respectively, of the normal control mean, suggesting that the intron mutation affects enzyme activity. In all cases when ITPase activity was below the normal range, one or both mutations were found. The ITPA genotype did not correspond to any identifiable red cell phenotype. A possible relationship between ITPase deficiency and increased drug toxicity of purine analogue drugs is proposed. [ABSTRACT FROM AUTHOR]

BSTRACT Fish freshness was assessed using capillary electrophoresis and an immobilized enzyme procedure to monitor degradation of inosine-5′-monophosphate (IMP), inosine (HxR) and hypoxanthine (Hx). The enzymatic method used an amperometric probe at + 0.7 V (platinum vs silver/silver chloride) with immobilized xanthine oxidase, catalase, nucleoside phosphorylase, and nucleotidase for converting Hx, HxR or IMP to uric acid. Capillary electrophoresis resolved IMP, inosine and Hx by migration rates resulting from an applied electric field (416 V/cm, 50 μA). Components were detected at 250 nm. The H ratio of Hx/[IMP + HxR + Hx] and simplified K value of [HxR + Hx]/ [IMP + HxR + Hx] were determined in cod, salmon and trout stored on ice (0-4°C) and at 20°C. The two procedures agreed and for all species H ratio and K values increased with storage time. [ABSTRACT FROM AUTHOR]

Discrimination in umami taste of inosine 5' -monophosphate (IMP) solution caused by thermal degradation was investigated by sensory evaluation. The difference threshold of umami taste of 0.005% IMP solution in the presence of 0.05% monosodium glutamate (MSG) was 0.002%. The difference threshold of a 0.005% IMP solution decreased by about one half when heated at 95°C for 15 h. Inosine, one of the main products of the thermal degradation of IMP, had a-bitter taste. The detection threshold of inosine varied widely among panelists. Heating a 0.005% IMP solution at 95°C for 15 h formed inosine at about one tenth of its lowest detection threshold. [ABSTRACT FROM AUTHOR]

The article offers information on the expanding universe of microRNA (mRNA) internal base modifications. Topics discussed include the RNA editing, which demands of conversion of A residues to inosine, the pseudouridine which is formed by a remarkable mechanism which requires the U-base detachment, and the various stress stimuli including nutrient deprivation in yeast, heat shock, and rRNA pseudouridylation.

The author reflects on the valuable outcomes of the study conducted by Markowitz and colleagues on inosine and multiple sclerosis (MS). He explains that the study aimed at showing the role of oral administration of inosine in patients with relapsing-remitting MS through the increase of uric acid (UA) levels. The author indicates that the results from the study demonstrate the beneficial role of inosine supplementation in people with relapsing-remitting MS.