Synthesis Of Acute Phase Proteins Research Articles

The connections of sialic acids and diabetes mellitus: therapeutic or diagnostic value?

Modulation of sialic acids is one of the important pathological consequences of both type 1 and type 2 diabetes mellitus with or without the micro- and macrovascular complications. However, the mechanistic, therapeutic and/or diagnostic implications of these observations are uncoordinated and possibly conflicting. This review critically analyses the scientific investigations connecting sialic acids with diabetes mellitus. Generally, variations in the levels and patterns of sialylation, fucosylation and galactosylation were predominant across various tissues and body systems of diabetic patients, but the immune system seemed to be most affected. These might be explored as a basis for differential diagnosis of various diabetic complications. Sialic acids are predominantly elevated in nearly all forms of diabetic conditions, particularly nephropathy and retinopathy, which suggests some diagnostic value but the mechanistic details were not unequivocal from the available data. The plausible mechanistic explanations for the elevated sialic acids are increased desialylation by sialidases, stimulation of hexosamine pathway and synthesis of acute phase proteins as well as oxidative stress. Additionally, sialic acids are also profoundly associated with glucose transport and insulin resistance in human-based studies while animal-based studies revealed that the increased desialylation of insulin receptors by sialidases, especially NEU1, might be the causal link. Interestingly, inhibition of the diabetes-associated NEU1 desialylation was beneficial in diabetes management and might be considered as a therapeutic target. It is hoped that the article will provide an informed basis for future research activities on the exploitation of sialic acids and glycobiology for therapeutic and/or diagnostic purposes against diabetes mellitus.

Comparison of some cytokines, acute phase proteins and citrulline levels in healthy and canine distemper infected dogs.

Canine distemper virus (CDV) is the etiological agent of severe disease in domestic and wild carnivores. Clinical diagnosis of CDV is challenging because of its similarity to other canine respiratory and intestinal diseases. We aimed to determine certain cytokine (interleukin [IL]-1β, IL-2, IL-4, IL-6, IL-10, and tumor necrosis factor-α [TNF-α]), interferon (IFN)-γ, canine serum amyloid A (SAA), and canine citrulline (CIT) levels for the first time in CDV-positive dogs. For this purpose, 10 CDV-positive dogs with compatible clinical findings (i.e., neurological symptoms such as tremors and myoclonus, ocular and nasal discharge, and wheezing) and 10 healthy dogs based on the clinical examinations and rapid test results were enrolled. It was observed that the CIT, INF-γ, IL-1β, IL-2, IL-6, and TNF-α levels were significantly decreased in the CDV-positive dogs than that of the healthy ones (P<0.05). As a result, it was observed that CDV causes immunosuppression and accordingly, the inflammatory response might cause decreased cytokine and acute-phase protein synthesis. Therefore, it was concluded that further investigation of inflammatory pathways and CIT interactions may provide crucial clinical information at different stages of CDV, and aforementioned parameters may serve as important biomarkers for CDV in terms of demonstrating the presence of immunosuppression.

Clinical and Diagnostic Significance of Sialic Acids Determination in Biological Material.

Sialic acids (SA) are neuraminic acid derivatives, located at the terminal position in the chains of monosaccharide residues of various glycoconjugates. SA play a dual role: they either mask recognition sites, or, on the contrary, represent biological targets that can be recognized by receptor proteins and serve as ligands. The desialylation/sialylation processes can be considered as a dynamic modification regulated by sialyltransferases and sialidases in response to external or internal stimuli. This review describes the structural and functional diversity and the potential use of SA fractions as biomarkers for various pathological conditions. Almost any extreme impact on the body and inflammatory processes are accompanied by an increase in the level of both total and free SA in the blood and tissues. Possible reasons for the increase of sialoglycoconjugate metabolism indicators in biological material include: (i) activation of the hepatocyte synthesis and secretion of various acute-phase proteins, many of which are sialoglycoproteins, (ii) impaired membrane integrity and destruction of body cells, (iii) high activity of sialidases (neurominidases) and sialyltransferases. Most acute and chronic liver diseases are characterized by the decrease in the total level of SA in the blood serum (because many plasma proteins are synthesized and glycosylated in hepatocytes). Aberrant sialylation results in changes of sialoglycoconjugate structure, its ability to perform biological functions and sialoglycoconjugate half-life. Glycosylation is the most common post-translational modification of proteins in the virus, which not only promotes the formation of specific conformation of viral proteins, but also modulates their interaction with receptors and affects host cell recognition, viral replication and infectivity. Serum total SA concentration increases in some benign and inflammatory conditions, which indicates a lack of specificity and limits their use for early detection and screening of neoplastic diseases. Clinical and diagnostic value of determining the sialoglycoconjugate metabolic indicators, including changes in the content of both SA fractions and specific proteins in various biological fluids and tissues, consists in establishing the causes and mechanisms of biochemical changes in the body in certain diseases. In combination with the measurement of existing markers, they can be used to improve diagnosis, staging and monitoring of therapeutic response in some pathological conditions where the need for specificity is less than for specific diagnostics.

MO736: The Role of Uremic Retention Solutes in the MIA Syndrome in Haemodialysis Subjects

Abstract BACKGROUND AND AIMS In end-stage renal disease (ESRD), the high morbidity and mortality risk for cardiovascular disease (CVD) is not easily explained only on the basis of traditional factors. Among non-traditional ones, malnutrition, inflammation and atherosclerosis/calcification have been described as the ‘MIA syndrome’. METHOD In this study, we evaluated the association between the variation in serum levels of 27 uremic retention solutes plus 6 indexes related to the MIA syndrome processes in dialysis patients. Uremic retention solute levels were detected by the ELISA or using an ultra-performance liquid chromatography—tandem mass spectrometry method. The pro-calcifying, pro-apoptotic and pro-necrotic effects of uremic serum were evaluated in an in vitro model of high-Pi induced calcification in vascular smooth muscle cells (VSMC). RESULTS As expected, we found reciprocal correlations between serum albumin, total cholesterol and phosphate, linking a better nutritional status with higher phosphate levels (r = 0.37, r = 0.40, r = 0.54, respectively; P &amp;lt; 0.05). The relationship between malnutrition and inflammation is highlighted by the negative correlation of serum cholesterol levels with serum alpha-1 acid glycoprotein and IL-6 levels (r = –0.56, r = –0.39, respectively; P &amp;lt; 0.05). These results suggest that the increase in inflammatory mediators is probably higher in malnourished patients, and a better nutritional state seems to correlate with lower inflammatory marker levels. Moreover, we found a significant direct correlation between alpha-1 acid glycoprotein and IL-6 with a correlation coefficient of 0.54 and P &amp;lt; 0.01, indicating that both these uremic toxins might participate in the maintenance of the inflammation. The relation between inflammation and atherosclerosis/calcification is supported by the correlations between IL-6 variations that significantly correlate with both PTX3 and VEGF (r = 0.36 and r = 0.81; P &amp;lt; 0.05) and with VSMC in vitro high-Pi induced calcification (r = 0.66; P &amp;lt; 0.01). Thus, IL-6, a regulator of acute phase protein synthesis, seems to be related to CVD markers (PTX3 and VEGF) and in vitro calcification, two robust indexes of increased cardiovascular risk. In addition, the Kyn/Try ratio directly correlates with serum FGF23 levels with a correlation coefficient r of 0.60 and P &amp;lt; 0.01. Regarding atherosclerosis/calcification, we found that PTX3, TMAO, IS, myoglobin and FGF23 correlate with each other in several combinations, reflecting the elevated cardiovascular risk present in ESRD. PTX3 shows a trend towards a direct correlation with TMAO (r = 0.37 and P &amp;lt; 0.05), and IS shows a trend towards a direct correlation both with TMAO, FGF23 and myoglobin (r = 0.46, r = 0.45 and r = 0.42; P &amp;lt; 0.05). Moreover, IS and TMAO correlate also with two processes strictly related to VSMC calcification, such as apoptosis and necrosis (IS: apoptosis r = 0.69 and necrosis r = 0.47; P &amp;lt; 0.05; TMAO: apoptosis r = 0.42 and necrosis r = 0.40 with P &amp;lt; 0.05). Finally, VEGF shows a robust correlation with in vitro calcification (r = 0.74; P &amp;lt; 0.01). CONCLUSION Among all the correlations found between uremic toxin variations in dialysis patients, IL-6 seems to have a central role correlating with malnutrition and several CV markers together with vascular calcification (VC). This might be explained by the characteristics of IL-6 being contemporary an inflammatory and a CVD marker in ESRD. On the other hand, IS has a potential role in VC, suggesting a central role of the uremic milieu in MIA syndrome development. Therefore, there is an urgent need to find a more efficient dialysis treatment to improve the clearance of uremic retention solutes in order to try to ameliorate CV outcomes in ESRD patients.

Дослідження цитокінового спектру ротової рідини хворих із генералізованим пародонтитом на тлі метаболічного синдрому

The purpose of the study was to study the state of cytokine regulation of oral fluid in patients with generalized periodontitis and metabolic syndrome. Materials and methods. For this study, 3 groups of surveys were formed. The main group included 30 people with generalized periodontitis on the background of metabolic syndrome; 30 people with generalized periodontitis, without somatic pathology, formed a comparison group. The obtained results were compared with the data of 20 practically healthy individuals with intact periodontium who were included in the control group. The content of pro-inflammatory cytokines IL-1β, IL-6, TNF-α and anti-inflammatory cytokines IL-4, TGF-β1 in the oral fluid of the study groups was determined by solid-phase enzyme-linked immunosorbent assay. Results and discussion. According to the research, on average, the highest levels of pro-inflammatory cytokines (IL-1β, IL-6, TNF-α) were observed in patients with periodontal disease on the background of metabolic syndrome. We investigated increase in the concentration of proinflammatory IL-1β. The average value of IL-6 in the oral fluid of patients with metabolic syndrome exceeded this figure in persons not burdened with somatic pathology by 1.3 times, the difference with healthy individuals was more significant: the indicators differed by 2 times. That can be considered an immune response to the inflammatory process in periodontal tissues. The next stage is the beginning of the cytokine cascade, which is characterized by increased production of IL-6 and TNF-α – inducers of acute phase protein synthesis. TNF-α causes an increase in the number of free radicals and can lead to intensification of apoptosis. Due to the fact that anti-inflammatory IL-4 blocks the induced expression of pro-inflammatory IL-6 and TNF-α, a decrease in its level in oral fluid can be considered an unfavorable factor in the course of inflammatory-dystrophic periodontal lesions in patients with syndrome X. Given that TGF-β1 is an immunosuppressive factor, a decrease in its concentration indicates a deficiency of local factors of immune protection in patients with periodontal disease on the background of metabolic syndrome. Conclusion. Patients with metabolic syndrome and periodontal disease have significant disorders of cytokine regulation, which are complicated by age: expression of proinflammatory IL-1β, IL-6, TNF-α on the background of reduced anti-inflammatory cytokines IL-4 and TGF-β1. Such changes in cytokine homeostasis indicate chronic inflammation, insufficient efficiency of regenerative processes in tooth-retaining tissues, and, as a consequence, lead to a more severe course of periodontal disease in people with metabolic syndrome

Clinical and diagnostic significance of sialic acids determination in biological material

Sialic acids (SA) are derivatives of neuraminic acid; they are located at the terminal position in the chains of monosaccharide residues of various glycoconjugates. SA play a dual role, they either mask recognition sites, or, on the contrary, represent biological targets that can be recognized by receptor proteins and serve as ligands. The desialylation/sialylation processes can be viewed as a dynamic modification regulated by sialyltransferases and sialidases in response to external or internal stimuli. This review describes the structural and functional diversity and the potential use of SA fractions as biomarkers for various pathological conditions. Almost any extreme effects on the body and inflammatory processes lead to an increase in the level of both total and free SA in the blood and tissues. Possible reasons for the increase of sialoglycoconjugate metabolism indicators in biological material include activation of the hepatocyte synthesis and secretion of various acute-phase proteins, many of which are sialoglycoproteins, violation of the membrane integrity and destruction of body cells, and also high activity of sialidases (neurominidases) and sialyltransferases. Most acute and chronic liver diseases are characterized by the decrease in the total level of SA in the blood serum (because many plasma proteins are synthesized and glycosylated in hepatocytes). Aberrant sialylation results in changes of sialoglycoconjugate structure, its ability to perform biological functions and half-life. Glycosylation is the most common post-translational modification of proteins in the virus, which not only promotes the formation of specific conformation of viral proteins, but also modulates their interaction with receptors and affects host cell recognition, viral replication and infectivity. Serum total SA concentration increases in some benign and inflammatory conditions, which indicates a lack of specificity and limits their use for early detection and screening of neoplastic diseases. Nevertheless, determining blood SA level and measuring concentration of existing biomarkers can be used to improve diagnostic indicators, to stage and monitor therapeutic response in some types of cancer, when the need for specificity is less than for diagnosis. Clinical and diagnostic value of determining the sialoglycoconjugate metabolic indicators, including changes in the content of both SA fractions and specific proteins in various biological fluids and tissues, lies in establishing the causes and mechanisms of biochemical changes in the body in certain diseases.

Abstract PO-029: Pancreatic cancer-associated cachexia as a 3-stage systemic disease with changes in body composition, tissue-specific wasting across time and alterations in glucose metabolism

Abstract Pancreatic ductal adenocarcinoma (PDAC) is a devastating disease that rapidly deteriorates the organism resulting in &amp;lt;10% 5-years survival in humans. Cancer-associated cachexia (CAC) is a multi-organ complex syndrome that accompanies PDAC in 85% of the cases. CAC is often characterized by the loss of body weight, including loss of muscle and fat tissues. Chronic inflammation, myokines and adipokines (released from muscle and fat, respectively), together with few recent tumor-derived factors, have been shown to collectively induce some of the metabolic changes in peripheral tissues that lead to wasting. Those include the synthesis of acute phase proteins in the liver, lipolysis and browning of the white adipose tissues (WAT), and protein degradation in the skeletal muscle. However, how these changes affect systemic metabolism, such as amino-acid utilization for liver gluconeogenesis, the systemic consequences of increased free fatty acids from lipolysis and their final destination for b-oxidation, or the rewiring of glucose metabolism, are processes not fully understood during cachexia. Here we established a 3-stage model of cachexia progression, including pre-, early- and late-CAC stages, in a doxycycline inducible murine model of PDAC (p48(Cre/+);tetKRAS(LSL/+);p53(fl/fl)), in both genders. We have monitored body weight loss, changes in body composition using DEXA scan, food intake and survival, across time since the start of doxycycline administration (i.e. tumor initiation). We have submitted these mice to metabolic cages aiming to distinguish in which of the 3 stages fat consumption starts, as well as monitored the weight of 8 tissue types (pancreas, liver, iWAT, eWAT, brown adipose tissue, quadriceps, gastrocnemius and soleus) over time. Overall, we have defined pre-CAC as “weight-gaining stage, before body weight peaks”, early-CAC as &amp;lt;10% and late-CAC as &amp;gt;10% of body weight loss, together with specific changes in body composition in each stage, food intake only happening at the very end stage, while all non-tumoral tissues present significant reduced weight at early stages. We have performed metabolomics and lipidomics in all peripheral tissues, aiming to identify changes that occur not only at early- but also at the pre-CAC stages, when pancreatic tumors already weighed more than double of the normal pancreas. In addition, glucose tolerance test analyses showed that tumor-bearing mice cleared the glucose more rapidly than control mice, even at pre-CAC stages, opening new avenues to continue studying glucose metabolism in the periphery such as increased liver gluconeogenesis and peripheral insulin resistance. Together, these results allowed us to establish a murine model to study cachexia in 3 stages, similar to what happens in humans. Furthermore, metabolomic data from the peripheral tissues, tumor interstitial fluid (TIF) and plasma, will allow us to identify the metabolic landscape of the entire organism throughout the progression of the disease, and potentially propose new therapeutic windows to target or prevent wasting in cancer. Citation Format: Blanca Majem, Insia Naqvi, Courtney Dennis, Lucas Dailey, Clary B. Clish, Nada Kalaany. Pancreatic cancer-associated cachexia as a 3-stage systemic disease with changes in body composition, tissue-specific wasting across time and alterations in glucose metabolism [abstract]. In: Proceedings of the AACR Virtual Special Conference on Pancreatic Cancer; 2021 Sep 29-30. Philadelphia (PA): AACR; Cancer Res 2021;81(22 Suppl):Abstract nr PO-029.

Acute-phase protein synthesis: a key feature of innate immune functions of the liver.

The expression of acute-phase proteins (APP's) maintains homeostasis and tissue repair, but also represents a central component of the organism's defense strategy, especially in the context of innate immunity. Accordingly, an inflammatory response is accompanied by significant changes in the serum protein composition, an aspect that is also used diagnostically. As the main site of APP synthesis the liver is constantly exposed to antigens or pathogens via blood flow, but also to systemic inflammatory signals originating either from the splanchnic area or from the circulation. Under both homeostatic and acute-phase response (APR) conditions the composition of APP's is determined by the pattern of regulatory mediators derived from the systemic circulation or from local cell populations, especially liver macrophages. The key regulators mentioned here most frequently are IL-1β, IL-6 and TNF-α. In addition to a variety of molecular mediators described mainly on the basis of in vitro studies, recent data emphasize the in vivo relevance of cellular key effectors as well as molecular key mediators and protein modifications for the regulation and function of APP's. These are aspects, on which the present review is primarily focused.

Characterization of toxicological effects of complex nano-sized metal particles using in vitro human cell and whole blood model systems.

Metal oxide fumes form at high temperatures, for instance, during welding or firing ammunition. Inhalation exposure to high levels of airborne metal oxide particles can cause metal fume fever, cardiovascular effects, and lung damage in humans, but the associated underlying pathological mechanisms are still not fully understood. Using human alveolar epithelial cells, vascular endothelial cells, and whole blood model systems, we aimed to elucidate the short-term effects of well-characterized metal particles emitted while firing pistol ammunition. Human lung epithelial cells exposed to gunshot smoke particles (0.1-50 μg/ml) produced reactive oxygen species (ROS) and pro-inflammatory cytokines (interleukin 8 (IL-8), granulocyte-macrophage colony-stimulating factor (GM-CSF)) that activate and recruit immune cells. Particles comprising high copper (Cu) and zinc (Zn) content activated human endothelial cells via a non-ROS-mediated mechanism that triggered immune activation (IL-8, GM-CSF), leukocyte adhesion to the endothelium (soluble intercellular adhesion molecule 1 (sICAM-1)), and secretion of regulators of the acute-phase protein synthesis (interleukin 6 (IL-6)). In human whole blood, metal oxides in gunshot smoke demonstrated intrinsic properties that activated platelets (release of soluble cluster of differentiation 40 ligand (sCD40L), platelet-derived growth factor B-chain homodimer(PDGF-BB), and vascular endothelial growth factor A (VEGF-A)) and blood coagulation and induced concomitant release of pro-inflammatory cytokines from blood leukocytes that further orchestrate thrombogenesis. The model systems applied provide useful tools for health risk assessment of particle exposures, but more studies are needed to further elucidate the mechanisms of metal fume fever and to evaluate the potential risk of long-term cardiovascular diseases.

Serum Level of Ferritin and Fibrinogen as Prognostic Indicator for Acute Ischemic Stroke

Abstract: Background: Stroke is the main cause of disability worldwide, the second common cause of dementia and the second main cause of death after ischemic heart diseases. Acute phase response proteins i.e. ferritin, fibrinogen and others play an important role in the pathogenesis of ischemic stroke because acute cerebral ischemia triggers interleukin-6 release into cerebrospinal fluid and blood, which is a key mediator of acute phase reaction and induces synthesis of acute phase proteins during ischemia. Aim: This study aims to explore the correlation between serum ferritin and plasma fibrinogen levels and the neurological disability of acute ischemic stroke. Methods: This study was carried out in the Department of Neurology, Benha University from December 2019 to January 2021 to compare serum ferritin and plasma fibrinogen levels between a group of fifty stroke patients and fifty control, then to correlate their levels with clinical outcome in patients Results: Our study revealed that means of serum ferritin and plasma fibrinogen levels were 143.17 ng/ml and 2.61 mg/ml in patients, while in control they were 78.36 ng/ml and 2.0 mg/ml respectively. We also found that high levels of ferritin and fibrinogen among cases were associated with poor outcome, as clarified by GCS and NIHSS scores and by infarct volume. Conclusion: It may be concluded that serum ferritin and plasma fibrinogen are significantly higher in AIS patients, and their elevated levels are associated with early neurological deterioration.List of Abbreviations: AIS (acute ischemic stroke)

Ozone-induced acute phase response in lung versus liver: the role of adrenal-derived stress hormones

ABSTRACT Acute-phase response (APR) is an innate stress reaction to tissue trauma or injury, infection, and environmental insults like ozone (O3). Regardless of the location of stress, the liver has been considered the primary contributor to circulating acute-phase proteins (APPs); however, the mechanisms underlying APR induction are unknown. Male Wistar–Kyoto rats were exposed to air or O3 (1 ppm, 6-hr/day, 1 or 2 days) and examined immediately after each exposure and after 18-hr recovery for APR proteins and gene expression. To assess the contribution of adrenal-derived stress hormones, lung and liver global gene expression data from sham and adrenalectomized rats exposed to air or O3 were compared for APR transcriptional changes. Data demonstrated serum protein alterations for selected circulating positive and negative APPs following 2 days of O3 exposure and during recovery. At baseline, APP gene expression was several folds higher in the liver relative to the lung. O3-induced increases were significant for lung but not liver for some genes including orosomucoid-1. Further, comparative assessment of mRNA seq data for known APPs in sham rats exhibited marked elevation in the lung but not liver, and a near-complete abolishment of APP mRNA levels in lung tissue of adrenalectomized rats. Thus, the lung appears to play a critical role in O3-induced APP synthesis and requires the presence of circulating adrenal-derived stress hormones. The relative contribution of lung versus liver and the role of neuroendocrine stress hormones need to be considered in future APR studies involving inhaled pollutants.

Liver\u2013lung interactions in acute respiratory distress syndrome

Patients with liver diseases are at high risk for the development of acute respiratory distress syndrome (ARDS). The liver is an important organ that regulates a complex network of mediators and modulates organ interactions during inflammatory disorders. Liver function is increasingly recognized as a critical determinant of the pathogenesis and resolution of ARDS, significantly influencing the prognosis of these patients. The liver plays a central role in the synthesis of proteins, metabolism of toxins and drugs, and in the modulation of immunity and host defense. However, the tools for assessing liver function are limited in the clinical setting, and patients with liver diseases are frequently excluded from clinical studies of ARDS. Therefore, the mechanisms by which the liver participates in the pathogenesis of acute lung injury are not totally understood. Several functions of the liver, including endotoxin and bacterial clearance, release and clearance of pro-inflammatory cytokines and eicosanoids, and synthesis of acute-phase proteins can modulate lung injury in the setting of sepsis and other severe inflammatory diseases. In this review, we summarized clinical and experimental support for the notion that the liver critically regulates systemic and pulmonary responses following inflammatory insults. Although promoting inflammation can be detrimental in the context of acute lung injury, the liver response to an inflammatory insult is also pro-defense and pro-survival. A better understanding of the liver–lung axis will provide valuable insights into new diagnostic targets and therapeutic strategies for clinical intervention in patients with or at risk for ARDS.

Acute Phase Proteins and Vitamin D Seasonal Variation in End-Stage Renal Disease Patients.

End-stage renal disease (ESRD) patients are vulnerable to vitamin D deficiency due to impaired renal hydroxylation, low dietary intake and inadequate sun exposure. Vitamin D plays a role in innate and adaptive immunity and its seasonal variation has been linked to mortality. ESRD is associated with inadequate removal of pro-inflammatory cytokines regulating acute phase protein (APP) synthesis. Our aim was to look for associations between lifestyle factors, diet, and vitamin D seasonal variation and their relationship with selected APPs and calcium-phosphate metabolism. The study included 59 ESRD patients treated with maintenance hemodialysis. A 24-hour dietary recall was conducted in the post-summer (November 2018, PS) and post-winter (February/March 2019, PW) period, and blood was collected for the measurements of serum total vitamin D, α1-acid glycoprotein (AGP), C-reactive protein (CRP), albumin, prealbumin (PRE), parathormone, calcium and phosphate. A self-constructed questionnaire gathered information on vitamin D supplementation, sun exposure and physical activity. Higher caloric intake was observed PW compared PS. Less than 15% of participants met the dietary recommendations for energy, protein, fiber, vitamin D and magnesium intake. Vitamin D supplementation was associated with higher serum vitamin D regardless of season. AGP, PRE, albumin, and vitamin D presented seasonal changes (higher values PS). In patients with serum vitamin D below 25 ng/mL, vitamin D seasonal change correlated with CRP and prealbumin change. Phosphate and Ca × P correlated positively with AGP. A low vitamin D serum level could impact the inflammatory process; however, more studies are needed to confirm the relationship.

The effect of feed supplementation with Transcarpathian zeolite (clinoptilolite) on the concentrations of acute phase proteins and cytokines in the serum and hepatic tissue of chickens

The aim of the this study was to determine the effect of different levels of Transcarpathian zeolite (clinoptilolite) on selected indicators of the immune response in chickens by assessing the concentrations of the acute phase proteins haptoglobin, C-reactive protein (CRP), serum amyloid A, transferrin, and alpha-1-acid glycoprotein and the cytokines tumor necrosis factor-α (TNF-α), interferon-γ (IFN-γ), IL-2, and IL-10 in the serum and hepatic tissues of chickens. The study was conducted on 450 one-day-old male Ross 308 chickens. The total rearing period was 42 D. The samples of blood and liver were collected before the start of the study (day 0) and on day 42, after rearing was completed. ELISA kits specific for chicken CRP, haptoglobin, alpha-1-acid glycoprotein, serum amyloid A, transferrin, TNF-α, IFN-γ, IL-2, and IL-10 were used to determine the levels of acute phase proteins and cytokines in the serum and liver homogenates. The results of immunological tests suggest that for long-term maintenance of homeostasis in chickens, the addition of 2% zeolite as a feed additive is most beneficial. The results indicate that 3% clinoptilolite induce production of Th1 pro-inflammatory cytokines, increasing the synthesis of IL-2, IFN-γ, and TNF-α. The high concentration of IL-10 after the use of zeolite in conjunction with the high concentration of IL-2, TNF-α, and IFN-γ indicates a reduction in the intensity of inflammatory processes, the enhancement of the humoral immune response, and the simultaneous inhibition of the production of Th1-type cytokines. The increase of CRP concentration in conjunction with high concentrations of pro- and anti-inflammatory cytokines in the birds from the group receiving 3% clinoptilolite demonstrates indicates that it can influence the development of local inflammatory processes and enhance immune regulation in birds. Our research has shown that clinoptilolite influences on an increase in birds' resistance to infection, as confirmed by clinical observations and anatomopathological examination and by the increase in the synthesis of acute phase proteins with immunoregulatory properties.

Peculiarities of hemorrhagic vasculitis coexisting with liver steatosis

Our previous study revealed that 73.9 % of patients with adult-onset hemorrhagic vasculitis (HV) - IgA vasculitis have sonographic features of liver involvement and 61.3% of patients have gallbladder pathology, whereas liver functional tests were within normal limits. This study aimed to determine the clinical characteristics of adult-onset HV coexisting with liver steatosis (LS) as a first step of nonalcoholic non-alcoholic fatty liver disease. Methods. We retrospectively reviewed the medical records of 50 adult-onset HV patients, 20 were male and 30 female with a mean age of 46.0±2.0 years. Clinical, echocardiography, electrocardiography, abdominal sonogram and routine laboratory tests data (complete blood count, liver and renal function tests, C-reactive protein (CRP), glucose, uric acid, fibrinogen, serum protein electrophoresis) were analyzed. Patients were divided into two groups in order to evaluate the impact of LS on clinical course of adult-onset HV. In the main group with LS there were 15 male and 16 female with a mean age of 49.4±2.5 years, duration of treatment was 11.5±0.7 days). The control group without LS comprised five male and 14 female (39.0±3.0 years) with treatment duration 12.3±1.2 days. For normally distributed data, means for the two groups were compared using Student's t-test; Pearson's correlation was calculated to examine the association between two continuous variables. Results. In adult-onset HV patients with LS, inflammatory responses with elevated serum CRP level and leukocytosis have been observed. High functional activity of hepatocytes with increased acute-phase protein synthesis (CRP 2.2±0.37 vs 0.71±0.47, р&lt;0.05), uric acid (0.35±0.02 vs 0.28±0.02 mcmol/l, р&lt;0.05), and leakage of alanine aminotransferase (0.33±0.05 vs 0.21±0.02 mmol/g/l, р&lt;0.05) from the mitichondrias of hepatocytes into the blood occurs following a hepatocellular injury. Adult-onset HV patients with LS had a higher frequency of gallbladder disorders (OR 3.43), and significantly larger sizes of left and right ventricles, left atrial and aortic root diameters (all р&lt;0,05).

Invited Review: Adaptations of protein and amino acid metabolism to heat stress in dairy cows and other livestock species

ABSTRACT The reduction of productivity and efficiency of nutrient utilization in heat-stressed dairy cattle is mediated by physiological and molecular alterations. Heat stress impairs the digestive and absorptive capacity of the gastrointestinal tract, and this effect is independent of nutrient intake. The shift in blood flow away from the splanchnic tissues to the skin reduces nutrient delivery to the small intestine and increases mucosal cell damage. The translocation of individual AA and the availability of total and individual AA to peripheral tissues is impaired during heat stress. In addition, heat stress alters tissue-specific demands for individual AA, protein synthesis, and whole-body protein degradation. For example, heat stress and the associated systemic inflammatory response alters the use of AA in metabolic tissues, increasing their demand. Glutamate, Gln, Arg, and Leu appear to ameliorate the inflammatory state of the intestine by preventing villi atrophy and improving synthesis of tight junction proteins and the intestinal barrier function. Moreover, heat stress increases the synthesis of acute phase proteins and heat-shock proteins and appears to promote hepatic removal of individual AA to sustain augmented protein synthesis. The fractional rates of extraction of total AA that reach the liver increase during systemic inflammation. An increase in intestinal and hepatic utilization of AA alters the net supply and the pattern of AA available to peripheral tissue. Whole-body protein breakdown and synthesis of urea increases in heat-stressed animals. This result suggests that AA are mobilized to meet the animal needs. Finally, local effects of heat stress may impair the synthesis of proteins in the mammary glands and reduce α-S2 casein and whey fractions, milk protein content, and milk protein yield, probably via reduced signaling activity. Collectively, heat stress alters the use of AA in absorptive and postabsorptive tissues, reducing AA availability to sustain animal production.

Nutritional Status of Elderly Patients after Coronary Artery Bypass Surgery.

Surgical trauma can result in immobilization of biological material, degradation of muscle proteins, synthesis of acute-phase proteins in the liver, occurrence of catabolism phase and anabolism simultaneously, and as a consequence weight loss and nutritional deficiencies. The aim of this study was to assess the nutritional status of patients with ischemic heart disease subjected to coronary artery bypass surgery and physical activity and postoperative complications. The analysis among 96 men included total number of lymphocytes (TNL), body mass index (BMI), case history of a patient and results of laboratory tests. The activities of daily living (ADL) and the mini nutritional assessment (MNA) questionnaires were used. According to TNL, before the procedure malnutrition occurred in 46% of patients. BMI revealed overweight in 62.5% and obesity in 26.0%. After the surgery, no changes were observed. According to MNA, 59% of patients before the surgery were at risk of malnutrition. After the operation, the number of people at risk of malnutrition increased by 50% (p < 0.0001). The correlation was noted between BMI and patients’ efficiency in the fifth day after the surgery (p = 0.0031). Complications after the surgery occurred in 35.4% of patients. After the surgery, the risk of malnutrition increased, decreased activity and complications occurred more frequently in people with underweight, obesity, and overweight than in people with normal BMI.

CHANGES IN CERTAIN ACUTE PHASE PROTEINS OF COMMON CARP (Cyprinus carpio) EXPOSED TO ORGANOPHOSPHATE INSECTICIDES

The acute phase response (APR) is a nonspecific reaction of fish to disturbances in homeostasis. The aim of present study was to investigate quantitative changes that occur in the concentration of acute phase proteins (APPs) in the blood of commercial size common carp ( Cyprinus carpio L. ) exposed to organophosphate insecticides within the month of April during ameliorative activities. Parameters examined were fibrinogen (Fib), ceruloplasmin (Cp) as a positive APPs and albumin (Alb) as a negative APP. Histological sections of the hepatopancreas and kidneys from 25 fish have been examined. The hepatopancreas was chosen for this investigation as it is the primary site of acute phase protein synthesis. APP parameters plasma fibrinogen ( P <0.05) registered a significantly increased and albumin ( P <0.05) exhibited statistically declined in treated group. Based on the data acquired in this study, it was concluded that, the carp do not exhibit a strong APP synthesis during the early stages of an APR after spraying with organophosphate insecticides. The results from this study show that t he concentrations of fibrinogen are not significantly increase as well as the levels of ceruloplasmin remained unchanged.

Zinc and Sepsis.

Sepsis, defined as a “life-threatening organ dysfunction caused by a dysregulated host-response to infection” is a major health issue worldwide and still lacks a fully elucidated pathobiology and uniform diagnostic tests. The trace element zinc is known to be crucial to ensure an appropriate immune response. During sepsis a redistribution of zinc from serum into the liver has been observed and several studies imply a correlation between zinc and sepsis outcome. Therefore the alterations of zinc concentrations in different tissues might serve as one part of the host’s defense mechanism against pathogens during sepsis by diverse mechanisms. It has been suggested that zinc is involved in nutritional immunity, acts as a hepatoprotective agent, or a differentiation signal for innate immune cells, or supports the synthesis of acute phase proteins. Further knowledge about these events could help in the evaluation of how zinc could be optimally applied to improve treatment of septic patients. Moreover, the changes in zinc homeostasis are substantial and correlate with the severity of the disease, suggesting that zinc might also be useful as a diagnostic marker for evaluating the severity and predicting the outcome of sepsis.

Effects of feed intake restriction during late pregnancy on the function, anti-oxidation capability and acute phase protein synthesis of ovine liver.

ObjectiveAn experiment was conducted to investigate the effects of feed intake restriction during late pregnancy on the function, anti-oxidation capability and acute phase protein synthesis of ovine liver.MethodsEighteen time-mated ewes with singleton fetuses were allocated to three groups: restricted group 1 (RG1, 0.18 MJ ME/kg W0.75 d, n = 6), restricted group 2 (RG2, 0.33 MJ ME/kg W0.75 d), n = 6) and a control group (CG, ad libitum, 0.67 MJ ME/kg W0.75 d, n = 6). The feed restriction period was from 90 days to 140 days of pregnancy.ResultsThe ewe’s body weight, liver weights, water, and protein content of liver in the restricted groups were reduced compared with the CG group (p<0.05), but the liver fat contents in the RG1 group were higher than those of the CG group (p<0.05). The increased hepatic collagen fibers and reticular fibers were observed in the restricted groups with the reduction of energy intake. The concentrations of nonesterified free fatty acids in the RG1 and RG2 groups were higher than those of the CG group with the reduction of energy intake (p<0.05), but there were decreased concentrations of lipoprotein lipase and hepatic lipase in both restricted groups compared with the CG group (p<0.05). In addition, the increased concentrations of β-hydroxybutyric acid, triglycerides, malondialdehyde, total antioxidant capacity and activities of superoxide dismutase activity and catalase were found in the RG1 group, and the concentrations of cholinesterase in the RG1 group were reduced compared with the CG group (p<0.05). For the concentrations of acute phase proteins, the C-reactive protein (CRP) in the RG1 group were reduced compared with the CG group, but there were no differences in haptoglobin relative to the controls (p>0.05).ConclusionThe fat accumulation, increased hepatic fibrosis, antioxidant imbalance and modified synthesis of acute phase proteins were induced in ewe’s liver by maternal malnutrition during late pregnancy, which were detrimental for liver function to accommodate pregnancy.