Acid In Pathogenesis Research Articles

Exploring the Association of Serum Uric Acid Levels with Benign Paroxysmal Positional Vertigo: A Systematic Review and Meta-Analysis.

Objectives: The role of uric acid in pathogenesis of benign paroxysmal positional vertigo (BPPV) is not fully understood. It is aimed to assess the serum uric acid levels in BPPV patients compared to healthy controls. Study design: Systematic review and meta-analysis. Methods: Web of science, PubMed, Scopus, Google Scholar, Embase, Medline, and Cochrane library were systematically searched. The Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) and Problem/Population, Intervention, Comparison, and Outcome (PICO) guidelines were used. Results: In total, 20 studies including 3967 participants met the inclusion criteria. Ten studies (50%) reported higher uric acid (UA) levels in BPPV patients, 4 studies (20%) indicated lower UA levels in BPPV patients, while 6 studies (30%) found no significant difference in UA levels between BPPV patients and healthy controls. The overall mean serum levels of UA (SMD: 0.265, [-0.163 to 0.693]) were higher in BPPV patients than control group. However, this difference was not statistically significant (P-value: .225). Conclusion: There is no significant difference in serum level of UA between BPPV patients and healthy controls. It means that serum level of UA (whether low or high) is not likely the underlying factor of development of BPPV.

Role of Tryptophan Metabolites and Short-Chain Fatty Acids in Pathogenesis of Autoimmune Diseases

Role of Tryptophan Metabolites and Short-Chain Fatty Acids in Pathogenesis of Autoimmune Diseases

Identification of a tractable model system and oxalic acid‐dependent symptom development of the dollar spot pathogen Clarireedia jacksonii

AbstractClarireedia jacksonii causes dollar spot disease of cool‐season turfgrasses in the United States and produces the phytotoxin oxalic acid. The role of oxalic acid in host–pathogen interactions of C. jacksonii is unknown and there are multiple challenges to studying these interactions in natural turfgrass hosts. Consequently, identification of model plants to study C. jacksonii–host interactions and the role of oxalic acid in pathogenesis is necessary. Controlled environment inoculation assays were used to evaluate pathogenesis of C. jacksonii in various model plants and investigate the role of oxalic acid in symptom development. Observations at microscopic and macroscopic levels demonstrated that infection progressed similarly in all monocots tested (creeping bentgrass, wheat, barley, rice, Brachypodium distachyon) but not in the dicot Arabidopsis thaliana. Plant oxalic acid content increased from near zero to around 0.2–0.4 mM following inoculation with C. jacksonii in creeping bentgrass, barley, and wheat. Conversely, oxalic acid content remained near zero in A. thaliana and was not well correlated with inoculation in rice and B. distachyon, both of which had higher endogenous oxalic acid levels than other monocots. Time‐course oxalic acid quantification experiments with creeping bentgrass and B. distachyon further supported a link between symptom development and in planta oxalic acid content and identified 48 hr postinoculation as a critical time‐point for investigating the role of oxalic acid in C. jacksonii pathogenesis. These studies demonstrate that various monocots can serve as tractable model systems for studying C. jacksonii–host interactions and that increases in oxalic acid content are associated with C. jacksonii symptom development.

Fatty acids and cardiometabolic health: a review of studies in Chinese populations

Rapid nutrition transition from plant-based traditional diet to westernized diet has led to dramatically heightening burdens of cardiometabolic diseases in China in past decades. Recently, national surveys reported that poor dietary quality including low marine n-3 fatty acids and high intakes of red meat and processed meat was associated with considerably elevated cardiometabolic deaths. Previous studies mainly from Western population-based cohorts have indicated that not only fat quantity but also quality linked with different cardiometabolic outcomes. Compared with Western peoples, Asian peoples, including Chinese, are known to have different dietary patterns and lifestyle, as well as genetic heterogeneities, which may modify fatty acid metabolism and disease susceptibility in certain degree. To date, there were limited prospective studies investigating the relationships between fatty acids and cardiometabolic disease outcomes in Chinese, and most existing studies were cross-sectional nature and within one or two region(s). Notably, shifting dietary patterns could change not only amount, types, and ratio of fatty acids accounting for overall energy intake, but also their food sources and ratio to other macronutrients. Moreover, large geographic and urban-rural variations in prevalence of cardiometabolic diseases among Chinese may also reflect the effects of socioeconomic development and local diets on health status. Therefore, current review will summarize available literatures with more focus on the Chinese-based studies which may extend current knowledge about the roles of fatty acids in pathogenesis of cardiometabolic diseases for Asian populations and also provide useful information for trans-ethnic comparisons with other populations.

Structural and functional characterization of CMP-N-acetylneuraminate synthetase from Vibrio cholerae.

Several pathogenic bacteria utilize sialic acid, including host-derived N-acetylneuraminic acid (Neu5Ac), in at least two ways: they use it as a nutrient source and as a host-evasion strategy by coating themselves with Neu5Ac. Given the significant role of sialic acid in pathogenesis and host-gut colonization by various pathogenic bacteria, including Neisseria meningitidis, Haemophilus influenzae, Pasteurella multocida and Vibrio cholerae, several enzymes of the sialic acid catabolic, biosynthetic and incorporation pathways are considered to be potential drug targets. In this work, findings on the structural and functional characterization of CMP-N-acetylneuraminate synthetase (CMAS), a key enzyme in the incorporation pathway, from Vibrio cholerae are reported. CMAS catalyzes the synthesis of CMP-sialic acid by utilizing CTP and sialic acid. Crystal structures of the apo and the CDP-bound forms of the enzyme were determined, which allowed the identification of the metal cofactor Mg2+ in the active site interacting with CDP and the invariant Asp215 residue. While open and closed structural forms of the enzyme from eukaryotic and other bacterial species have already been characterized, a partially closed structure of V.cholerae CMAS (VcCMAS) observed upon CDP binding, representing an intermediate state, is reported here. The kinetic data suggest that VcCMAS is capable of activating the two most common sialic acid derivatives, Neu5Ac and Neu5Gc. Amino-acid sequence and structural comparison of the active site of VcCMAS with those of eukaryotic and other bacterial counterparts reveal a diverse hydrophobic pocket that interacts with the C5 substituents of sialic acid. Analyses of the thermodynamic signatures obtained from the binding of the nucleotide (CTP) and the product (CMP-sialic acid) to VcCMAS provide fundamental information on the energetics of the binding process.

Lysophosphatidic acid in pathogenesis of HNF1B-MODY syndrome

Lysophosphatidic acid in pathogenesis of HNF1B-MODY syndrome

The concentration of free amino acids in blood serum of dairy cows with primary ketosis.

Ketosis is a common condition found in the initial stages of lactation in high-yielding dairy cows. The major cause of ketosis is a negative energy balance. During the energy deficiency, proteolysis processes develop parallel to lipolysis. During proteolysis, muscle tissue can be used as a source of amino acid. To date, the participation of amino acids in gluconeogenesis (glucogenic amino acids) and ketogenesis (ketogenic amino acids) has not been determined in detail. This paper presents the study on determination of the parameters of protein and free amino acid metabolism in blood serum of dairy cows with primary ketosis compared to healthy cows. This study contributes to better understanding of the role of amino acids in pathogenesis of ketosis. A total of 30 cows, divided into two groups: experimental (15 cows with ketosis) and control (15 healthy cows), were included in the study. The concentrations of glucose, β-hydroxybutyrate, total protein, albumin, urea, and free amino acids were determined in peripheral blood. Statistically significantly higher concentrations of glutamine, glutamic acid, isoleucine (p≤0.001), and tyrosine (p≤0.05) were found in cows with primary ketosis compared to healthy cows. Significant decrease in the concentrations of asparagine, histidine, methionine, and serine (p≤0.001), alanine, leucine, lysine and proline (p≤0.05) was observed. Significant increase of total ketogenic and glucogenic amino acids (p≤0.05), and an increased ratio of total ketogenic and glucogenic amino acids to total amino acids (p≤0.001) were noted in cows with ketosis. In our study, the changes, in particular observed in amino acid concentration in cows with primary ketosis, indicate its intensive use in both ketogenesis and gluconeogenesis processes. Therefore, a detailed understanding of the role that amino acids play in gluconeogenesis and ketogenesis will improve ketosis diagnostics and monitoring the course of a ketosis episode. Perhaps, the prevention of this disease is possible by balancing the appropriate feed ration in terms of amino acid content.

Bile acids promote diethylnitrosamine-induced hepatocellular carcinoma via increased inflammatory signaling.

Hepatocellular carcinoma (HCC) is the most common hepatic malignancy and the third leading cause of cancer related deaths. Previous studies have implicated bile acids in pathogenesis of HCC, but the mechanisms are not known. We investigated the mechanisms of HCC tumor promotion by bile acids the diethylnitrosamine (DEN)-initiation-cholic acid (CA)-induced tumor promotion protocol in mice. The data show that 0.2% CA treatment resulted in threefold increase in number and size of DEN-induced liver tumors. All tumors observed in DEN-treated mice were well-differentiated HCCs. The HCCs observed in DEN-treated CA-fed mice exhibited extensive CD3-, CD20-, and CD45-positive inflammatory cell aggregates. Microarray-based global gene expression studies combined with Ingenuity Pathway Analysis revealed significant activation of NF-κB and Nanog in the DEN-treated 0.2% CA-fed livers. Further studies showed significantly higher TNF-α and IL-1β mRNA, a marked increase in total and phosphorylated-p65 and phosphorylated IκBα (degradation form) in livers of DEN-treated 0.2% CA-fed mice. Treatment of primary mouse hepatocytes with various bile acids showed significant induction of stemness genes including Nanog, KLF4, Sox2, and Oct4. Quantification of total and 20 specific bile acids in liver, and serum revealed a tumor-associated bile acid signature. Finally, quantification of total serum bile acids in normal, cirrhotic, and HCC human samples revealed increased bile acids in serum of cirrhotic and HCC patients. Taken together, these data indicate that bile acids are mechanistically involved pathogenesis of HCC and may promote HCC formation via activation of inflammatory signaling.

Bile Acids Promote Diethylnitrosamine‐induced Hepatocellular Carcinoma via Increased Inflammatory Signaling.

Hepatocellular carcinoma (HCC) is the most common hepatic malignancy and the third leading cause of cancer related deaths. Previous studies have implicated bile acids in pathogenesis of HCC but the mechanisms are not known. We investigated the mechanisms of bile acid‐mediated promotion of HCC using a diethylnitrosamine (DEN)‐mediated initiation‐cholic acid (CA)‐induced tumor promotion protocol in mice. The data show that 0.2% CA treatment resulted in 3‐fold increase in number and size of DEN‐induced liver tumors. All tumors observed in DEN‐treated mice were well‐differentiated HCCs. Microarray based global gene expression studies combined with Ingenuity Pathway Analysis revealed NF‐κB pathway as the main signaling pathways activated in the DEN‐treated 0.2% CA‐fed livers. Further studies showed significantly higher TNFα, IL‐1β, MCP‐1 mRNA, a significant increase in total and phosphorylated‐p65 and phosphorylated IκBa (degradation form) and higher EGR1 mRNA and protein in livers of DEN‐treated 0.2% CA‐fed mice. Interestingly, total bile acid quantification revealed increase in hepatic and serum bile acids in both DEN‐treated and DEN‐treated 0.2% CA‐fed mice, which was higher in the latter group. Finally, quantification of total serum bile acids in normal, cirrhotic and HCC human samples revealed increased bile acids in serum of cirrhotic and HCC patients. Taken together, these data indicate that bile acids are mechanistically involved pathogenesis of HCC and may promote HCC formation via activation of inflammatory signaling.

Circulating purine compounds, uric acid, and xanthine oxidase/dehydrogenase relationship in essential hypertension and end stage renal disease

Purine nucleotide liberation and their metabolic rate of interconversion may be important in the development of hypertension and its renal consequences. In the present study, blood triphosphate (ATP), adenosine diphosphate (ADP), and adenosine monophosphate (AMP) breakdown pathway was evaluated in relation to uric acid concentration and xanthine dehydrogenase/xanthine oxidase (XDH/XO) in patients with essential hypertension, patients with chronic renal diseases on dialysis, and control individuals. The pattern of nucleotide catabolism was significantly shifted toward catabolic compounds, including ADP, AMP, and uric acid in patients on dialysis program. A significant fall of ATP was more expressed in a group of patients on dialysis program, compared with the control value (p < 0.001), while ADP and AMP were significantly increased in both groups of patients compared with control healthy individuals (p < 0.001), together with their final degradation product, uric acid (p < 0.001). The index of ATP/ADP and ATP/uric acid showed gradual significant fall in both the groups, compared with the control value (p < 0.001), near five times in a group on dialysis. Total XOD was up-regulated significantly in a group with essential hypertension, more than in a group on dialysis. The activity of XO, which dominantly contributes reactive oxygen species (ROS) production, significantly increased in dialysis group, more than in a group with essential hypertension. In conclusion, the examination of the role of circulating purine nucleotides and uric acid in pathogenesis of hypertension and possible development of renal disease, together with XO role in ROS production, may help in modulating their liberation and ROS production in slowing progression from hypertension to renal failure.

Bile acid depletion increases susceptibility to acetaminophen‐induced hepatotoxicity in mice

Bile acids are known to play significant role in liver homeostasis. However, the role of bile acids in pathogenesis of acetaminophen (APAP)‐induced acute liver failure (ALF) is not known. Here we report that depletion of bile acids using cholestyramine (CSA), a bile acid sequestering resin, increases susceptibility of C57BL6 mice to APAP‐induced hepatotoxicity. C57BL6 mice were fed either normal diet or 2% CSA containing diet for 1 week, treated with 400 mg/kg APAP (ip) and analyzed over a time course of 0 to 24 hr. The CSA‐fed mice developed rapid and higher liver injury after APAP treatment. Depletion of bile acids by CSA did not alter metabolism of APAP. However, CSA‐fed mice exhibited rapid and significantly higher activation of c‐Jun N‐terminal protein Kinase (JNK) following APAP treatment. Furthermore, a significant decrease in intestinal fibroblast growth factor 15 (FGF15) mRNA was observed in CSA fed mice before and after APAP treatment. Compensatory liver regeneration following APAP overdose was delayed in the CSA‐fed mice up to 12 hr but was not different than the normal diet fed mice at 24 hr after APAP treatment. Taken together, these data indicate that depletion of intestinal bile acid increases susceptibility to APAP by rapid and higher hepatic JNK activation. These data indicate that bile acids and FGF15‐mediated gut‐liver signaling axis play an important role in cytoprotection following APAP‐induced ALF.These studies were supported by NIH ‐ P20 RR021940 (Udayan Apte), and AASLD/ALF Liver Scholar Award (Udayan Apte)

The role of nonesterified fatty acids in pathogenesis of cardiovascular diseases

The paper reviews publications concerned the role of nonesterifi ed fatty acids (NEFA) in pathogenesis of cardiovascular diseases. NEFAs are four and more carbons chain length carbonic acids and they are presented in free form (nonesterifi ed) in human body. Plasma NEFAs are produced by the adipose tissue triglyceride lipolysis, another source are lipoproteins such as chylomicrons, very low density lipoproteins and intermediate density lipoproteins. Elevated NEFA concentrations in plasma are the risk factor of cardiovascular diseases and type 2 diabetes mellitus and the independent risk factor of hypertension and sudden death. NEFA plasma concentration is elevated in atherosclerosis, acute myocardial infarction, diabetes mellitus, obesity, hypertension, and often in metabolic syndrome. A probable cause of NEFAs accumulation in plasma may be overeating and low physical activity, which result in increase of adipose tissue mass, lipolysis intensifi cation and elevation of NEFAs concentration in plasma. The role of elevated plasma NEFA concentration in a number of conditions (abdominal obesity, atherogenic dyslipidemia, insulin resistance, type 2 diabetes mellitus, endothelial dysfunction, vascular infl ammation, atherosclerosis, hypertension, ischemic heart disease, rhythm disturbances, sudden death) and possible ways of their correction are discussed.

Role of blood plasma fatty acids in pathogenesis of stable anginapectoris

In men and women suffering from stable angina pectoris of 1-2 functional classes and aged from 35 to 69 years old, decrease of C 23:0 and increase of C 18:1(11) fatty acids was observed regardless of sex, the content of the rest fatty acids changed depending on patients sex. Correlation was found that metabolism of fatty acids in this pathology group depends on patients sex: men in the control group showed decrease in the sum of omega-3 fatty acids as well as in the omega-3/omega-6 fatty acid ratio, while women showed decrease of omega-6 fatty acids at the constant sum of omega-3 fatty acids. Regardless of sex, the presence of this pathology is accompanied with decrease in correlations between fatty acids, as the number of correlations between saturated fatty acids increases and the number of correlations between not saturated and saturated fatty aсids decreases. Change in correlations between not saturated fatty acids depends on sex. In the number of patients having supernormal fatty acid contents, no pronounced differences were found between men and women.

Role of Refluxed Acid in Pathogenesis of Laryngeal Disorders

The neuroanatomic proximity of the larynx to the hypopharynx and proximal esophagus make it particularly vulnerable to diseases that occur in those 2 areas. This is particularly true of gastroesophageal reflux disease (GERD). There is increasing awareness of this relationship, and dysphonias from gastroesophageal reflux (GER) are far more common than previously realized. The symptoms and findings of reflux laryngitis, vocal nodules, Reinke’s edema, contact ulcer and granuloma, laryngeal stenosis, and paroxysmal laryngospasm are presented, and diagnostic protocols for each disorder are suggested. The treatment varies with the severity of each problem. Conservative lifestyles and dietary control are helpful, but long-term medical therapy with H 2, H 1, and prokinetic drugs are usually needed. Surgical therapy may be indicated for such life-threatening problems as laryngeal stenosis and paroxysmal laryngospasm. The need for physician and patient awareness, research, and improved and less expensive therapy are discussed.

Oxalate production by fungi: its role in pathogenicity and ecology in the soil environment

Oxalate secretion by fungi provides many advantages for their growth and colonization of substrates. The role of oxalic acid in pathogenesis is through acidification of host tissues and sequestration of calcium from host cell walls. The formation of calcium oxalate crystals weakens the cell walls, thereby allowing polygalacturonase to effect degradation more rapidly in a synergistic response. There is good correlation between pathogenesis, virulence, and oxalic acid secretion. Solubility of soil nutrients is achieved by soil-living species, when cations freed by oxalate diffusing in clay layers increases the effective solubility of Al and Fe. Oxalate retained in hyphal mats of mycorrhizal species increases phosphate and sulphate availability. The formation of calcium oxalate crystals provides a reservoir of calcium in the ecosystem. The ability of oxalate to bind divalent cations permits detoxification of copper, particularly evident in wood preserved with copper salts. Oxalate plays a unique role in lignocellulose degradation by wood-rotting basidiomycetes, acting as a low molecular mass agent initiating decay. In addition, in white-rot fungi oxalate acts as a potential electron donor for lignin-peroxidase catalysed reduction and chelates manganese, allowing the dissolution of Mn3+from the manganese–enzyme complex and thus stimulating extracellular manganese peroxidase activity. The biosynthesis and degradation of oxalate are discussed.Key words: oxalic acid, calcium oxalate, pathogenicity, fungi.

Role of erucic acid in pathogenesis of idiopathic heart block

Role of erucic acid in pathogenesis of idiopathic heart block

Light and scanning electron microscopic observations of calcium oxalate crystals produced during growth of Sclerotium rolfsii in culture and in infected tissue

Crystals produced during growth of Sclerotium rolfsii on cellophane overlaying water agar were identified as calcium oxalate based on their solubility characteristics in certain acids, positive staining reaction with silver nitrate – dithiooxamide, and characteristic energy-dispersive X-ray emission spectrum. Addition of calcium salts to water agar enhanced crystal formation. Similar crystals of calcium oxalate were observed with the light and scanning electron microscopes in sugar beet and carrot leaf tissues infected by Sclerotium rolfsii. They frequently formed along the infecting hyphae or were associated with hyphal aggregates and were observed in abundance within the tissue. Addition of oxalic acid solutions to leaf discs resulted in necrosis of the tissue, and crystals similar in all respects to those produced in infected tissues were formed. These observations indicate that the oxalic acid produced by Sclerotium rolfsii in culture or in diseased tissue may sequester available calcium to form calcium oxalate, and provide evidence for the role of oxalic acid in pathogenesis.

Propionate metabolism by cultured skin fibroblasts from normal individuals and patients with methylmalonicaciduria and propionicacidemia

The incorporation of [1- 14C]propionate into trichloroacetic acid-precipitable material was found to be greater in normal fibroblasts than in cells cultured from patients with PrAE and MMAU. In MMAU cells, the metabolic pathway leading into the TCA cycle appeared to be completely blocked. In PrAE cells, however, trace amounts of labeled TCA cycle intermediates and lactic acid were detected, indicating an incomplete block in the propionate pathway. A large accumulation of labeled long-chain fatty acids by affected cell lines points to a possible role of fatty acids in pathogenesis of these disorders.

Studies on Auxins in the Phytophthora Disease of the Potato Tuber I. Role of indole‐acetic acid in pathogenesis

Studies on Auxins in the <i>Phytophthora</i> Disease of the Potato Tuber I. Role of indole‐acetic acid in pathogenesis