Pathogenic Aspects Research Articles

Pathogenic aspects of stomach ulcerogenesis in acute intestinal obstruction

To identify the patterns and the correlation of morphological and functional changes in stomach wall with the dynamics of different types of acute intestinal obstruction. The study was performed on 33 adult mongrel dogs of both genders weighing 17-20 kg. All researches were conducted in accordance with the documents, such as the 'Guide for the Care and Use of laboratory animals of the National Institute of Health (National Institute of Health - NIH, Bethesda, USA)' and 'Rules of work with experimental animals'. The same methods were used to study the morphology of stomach wall in normal conditions and after intestinal obstruction simulation. We used H & E stain, Van Gieson's picrofuchsin staining combined with Mallory. The choice of histochemical methods was determined by the need to study metabolic processes in epithelial cells and gastric mucosa glands. Einarson method for detecting total nucleic acids was used. The last group of methods was statistical analysis. We determined the regularities of structural organization of microcirculation in various parts of the stomach, the correlation of morphological and functional changes in stomach wall with the dynamics of different types of acute intestinal obstruction. Our data indicate proximal-distal gradient of gastric perfusion: the most pronounced vascular network and maximum blood flow are observed in proximal stomach in both normal conditions and acute intestinal obstruction. More tenuous and reduced blood flow was revealed in the antrum, that is morphological basis of the most frequent localization of acute ulcers in this department.

Cytoprotection in Multiple Sclerosis and Ischemic Stroke with C-Phycocyanin and Phycocyanobilin

Cytoprotection in human diseases can be achieved by avoiding and ameliorating tissue damage or by restoring the homeostatic balance either as a local or a systemic defense response. Multiple Sclerosis (MS) and Ischemic Stroke (IS) although being different central nervous system diseases, have common pathogenic aspects such as a deregulated inflammatory response, a toxic redox imbalance and a prominent neuronal dysfunction.

RNA toxicity induced by expanded CAG repeats in Huntington's disease.

Huntington's disease (HD) belongs to the group of inherited polyglutamine (PolyQ) diseases caused by an expanded CAG repeat in the coding region of the Huntingtin (HTT) gene that results in an elongated polyQ stretch. Abnormal function and aggregation of the mutant protein has been typically delineated as the main molecular cause underlying disease development. However, the most recent advances have revealed novel pathogenic pathways directly dependent on an RNA toxic gain-of-function. Expanded CAG repeats within exon 1 of the HTT mRNA induce toxicity through mechanisms involving, at least in part, gene expression perturbations. This has important implications not only for basic and translational research in HD, but also for other types of diseases carrying the expanded CAG in other genes, which likely share pathogenic aspects. Here I will review the evidence and mechanisms underlying RNA toxicity in CAG repeat expansions, with particular focus on HD. These comprise abnormal subcellular localization of the transcripts containing the expanded CAG repeats; sequestration of several types of proteins by the expanded CAG repeat which results in defects of alternative splicing events and gene expression; and aberrant biogenesis and detrimental activity of small CAG repeated RNAs (sCAG) that produce altered gene silencing. Although these altered pathways have been detected in HD models, their contribution to disease development and progress requires further study.

The neurological disorders under schizophrenia: clinical characteristics and pathogenic aspects

The review considers neurological disorders diagnosed in patients with schizophrenia. It is emphasized that these disorders can occur in patients without treatment with neuroleptics. The light neurological disorders are quite often given no proper consideration. The development of these disorders is based on phenomenon of uncoupling of frontal lobes with other sections of brain, both cortical and sub cortical ones. The description of disorders of motor functions is presented. At that, particular attention is paid to parkinsonism, dyskinesia, oculomotor disorders. The pathogenic aspects of neurological disorders in patients with schizophrenia are considered. The results of study applied to this category of patients using technique of structural and functional neurovisualization are presented. It is emphasized that further investigation of this problem will permit bettering comprehend pathogenesis of this disease with the purpose of development of more effective therapy.

Homogeneity of Severe Posttraumatic Stress Disorder Symptom Profiles in Children and Adolescents Across Gender, Age, and Traumatic Experiences Related to 9/11.

Patients with a posttraumatic stress disorder (PTSD) diagnosis according to the Diagnostic and Statistical Manual of Mental Disorders (4th ed., DSM-IV; American Psychiatric Association, 1994) will very likely not share all of the same symptoms, a consequence of the polythetic approach used in the DSM. We examined heterogeneity in the latent structure of PTSD symptoms using data from a previously published sample of 8,236 youth a subset of which had been exposed to the September 11, 2001 attacks (N = 6,670; Hoven etal., 2005). Latent class analysis was applied (a) to PTSD symptoms alone, (b) to symptoms in combination with impairment indicators, and (c) to PTSD symptoms when stratified by age and gender, as well as by empirically defined classes of exposure. We identified 4 symptom classes: no disturbance (49.4%), intermediate disturbance (2 classes; 21.5% and 18.6%, respectively), and severe disturbance (10.5%). These classes varied not only in the severity of symptoms, but also in the configuration of symptoms. We observed a high probability of endorsing both PTSD symptoms and indicators of impairment only in the severe disturbance class. A similar 4-class structure was found when the data were stratified by age, gender, and exposure classes. There were no significant differences as a function of age, gender, or exposure in the presence of severe PTSD. Heterogeneity was observed at intermediate levels of PTSD symptom severity. The specific PTSD symptoms that defined the severe PTSD profile could constitute the pathogenic aspects of a largely invariant and clinically meaningful PTSD syndrome.

Banded leaf and sheath blight: A menacing disease of maize (Zea mays L.) and its management

Maize (Zea mays L.) crop is attacked by number of fungal, bacterial and viral diseases, out of which banded leaf and sheath blight (BLSB) caused by anastomosis group 1-IA of Rhizoctonia solani f. sp. sasakii Exner. is one of the most widespread and destructive disease of maize in Southeast Asian countries. The occurrence of this disease has also been reported from other parts of the world, which causes significant yield loss up to 100%. R. solani can survive in the soil for several years and able to infect plants belonging to more than 32 families, including many economically important monocots and dicots plants. The severity of the disease favoured by humid weather with temperature around 28°C, poses challenge to maize growers due to its soil borne nature and lack of resistance cultivars. It is indicated that none of the disease management approaches are effective against BLSB. Banded leaf and sheath blight is difficult to control through either fungicide or crop rotation alone. A number of quantitative trait loci (QTLs) controlling BLSB have been identified that would help the development of maize hybrids resistance to this disease. Management of BLSB requires an integrated approach based on the knowledge of each stage of the disease and molecular aspect of maize defence responses against R. solani. Mention conclusion statement and novelty of the work. The present review summarizes consolidated information on distribution, yield loss, symptoms, pathogen life cycle, epidemiology, genetic structure of the pathogen population, molecular aspect of pathogenicity and its integrated management through cultural, biological, chemical and genetic means. The consolidated knowledge presented in this review should help better disease management and reduce crop yield loss due to banded leaf and sheath blight pathogen.

EVALUATION OF THE METHODS OF IMAGING IN THE DIAGNOSIS OF LIVER CIRRHOSIS AND PORTAL HYPERTENSION

Objective: to evaluate the prospects and role of the methods of imaging (ultrasound and CT) in the diagnosis of the pathogenic aspects of the development and correction of portal hypertension in liver cirrhosis. Material and methods. Patients with liver cirrhosis and portal hypertension, Doppler ultrasound, multislice computed tomography. Conclusion. The combined use of ultrasound and computed tomography facilitates tracing of the dynamics of the disclosure of portocaval anastomoses and predict the course of liver cirrhosis and portal hypertension. The application of the integrated ultrasound to determine the rate of blood flow volume in vessels of portal system and portocaval anastomosis will enable development of differential diagnostic criteria for the early diagnosis of portal hypertension. The detection of recanalized umbilical vein by means of 3D-visualization of its anatomy makes it possible to use it for delivering of therapeutic agents to the liver in its pathology.

The Sclerotinia sclerotiorum Slt2 mitogen-activated protein kinase ortholog, SMK3, is required for infection initiation but not lesion expansion

Mitogen-activated protein kinases (MAPKs) play a central role in transferring signals and regulating gene expression in response to extracellular stimuli. An ortholog of the Saccharomyces cerevisiae cell wall integrity MAPK was identified in the phytopathogenic fungus Sclerotinia sclerotiorum. Disruption of the S. sclerotiorum Smk3 gene severely reduced virulence on intact host plant leaves but not on leaves stripped of cuticle wax. This was attributed to alterations in hyphal apical dominance leading to the inability to aggregate and form infection cushions. The mutation also caused loss of the ability to produce sclerotia, increased aerial hyphae formation, and altered hyphal hydrophobicity and cell wall integrity. Mutants had slower radial expansion rates on solid media but more tolerance to elevated temperatures. Loss of the SMK3 cell wall integrity MAPK appears to have impaired the ability of S. sclerotiorum to sense its surrounding environment, leading to misregulation of a variety of functions. Many of the phenotypes were similar to those observed in S. sclerotiorum adenylate cyclase and SMK1 MAPK mutants, suggesting that these signaling pathways co-regulate aspects of fungal growth, physiology, and pathogenicity.

Characterization of Rhizoctonia solani Associated with Black Scurf in Cyprus.

During 2011, 96 sclerotial isolates of Rhizoctonia solani were collected from potato tubers from all main potato-cultivating regions of Cyprus. All isolates were found to be multinucleate. Characterization of anastomosis groups (AG) based on hyphal anastomosis reactions showed that 91 isolates belonged to AG3 and 5 to AG4. Sequence analysis of the internal transcribed spacer (ITS) regions (ITS1 and ITS2) of ribosomal DNA (rDNA) of 68 isolates confirmed the prevalence of AG3. In addition, phylogenetic analysis found that AG3 isolates were of the potato type, distinctly separated from the AG3 tobacco type, while AG4 isolates were separated into two different subgroups (HGI and HGII). Temperature studies showed that isolates belonging to both AG4 subgroups had significantly higher optimum growth temperatures compared with AG3. In vitro sensitivities to the fungicide pencycuron, in terms of concentrations where 50% growth inhibition was observed, ranged from 0.012 to 0.222 μg/ml. Pathogenicity and aggressiveness of the isolates was determined on 'Annabelle' potato sprouts and seedlings of a number of selected hosts, based on crop rotations followed in Cyprus. The majority of the isolates were pathogenic to potato sprouts, with disease severity (DS) values ranging from 0 to 88%. Mean DS values were statistically different among AG and subgroups, with AG4-HGI (69.25%) and AG4-HGII (3.12%) being the most and least aggressive, respectively. However, AG4-HGII isolates were the most aggressive in all rotational hosts tested, while AG3 isolates were the least aggressive. More specifically, the highest DS levels by AG4-HGI were recorded to barley, by AG4-HGII to lettuce and melon, and by AG3 isolates to vetch. This is the first comprehensive study to elucidate the AG composition, pathogenicity and other biological aspects of R. solani isolates associated with potato black scurf in Cyprus.

The epidemiological and pathogenic aspects of acute pancreatic encephalopathy

The article considers particular aspects of epidemiology and pathogenesis of neurological disorders detected in patients with acute pancreatitis. The pancreatic encephalopathy characterizing by various focal neurological symptomatic and sometimes rapid development of dementia is considered as a rare complication of acute pancreatitis developing in 9-35% of patients with diseases of pancreas. Factually, every patient with acute pancreatitis has a risk of development of pancreatic encephalopathy which significantly increases graveness of course and lethality of disease. Therefore, the emphasis is made on development of diagnostic algorithm under pancreatic encephalopathy permitting discovering this complication of acute pancreatitis at as much as possible early even possibly at pre-clinical stage. The comprehensive investigation of pathogenesis of pancreatic encephalopathy with the purpose of elaboration of pathogenetically conditioned therapeutic algorithm considering all parts of pathogenesis.

An Overview on Biopesticidal and Virulent nature with Pathogenic aspects of Entomopathogenic fungi on Insects

Entomopathogenic fungi are very heterogeneous group used for management of insect pest. From last 2 decade in the search for new avenues in biological control, the importance of entomopathogens has been highlighted as an environmental friendly pest control method came in existence which is sustainable solution towards integrated pest control program. Fungi, which induce disease symptoms in insects, include fungi from quick killers to absolute parasites that provide disease symptoms in the host. Insect order and families are reviewed which were affected severely by entomopathogenic fungi.

Escherichia coli: an old friend with new tidings.

Escherichia coli is one of the most-studied microorganisms worldwide but its characteristics are continually changing. Extraintestinal E. coli infections, such as urinary tract infections and neonatal sepsis, represent a huge public health problem. They are caused mainly by specialized extraintestinal pathogenic E. coli (ExPEC) strains that can innocuously colonize human hosts but can also cause disease upon entering a normally sterile body site. The virulence capability of such strains is determined by a combination of distinctive accessory traits, called virulence factors, in conjunction with their distinctive phylogenetic background. It is conceivable that by developing interventions against the most successful ExPEC lineages or their key virulence/colonization factors the associated burden of disease and health care costs could foreseeably be reduced in the future. On the other hand, one important problem worldwide is the increase of antimicrobial resistance shown by bacteria. As underscored in the last WHO global report, within a wide range of infectious agents including E. coli, antimicrobial resistance has reached an extremely worrisome situation that ‘threatens the achievements of modern medicine’. In the present review, an update of the knowledge about the pathogenicity, antimicrobial resistance and clinical aspects of this ‘old friend’ was presented.

Flagellar Cap Protein FliD Mediates Adherence of Atypical Enteropathogenic Escherichia coli to Enterocyte Microvilli.

The expression of flagella correlates with different aspects of bacterial pathogenicity, ranging from adherence to host cells to activation of inflammatory responses by the innate immune system. In the present study, we investigated the role of flagella in the adherence of an atypical enteropathogenic Escherichia coli (aEPEC) strain (serotype O51:H40) to human enterocytes. Accordingly, isogenic mutants deficient in flagellin (FliC), the flagellar structural subunit; the flagellar cap protein (FliD); or the MotAB proteins, involved in the control of flagellar motion, were generated and tested for binding to differentiated Caco-2 cells. Binding of the aEPEC strain to enterocytes was significantly impaired in strains with the fliCa nd fliD genes deleted, both of which could not form flagella on the bacterial surface. A nonmotile but flagellated MotAB mutant also showed impaired adhesion to Caco-2 cells. In accordance with these observations, adhesion of a EPEC strain 1711-4 to Caco-2 cells was drastically reduced after the treatment of Caco-2 cells with purified FliD. In addition, incubation of a EPEC bacteria with specific anti-FliD serum impaired binding to Caco-2 cells. Finally, incubation of Caco-2 cells with purified FliD, followed by immunolabeling, showed that the protein was specifically bound to the microvillus tips of differentiated Caco-2 cells. The a EPEC FliD or anti-FliD serum also reduced the adherence of prototype typical enteropathogenic, enterohemorrhagic, and enterotoxigenic E. coli strains to Caco-2 cells. In conclusion, our findings further strengthened the role of flagella in the adherence of a EPEC to human enterocytes and disclosed the relevant structural and functional involvement of FliD in the adhesion process.

High-mobility group box 1 potentiates antineutrophil cytoplasmic antibody-inducing neutrophil extracellular traps formation.

BackgroundRecent studies found that the circulating high-mobility group box 1 (HMGB1) levels could reflect the disease activity of antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV). HMGB1 could prime neutrophils by increasing ANCA antigens translocation for ANCA-mediated respiratory burst and degranulation. The current study aimed to investigate whether HMGB1 participates in ANCA-induced neutrophil extracellular traps (NETs) formation, which is one of the most important pathogenic aspects in the development of AAV.MethodsNETs were induced by treating neutrophils with HMGB1 and ANCA-positive IgG in vitro. NETs formation was assessed using immunofluorescence microscopy and fluorescence probe. Antagonist for relevant receptors Toll-like receptor (TLR)2, TLR4 and the receptor for advanced glycation end products (RAGE), as well as NADPH oxidase molecules were employed.ResultsThe percentage of NETs formation was significantly higher in neutrophils stimulated with HMGB1 plus ANCA-positive IgG than that in neutrophils incubated with HMGB1 or ANCA-positive IgG alone. Consistently, compared with the nonstimulated neutrophils, the cell-free DNA (cfDNA) concentration of NETs was significantly increased from 334.09 ± 46.89 ng/ml to 563.32 ± 122.07 ng/ml in the neutrophils incubated with HMGB1 plus MPO-ANCA-positive IgG (P < 0.001), and from 303.44 ± 37.14 ng/ml to 563.79 ± 145.94 ng/ml in the neutrophils incubated with HMGB1 plus PR3-ANCA-positive IgG (P < 0.001). The aforementioned effect was significantly attenuated by antagonist for relevant receptors TLR2, TLR4 and RAGE, as well as blocking NADPH oxidase.ConclusionsHMGB1 can potentiate ANCA-inducing NETs formation and may be involved in the pathogenesis of AAV. HMGB1 exerts effects on NETs formation through interaction with TLR2, TLR4 and RAGE, and the process is NADPH oxidase dependent.Electronic supplementary materialThe online version of this article (doi:10.1186/s13075-015-0903-z) contains supplementary material, which is available to authorized users.

Phytophotodermatitis: A Review of Its Clinical and Pathogenic Aspects

Phytodermatoses are diseases caused by the contact of human beings with plants. Phytophotodermatitis is a phototoxic reaction entirely independent from the immune system. This reaction occurs when the skin is exposed to photosensitizer substances and to ultraviolet radiation, different from the photoalergic reactions, in which there is an immunologic component. Phytophotodermatitis has a wide range of clinical presentations, the hands are the most common localisation. The Tahiti lemon is the most common cause in Brazil. Experimental researches in animals showed that after 24 hours there are histological changes, characterized by vacuolization and keratinocyte necrosis, which evolves to blister formation after 48 hours, when clinically erythema and blisters could be seen. The initial lesion occurs in the cell membrane and in the desmosomes.

Abstract IA16: Mapping metabolic drivers of cancer using chemoproteomic and metabolomic platforms

Abstract Cancer cells possess fundamentally altered cellular metabolism that not only leads to a re-wiring of cellular biochemistry, but also drives nearly every aspect of cancer cell pathogenicity. While targeting dysregulated metabolism is a promising strategy for cancer treatment, much of cancer metabolism has focused on well-understood metabolic pathways in central carbon metabolism (e.g. glycolytic or glutamine metabolism) underlying cellular transformation and early-stages of cancer, and has largely ignored many of cellular metabolic pathways or those networks involved in cancer progression, despite clear genetic or metabolic evidence of their involvement in cancer. Here, we describe chemoproteomic and metabolomic technologies that we have utilized to identifying unique and novel dysregulated metabolic drivers of cancer. In particular, we have identified several unique nodes within lipid and sialic acid metabolism that are essential in driving cancer pathogenicity. Citation Format: Daniel Nomura. Mapping metabolic drivers of cancer using chemoproteomic and metabolomic platforms. [abstract]. In: Proceedings of the AACR Special Conference: Metabolism and Cancer; Jun 7-10, 2015; Bellevue, WA. Philadelphia (PA): AACR; Mol Cancer Res 2016;14(1_Suppl):Abstract nr IA16.

Pathogenic aspects and therapeutic avenues of intestinal fibrosis in Crohn's disease.

In Crohn's disease, one of the two major forms of inflammatory bowel diseases in human beings, persistent and chronic inflammation promotes fibrotic processes thereby facilitating formation of strictures, the most common indication for surgical intervention in this disorder. The pathogenesis of Crohn's disease-associated fibrosis is not fully understood, but variants of genes involved in the recognition of microbial components/products [e.g. CARD15 (caspase-activating recruitment domain 15) and ATG16L1 (autophagy-related 16-like 1)] are associated with this phenotype, and experimental evidence suggests that intestinal fibrosis results from an altered balance between deposition of ECM (extracellular matrix) and degradation of ECM by proteases. Studies have also contributed to identify the main phenotypic and functional alterations of cells involved in the fibrogenic process, as well as molecules that stimulate such cells to produce elevated amounts of collagen and other ECM-related proteins. In the present review, we assess the current knowledge about cellular and molecular mediators of intestinal fibrosis and describe results of recent studies aimed at testing the preventive/therapeutic effect of compounds in experimental models of intestinal fibrosis.

Web-based Gene Pathogenicity Analysis (WGPA): a web platform to interpret gene pathogenicity from personal genome data.

Summary: As the volume of patient-specific genome sequences increases the focus of biomedical research is switching from the detection of disease-mutations to their interpretation. To this end a number of techniques have been developed that use mutation data collected within a population to predict whether individual genes are likely to be disease-causing or not. As both sequence data and associated analysis tools proliferate, it becomes increasingly difficult for the community to make sense of these data and their implications. Moreover, no single analysis tool is likely to capture all relevant genomic features that contribute to the gene’s pathogenicity. Here, we introduce Web-based Gene Pathogenicity Analysis (WGPA), a web-based tool to analyze genes impacted by mutations and rank them through the integration of existing prioritization tools, which assess different aspects of gene pathogenicity using population-level sequence data. Additionally, to explore the polygenic contribution of mutations to disease, WGPA implements gene set enrichment analysis to prioritize disease-causing genes and gene interaction networks, therefore providing a comprehensive annotation of personal genomes data in disease.Availability and implementation: wgpa.systems-genetics.netContact: enrico.petretto@duke-nus.edu.sgSupplementary information: Supplementary data are available at Bioinformatics online.

Manifestaciones psiquiátricas por priones. Una revisión narrativa

Prion diseases are a group of rare and rapidly progressive neurodegenerative conditions that may cause neuropsychiatric symptoms. This group of diseases has been described since the 18th century, but they were recognized decades later, when it became clear that the humans were affected by infected animals. There was controversy when the problem was attributed to a single protein with infective capacity. The common pathological process is characterized by the conversion of the normal cellular prion protein into an abnormal form. In humans, the illness has been classified as idiopathic, inherited and acquired through exposure to exogenous material containing abnormal prions. The most prominent neurological manifestation of prion diseases is the emergence of a rapidly progressive dementia, mioclonus associated with cerebellar ataxia and also extra pyramidal symptoms. Psychiatric symptoms occur in early stages of the illness and can contribute to timely diagnosis of this syndrome. Psychiatric symptoms have traditionally been grouped in three categories: affective symptoms, impaired motor function and psychotic symptoms. Such events usually occur during the prodromal period prior to the neurological manifestations and consists in the presence of social isolation, onset of delusions, irritability/aggression, visual hallucinations, anxiety and depression, and less frequent first-rank symptoms among others. Definite diagnosis requires post mortem examination. The possibility that a large number of cases may occur in the next years or that many cases have not been considered with this diagnosis is a fact.In our opinion, psychiatrists should be aware of symptoms of this disease. The main objective of this research consisted of assessing the correlation between this disturbance and neuro-psychiatric symptoms and particularly if this psychiatric manifestations integrate a clinical picture suggestive for the diagnosis of these diseases, but firstly reviewed taxonomic, pathogenic and pathological aspects. The authors of this project also added an element in relation to some diagnostic considerations based on scientific evidence. For the search controlled descriptors applied to the research for indexing scientific articles in databases were used. The electronic data bases used were PubMed, EMBASE and also PsycInfo. The descriptors were prion diseases, psychotic disorders, depression, mood disorders, pathology, classification, prion protein, history, neurological manifestations, and psychiatric manifestations. The selection criteria for the material were qualitative. To conclude, and based on the extensive literature review, the authors propose that the period where the evidence is more robust for mental impaired is named “psychiatric symptoms phase, which can be extended for a few months, being the psychiatric affective symptoms the most characteristic of this phase. In conclusion, we considered that the identification of these symptoms in a patient with risk factors for developing the disease will contribute to the early identification, and would regulate the guidelines in suspected diagnosis of this group of disorders. The intention is provide a better quality of life to the sick people.

Book Review: “Cerebral Small Vessel Disease”. What’s the Big Deal about Small Vessels?

Book Review: “Cerebral Small Vessel Disease”. What’s the Big Deal about Small Vessels?