Obesity and polycystic ovary syndrome influence on intestinal permeability at fasting, and modify the effect of diverse macronutrients on the gut barrier.

Women with the extremely prevalent polycystic ovary syndromegather multiple cardiovascular risk factors and chronic subclinical inflammation. Interactions between diet, adiposity, and gut microbiota modulate intestinal permeabilityand bacterial product translocation, and may contribute to the chronic inflammation process associated with the polycystic ovary syndrome. In the present study, we aimed to address the effects of obesity, functional hyperandrogenism, and diverse oral macronutrients on intestinal permeabilityby measuring circulating markers of gut barrier dysfunction and endotoxemia. Participants included 17 non-hyperandrogenic control women, 17 women with polycystic ovary syndrome, and 19 men that were submitted to glucose, lipid, and protein oral loads. Lipopolysaccharide-binding protein, plasma soluble CD14, succinate, zonulin family peptide, and glucagon-like peptide-2 were determined at fasting and after oral challenges. Macronutrient challenges induced diverse changes on circulating intestinal permeabilitybiomarkers in the acute postprancial period, with lipids and proteins showing the most unfavorable and favorable effects, respectively. Particularly, lipopolysaccharide-binding protein, zonulin family peptide, and glucagon-like peptide-2 responses were deregulated by the presence of obesity after glucose and lipid challenges. Obese subjects showed higher fasting intestinal permeabilitybiomarkers levels than non-obese individuals, except for plasma soluble CD14. The polycystic ovary syndromeexacerbated the effect of obesity further increasing fasting glucagon-like peptide-2, lipopolysaccharide-binding protein, and succinate concentrations. We observed specific interactions of the polycystic ovary syndromewith obesity in the postprandial response of succinate, zonulin family peptide, and glucagon-like peptide-2. In summary, obesity and polycystic ovary syndromemodify the effect of diverse macronutrients on the gut barrier, and alsoinfluence intestinal permeabilityat fasting,contributing to the morbidity of functional hyperandrogenism by inducing endotoxemia and subclinical chronic inflammation.

Concentrations of selected immunological parameters in the serum and processing fluid of suckling piglets and the serum and colostrum of their mothers.

BACKGROUND: Blood sampling from neonatal piglets is related to multiple disadvantages. Therefore, a new, alternative matrix is required to assess piglets' early immune status efficiently. The present study aimed to assess the usefulness of processing fluid for determining selected piglets' immune parameters. 264 pigs - 31 sows, 146 male piglets, and 87 female piglets from commercial indoor farrow-to-finish pig herd were included in this study. 264 serum, 31 colostrum, and 146 processing fluid samples were collected. Serum was collected from all animals, colostrum was collected from sows, and processing fluid was collected from male piglets only. Using commercial ELISA tests, the concentration of various immunoglobulins, cytokines, and acute phase proteins was assessed in each matrix. Statistical analyses were employed to determine differences in the concentration of measured indices between piglets' serum and processing fluid and correlations in the concentration of tested indices between particular sets of matrices. RESULTS: Statistical analyses did not reveal significant differences in the IgG, IgA, IL-1ß, IL-4, IL-6, and IFN-γ concentration between piglets' serum and processing fluid (p > 0.05). A positive correlation (p < 0.05) regarding the concentration of some indices between processing fluid and samples collected from sows was also observed. CONCLUSIONS: Processing fluid can be considered a promising alternative to blood for assessing some immunological indices in piglets, such as IgG, IgA, IL-1ß, IL-4, IL-6, and IFN-γ, and, possibly, in the indirect assessment of some indices in lactating sows, including IgA, IL-1ß, IL-4, IL-6, IL-8, IFN-γ, or Pig-MAP.

Lipopolysaccharide binding protein resists hepatic oxidative stress by regulating lipid droplet homeostasis.

Oxidative stress-induced lipid accumulation is mediated by lipid droplets (LDs) homeostasis, which sequester vulnerable unsaturated triglycerides into LDs to prevent further peroxidation. Here we identify the upregulation of lipopolysaccharide-binding protein (LBP) and its trafficking through LDs as a mechanism for modulating LD homeostasis in response to oxidative stress. Our results suggest that LBP induces lipid accumulation by controlling lipid-redox homeostasis through its lipid-capture activity, sorting unsaturated triglycerides into LDs. N-acetyl-L-cysteine treatment reduces LBP-mediated triglycerides accumulation by phospholipid/triglycerides competition and Peroxiredoxin 4, a redox state sensor of LBP that regulates the shuttle of LBP from LDs. Furthermore, chronic stress upregulates LBP expression, leading to insulin resistance and obesity. Our findings contribute to the understanding of the role of LBP in regulating LD homeostasis and against cellular peroxidative injury. These insights could inform the development of redox-based therapies for alleviating oxidative stress-induced metabolic dysfunction.

The acute phase reactant orosomucoid-2 directly promotes rheumatoid inflammation.

Acute phase proteins involved in chronic inflammatory diseases have not been systematically analyzed. Here, global proteome profiling of serum and urine revealed that orosomucoid-2 (ORM2), an acute phase reactant, was differentially expressed in rheumatoid arthritis (RA) patients and showed the highest fold change. Therefore, we questioned the extent to which ORM2, which is produced mainly in the liver, actively participates in rheumatoid inflammation. Surprisingly, ORM2 expression was upregulated in the synovial fluids and synovial membranes of RA patients. The major cell types producing ORM2 were synovial macrophages and fibroblast-like synoviocytes (FLSs) from RA patients. Recombinant ORM2 robustly increased IL-6, TNF-α, CXCL8 (IL-8), and CCL2 production by RA macrophages and FLSs via the NF-κB and p38 MAPK pathways. Interestingly, glycophorin C, a membrane protein for determining erythrocyte shape, was the receptor for ORM2. Intra-articular injection of ORM2 increased the severity of arthritis in mice and accelerated the infiltration of macrophages into the affected joints. Moreover, circulating ORM2 levels correlated with RA activity and radiographic progression. In conclusion, the acute phase protein ORM2 can directly increase the production of proinflammatory mediators and promote chronic arthritis in mice, suggesting that ORM2 could be a new therapeutic target for RA.

Can neutrophil gelatinase-associated lipocalin be a novel and efficient marker to predict the clinical course of acute pancreatitis?

OBJECTIVE: This study aimed to determine the value of serum Neutrophil Gelatinase-Associated Lipocalin (NGAL) levels to predict the severity of the disease and to identify its correlation with White Blood Cell (WBC), C-reactive protein (CRP), and high-sensitivity C-reactive protein (hs-CRP) levels in acute pancreatitis (AP). PATIENTS AND METHODS: The study sample included 86 AP-diagnosed patients in the study group and 77 age- and gender-matched healthy volunteers with no comorbidity in the control group. The WBC, CRP, hs-CRP, and NGAL levels were examined at the time and 24 hours after diagnosis. RESULTS: Between the control group and the study group, a significant difference with and without necrosis in terms of NGAL averages (p=0.003) at the time of admission was observed. The mean level of the 24th-hour NGAL in the study group with necrosis (132.7±11.7 ng/ml) was found to be higher than the mean of the 24th-hour NGAL (117.5±22.6 ng/ml) in the study group without necrosis (p=0.032). Additionally, a significant difference was observed between the control group and the study group with and without necrosis in terms of CRP averages evaluated at admission. When the correlation of NGAL levels with WBC, CRP, and hs-CRP levels at the admission (r=0.224, p=0.038) and at the 24th h (r=0.389, p<0.001) are evaluated, weak correlations between NGAL and WBC levels were identified, but no correlation between NGAL and CRP and hs-CRP levels were observed. CONCLUSIONS: The usability of serum NGAL levels to predict the development of necrotizing pancreatitis in the early period was evaluated. Serum NGAL levels were found to be higher in the study group than in the control group, but there was no statistically significant difference between the mean values of 0th and 24th h NGAL values in any of the groups with/without pancreatic necrosis and the total study group was observed. More research is needed on the subject, with larger sampling sizes.

LCN2: Versatile players in breast cancer.

Lipocalin 2 (LCN2) is a secreted glycoprotein that is produced by immune cells, including neutrophils and macrophages. It serves various functions such as transporting hydrophobic ligands across the cellular membrane, regulating immune responses, keeping iron balance, and fostering epithelial cell differentiation. LCN2 plays a crucial role in several physiological processes. LCN2 expression is upregulated in a variety of human diseases and cancers. High levels of LCN2 are specifically linked to breast cancer (BC) cell proliferation, apoptosis, invasion, migration, angiogenesis, immune regulation, chemotherapy resistance, and prognosis. As a result, LCN2 has gained attention as a potential therapeutic target for BC. This article offered an in-depth review of the advancement of LCN2 in the context of BC occurrence and development.

Neutrophil Gelatinase-Associated Lipocalin in Peritoneal Dialysis-Related Peritonitis: Correlation with White Blood Cells over Time and a Possible Role as the Outcome Predictor.

INTRODUCTION: The present study aimed to monitor peritoneal neutrophil gelatinase-associated lipocalin (pNGAL) during peritonitis episodes and to enhance its diagnostic value by evaluating pNGAL at scheduled times in parallel with white blood cell (WBC) count. In addition, we investigated possible correlations between pNGAL and the etiology of peritonitis, evaluating it as a possible marker of the clinical outcome. METHODS: Twenty-two patients with peritoneal dialysis (PD)-related peritonitis were enrolled. Peritonitis was divided into Gram-positive, Gram-negative, polymicrobial, and sterile. WBC count and neutrophil gelatinase-associated lipocalin (NGAL) in PD effluent were measured at different times (days 0, 1, 5, 10, 15, and/or 20 and 10 days after antibiotic therapy discontinuation). NGAL was measured by standard quantitative laboratory-based immunoassay and by colorimetric NGAL dipstick (NGALds) (dipstick test). RESULTS: We found strong correlations between peritoneal WBC, laboratory-based NGAL, and NGALds values, both overall and separated at each time point. On day 1, we observed no significant difference in WBC, both NGALds (p = 0.3, 0.9, and 0.2) between Gram-positive, Gram-negative, polymicrobial, and sterile peritonitis. No significant difference has been found between de novo versus relapsing peritonitis for all markers (p > 0.05). We observed a parallel decrease of WBC and both NGAL in patients with favorable outcomes. WBC count and both pNGAL resulted higher in patients with negative outcomes (defined as relapsing peritonitis, peritonitis-associated catheter removal, peritonitis-associated hemodialysis transfer, peritonitis-associated death) at day 10 (p = 0.04, p = 0.03, and p = 0.05, respectively) and day 15 (p = 0.01, p = 0.04, and tendency for p = 0.005). There was a tendency toward higher levels of WBC and NGAL in patients with a negative outcome at day 5. No significant difference in all parameters was proven at day 1 (p = 0.3, p = 0.9, p = 0.2) between groups. CONCLUSION: This study confirms pNGAL as a valid and reliable biomarker for the diagnosis of PD-peritonitis and its monitoring. Its trend is parallel to WBC count during peritonitis episodes, in particular, patients with unfavorable outcomes.

Acute phase protein concentration in pharyngeal swabs from clinically healthy commercial dairy calves.

BACKGROUND: Early diagnosis of disease in calves is crucial for fast recovery and prudent use of antibiotics. The serum concentration of acute phase proteins (APPs) is up- or downregulated in response to tissue injury and has been studied widely in human medicine. There is growing interest in using APPs as biomarkers for different diseases and as a tool to initiate and monitor treatment in veterinary medicine as well. The concentration of APPs in saliva in healthy calves has not been established and the use of pharyngeal swabs offers a non-invasive alternative to blood sampling. Pharyngeal swabs, tracheal aspirate (TA) and blood samples were collected from 84 clinically healthy commercial dairy calves and analyzed for the APPs serum amyloid A (SAA), haptoglobin (Hp) and lipopolysaccharide binding protein (LBP). RESULTS: We found detectable concentrations of SAA, Hp and LBP in pharyngeal swabs from calves, as well as in TA and serum. There were no biologically interesting correlations between the SAA concentrations in serum and TA or pharyngeal swabs. This also applied to Hp and LBP concentrations in serum and TA or pharyngeal swabs. CONCLUSIONS: SAA, Hp and LBP can be measured in saliva and TA from calves, but there was no correlation between the specific APP concentration in serum and pharyngeal swab or TA. There was a considerable technical variation in the sampling method for both pharyngeal swab and TA, and further validation of the methods is needed.

The Effects of Stress on Hippocampal Neurogenesis and Behavior in the Absence of Lipocalin-2.

Lipocalin-2 (LCN2) is an acute phase protein able to bind iron when complexed with bacterial siderophores. The recent identification of a mammalian siderophore also suggested a physiological role for LCN2 in the regulation of iron levels and redox state. In the central nervous system, the deletion of LCN2 induces deficits in neural stem cells proliferation and commitment, with an impact on the hippocampal-dependent contextual fear discriminative task. Additionally, stress is a well-known regulator of cell genesis and is known to decrease adult hippocampal cell proliferation and neurogenesis. Although voluntary running, another well-known regulator of neurogenesis, is sufficient to rescue the defective hippocampal neurogenesis and behavior in LCN2-null mice by promoting stem cells' cell cycle progression and maturation, the relevance of LCN2-regulated hippocampal neurogenesis in response to stress has never been explored. Here, we show a lack of response by LCN2-null mice to the effects of chronic stress exposure at the cellular and behavioral levels. Together, these findings implicate LCN2 as a relevant mediator of neuronal plasticity and brain function in the adult mammalian brain.

Investigations of leukocyte and inflammatory markers in pregnancies complicated by preeclampsia.

OBJECTIVES: Preeclampsia is a frequent and potentially fatal pregnancy complication. It can be challenging to make a timely diagnosis. Identifying clinically useful biochemical markers would be a remedying tool to support the diagnosis of preeclampsia. The aim was to investigate differential cell counts and acute phase reactants as diagnostic markers of preeclamptic third-trimester pregnancies and in relation to pregnancy term, gravidity and the severity of hypertension. METHODS: Based on a cohort of 421 pregnant women, we included 174 participants (case n = 84, control n = 90) during the third trimester. Peripheral blood was sampled to measure differential white blood cell counts and acute phase reactants on the day of inclusion. RESULTS: The neutrophil-to-lymphocyte ratio and plasma haptoglobin levels were significantly increased in healthy pregnancies compared with preeclamptic pregnancies. Plasma ferritin levels and albumin levels were respectively increased and decreased in cases of preeclampsia compared with controls. Albumin was specific among multigravida. Plasma transferrin and high-sensitivity C-reactive protein (hs-CRP) levels were significantly decreased and increased, respectively, in cases with preterm preeclampsia compared with term preeclampsia. CONCLUSION: Plasma ferritin and albumin levels reflected higher inflammation in cases with preeclampsia compared with healthy pregnancies; the same did plasma transferrin and hs-CRP levels in preterm versus term preeclampsia. When considering the normal ranges plasma albumin and hs-CRP levels identified preeclamptic from healthy third-trimester pregnancies and preterm from term preeclampsia cases, respectively, with near-acceptable diagnostic performances. Further validation of the diagnostic value will require larger sample-sized studies with paired plasma and serum samples.

Astrocyte lipocalin-2 modestly effects disease severity in a mouse model of multiple sclerosis while reducing mature oligodendrocyte protein and mRNA expression.

Roles for lipocalin-2 (LCN2, also referred to as neutrophil gelatinase associated lipocalin, NGAL) in the progression of disease in multiple sclerosis and its animal models have been reported; however, the importance of astrocyte-derived LCN2, a major source of LCN2, have not been defined. We found that clinical scores in experimental autoimmune encephalomyelitis (EAE) were modestly delayed in mice with conditional knockout of LCN2 from astrocytes, associated with a small decrease in astrocyte GFAP expression. Immunostaining and qPCR of spinal cord samples showed decreased oligodendrocyte proteolipid protein and transcription factor Olig2 expression, but no changes in PDGFRα expression. These results suggest astrocyte LCN2 contributes to early events in EAE and reduces damage to mature oligodendrocytes at later times.

Evaluation of Oxidative Status, Cytokines, Acute Phase Proteins and Cardiac Damage Markers in Sheep Naturally Infected with Babesia ovis.

PURPOSE: Babesiosis is a tick-borne disease caused by protozoon species in the Babesia genus of the Babesiadae family. The systemic inflammatory response induced by infection is considered to be an important feature of the pathophysiology of ovine babesiosis. In this study, it was aimed to determine serum oxidative status, levels of some cytokines, acute phase proteins and heart damage markers in babesiosis infection. MATERIALS AND METHODS: A sample of 40 sheep was used for this purpose, of which 20 were healthy and 20 were infected with Babesia ovis. Babesia infection was diagnosed from Giemsa-stained peripheral blood smears. Infection was also confirmed by the polymerase chain reaction (PCR). Sera from blood samples was tested for oxidative stress parameters (malondialdehyde [MDA], total antioxidant status [TAS], superoxide dismutase [SOD], catalase [CAT] and glutathione peroxidase [GPx]), cytokines (interleukins IL-6, IL-1ß, IL-10, tumour necrosis factor α (TNF-α) and interferon-ϒ [IFN-ϒ]), acute-phase proteins (C-reactive protein [CRP], serum amyloid A [SAA] and haptoglobin [Hp]) and specific (troponin I [cTnI], creatine kinase-MB [CK-MB]) and nonspecific (lactate dehydrogenase [LDH], aspartate transaminase [AST]) cardiac damage markers. RESULTS: MDA, SOD, CAT, Hp, TAS, IL-6, IL-10, TNF-α, IL-1ß, INF-γ, AST, LDH, CK-MB mass and troponin I values were higher in the patient group than in the healthy group (P < 0.05). However, there was not found to be a statistical difference between the healthy and patient groups in terms of GPx, SAA and CRP values (P > 0.05). CONCLUSIONS: It can be stated that serum levels of oxidative stress, some acute phase proteins and cardiac damage markers may increase in naturally infected sheep with babesiosis.

Effect of short-term abomasal corn starch infusions on postruminal fermentation and blood measures.

It is possible that some of the systemic responses to subacute ruminal acidosis (SARA) may be caused by increased intestinal starch fermentation. The objective of this experiment was to evaluate the effect of abomasal infusion of up to 3 g of corn starch/kg body weight (approximately 1.6 kg of starch/d) on fecal measures of fermentation, plasma acute phase proteins, and white blood cell populations. Six ruminally cannulated cows in late lactation were randomly assigned to duplicate 3 × 3 Latin squares with 21-d periods. Cows were fed a 20.6% starch TMR twice daily and during the last 7 d of each period cows were abomasally infused with corn starch at 0 (CON), 1 (ST1), or 3 (ST3) g/kg body weight split into 2 bolus infusions, provided every 12 h. Fecal samples were collected at 0, 6, 12, and 18 h following feeding on d 21 and were analyzed for pH, VFA, lactic acid, and lipopolysaccharide (LPS). Composite fecal samples were used to estimate apparent total-tract nutrient digestibility using undigested neutral detergent fiber as an internal marker. Blood samples were collected at 0 and 6 h relative to feeding on d 14, 18, and 21 of each period. Concentrations of haptoglobin and serum amyloid A in plasma were measured in all samples, 0 h samples on d 14 and 21 were used to measure white blood cell populations, and 0 h samples from d 14, 18, and 21 were used for flow cytometric analysis of γδ T cells. Data were analyzed in SAS using models that included fixed effects of treatment and period and the random effects of cow and square. For blood measures, d 14 samples collected before the initiation of abomasal infusions were included as covariates. Time (d or h) was added as a repeated measure in variables that included multiple samples during the abomasal infusion period. A contrast was used to determine the linear effect of increasing abomasal corn starch. Abomasal corn starch linearly decreased fecal pH and linearly increased fecal total VFA and LPS, but effects were modest, with fecal pH, total VFA, and LPS changing from 6.96, 57.7 mM, and 4.14 log10 endotoxin units (EU) per gram for the CON treatment to 6.69, 64.1 mM, and 4.58 log10 EU/g for the ST3 treatment, respectively. This suggests that we did not induce hindgut acidosis. There were no effects of treatment on apparent total-tract starch digestibility or fecal starch content (mean of 96.9% and 2.2%, respectively). Treatment did not affect serum acute phase proteins or most circulating white blood cells, but the proportion of circulating γδ T cells tended to linearly decrease from 6.69% for CON to 4.61% for ST3. Contrary to our hypothesis, increased hindgut starch fermentation did not induce an inflammatory response in this study.

Fecal acute phase proteins in cats with chronic enteropathies.

BACKGROUND: Chronic enteropathies (CE) are common in cats and reliable biomarkers that can distinguish different causes and predict or monitor response to treatment are currently lacking. HYPOTHESIS: To evaluate certain acute phase proteins in feces that could potentially be used as biomarkers in cats with CE. ANIMALS: Twenty-eight cats with either inflammatory bowel disease (IBD; n = 13), food-responsive enteropathy (FRE; n = 3) or small cell gastrointestinal lymphoma (SCGL; n = 12) and 29 healthy control cats were prospectively enrolled. METHODS: Fecal concentrations of haptoglobin, alpha-1-acid-glycoprotein (AGP), pancreatitis-associated protein-1 (PAP-1), ceruloplasmin, and C-reactive protein (CRP) were measured using Spatial Proximity Analyte Reagent Capture Luminescence (SPARCL) immunoassays before and after initiation of treatment. Cats were treated with diet and/or prednisolone (IBD cats), plus chlorambucil (SCGL cats). RESULTS: Compared with controls, median fecal AGP concentrations were significantly lower (25.1 vs 1.8 µg/g; P = .003) and median fecal haptoglobin (0.17 vs 0.5 µg/g), PAP-1 (0.04 vs 0.4 µg/g) and ceruloplasmin (0.15 vs 4.2 µg/g) concentrations were significantly higher (P < .001) in cats with CE. Median fecal AGP concentrations were significantly lower (P = .01) in cats with IBD and FRE (0.6 µg/g) compared with cats with SCGL (10.75 µg/g). A significant reduction was found in CE cats after treatment for median fecal ceruloplasmin concentrations (6.36 vs 1.16 µg/g; P = .04). CONCLUSIONS: Fecal AGP concentration shows promise to differentiate cats with SCGL from cats with IBD and FRE. Fecal ceruloplasmin concentrations may be useful to objectively monitor response to treatment in cats with CE.

Normoferremia in Patients with Acute Bacterial Infections-A Hitherto Unexplored Field of the Dichotomy between CRP and Ferritin Expression in Patients with Hyper Inflammation and Failure to Increase Ferritin.

Ferritin is an acute phase response protein, which may not rise as expected in acute bacterial infections. This could be due to the time required for its production or to a lack of response of ferritin to the bacterial inflammatory process. Medical records of hospitalized patients with acute hyper inflammation were retrieved and studied, looking closely at two acute phase proteins: C-reactive protein (CRP) and ferritin. The estimated time between symptom onset and the procurement of blood tests was also measured. 225 patients had a median ferritin level of 109.9 ng/mL [IQR 85.1, 131.7] and a median CRP level of 248.4 mg/L [IQR 221, 277.5]. An infectious inflammatory process was identified in 195 patients. Ferritin levels were relatively low in comparison with the CRP in each group, divided according to time from symptom onset until the procurement of blood tests. The discrepancy between high CRP and low ferritin suggests that these two acute phase response proteins utilize different pathways, resulting in a failure to increase ferritin concentrations in a documented state of hyperinflammation. A new entity of normoferremic inflammation accounts for a significant percentage of patients with acute bacterial infections, which enables bacteria to better survive the inflammation and serves as a new "inflammatory stamp".

Endotoxic kidney injury in Beagle dogs assessed by serum creatinine and symmetric dimethylarginine, and urinary neutrophil gelatinase-associated lipocalin and clusterin.

Sepsis of Gram negative bacterial origin results in lipopolysaccharide-induced endotoxemia. This often leads to acute kidney injury (AKI) and its recognition remains a challenge and delays treatment. As renal damage occurs before a rise in serum creatinine is detected, new early biomarkers of kidney injury need to be explored. The aim of this study was to determine changes in serum parameters of renal function and urine biomarkers of renal injury. This was a descriptive study. Endotoxemia was induced intravenously in six anaesthetized Beagles (T1). To achieve normotension, dogs received fluids (T2), followed by a continuous infusion of noradrenaline and dexmedetomidine or 0.9% NaCl (T3). Ten minutes later, the dogs received fluids (T4) and noradrenaline and dexmedetomidine or 0.9% NaCl in a crossover manner (T5). At each timepoint, blood and urine were collected for serum creatinine, urea, symmetric dimethylarginine, urine protein/creatinine (UPC) ratio, urine neutrophil-gelatinase-associated lipocalin (U-NGAL), U-NGAL/creatinine ratio, urine clusterin (U-clusterin) and U-clusterin/creatinine ratio. Data were analyzed using a mixed-effect model taking into account time and stage of veterinary AKI (VAKI). Three of six dogs had a VAKI stage ≥1; one with anuria and elevated creatinine. Serum creatinine (P < 0.001), U-NGAL/creatinine ratio (P = 0.01) and U-clusterin/creatinine ratio increased over time (P < 0.01). The UPC ratio (mean (range) 0.68 (0.35-2.3) versus 0.39 (0.15-0.71) P < 0.01) and U-NGAL (3164 pg/mL (100-147,555) versus 100 (100-14,524), P = 0.01) were higher in VAKI stage ≥1 versus stage 0, respectively. Endotoxemia induced VAKI stage ≥1 in half of the dogs. Repeated measurement of selected parameters could detect AKI early.

Sepsis-mediated renal dysfunction: Pathophysiology, biomarkers and role of phytoconstituents in its management.

Sepsis has evolved as an enormous health issue amongst critically ill patients. It is a major risk factor that results in multiple organ failure and shock. Acute kidney injury (AKI) is one of the most frequent complications underlying sepsis, which portends a heavy burden of mortality and morbidity. Thus, the present review is aimed to provide an insight into the recent progression in the molecular mechanisms targeting dysregulated immune response and cellular dysfunction involved in the development of sepsis-associated AKI, accentuating the phytoconstituents as eligible candidates for attenuating the onset and progression of sepsis-associated AKI. The pathogenesis of sepsis-mediated AKI entails a complicated mechanism and is likely to involve a distinct constellation of hemodynamic, inflammatory, and immune mechanisms. Novel biomarkers like neutrophil gelatinase-associated lipocalin, soluble triggering receptor expressed on myeloid cells 1, procalcitonin, alpha-1-microglobulin, and presepsin can help in a more sensitive diagnosis of sepsis-associated AKI. Many bioactive compounds like curcumin, resveratrol, baicalin, quercetin, and polydatin are reported to play an important role in the prevention and management of sepsis-associated AKI by decreasing serum creatinine, blood urea nitrogen, cystatin C, lipid peroxidation, oxidative stress, IL-1ß, TNF-α, NF-κB, and increasing the activity of antioxidant enzymes and level of PPARγ. The plant bioactive compounds could be developed into a drug-developing candidate in managing sepsis-mediated acute kidney injury after detailed follow-up studies. Lastly, the gut-kidney axis may be a more promising therapeutic target against the onset of septic AKI, but a deeper understanding of the molecular pathways is still required.

Local and systemic inflammatory response to the intrauterine infusion of enzymes during estrus in water buffaloes with subclinical endometritis.

Our objective was to determine the effects of intrauterine infusion of proteolytic enzymes in buffaloes with subclinical endometritis (SCE) at estrus on the resolution of endometrial inflammation and reproductive performance. Buffaloes at spontaneous estrus (E1) were screened for SCE by endometrial cytology to identify SCE (≥5% PMN, n = 22) and non-SCE (<5% PMNs, n = 14) animals. All buffaloes underwent uterine ultrasonographic examination, low volume uterine lavage (cytokines and acute phase proteins) and blood sampling (cytokines and acute-phase proteins) at E1. On the same day (E1), SCE buffaloes were randomly selected either for intrauterine infusion of proteolytic enzymes (ENY, n = 11) or saline (PC, n = 11). Buffaloes without SCE were kept as untreated control (NC; n = 14). All buffaloes were re-examined and re-sampled during subsequent estrus (E2), inseminated during the following estrus (E3), and assessed for fertility related outcomes. Proteolytic infusion resulted a reduction in uterine PMN (P < 0.01) in SCE buffaloes. The concentrations of interleukin (IL)-1ß and tumor necrosis factor (TNF)-α in uterus, and TNF-α and IL-10 in serum were higher (P < 0.01) at E1 in buffaloes with SCE (PC and ENY) compared to NC. After treatment, uterine IL-1ß and TNF-α (P = 0.02), and serum TNF-α and IL-10 were lower within the animals of ENY group (P < 0.01). Before treatment, buffaloes with SCE had higher concentrations (P < 0.01) of serum and uterine amyloid-A and haptoglobin, which decreased (P < 0.01) after treatment in the ENY group. None of the fertility outcomes differ between the treatment groups. In conclusion, intrauterine infusion of proteolytic enzymes reduced endometrial inflammation; however, did not improve reproductive outcomes.

Proteomic methods for the study of porcine acute phase proteins - anything new to detect?

Acute phase proteins (APPs) reflect the health status of individuals and are important tools in diagnostics, as their altered levels are a sign of disturbed homeostasis. While, in most cases, quantitation of known serum APPs is routinely performed by immunoassays, proteomics is helpful in discovery of new biomarker candidates, especially in samples other than body fluids. Besides putting APP regulation into an overall context of differentially abundant proteins, this approach can detect further details or outright new features in protein structure or specific modifications, and help understand better their function. Thus, it can show up ways to make present diagnostic assays more sensitive and/or specific, or correlate regulations of disease-specific proteins. The APP repertoire is dependent on the species. The pig is both, an important farm animal and a model animal for human diseases, due to similarities in physiology. Besides reviewing existing literature, yet unpublished examples for two-dimensional electrophoresis in connection with pig APPs highlight some of the benefits of proteomics. Of further help would be the emerging targeted proteomics, offering the possibility to determine particular isoforms or proteoforms, without the need of specific antibodies, but this method is presently scarcely used in veterinary medicine.

Circulating oxidative stress and acute phase protein levels in horses infested with ticks.

Ticks have saliva rich in immunoregulatory molecules that interfere with the host's physiology in order to feed. This study aimed to evaluate the concentration of acute phase proteins and circulating oxidative stress in response to infestation by Amblyomma sculptum and Dermacentor nitens in two breed horses, Mangalarga Marchador and Breton Postier, to define resistance or susceptibility to ticks. Among the oxidative stress markers, we observed lower malondialdehyde and nitric oxide in horses with tick infestation, consequently not altering the antioxidant enzymes. Breton Postier with tick infestation showed a reduction in the ferric reducing ability of plasma (FRAP), which may be due to lower feeding of the host due to the stress caused by the infestation or even to sequestration of components induced by the tick during blood feeding. The alpha-1-antitrypsin, an acute phase protein, showed an increase in Mangalarga Marchador with tick infestation; curiously it is related to a protective action against tissue damage, pathogens and parasites. We could assume that Mangalarga Marchador showed a better response to ticks when compared to Breton Postier. However, it is still early to define the resistance or susceptibility to ticks, as we did not observe significant changes in most of the analyzed variables. Further studies are needed to understand the compounds and mechanisms of action of the tick saliva in the acute phase proteins and the possible relationships of oxidative stress in the host and the tick during blood feeding.