Elevated Thromboxane Levels in the Rat during Endotoxic Shock: Protective Effects of Imidazole, 13-azaprostanoic Acid, or Essential Fatty Acid Deficiency

The potential deleterious role of the proaggregatory vasoconstrictor, thromboxane A2, in endotoxic shock was investigated in rats. Plasma thromboxane A2 was determined by radioimmunoassay of its stable metabolite thromboxane B2. After intravenous administration of Salmonella enteritidis endotoxin (20 mg/kg), plasma thromboxane B2 levels increased from nondetectable levels (\u3c375 pg/ml) in normal control rats to 2,054±524 pg/ml (n = 8), within 30 min to 2,071+429 at 60 min, and decreased to 1,119+319 pg/ml, at 120 min. Plasma levels of prostaglandin E also increased from 146±33 pg/ml in normal controls (n = 5) to 2,161+606 pg/ml 30 min after endotoxin (n = 5). In contrast to shocked controls, rats pretreated with imidazole, a thromboxane synthetase inhibitor, or essential fatty acid-deficient rats, which are deficient in arachidonate and its metabolites, did not exhibit significant elevations in plasma levels of thromboxane B2. Imidazole did not however inhibit endotoxin-induced elevations in plasma prostaglandin E. Essential fatty acid deficiency significantly reduced mortality to lethal endotoxic shock. This refractoriness could be duplicated in normal rats pretreated with the fatty acid cyclo-oxygenase inhibitor, indomethacin (10 mg/kg), intravenously 30 min before endotoxin injection. Imidazole (30 mg/kg) administered intraperitoneally 1 h before or intravenously 30 min before endotoxin, also significantly (P \u3c 0.01) reduced mortality from lethal endotoxin shock to 40% compared to a control mortality of 95% at 24 h. Likewise pretreatment with 13-azaprostanoic acid (30 mg/kg), a thromboxane antagonist, reduced mortality from endotoxic shock at 24 h from 100% in control rats to only 50% (P \u3c 0.01). The results suggest that endotoxin induces increased synthesis of thromboxane A2 that may contribute to the pathogenesis of endotoxic shock

Organization of sorting and surgery of wounds with soft tissue defects during the joint force surgery

Introduction. The experience of providing medical care during the Anti-terrorist operation in eastern Ukraine showed that in the structure of modern combat surgical trauma gunshot wounds with soft tissue defects are between 64.9-68.2%, of which 36.4-37.5% are small and medium, 28.5-30.7% are large and very large defects.Aim: To improve the results of providing surgical care to the wounded with soft tissue defects by introducing a variety of surgical tactics of wound closure to the medical care levels.Material and Methods. The total array of the study was 2537 wounded with shrapnel, bullet and mine injuries from April 2014 to September 2018. The determination of surgical tactics for closing soft tissue defects was performed at the basis of metric classification taking into account the area, volume and anatomical areas of the lesion.Results. The combination of metric characteristics of wound defects by area, volume with localization of wounds in a single classification allowed the offer of a comprehensive approach to sorting the wounded at the level of medical care and to determine further surgical tactics to close soft tissue defects. In accordance with the sorting and evacuation purposes, the wounded with gunshot wounds to the foot and hand (third zone of injury) were treated in specialised centres to the fourth level of medical care. In the case of medium and large wounds of the thigh, leg, shoulder and forearm, medical care was provided at the second and third levels. And in the case of large and very large wounds of the specified localisation was provided in specialised clinics of the fourth level.Conclusions. The introduction of differentiated surgical tactics in the wounded with soft tissue defects at the levels of medical care has improved functional results: increase the proportion of good from 46.9% to 53.7%, reduce the relative number of unsatisfactory from 18.8% to 11, 6%

Особливості хірургічного лікування вогнепальних поранень живота

Особливості хірургічного лікування вогнепальних поранень живот

Peculiarities of surgical treatment of the abdominal gun–shot woundings

У структурі сучасної бойової травми зростає частка пошкоджень органів черевної порожнини, які супроводжуються розвитком травматичного шоку, поліорганної недостатності та високою летальністю. Трирічний досвід збройного конфлікту на сході України показав, що сучасна зброя – реактивні системи залпового вогню, касетні бомби, керовані вибухові пристрої високоточної дії тощо – завдає особливо тяжких поранень. Структура бойової травми живота залежить від характеру ведення бойових дій, який останніми роками також значно змінився, тому потрібні нові підходи до діагностичних заходів та хірургічного лікування

Consensus statement on surgical pathology of the aorta from the Society for Cardiovascular Pathology and the Association for European Cardiovascular Pathology: I. Inflammatory diseases

Abstract Inflammatory diseases of the aorta include routine atherosclerosis, aortitis, periaortitis, and atherosclerosis with excessive inflammatory responses, such as inflammatory atherosclerotic aneurysms. The nomenclature and histologic features of these disorders are reviewed and discussed. In addition, diagnostic criteria are provided to distinguish between these disorders in surgical pathology specimens. An initial classification scheme is provided for aortitis and periaortitis based on the pattern of the inflammatory infiltrate: granulomatous/giant cell pattern, lymphoplasmacytic pattern, mixed inflammatory pattern, and the suppurative pattern. These inflammatory patterns are discussed in relation to specific systemic diseases including giant cell arteritis, Takayasu arteritis, granulomatosis with polyangiitis (Wegener's), rheumatoid arthritis, sarcoidosis, ankylosing spondylitis, Cogan syndrome, Behcet's disease, relapsing polychondritis, syphilitic aortitis, and bacterial and fungal infections

Distribution and Effects of Nonsense Polymorphisms in Human Genes

BACKGROUND: A great amount of data has been accumulated on genetic variations in the human genome, but we still do not know much about how the genetic variations affect gene function. In particular, little is known about the distribution of nonsense polymorphisms in human genes despite their drastic effects on gene products. METHODOLOGY/PRINCIPAL FINDINGS: To detect polymorphisms affecting gene function, we analyzed all publicly available polymorphisms in a database for single nucleotide polymorphisms (dbSNP build 125) located in the exons of 36,712 known and predicted protein-coding genes that were defined in an annotation project of all human genes and transcripts (H-InvDB ver3.8). We found a total of 252,555 single nucleotide polymorphisms (SNPs) and 8,479 insertion and deletions in the representative transcripts in these genes. The SNPs located in ORFs include 40,484 synonymous and 53,754 nonsynonymous SNPs, and 1,258 SNPs that were predicted to be nonsense SNPs or read-through SNPs. We estimated the density of nonsense SNPs to be 0.85x10(-3) per site, which is lower than that of nonsynonymous SNPs (2.1x10(-3) per site). On average, nonsense SNPs were located 250 codons upstream of the original termination codon, with the substitution occurring most frequently at the first codon position. Of the nonsense SNPs, 581 were predicted to cause nonsense-mediated decay (NMD) of transcripts that would prevent translation. We found that nonsense SNPs causing NMD were more common in genes involving kinase activity and transport. The remaining 602 nonsense SNPs are predicted to produce truncated polypeptides, with an average truncation of 75 amino acids. In addition, 110 read-through SNPs at termination codons were detected. CONCLUSION/SIGNIFICANCE: Our comprehensive exploration of nonsense polymorphisms showed that nonsense SNPs exist at a lower density than nonsynonymous SNPs, suggesting that nonsense mutations have more severe effects than amino acid changes. The correspondence of nonsense SNPs to known pathological variants suggests that phenotypic effects of nonsense SNPs have been reported for only a small fraction of nonsense SNPs, and that nonsense SNPs causing NMD are more likely to be involved in phenotypic variations. These nonsense SNPs may include pathological variants that have not yet been reported. These data are available from Transcript View of H-InvDB and VarySysDB (http://h-invitational.jp/varygene/)

Schizophrenia-associated HapICE haplotype is associated with increased NRG1 type III expression and high nucleotide diversity

Excitement and controversy have followed neuregulin (NRG1) since its discovery as a putative schizophrenia susceptibility gene; however, the mechanism of action of the associated risk haplotype (HapICE) has not been identified, and specific genetic variations, which may increase risk to schizophrenia have remained elusive. Using a postmortem brain cohort from 37 schizophrenia cases and 37 controls, we resequenced upstream of the type I–IV promoters, and the HapICE repeat regions in intron 1. Relative abundance of seven NRG1 mRNA transcripts in the prefrontal cortex were determined and compared across diagnostic and genotypic groups. We identified 26 novel DNA variants and showed an increased novel variant load in cases compared with controls (χ2=7.815; P=0.05). The average nucleotide diversity (θ=10.0 × 10−4) was approximately twofold higher than that previously reported for BDNF, indicating that NRG1 may be particularly prone to genetic change. A greater nucleotide diversity was observed in the HapICE linkage disequilibrium block in schizophrenia cases (θ(case)=13.2 × 10−4; θ(control)=10.0 × 10−4). The specific HapICE risk haplotype was associated with increased type III mRNA (F=3.76, P=0.028), which in turn, was correlated with an earlier age of onset (r=−0.343, P=0.038). We found a novel intronic five-SNP haplotype ∼730 kb upstream of the type I promoter and determined that this region functions as transcriptional enhancer that is suppressed by SRY. We propose that the HapICE risk haplotype increases expression of the most brain-abundant form of NRG1, which in turn, elicits an earlier clinical presentation, thus providing a novel mechanism through which this genetic association may increase risk of schizophrenia