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The economic efficiency of dairy farms is directly influenced by reproductive performance. Reproductive performance is affected by postpartum health; however, it is unknown which diseases reduce reproductive performance or how often these diseases occur in tie-stall dairy farms. In this study, the 15 most frequent diseases in tie-stalls and their impact on reproduction were determined by logistic analysis. Data from reproductive and veterinary records of 814 cows (473 Holstein) calving between April 2016 and March 2018 reared in 9 tie-stall commercial dairy farms were used. The 15 most frequent diseases were identified by medical records. The odds ratio (OR) of the diseases reducing reproductive performance (days open, number of artificial insemination, and first artificial insemination days in milk) was measured by logistic regression analysis. We focused on mastitis, and factors (inflammation grade, causative bacteria) having a negative effect on reproduction were measured similarly. Of the 15 most frequent diseases, endometritis (OR: 5.45, p 0.001), ovarian quiescence (OR: 3.95, p 0.001), mastitis (OR: 2.49, p 0.001), and follicular cyst (OR: 2.33, p = 0.006) significantly prolonged days open after adjusting for environmental factors (farm, parity, and calving season). Focusing on mastitis, mastitis with mild inflammation significantly prolonged days open. Mastitis and genital diseases were frequent diseases that reduced reproductive performance. Strategies to reduce the incidence of these diseases are considered effective for the economics of tie-stall dairy farms.

The present study aimed to clarify the alkalizing ability of 1.35% isotonic sodium bicarbonate solution (ISBS), which did not contain dextrose, compared with that of 1.35% isotonic bicarbonate sodium solution containing 4.03% dextrose (ISBD) in healthy calves. The calves were intravenously administered with 20.7 mL/kg of the solutions for 30 min as the volume required to correct base deficit of 10 mM. ISBS increased the blood pH, HCO

This study aimed to clarify the relationship between acute phase protein (APP) concentrations and serum Fe concentrations to determine whether serum iron (Fe) can be clinically applied as a substitute for APPs in cows. One hundred five Holstein-Friesian breed lactating dairy cows were enrolled in this study. Cows with inflammatory diseases were 16 subclinical, and 15 severe mastitis cows, in addition to 15 mild and 16 severe sole ulcer cows. The plasma haptoglobin (HPT), alpha-1 acid glycoprotein (AGP), SAA, serum Fe levels, and other biochemical parameters in the cows were measured. The two-sample t-tests and multiple logistic regression analysis were used to compare the control and inflammatory disease groups. ROC analysis was used to evaluate the ability to diagnose inflammation disease. From the results, the proposed diagnostic cutoff value for plasma SAA and serum Fe concentrations to identify dairy cows with inflammatory diseases based on analyses of ROC curves were set at 3.65 mg/l and 120.50 µg/dl, respectively. Therefore, instead of using expensive inflammatory markers to evaluate the inflammatory state at the first treatment day for inflammatory diseases in cow, it shows the useful for screening with serum Fe concentration that can be measured easily and inexpensively as alternative inflammatory biomarkers.

This study aimed to clarify the relationship between acute phase protein (APP) concentrations and serum Fe concentrations to determine whether serum iron (Fe) can be clinically applied as a substitute for APPs in cattle. One hundred and five Holstein-Friesian breed dairy cows were enrolled in this study. The cows were divided into forty-three healthy cows and sixty-two cows with inflammatory diseases. The plasma haptoglobin (HPT), alpha-1 acid glycoprotein (AGP), serum amyloid A (SAA), serum Fe levels, and other biochemical parameters in the cows were measured. From the results, HPT and AGP were significantly higher in inflammatory disease cattle compared with the control group, but no odds ratios were determined in the binomial analysis. Significant differences in SAA and serum Fe concentrations were observed between the inflammatory disease and control groups and odds ratios were determined in the binomial analysis. In addition, the cutoff value of Fe could be used to diagnose the inflammatory disease to the same degree as the cutoff value of SAA. The results suggested that serum Fe can be used as a substitute for APPs in the production of animal medicine.

We hypothesized that the serum iron (Fe) concentration in cows with respiratory diseases is a satisfactory substitute for major inflammatory markers such as haptoglobin (HPT) and serum amyloid A (SAA). Twenty Japanese Black cows aged 279.6 ± 120.0 days were enrolled, and divided into respiratory diseases and control groups based on the presence of clinical findings of respiratory diseases. As a result, area under the receiver operating characteristic curves for plasma HPT, SAA and serum Fe concentrations for respiratory disease-associated systemic inflammation were excellent, at 1.00, 0.96 and 0.97, respectively. Therefore we confirmed that the serum Fe concentration is a satisfactory substitute for HPT and SAA in beef cows with respiratory diseases.

Point-of-care (POC) devices that veterinary practitioners can use to easily and rapidly measure blood ionized calcium (iCa) levels in cows immediately after withdrawing a blood sample on the dairy farm are needed. Aims of present studies was to compare the commercially available ion-selective electrode handheld iCa meter (bovine blood iCa checker) with the benchtop blood gas analyzer GEM premier 3500 and handheld analyzer i-STAT 1. Sixty-two paired-point whole blood samples were obtained from three cows with hypocalcemia experimentally induced by Na2-EDTA infusion. Whole blood samples were also obtained from the 36 cows kept on a farm in field conditions. The results using the bovine blood iCa checker correlated with those using the GEM premier 3500 and i-STAT 1. Bovine blood iCa checker was “compatible” with the GEM premier 3500 and i-STAT 1 because the frequency of differences between the measurements within ± 20% of the mean were 100% (65/65, >75%) and 90.8% (59/65, >75%), respectively. In the field trial, the blood iCa concentration measured by the bovine blood Ca checker was significantly positively correlated with that measured by the i-STAT 1 portable analyzer. Bovine blood iCa checker was “compatible” with the i-STAT 1 because the frequency of differences between the measurements within ± 20% of the mean was 100% (36/36, >75%). Results from these findings, the bovine blood iCa checker may be applied as a simplified system to measure the iCa concentration in bovine whole blood.

The patient was a 65-year-old man with alcoholic liver cirrhosis who had been admitted to hospital 5 times for repeated and recurrent overt hepatic encephalopathy (HE) despite numerous therapies, including disaccharide, branched-chain amino acid (BCAA) formula, L-carnitine and zinc. After the additional administration of rifaximin (1,200 mg/day orally), his consciousness level was well controlled for 3 years without any adverse effects. The long-term administration of rifaximin may be useful and safe for managing recurrent overt HE, although the maintenance dosage and duration of rifaximin and safety should be evaluated in patients with ameliorated HE.

Background and Aim Because covert hepatic encephalopathy (CHE) has been shown to affect the prognosis of cirrhotic patients, early diagnosis of hepatic encephalopathy (HE) is a prerequisite for the preservation of patients' quality of life and for prophylaxis of overt HE. The aim of this study was to identify a clinical parameter to predict impairment of cognitive function in cirrhotic patients with early‐stage HE. Methods We investigated the data from 172 patients with cirrhotic or idiopathic portosystemic shunt (PSS) in phase II/III trials of rifaximin in Japan. Classification and regression trees (CARTs) were constructed to identify clinical profiles related to cognitive dysfunction as indicated by the prolongation of time required for the Number Connection Test (NCT‐B). Results CART analysis detected age 65 years as the variable for the initial split, and serum albumin level was selected as the variable for the second split among patients aged ≤65 years. In 27 cirrhotic patients aged ≤65 years without PSS, receiver operating characteristic curve analysis revealed that the optimal albumin level cutoff point was 3.05 g/dL, and the area under the curve was 0.80 for the prolongation of NCT‐B time, which was higher than that of the branched‐chain amino acids‐to‐tyrosine ratio (0.46), the prothrombin time–international normalized ratio (PT‐INR) (0.68), serum ammonia (0.61), and total bilirubin (0.69). Conclusions Lower serum albumin level as a clinical biomarker associated with impaired cognitive function may be available as a screening examination for early‐stage HE in cirrhotic patients aged ≤65 years without PSS before undergoing neuropsychological tests., The aim of this study was to identify a clinical parameter to predict the prolongation of time required for the Number Connection Test (NCT‐B), a measure of cognitive function, in patients with early‐stage HE. A lower level of serum albumin was the major clinical parameter related to liver cirrhosis that was associated with prolongation of the time required for the NCT‐B in cirrhotic patients aged 65 years.

This study established the precision and accuracy of a modified latex agglutination turbidimetric immunoassay (LATIA) reagent, and evaluated the ability of the measurement of serum amyloid A (SAA) compared to haptoglobin and α1-acid glycoprotein, which are acute phase proteins (APPs), for diagnosis of clinical mastitis. Concentrations of APPs in cows with mastitis were significantly higher than those in healthy cow. Only the plasma SAA concentration in cows with clinical mastitis (44.90 mg/l; n=15) was significantly higher than that in those with subclinical mastitis (10.70 mg/l; n=16), enabling their diagnosis in contrast to other APPs. Thus, the SAA assay using a LATIA reagent is useful in assessing mastitis severity due to its higher sensitivity and specificity than other APP assays.

The aims of studies were to estimate the withdrawal period of antibiotic from milk after the intramammary infusion of cefazolin sodium (CEZ) in cows with difficulties in frequent milk discharge due to disease such as teat injury. The period was compared among cows milked twice a day after 150 or 450 mg of CEZ were administered to all quarters (Study 1, 2) and the cows in which milking of front-right quarter was ceased for five days after administration of these infusions to only that quarter (Study 3). In Studies 1 and 2, the median of 17.66 µg/ml and 83.18 µg/ml of CEZ were detected in the samples of first milking after intramammary administration, respectively; however, there was no residual antibiotic by 72 hr in all cows. In Study 3, the median of 1.96 µg/ml of CEZ was detected in the sample after the resumption of milking at 120 hr, and the residual was eliminated by 174 hr. The withdrawal period may be prolonged by the cessation of milking after administration, and the period is the total time from cessation to 72 hr after the resumption of milking.

Introduction: Panobinostat, bortezomib, and dexamethasone combination therapy demonstrated progression-free survival (PFS) benefit over bortezomib and dexamethasone alone in the PANORAMA-1 study in relapsed/refractory multiple myeloma (MM). Here, we present data from a phase II study (NCT02290431) of this combination in Japanese patients with relapsed or relapsed-and-refractory MM. Methods: Patients received 3-week cycles of 20-mg oral panobinostat (weeks 1 and 2), 1.3-mg/m2 subcutaneous bortezomib (days 1, 4, 8, and 11), and 20-mg oral dexamethasone (day of and the day following bortezomib administration) for a total of 8 cycles (24 weeks; treatment phase 1). Patients with treatment benefit had an option to enter the extension phase to receive 6-week (42-day) cycles of panobinostat (weeks 1, 2, 4, and 5) plus bortezomib (days 1, 8, 22, and 29) and dexamethasone (day of and the day following bortezomib treatment) for 24 weeks. The primary objective was complete response (CR) + near CR (nCR) rate after treatment phase 1 as per the modified European Society for Blood and Marrow Transplantation criteria. Results: Of the 31 patients, 4 (12.9%) completed the treatment and 27 (87.1%) discontinued; 17 (54.8%) entered the extension phase. In total, 24 patients (77.4%) entered the survival follow-up phase and followed until study closure when the last patient was treated for 1 year after treatment phase 1. The CR + nCR rate was 48.4% (90% CI: 33.6–63.2). The overall response rate (CR + nCR + partial response) was 80.6%. The median PFS, duration of response, time to response, and time to progression were 15.3, 22.7, 1.4, and 15.3 months, respectively. All patients experienced adverse events (AEs), with diarrhea (80.6%), decreased appetite (58.1%), and thrombocytopenia (54.8%) being the most frequent, regardless of relationship to the study treatment. Thrombocytopenia (48.4%), fatigue (25.8%), diarrhea (22.6%), neutrophil count decrease (22.6%), platelet count decrease (22.6%), and lymphocyte count decrease (22.6%) were the most frequent grade 3/4 AEs. Conclusion: The study met the primary objective with 48.4% CR + nCR rate. The AEs associated with the combination treatment were safely managed using the existing AE management guidelines, including dose interruption/modification and/or supportive medical intervention. This treatment regimen is an effective option with a favorable benefit/risk profile for Japanese patients with relapsed/refractory MM.

We hypothesize that some amino acid abnormalities in diarrheic calves are useful for understanding intestinal mucosal damage, as in humans. However, few reports have revealed the relationship between intestinal mucosal damage and plasma amino acids in diarrheic calves. Therefore, the aim of present study was to investigate whether there is a relationship between the amino acid status and plasma diamine oxidase (DAO) activity, which is known to be a biomarker for intestinal mucosal damage in diarrheic calves. Twenty Holstein calves aged 12.6 ± 4.2 days old were enrolled in this study. In the diarrhea group (n = 10), there were yellow loose feces within the rectum and Cryptosporidium parvum (C. parvum) was detected in all fecal samples. These calves were clinically normal except for diarrhea. All calves in the control group (n = 10) appeared to be healthy based on clinical findings with normal feces production and the absence of C. parvum. Plasma amino acid concentrations and DAO activity were measured. The relationships between plasma DAO activity and the concentration of each plasma amino acid were investigated using Spearman’s rank test. The plasma DAO activity was significantly lower in the diarrhea group (176.1 ± 60.1 IU mL−1) than in the control group (309.3 ± 74.8 IU mL−1) (p

The objective of the present study was to elucidate sequential changes in mRNA abundance of serum amyloid A (SAA) isotypes in endotoxin (ETX) challenge model cattle. Ten healthy cattle were separated to 2 groups: control and ETX groups. Cattle in the ETX group were challenged by 2.5 µg/kg of O111:B4 lipopolysaccharide in 4 ml of autologous serum. Blood samples were withdrawn at pre, 0.5, 1, 2, 4, 8, 12, 24, 48, 72 and 96 hr after ETX challenge. Plasma ETX activity, serum SAA concentrations, mRNA abundance of interleukin (IL)-6, SAA2 and SAA4 in the liver and polymorphonuclear leukocytes were measured. The plasma ETX activity in the ETX group increased at 0.5 hr after the ETX challenge. The serum SAA value remained higher between 12 and 72 hr after the ETX challenge than that of the control group. Hepatic IL-6 mRNA abundance in the ETX group increased at 2 hr after the ETX challenge. Hepatic SAA2 and SAA4 mRNA abundance significantly increased from 4 hr after administration, and remained significantly higher than those pre-values up to 12 and 24 hr, respectively. The abundance ratio of hepatic SAA2 was much higher than that of SAA4. The major isotype was SAA2 in liver tissue, and it is indicating systemic inflammation in cattle.

The objective of this study was to evaluate effects of butyrate supplementation on plasma concentration of glucagon-like peptide-2 (GLP-2), apparent total-tract digestibility, and responses to a grain challenge of lactating dairy cows fed diets differing in starch content. Eight Holstein cows averaging 58.6 ± 9.96 d in milk (4 primiparous cows fitted with rumen cannula and 4 multiparous intact cows) were blocked by parity and assigned to one of two 4 × 4 Latin squares balanced for carryover effects with a 2 × 2 factorial arrangement of treatments. Treatments were dietary starch content [20.6 vs. 27.5%, respectively, for low starch (LS) and high starch (HS)] and butyrate supplementation (butyrate vs. control) with 21-d periods. Butyrate was provided as Gustor BP70 WS (Norel, S.A., Madrid, Spain), containing 70% sodium butyrate and 30% fatty acid mixture, at 2% of dietary dry matter (providing butyrate at 1.1% of dietary dry matter), and control premix contained 70% wheat bran and 30% fatty acid mixture. Feeds, orts, and fecal samples were collected from d 17 to 19 to determine apparent total-tract nutrient digestibility. Blood and rumen fluid samples were collected on d 19. The baseline of dry matter intake (DMI) was determined as average DMI from d 17 to 19 for each cow, and cows were feed-restricted at 60% of the baseline DMI on d 20, and a grain challenge was conducted by providing steam-flaked corn grain at 0.6% of body weight, on an as-fed basis, in addition to each treatment diet on d 21, and blood and ruminal fluid samples were collected. The interaction of dietary starch content by butyrate supplementation was significant for plasma GLP-2 concentration, being greater for cows fed butyrate with the HS diet than those fed the other 3 diets. Cows fed butyrate increased n-butyrate concentration in the ruminal fluid and tended to increase dry matter and organic matter digestibility compared with the control. During the grain challenge, rumen endotoxin concentration increased over time and was higher for cows fed the HS diets compared with those fed LS diets. However, response variables related to inflammation were not affected by the grain challenge. However, serum haptoglobin, lipopolysaccharide-binding protein, and serum amyloid-A concentrations were greater for cows fed butyrate with the LS diet, but not for those fed the HS diet. These results indicate that butyrate supplementation may increase plasma GLP-2 concentration for cows fed HS diets, and total-tract digestibility regardless of dietary starch content. However, butyrate supplementation did not mitigate inflammation in this study.

The objective of this study was to examine whether serum iron (Fe) concentration is useful as a prognostic biomarker for cows with acute coliform mastitis (ACM). Our study was composed of determining the reproducibility of serum Fe concentration as a prognostic criterion in cows with ACM (Study 1) and clarifying the sequential changes in serum Fe concentration in cattle that received endotoxin (Study 2). Seventy-seven cows with (n = 47) or without (n = 30) ACM were enrolled in Study 1. The proposed diagnostic cut-off value of serum Fe concentration indicating a poor prognosis of ACM based on the analysis of the receiver operating characteristic curves was < 31.5 µg/dL. Ten young cattle aged 176.8 ± 23.7 days were enrolled in Study 2. Five young cattle received endotoxin (LPS group) and the remaining five received physiological saline (control group). Blood collections were carried out before endotoxin challenge (pre), and 0.5, 1, 2, 4, 8, 12, 24, and 48 h after the challenge. As a result, a significant decrease in serum Fe concentration was not observed until 24 h after endotoxin challenge. Because in cows with clinical ACM it is difficult to know the time course after infection, the alteration in serum Fe concentrations alone may be an insufficient prognostic criterion.

The aim of present study was to evaluate the precision of plasma haptoglobin (HPT), serum iron (Fe) and plasma transferrin (Tf) concentrations as biomarkers of the severity of acute mastitis (AM) in cows. Fourteen Holstein Friesian cows with AM were divided into severe (n=8) and mild groups (n=6) based on systemic and local inflammation, and 12 healthy cows were also enrolled as controls. As a result, significant changes were observed in plasma HPT and serum Fe concentrations. The proposed cut-off points for plasma HPT and serum Fe concentrations for the severity of AM in cows based on receiver operating characteristic analyses were >10.3 µg/ml and

The aim of this study was to examine whether 2.16% hypertonic saline solution (HSS) is useful for the treatment of diarrheic calves with hyponatremia. Eleven of 13 female Holstein calves exhibiting moderate diarrhea and hyponatremia received 1,250 ml of 2.16% HSS over 15 min regardless of body weight. The remaining two calves that were unable to stand and had severe hyponatremia received 2,500 ml of 2.16% HSS intravenously over 30 min. As a result, hyponatremia in all diarrheic calves was significantly improved by the administration of 2.16% HSS from 122.2 ± 7.0 mEq/l at pre to 134.8 ± 3.7 mEq/l at post, which was above the threshold of 132 mEq/l for hyponatremia. Therefore, 2.16% HSS may be useful for hyponatremia in calves with diarrhea.

The aim of study was to investigate the relationships among serum diamine oxidase (DAO) activity, postnatal days and the plasma copper (Cu) concentration, using calves with or without diarrhea. In healthy calves, the serum DAO activity was significantly higher at 2 postnatal days than at ≥7 postnatal days, and no significant changes were observed after 7 postnatal days. In addition, no significant correlation was found between serum DAO activity and plasma Cu concentration at all postnatal days in healthy calves. Although, the serum DAO activity in 14 diarrheic calves (66.78 ± 14.37 IU/ml) was lower than that in 19 healthy calves (170.33 ± 97.83 IU/ml, P

Background: Some foods can exacerbate the symptoms of irritable bowel syndrome (IBS), although the associations between the pathophysiology of IBS and IgG food antibodies levels are not well known. We examined IgG antibodies elicited in response to food and celiac disease in diarrhea-predominant IBS (IBS-D). Methods: Twenty patients with IBS-D and 20 healthy controls (HC), were enrolled. Serum immunoglobulin (Ig) G antibodies to 88 dietary items were measured and scored in accordance with the rate of antibody positivity. Serum tissue transglutaminase-IgA (tTG-IgA) and IgA endomysial antibody (EMA) were measured as markers of celiac disease. Serum IgE antibodies were also measured. Results: For the 88-item food-related IgG scores there was no significant difference in the number of dietary items with a ≥ 0.5 IgG score between the IBS and HC groups. Total IgG scores between groups were not significantly different. Scores for wheat, rye, and oats were not significantly different for the IBS versus the HC group. IgG scores for apples were significantly higher in the IBS versus the HC group. Serum tTG-IgA and EMA titers were negative in both groups and not significantly different between groups. Serum IgE was also not significantly different between groups. One patient with high titers for wheat, rye, and oats had duodenal mucosa histology classified as Marsh 1 and was negative for human leukocyte antigen DQ haplotypes HLA-DQ2/HLA-DQ8. Conclusions: We investigated IgG antibodies to food, tTG-IgA, and EMA in patients with IBS-D in whom IgG levels are likely influenced by dietary habits.