Serum Haptoglobin Research Articles

Characterizing pregnancy losses in lactating Holstein cows receiving a fixed-timed artificial insemination protocol.

This experiment assessed pregnancy losses from day 31 of gestation to calving in lactating Holstein cows reared in tropical conditions, and evaluated if serum concentrations of haptoglobin and pregnancy-associated glycoproteins (PAGs) during early gestation differs according to pregnancy losses. Cows (708 primiparous and 844 multiparous) were assigned to an ovulation synchronization + fixed-time artificial insemination (FTAI) protocol (day -11-0 of the experiment). Pregnancy status was verified using transrectal ultrasonography on days 31, 62, 120, and according to calf birth. Blood samples were collected from all cows on day 24, and from cows diagnosed as pregnant on day 31. Pregnancy losses were greater (P < 0.01) from day 31-62 (12.8 %) and day 120 to calving (12.1 %) compared with day 62-120 (6.42 %). Pregnancy losses were greater in multiparous compared with primiparous cows from day 31-62 (17.1 vs. 9.5 %) and from 120 to calving (15.4 vs. 7.7 %). Serum PAGs concentrations on day 31 were less (P ≤ 0.03) in cows that lost the pregnancy from day 31-62 (3.57 ng/mL) and from day 62-120 (4.40 ng/mL) compared to cows that maintained the pregnancy (5.57 and 5.66 ng/mL, respectively). Cows that experienced pregnancy loss from day 31-62 had greater (P = 0.05) serum haptoglobin concentrations on day 24 (0.414 mg/mL) compared with cows that maintained the pregnancy (0.271 mg/mL). Collectively, this experiment provides novel information about pregnancy losses after day 31 of gestation in lactating Holstein cows reared in tropical environments.

Well-Being and Performance of Nursery Pigs Subjected to Different Commercial Vaccines Against Porcine Circovirus Type 2, Mycoplasma hyopneumoniae and Lawsonia intracellularis

Background/Objectives: Vaccination is a strategy in pig farming for the control of several pathogens, but commercial vaccines may have detrimental side effects. This study aimed to evaluate the effects of commercial vaccines on the control of porcine circovirus type 2 (PCV2), Mycoplasma hyopneumoniae (Mhp), and Lawsonia intracellularis (L. intracellularis) and their potential side effects on welfare, behavior, acute inflammation biomarkers (C-reactive protein and haptoglobin), and the performance of piglets during the nursery phase. Methods: A total of 240 piglets, both female and castrated males, with an average weight of 6.3 ± 0.9 kg were subjected to four treatments: T1-FLEXcombo® (Ingelvac®CircoFLEX and Ingelvac®MycoFLEX) + Enterisol® Ileitis; T2-FLEXCombo® + Porcilis® Ileitis; T3-Porcilis® PCV M HYO + Porcilis® Ileitis; and T4-FLEXCombo® + 0.9% saline solution. This study measured therapeutic interventions, body condition score, behavioral changes, rectal temperature, and inflammation biomarkers post-vaccination. Results: The T3 group required more therapeutic interventions and exhibited a 23.1% higher incidence of thin body condition (p &lt; 0.05) and 10 times more animals with depressed behavior than T1 (p &lt; 0.05). The piglets vaccinated for L. intracellularis (T2 and T3) had rectal temperatures exceeding 39.7 °C post-vaccination, significantly higher than in T1 (p &lt; 0.05). The T1 animals showed five times more positive behavior traits 24 h after vaccination (p &lt; 0.05). Touch response was 29% lower in the T2 and T3 groups, and the lying down behavior was higher in these groups compared to T1. Additionally, 41.7% of the T3 animals exhibited a sitting posture 48 h after vaccination. Higher serum C-reactive protein and haptoglobin levels were observed in T3 (p &lt; 0.05) at 24 and 48 h post-vaccination. Feed intake was higher in T1 compared to T3 between 29 and 35 days of age. It is important to note that this study did not measure immune responses to the pathogens and did not include challenge tests, and therefore, it does not assess which vaccine is superior in pathogen control. Conclusions: The vaccine programs resulted in similar zootechnical performance. However, T1, T2, and T4 showed better effects on piglet welfare and behavior compared to T3.

Simultaneous Genotyping of Three SNVs, rs5471, rs5472, and rs2000999 Involved in Serum Haptoglobin Levels by Fluorescent Probe-Based Melting Curve Analysis.

Haptoglobin (Hp) is a hemoglobin-binding acute-phase serum protein. Several single nucleotide variations (SNVs) within the Hp gene (HP) or Hp-related protein gene (HPR), such as rs5471 (A>C) and rs5472 (A>G) in HP promoter region and rs2000999 (G>A) in intron 2 of HRP, are suggested to correlate with the serum Hp levels. To determine these three SNVs simultaneously, a genotyping assay based on duplex dual-labeled fluorescent probes was developed. The method was then validated by analyzing genomic DNA from 121 Ghanaian and two Japanese subjects who had been previously genotyped for rs5471, rs5472, and rs2000999. Both rs5471 and rs5472 could be determined as haplotypes with a single FAM-labeled fluorescent probe, and rs2000999 could be genotyped with a HEX-labeled fluorescent probe. The results obtained with the present method were consistent with the previous results except for those of three Ghanaian subjects. All three subjects appear to have multiple HPR copy number variants characteristic of African populations, which may have led to incorrect results during previous genotyping. This method allows us to genotype these three SNVs in a relatively large number of samples, especially in African populations where rs5471 is uniquely distributed.

Effects of monoglyceride blend on systemic and intestinal immune responses, and gut health of weaned pigs experimentally infected with a pathogenic Escherichia coli

BackgroundMonoglycerides have emerged as a promising alternative to conventional practices due to their biological activities, including antimicrobial properties. However, few studies have assessed the efficacy of monoglyceride blend on weaned pigs and their impacts on performance, immune response, and gut health using a disease challenge model. Therefore, this study aimed to investigate the effects of dietary monoglycerides of short- and medium-chain fatty acids on the immunity and gut health of weaned pigs experimentally infected with an enterotoxigenic Escherichia coli F18.ResultsPigs supplemented with high-dose zinc oxide (ZNO) had greater (P < 0.05) growth performance than other treatments, but no difference was observed in average daily feed intake between ZNO and monoglycerides groups during the post-challenge period. Pigs in ZNO and antibiotic groups had lower (P < 0.05) severity of diarrhea than control, but the severity of diarrhea was not different between antibiotic and monoglycerides groups. Pigs fed with monoglycerides or ZNO had lower (P < 0.05) serum haptoglobin on d 2 or 5 post-inoculation than control. Pigs in ZNO had greater (P < 0.05) goblet cell numbers per villus, villus area and height, and villus height:crypt depth ratio (VH:CD) in duodenum on d 5 post-inoculation than pigs in other treatments. Pigs supplemented with monoglycerides, ZNO, or antibiotics had reduced (P < 0.05) ileal crypt depth compared with control on d 5 post-inoculation, contributing to the increase (P = 0.06) in VH:CD. Consistently, pigs in ZNO expressed the lowest (P < 0.05) TNFa, IL6, IL10, IL12, IL1A, IL1B, and PTGS2 in ileal mucosa on d 5 post-inoculation, and no difference was observed in the expression of those genes between ZNO and monoglycerides. Supplementation of ZNO and antibiotic had significant impacts on metabolic pathways in the serum compared with control, particularly on carbohydrate and amino acid metabolism, while limited impacts on serum metabolites were observed in monoglycerides group when compared with control.ConclusionsThe results suggest that supplementation of monoglyceride blend may enhance disease resistance of weaned pigs by alleviating the severity of diarrhea and mitigating intestinal and systemic inflammation, although the effectiveness may not be comparable to high-dose zinc oxide.

Diagnostic Utility of Canine C-Reactive Protein, Haptoglobin, and 25-Hydroxyvitamin-D in Dogs with Nasal Cavity Disease

In this prospective blinded study, canine C-reactive protein (c-CRP), haptoglobin (HPT), and 25-hydroxyvitamin-D (25(OH)D) were investigated for their diagnostic value in 55 dogs with nasal cavity disease (ND). After comprehensive diagnostics including a culture-dependent microbiological examination (ME) of nasal swabs, 17 dogs were excluded due to additionally detected systemic diseases or steroid pre-treatment. Included were 25 dogs with malignant ND (13 carcinomas and 12 sarcomas) and 30 dogs with benign ND (7 benign tumors, 13 idiopathic rhinitis (IR), and 10 others), as well as 10 controls. In none of the 72 dogs with ND was primary bacterial rhinitis diagnosed. Although within the reference interval, compared to the controls, c-CRP was significantly higher in dogs with ND in general and in every subgroup except for benign tumors. Serum HPT concentrations were not different among groups. Compared to the controls, 25(OH)D concentrations were significantly lower (p = 0.041) in malignant ND and sarcomas (p = 0.025). Despite pre-treatment with antibiotics (40/54; 74.1%), in 23/51 (45%) dogs, the ME was positive. Cultivated bacteria did not differ significantly between nasal diseases. The serum markers were not significantly different regarding the positivity of ME. In conclusion, the investigated serum markers were not clinically useful for the reliable detection of canine ND, as was the ME. Because of the low number of dogs with IR and positive or negative ME, further studies regarding c-CRP are needed in a larger group of IR dogs without concomitant diseases to reliably evaluate its utility in IR dogs with suspected secondary bacterial nasal infection.

Further Insights into The Pathogenic Mechanisms of Haemotropic Mycoplasma ovis.

In this study, we examined the effects of experimental intraperitoneal infection with haemotropic Mycoplasma ovis (0.5 mL of blood containing 80% parasitaemia) on selected serum biomarkers and cellular pathology in mice. After infection, M. ovis cells appeared in the blood films within one week. A dose-dependent peak of parasitemia was observed during the 3rd-week post-infection (pi), with a significant decrease in mean PCV between treatment versus control group at week 3 (t 14 = -3.693, P < 0.02), week 5 (t 14 = -2.096, P = 0.055), and week 7 (t 14 = -4.329, P = 0.001). There was a significantly (t 8 = -2.330, P = 0.048) lower serum oestrogen in treatment (10.38 ± 5.07) than control (17.43 ± 4.48), while serum progesterone was significantly (t 8 = 5.415, P = 0.001) increased in treatment (27.37 ± 2.17) than control (15.92 ± 4.20). Serum haptoglobin was significantly (t 8 = 8.525, P < 0.01) lower in treatment (8.72 ± 1.49) than control (18.16 ± 1.98) while the SAA was significantly (t 8 = 3.362, P = 0.01) higher in treatment (16.79 ± 2.71) than control (11.59 ± 2.15). Prominent lesions observed in the ovary include degeneration, necrosis, vacuolation, and hypertrophy of the lutein cells in corpora lutea. In the lymph nodes, diffused cellular hyperplasia of the lymphoid tissue in the cortex. In the liver, degeneration and necrosis accompanied by leucocytic cellular infiltration and Kupffer cell proliferation within the sinusoids. There were diffused leucocytic infiltrations and proliferative lesions in the glomerulus of the kidneys. The disturbance in progesterone and ovarian pathology highlights the potential role of haemotropic M. ovis in reproductive disorders. The observed changes in biomarkers and cellular reactions following M. ovis infection in the mouse may be further advanced in sheep and goats.

Association between lung consolidation and serum amyloid-A and haptoglobin, and the potential of acute phase proteins to differentiate primary respiratory tract pathogens in calves

Bovine respiratory disease (BRD) remains a leading cause of economic losses, hampered animal welfare and antimicrobial use. The use of acute phase proteins (APPs), such as serum amyloid A (SAA) and haptoglobin (Hp), has been explored for the detection of BRD, as defined by clinical signs. However, whether these APPs are also associated with lung consolidation, as determined by thoracic ultrasonography, and have the potential to differentiate causative pathogens is unknown. Therefore, the primary objective of this study was to explore the association between lung consolidation and SAA and Hp. The second objective was to determine the ability of both SAA and Hp to differentiate pathogen groups (Mycoplasmopsis bovis, viruses and Pasteurellaceae). A cross-sectional study including 170 calves from 25 different herds with a history of Mycoplasmopsis bovis (M. bovis) (endemic, n = 94, 9 herds) or herds (including M. bovis positive herds) that met the inclusion criteria of an outbreak of BRD (i.e., the presence of one or more clinical signs associated with BRD, affecting multiple animals (5 animals; 15% ill animals in the same airspace on a farm within a 48-h period) (epidemic, n = 76, 16 herds) was conducted between 2020 and 2022 in Belgium. Clinical examination, quick thoracic ultrasonography (qTUS), blood sampling and non-endoscopic bronchoalveolar lavage (nBAL) were performed on each calf. Linear mixed effect models with a random intercept for herd were fitted, to determine the association between lung consolidations (depth ≥ 1 cm or ≥3cm) or clinical BRD (UC Davis BRD scorecard positive) and serum SAA and Hp concentrations. Furthermore, multivariable models (linear mixed effect models) were used to evaluate the mutually adjusted associations between pathogen groups and APP concentrations. Test characteristics of APP concentrations to predict the presence of lung consolidation or pathogen groups were assessed, and potential SAA and Hp cutoffs, determined by Youden index, were evaluated. Lung consolidation (≥1 cm) was positively association with higher Hp concentrations in epidemic conditions [regression coefficient (β): 5.3 (95% confidence interval (CI): 1.4-20.3)], while more severe lung consolidation (≥3 cm) was associated with higher Hp concentrations in endemic conditions [β: 3.6 (95% CI: 1.2-11.0)]. No positive association was found between lung consolidation and SAA. Yet, a positive association between M. bovis and SAA was observed [β: 2.3 (95% CI: 1.3-4.3)]. At last, no association was found between M. Bovis and Hp. For Hp, the best cutoff to predict a lung consolidation (≥1 cm) was 2.33 µg/mL (Se: 81.8% and Sp: 66.7%). Moreover, to detect M. bovis among calves with a lung consolidation (≥1 cm), a SAA cutoff of 174.84 µg/mL was determined (Se: 77.8% and Sp: 87.5%). Despite the observed relationships between lung consolidation, pathogen groups, and APPs, the test characteristics in this study suggest that Hp and SAA are currently limited in their (practical) use for the detection of lung consolidation or M. bovis.

Effects of natural additives as an alternative to ionophores on performance and carcass traits of Nellore cattle in feedlot submitted to transport stress

The present study aimed to evaluate the use of natural additives, based on essential oils and yeast cell wall products, as alternatives for monensin as a growth promoter for beef cattle. A total of 160 Nellore bulls with an average initial body weight of 352 kg were randomly distributed (40 animals/treatment) in four collective pens equipped with 24 automatic feeders (6 devices per pen). The feedlot period lasted 116 days, with a 14-day period of animal adaptation to the facilities. After the adaptation period, a transport stress (8 hours/400 km) was induced in all animals to simulate a commercial feedlot situation. The treatments were: 1) CON - Negative control (no additive); 2) MON - Monensin (27 mg/kg of dry matter (DM)); 3) EO - Essential oil-based additive (Valkalor Plus: 1.3 g/ kg DM); 4) EOYW - Essential oil and yeast cell wall-based additive (Viandi Plus: 1.8 g/ kg DM). The EO additive Valkalor Plus (IDENA®, Sautron, France) consists of a blend of essential oils (eugenol and geranyl acetate), while the EOYW additive Viandi Plus (IDENA®, Sautron, France) contains a combination of essential oils (linalol and geranyl acetate) with yeast cell wall. All statistical analyses were performed in SAS version 9.4 (SAS Institute Inc.), using GLIMMIX procedure and comparing the least square means by Tukey’s test at P < 0.05 and tendency between 0.05 <P < 0.10. A tendency (P = 0.091) and a significant effect (P = 0.032) were observed for final body weight (FBW) and average daily gain (ADG), respectively. Treatment MON presented greater FBW and ADG compared to CON (546 kg; 1.656 kg/d vs. 529 kg; 1.486 kg/d) but did not differ from treatment EO and EOYW. Dietary treatment EOYW presented greater dry matter intake (DMI), compared to MON (7 %; P = 0.006), but did not differ from CON and EO (P > 0.10). On the other hand, dietary treatment MON presented greater gain: feed ratio than all other treatments (P = 0.003). The treatments CON and EO presented greater presence of liver abscesses compared to MON and EOYW (P = 0.030). On average, the presence of liver abscess was 4.62 % for MON and EOYW vs. 23 % for CON and EO. Animals fed EO and EOYW diets, particularly during the initial adaptation period (0–12 days), had greater fluctuations in DMI compared to bulls fed CON and MON diets (P < 0.0001). Bulls treated with MON spent more time eating and had a greater DMI rate (min/kg; P < 0.0001) per kg compared to EOYW bulls during both the adaptation phase and the entire study period. In terms of daily feeding behavior, MON and EO-treated bulls exhibited more visits than EOYW bulls throughout the adaptation, final, and overall study periods (P < 0.0001). The serum haptoglobin concentration was greater for animals fed EO and EOYW compared to other treatments on average and at d 116 after enrollment (P < 0.0001). Altogether, these outcomes indicate that EOYW may be a viable alternative to MON in feedlot diets for finishing animals.

Clinical value of Hemoglobin in Combination with Neutrophil-to-Lymphocyte Ratio and Platelet-to-Lymphocyte Ratio as a Prognostic Factor in Advanced Lung Cancer

The absence of effective prognostic factors for assessing the survival outlook of patients with lung cancer has not significant improvement. Thus, this study aims to investigate the potential of a combination of serum haptoglobin (Hp), neutrophil-to-lymphocyte ratio (NLR), and platelet-to-lymphocyte ratio (PLR) in blood as reliable prognostic markers for lung cancer patients. There were 62 lung cancer patients (male and female) at advanced stage (stage III and IV) with age mean (65.25) years, and 62 healthy participants with age mean 64.27 years. The levels of some hematological parameters were estimated by a hematology analyzer. Heptoglobin level was evaluated in serum by ELISA technology. There was significant increase in mean of haptoglobin, NLR, and PLR in SCLC (3.43 ±0.16, 2.47±0.88, and 221 ±23.21, respectively) and NSCLC groups (3.64 ±0.09, 3.68±1.3, and 210.26±12.6, respectively) compared with control group. Haptoglobin, NRL and PRL did not differ significantly between SCLC and NSCLC. The results indicate that the mean haptoglobin, NLR, and PLR were significantly increased in lung cancer group in contrast to controls and also showed a positive association with the severity of the disease, where they increased in patients at stage IV and receiving chemotherapy for 2 months. This makes them possible markers for prognostic advanced lung cancer and predictive responses to chemotherapy in lung cancer patients.

Salivary and serum haptoglobin, adenosine deaminase, and immunoglobulin G in growing pigs

BackgroundIdentification of animals in need of medical treatment is important in porcine health management, where analytical samples applicable at farm level could be utilized. Several biomarkers are measurable in saliva, which is less stressful to collect than blood. Saliva sampling is easy to learn and repeatable, making it suitable for monitoring purposes. Previous research suggests that porcine health biomarkers are dependent on production stage and gender, and that combining biomarkers improves diagnostic sensitivity. However, proper monitoring of biomarkers during the complete production cycle has not been studied. We aimed to describe the dynamics of salivary and serum haptoglobin (Hp), adenosine deaminase (ADA), and immunoglobulin G (IgG) in four production stages (suckling, early growing, late growing, finishing), on commercial Finnish pig farms using a total of 117 piglets. The relationship between gender and biomarker dynamics was investigated, as well as the relationships between these biomarkers in saliva and serum.ResultsThe highest salivary concentrations of Hp, ADA and IgG were measured in suckling piglets. The differences between production stages were generally larger in saliva than for the corresponding serum biomarkers. All correlation coefficients between salivary biomarkers were positive in each production stage and the strength of the correlation varied from 0.245 to 0.762. No similar trend was observed regarding correlation coefficients either between serum biomarkers or between salivary and serum biomarkers. Gender was associated with some biomarker concentrations.ConclusionsThe biomarker dynamics supported previous findings that collection of analytical samples should be conducted in age-matched populations. Positive and even strong relationships between salivary biomarkers indicate the potential to use especially saliva for health monitoring. Our results also suggest the importance of considering gender effects when assessing some salivary or serum biomarkers.

Progesterone profiles in postpartum dairy cows with inflammatory disorders

The objective of this prospective cohort study was to determine if progesterone (P4) profiles differed between dairy cows with or without inflammatory disorders early postpartum. A total of 708 cows from 2 commercial herds were enrolled 3 wk before parturition and examined for clinical health disorders (difficult calving, retained placenta, metritis, displaced abomasum, mastitis, or lameness) until 5 wk postpartum. Serum haptoglobin (Hp) was measured in blood at 2 and 6 DIM (range ±2 d); metritis was assessed at 4, 8, 11, and 15 DIM; and purulent vaginal discharge and endometritis (≥6% PMN in endometrial cytology sampled by cytobrush) were assessed at 35 ± 3 DIM. As Hp ≥0.8 g/L or endometritis were associated with ovarian dysfunction in previous studies, cows with serum Hp ≥0.8 g/L at either time point and endometritis, regardless of clinical disease, were classified as the cohort with inflammatory disorders (INFLAM; n = 139). Clinically healthy cows without difficult calving, with singleton birth, with Hp <0.8 g/L at both sampling times, without endometritis or purulent vaginal discharge, and BCS ≥3.00 (1 to 5 scale) were classified as healthy (n = 133). Cows with only one of the 2 conditions (high Hp or endometritis) were excluded. Cohorts had serum P4 measured twice weekly from 35 to 70 DIM (±3 d), and the first detected luteal phase (LP) during the sampling period was defined as the period from onset of luteal activity (P4 increase to ≥1 ng/mL) until decline of P4 to <1 ng/mL. The odds of prolonged LP (≥21 d long), average LP length, peak P4, and time to P4 decline (hazard rate) were analyzed using multivariable mixed logistic, linear, or Cox proportional hazard regression models including INFLAM status, parity, sampling day (when applicable), and herd as a random effect considering the covariates of season, milk yield at first DHIA test, and DIM at onset of cyclicity or LP length (when applicable). Cows with INFLAM had greater odds of prolonged LP (LSM ± SEM; 67% vs. 37% ± 7%), greater average LP length (17 vs. 15 ± 2 d), lesser P4 at d 4 (4.6 vs. 5.5 ± 0.3 ng/mL) and d 7 (6.0 vs. 7.7 ± 0.3 ng/mL) of the LP, and lesser peak P4 (6.9 vs. 8.2 ± 0.3 ng/mL) during the LP than healthy cows. Status of INFLAM was associated with time to P4 decline in multiparous but not primiparous cows; the LP of INFLAM multiparous cows was less likely to have luteolysis (P4 decline) by d 14 (adjusted hazard ratio [AHR] and 95% CI: 0.54; 0.31 to 0.94) or by d 21 (AHR: 0.32; 0.12 to 0.84) than in healthy multiparous cows. In conclusion, postpartum cows with markers of systemic inflammation at wk 1 and uterine inflammation at wk 5 had altered luteal function (prolonged LP and lower P4 concentrations) before first breeding, which is a possible pathway linking postpartum health disorders and reduced fertility.

73 Effects of blend of organic acids and monoglycerides on immune responses of weaned pigs experimentally infected with enterotoxigenic Escherichia coli F18

Abstract Our previous research implies that dietary supplementation of organic acids blend, monoglycerides blend, and the combination of both can mitigate diarrhea of weaned pigs infected with Escherichia coli (E. coli) F18. The objective of this study was to investigate the effects of dietary supplementation with a blend of organic acids, a blend of monoglycerides, or the combination of both on immune responses of weaned pigs experimentally infected with E. coli F18. Forty pigs [average body weight (BW) = 7.81 ± 0.84 kg] were individually housed and randomly assigned to one of four treatment groups with 10 replicate pigs per treatment. The four dietary treatments were: () Control: nursery basal diet, 2) Acids: basal diet supplemented with a blend of organic acids (formic acid, lactic acid, and sodium formate) at 0.3%, 3) Monoglycerides: basal diet supplemented with a blend of monoglycerides of fatty acids at 0.3%, or 4) Combination of acids and monoglycerides: basal diet added with the acids blend at 0.2% and the monoglycerides blend at 0.2%. The experiment lasted 28 d, with 7 d before and 21 d after the first inoculation (d 0). All pigs were orally inoculated with E. coli F18 (1010 CFU/3 mL) for 3 consecutive days from d 0. Serum samples were collected on d 0, 2, 5, and 14 post-inoculation (PI) to measure the concentration of C-reactive protein (CRP) and haptoglobin using ELISA. Porcine Cytokine/Chemokine13-Plex Discovery Assay (Eve Technology, Canada) was also conducted with serum samples from d 0, 5, and 14 PI. Data were analyzed by ANOVA using PROC MIXED of SAS with a randomized complete block design. The concentrations of serum CRP and haptoglobin were increased (P &amp;lt; 0.0001) on d 2 PI and then gradually decreased on d 5 and 14 PI. However, no differences were observed in serum CRP and haptoglobin concentrations among all treatment groups throughout the experiment. Pigs fed with monoglycerides tended (P &amp;lt; 0.10) to have decreased serum granulocyte-macrophage colony-stimulating factor (GM-CSF), interleukin 1-alpha (IL-1α), and tumor necrosis factor-alpha (TNF-α) concentrations on d 0 PI compared with other treatments. Pigs supplemented with monoglycerides also tended (P &amp;lt; 0.10) to have decreased GM-CSF on d 5 PI and less IL-1α on d 14 PI among all treatments. Supplementation of the combination tended (P &amp;lt; 0.10) to have greater GM-CSF concentration on d 5 PI compared with other treatments. In conclusion, dietary supplementation of monoglycerides blend or the combination of organic acids and monoglycerides alleviates systemic inflammation of weaned pigs during E. coli F18 infection by modulating related cytokines. However, additional research is needed to understand the modulation mechanisms.

PSIV-17 Effects of butyrin-based additive supplementation on nursery pig performance, fecal dry matter, serum cytokines, short chain fatty acid production, and serum chemistry

Abstract Two experiments were conducted to determine the effects of butyrin-based feed additives on nursery pig performance, fecal dry matter (DM), serum chemistry, and short chain fatty acid (SCFA) production. In Exp. 1, 250 pigs (initially body weight = 5.6 kg) were randomly allotted to 1 of 5 treatments. There were 5 pigs/pen and 10 replications/treatment. Treatments consisted of a negative control, a positive control, and three diets containing various butyrin-based feed additives. The negative control was a corn-soybean meal-based diet with no antibiotics or pharmacological content of Zn or Cu. The positive control contained 3,000 and 2,000 mg/kg of Zn from ZnO in phase 1 (d 0 to 10) and 2 (d 10 to 24), respectively, 250 mg/kg of Cu from CuSO4 in phase 3 (d 24 to 38), and 55 mg/kg of carbadox (Mecadox; Phibro Animal Health Corp., Teaneck, NJ) across all phases. The butyrin-based feed additives were added at 0.1% to the negative control diet and consisted of monobutyrin, mono-tributyrin, or tributyrin. In Exp. 2, 1,492 pigs (initially 5.1 kg) were randomly allotted to 1 of 4 treatments. There were 26 or 27 pigs/pen and 14 replications/treatment. Treatments were fed over 3 phases consisting of a control diet and 3 diets containing different mono-tributyrin blends. In phase 1 and 2, the control diet contained 55 mg/kg of carbadox and 3,000 and 2,000 mg/kg of Zn from ZnO, respectively. Each feed additive was added at 0.3% to the control diet in phase 1 and 2, and 0.1% in phase 3. Phases 1 and 2 were fed by feed budget of 2.3 and 5.4 kg/pig, respectively, and phase 3 until the completion of the study. Overall, for Exp. 1, pigs fed the positive control had increased (P &amp;lt; 0.05) average daily gain (ADG) and average daily feed intake (ADFI) compared with all other treatments (Table). Pigs fed monobutyrin had decreased (P &amp;lt; 0.05) gain to feed ratio (G:F) compared with all other treatments. On d 24, pigs fed the positive control and mono-tributyrin had increased (P&amp;lt; 0.05) fecal DM compared with pigs fed monobutyrin and tributyrin with the negative control intermediate. On d 38, pigs fed mono-tributyrin had increased (P &amp;lt; 0.05) serum haptoglobin and cecal butyrate concentration compared with pigs fed the positive and negative control, respectively, with other treatments intermediate. For Exp. 2, there were no differences in growth performance throughout the study. On d 10, pigs fed mono-tributyrin blend 3 had increased (P&amp;lt; 0.05) fecal DM compared with mono-tributyrin blend 2 with other treatments intermediate. On d 24 and 42, pigs fed mono-tributyrin blend 1 had the highest (P ≤ 0.012) IL-12 concentration, without significant mean separation on d 24. In summary, butyrin-based feed additives had limited effects on growth performance. However, supplementing butyrin-based feed additives led to alterations in fecal consistency, SCFA production, and serum chemistry.

178 Effects of L-glutamate and L-aspartate supplementation on systemic and intestinal immune responses of weaned piglets challenged with F18 enterotoxigenic Escherichia coli challenge

Abstract L-glutamate (Glu) and L-aspartate (Asp) are pivotal components in the cellular metabolic pathways and immune regulation of pigs. This study aimed to investigate the effects of Glu and Asp on systemic and intestinal immune responses of weaned piglets challenged with an enterotoxigenic Escherichia coli (ETEC) F18. A total of 49 weaned pigs [initial body weight (BW) = 8.18 ± 1.54 kg] were randomly assigned to one of seven treatments, with seven piglets per treatment. The treatments included negative control (NC) and positive control (PC) that were fed with control diet without or with F18 enterotoxigenic Escherichia coli (ETEC) challenge, respectively. The other five dietary treatments were supplemented with either 1% or 2% Glu or Asp, or 50 mg/kg of Carbadox, and were challenged with ETEC. All pigs except for NC were challenged with F18 ETEC orally for three consecutive days at the dose of 1010 CFU•dose-1•d-1. The study period lasted for 3 wk, with a 7-d adaptation period and 14 d post-inoculation (PI). Blood samples were collected on d 0 before ETEC inoculation, and on d 2, 5, and 14 PI to analyze systemic inflammatory markers by the enzyme-linked immunosorbent assays. On d 14 PI, intestinal mucosa from jejunum and ileum were collected to analyze the mRNA expression of inflammatory cytokines by quantitative polymerase chain reaction. All data were analyzed with ANOVA using the PROC MIXED of SAS with pig as the experimental unit. Among all treatments, pigs fed with carbadox had the least (P &amp;lt; 0.05) serum TNF-α, haptoglobin, and C-reactive protein throughout the experiment. Pigs supplemented with 1% Glu had similar concentrations of TNF-α, haptoglobin, and C-reactive protein, while pigs fed with 2% Asp had similar serum haptoglobin compared with pigs fed with carbadox. Compared with PC, supplementing Glu and Asp reduced (P &amp;lt; 0.05) the mRNA expression of IL12 in jejunal mucosa. Pigs fed with carbadox tended to have greater (P &amp;lt; 0.10) expression of IFNG in ileal mucosa than pigs in PC, while no difference was observed in IFNG expression among 1% Glu, 1% or 2% Asp, and carbadox groups. In addition, pigs fed with 1% Glu or 2% Asp had greater (P &amp;lt; 0.05) expression of IL12 in ileal mucosa than pigs in PC. However, dietary treatments did not affect the gene expression of TNFA, IL1B and TGFB in jejunal and ileal mucosa of pigs. In conclusion, results of the present study indicate that dietary supplementation of 1% Glu or 2% Asp affected both systemic and intestinal immune responses of ETEC challenged weaned pigs with similar trend as the supplementation of carbadox.

Use of rumination time in health risk assessment of prepartum dairy cows

The objectives of this observational cohort study were to evaluate the associations of rumination time (RT) in the last week of pregnancy with transition cow metabolism, inflammation, health, and subsequent milk production, reproduction, and culling. Pregnant nulliparous (n = 199) and parous (n = 337) cows were enrolled 21 d before the expected calving. RT and physical activity were monitored automatically by sensors from d -21 to 15 relative to calving. Blood samples were collected on d -14, -5, 4, 8, and 12 ± 1 relative to calving. Diagnoses of clinical health problems were performed by researchers from calving to 15 d in milk (DIM). In classification 1, cows were ranked based on average daily RT in the last week of pregnancy and classified into terciles as short RT (SRT), moderate RT (MRT), or long RT (LRT) for association analyses. In classification 2, RT deviation from the parity average was used in a receiver operating characteristic curve to identify the best threshold to predict postpartum clinical disease. Cows were then classified as above the threshold (AT) or below the threshold (BT). Compared with cows with LRT, cows with SRT had greater serum concentrations of NEFA (0.47 vs 0.40 ± 0.01 mmol/L), BHB (0.58 vs 0.52 ± 0.01 mmol/L), and haptoglobin (0.22 vs 0.18 ± 0.008 g/L) throughout the transition period, and reduced concentrations of glucose, cholesterol, albumin, and magnesium in a time-dependent manner. Parous cows with SRT had higher odds of postpartum clinical disease (adjusted odds ratio [AOR]: 3.7; 95% confidence interval [CI]: 2.1-6.4), lower odds of pregnancy by 210 DIM (AOR: 0.34; CI: 0.15-0.75), and lower milk production (46.9 vs 48.6 ± 0.5 kg/d) than parous cows with LRT. Deviation in prepartum RT had good predictive value for clinical disease in parous cows (area under the curve [AUC]: 0.65; CI: 0.60-0.71) but not in nulliparous (AUC: 0.51; CI: 0.42-0.59). Separation of parous cows according to the identified threshold (≤-53 min from the parity average) resulted in differences in serum concentrations of NEFA (AT = 0.31 ± 0.006, BT = 0.38 ± 0.014 mmol/L), BHB (AT = 0.49 ± 0.008, BT = 0.53 ± 0.015 mmol/L), and globulin (AT = 32.3 ± 0.3, BT = 34.8 ± 0.5 g/L) throughout the transition period, as well as in serum cholesterol, urea, magnesium, albumin, and haptoglobin in a time-dependent manner. BT parous cows had higher odds of clinical disease (AOR: 3.7; CI: 2.1-6.4), reduced hazard of pregnancy (AHR: 0.64, CI: 0.47-0.89), greater hazard of culling (AHR: 2.1, CI: 1.2-3.6), and lower milk production (46.3 ± 0.7 vs 48.5 ± 0.3 kg/d). External validation using data from 153 parous cows from a different herd and the established threshold in RT deviation (≤-53 min) resulted in similar predictive value, with the odds of postpartum disease 2.4 times greater in BT than AT (37.5 vs 20.1%). In conclusion, RT in the wk preceding calving was a reasonable predictor of postpartum health and future milk production, reproduction, and culling in parous cows but not in nulliparous cows.

Randomized clinical trial of ketoprofen or ceftiofur for treatment of metritis in dairy cows

Our objectives were to compare the efficacy of ketoprofen or ceftiofur for treatment of metritis in dairy cows considering subsequent health, production, and reproduction. Cows from 2 commercial dairy farms in Ontario, Canada were examined with a Metricheck device 3 times per week from 2 to 14 d in milk (DIM). Cows with metritis (fetid vaginal discharge; n = 193) were blocked by parity and fever (rectal temperature ≥39.5°C or <39.5°C) and within each block per farm, randomly assigned to receive 3 mg/kg BW of ketoprofen (KET) or 2.2 mg/kg of ceftiofur hydrochloride (CEF), once a day for 3 d. Day of enrollment was considered study d 0. Rectal temperature and attitude were evaluated in cows with metritis on study d 0, 3, 4, 7, 10, and 13, and vaginal discharge was evaluated on study d 4, 7, 10, and 13. Body condition was scored at enrollment and 35 DIM, and serum concentration of haptoglobin was measured at d 0, 2, 4, and 7. Cows with rectal temperature ≥39.5°C or a depressed attitude on d 3 were classified as clinical failure and received treatment with ceftiofur for 3 d (KET), or 2 additional days (CEF), to a maximum of 5 d of treatment with ceftiofur. At 35 ± 3 DIM cows were examined for uterine involution by transrectal palpation, purulent vaginal discharge (PVD) by Metricheck, and endometritis by endometrial cytology. Time to onset of cyclicity was assessed by serum progesterone (P4) measurements at 28, 42, and 56 DIM. Contemporary cows from the same farms without metritis (NOMET; n = 1,043) were used for comparison. Data were analyzed with mixed linear or logistic regression or Cox's proportional hazard models, including herd as a random effect. The proportion of clinical resolution of metritis on d 3 (96% vs. 92%), of cows with fever (from d 3 to d 13 after enrollment) or fetid discharge (from d 4 to d 13 after enrollment), and the number of medical treatments (3.1 vs. 3.3) were not different between CEF and KET, respectively. Cows in KET received fewer antibiotic treatments than cows in CEF (0.3 vs. 3.1). Uterine involution, the prevalence of PVD (50% vs. 47%) and subclinical endometritis (6.6% vs. 4.3%), and the proportion of cyclic cows (82% vs. 86%) did not differ between CEF and KET. Cows in KET had greater serum haptoglobin concentration from d 2 to 7 after enrollment. The incidence of mastitis, lameness, or displaced abomasum to 60 DIM and subclinical ketosis to 21 DIM did not differ among CEF, KET, and NOMET. There were no differences in median days to first AI (CEF = 68 d; 95% CI: 65-70; KET = 69 d; 95% CI: 68-72; NOMET = 69 d; 95% CI: 68-70), and median days to pregnancy (CEF = 118 d; 95% CI: 92-145; KET = 113 d; 95% CI: 90-135; NOMET = 105 d; 95% CI: 101-109), pregnancy at first AI at 33 d after insemination (CEF = 42%; KET = 41%; NOMET = 41%), pregnancy loss after first AI (CEF = 8%; KET = 11%; NOMET = 8%), hazard of pregnancy or hazard of culling up to 300 DIM. Milk yield was not different between CEF and KET during the first 10 weeks, but lesser in KET at wk 2 and 4 and CEF at wk 2, 4, and 6 than in NOMET. In this pilot-scale study, given early detection, we did not detect differences in subsequent health, milk yield, or reproductive performance in cows with metritis initially treated for 3 d with CEF or KET. Additional, larger studies are warranted.

Wilson Disease: Copper-Mediated Cuproptosis, Iron-Related Ferroptosis, and Clinical Highlights, with Comprehensive and Critical Analysis Update.

Wilson disease is a genetic disorder of the liver characterized by excess accumulation of copper, which is found ubiquitously on earth and normally enters the human body in small amounts via the food chain. Many interesting disease details were published on the mechanistic steps, such as the generation of reactive oxygen species (ROS) and cuproptosis causing a copper dependent cell death. In the liver of patients with Wilson disease, also, increased iron deposits were found that may lead to iron-related ferroptosis responsible for phospholipid peroxidation within membranes of subcellular organelles. All topics are covered in this review article, in addition to the diagnostic and therapeutic issues of Wilson disease. Excess Cu2+ primarily leads to the generation of reactive oxygen species (ROS), as evidenced by early experimental studies exemplified with the detection of hydroxyl radical formation using the electron spin resonance (ESR) spin-trapping method. The generation of ROS products follows the principles of the Haber-Weiss reaction and the subsequent Fenton reaction leading to copper-related cuproptosis, and is thereby closely connected with ROS. Copper accumulation in the liver is due to impaired biliary excretion of copper caused by the inheritable malfunctioning or missing ATP7B protein. As a result, disturbed cellular homeostasis of copper prevails within the liver. Released from the liver cells due to limited storage capacity, the toxic copper enters the circulation and arrives at other organs, causing local accumulation and cell injury. This explains why copper injures not only the liver, but also the brain, kidneys, eyes, heart, muscles, and bones, explaining the multifaceted clinical features of Wilson disease. Among these are depression, psychosis, dysarthria, ataxia, writing problems, dysphagia, renal tubular dysfunction, Kayser-Fleischer corneal rings, cardiomyopathy, cardiac arrhythmias, rhabdomyolysis, osteoporosis, osteomalacia, arthritis, and arthralgia. In addition, Coombs-negative hemolytic anemia is a key feature of Wilson disease with undetectable serum haptoglobin. The modified Leipzig Scoring System helps diagnose Wilson disease. Patients with Wilson disease are well-treated first-line with copper chelators like D-penicillamine that facilitate the removal of circulating copper bound to albumin and increase in urinary copper excretion. Early chelation therapy improves prognosis. Liver transplantation is an option viewed as ultima ratio in end-stage liver disease with untreatable complications or acute liver failure. Liver transplantation finally may thus be a life-saving approach and curative treatment of the disease by replacing the hepatic gene mutation. In conclusion, Wilson disease is a multifaceted genetic disease representing a molecular and clinical challenge.

Endoscopic manifestation of intestinal transplant-associated microangiopathy after stem cell transplantation

BackgroundEndoscopic features of intestinal transplant-associated microangiopathy (iTAM) have not been comprehensively investigated. This study aimed to examine the endoscopic characteristics of patients diagnosed with iTAM.MethodsThis retrospective analysis included 14 patients pathologically diagnosed with iTAM after stem cell transplantation for hematolymphoid neoplasms (n = 13) or thalassemia (n = 1). The sex, age at diagnosis, endoscopic features, and prognosis of each patient were assessed. Serological markers for diagnosing transplant-associated thrombotic microangiopathy were also evaluated.ResultsThe mean age at the time of iTAM diagnosis was 40.2 years. Patients diagnosed based on the pathognomonic pathological changes of iTAM presented with diverse symptoms at the times of endoscopic examinations, including diarrhea (n = 10), abdominal pain (n = 5), nausea (n = 4), appetite loss (n = 2), bloody stools (n = 2), abdominal discomfort (n = 1), and vomiting (n = 1). At the final follow-up, six patients survived, while eight patients succumbed, with a median time of 100.5 days (range: 52–247) post-diagnosis. Endoscopic manifestations included erythematous mucosa (n = 14), erosions (n = 13), ulcers (n = 9), mucosal edema (n = 9), granular mucosa (n = 9), and villous atrophy (n = 4). Erosions and/or ulcers were primarily observed in the colon (10/14, 71%), followed by the ileum (9/13, 69%), stomach (4/10, 40%), cecum (5/14, 36%), duodenum (3/10, 30%), rectum (4/14, 29%), and esophagus (1/10, 10%). Cytomegalovirus infection (n = 4) and graft-versus-host disease (n = 2) coexisted within the gastrointestinal tract. Patients had de novo prolonged or progressive thrombocytopenia (6/14, 43%), decreased hemoglobin concentration (4/14, 29%), reduced serum haptoglobin level (3/14, 21%), and a sudden and persistent increase in lactate dehydrogenase level (2/14, 14%). Peripheral blood samples from 12 patients were evaluated for schistocytes, with none exceeding 4%.ConclusionsThis study provides a comprehensive exploration of the endoscopic characteristics of iTAM. Notably, all patients exhibited erythematous mucosa throughout the gastrointestinal tract, accompanied by prevalent manifestations, such as erosions (93%), ulcers (64%), mucosal edema (64%), granular mucosa (64%), and villous atrophy (29%). Because of the low positivity for serological markers of transplant-associated thrombotic microangiopathy in patients with iTAM, endoscopic evaluation and biopsy of these lesions are crucial, even in the absence of these serological features.

Influence of autolyzed yeast on the health of immunologically immature calves

Autolyzed yeast is a supplement option for calves due to its ability to stimulate the immune system and performance; however, there are few studies about the effect of different yeast derivatives. Autolyzed yeast is rich in immunomodulatory substances, such as mannan oligosaccharides and β-glucans. These substances enhance the innate and humoral immunity of calves, resulting in greater intestinal and respiratory health. Thus, the objective of the study was to evaluate whether supplementation with autolyzed yeast improves the health of calves, in the challenge of naturally acquired Eimeriosis and bovine respiratory disease (BRD). Twenty Holstein calves aged 15 days, which had already suckled colostrum, were studied for 36 days. At 15 days of life all animals had naturally acquired Eimeriosis. They were challenged with an intranasal BRD vaccine at 30 days of age. The Supplemented group (n=10) received autolyzed yeast (10 g animal -1 day -1), once a day in milk for 36 days, and the Control group (n=10) was not supplemented throughout the experiment. Blood neutrophil: lymphocyte ratio, oxidative metabolism of neutrophils (OM), serum immunoglobulins and haptoglobin, occurrence of diarrhea, BRD, and weight gain were measured. After vaccination, all animals increased the blood neutrophil: lymphocyte ratio, but only the control group showed a 20% reduction in OM three days after the vaccine. The supplement affected the immune response, preserving OM, increasing serum IgA levels by 10% (P=0.006), and reducing haptoglobin serum levels (P=0.05). In addition, the supplement attenuated diarrhea and BRD, which allowed for greater weekly weight gain (difference of 2 kg between treatments, P&lt;0.05), concluding that the autolyzed yeast showed some evidence that it can increase the health of calves challenged with Eimeriosis and the BRD vaccine.

Comparative Effects of Meloxicam and Phenylbutazone on Clinical Outcomes and Acute Phase Response in Sheep with Acute Respiratory Disease

The ovine respiratory complex (ORC) is one of the most common respiratory diseases observed in sheep. The objective of the present investigation was to evaluate the comparative therapeutic efficacy of two non-steroidal anti-inflammatory drugs (meloxicam and phenylbutazone) for the treatment of the ORC. For this purpose, 33 Ossimi sheep were randomly assigned into three treatment groups (11 each). Group 1 was treated with amoxicillin long-acting (LA) and meloxicam, group 2 received amoxicillin LA and phenylbutazone, and group 3 was treated with amoxicillin LA alone. Sheep were examined clinically and clinical index scores were recorded before and after treatment. Additionally, blood samples were collected from each sheep. After 14 days of treatment, sheep of group 1 indicated significant improvements in their clinical index scores and a reduction in total leukocyte count. However, there was a significant increase in red blood cell count, hemoglobin, and MCHC%. There was a significant decrease in the serum globulin, copper, and haptoglobin in group 1, compared to sheep of groups 2 and 3. Based on the results of this study, administering meloxicam to sheep with an ovine respiratory complex resulted in significant improvements in clinical outcomes and significant corrections in above mentioned hematological and biochemical parameters. Although phenylbutazone proved to be less effective, it still demonstrated some degree of efficacy in treating this condition. This study suggests that meloxicam may be a more effective treatment option for ORC with phenylbutazone. Keywords: Acute phase protein, Amoxicillin, Anti-inflammatory, Ovine respiratory complex