Sex-dependent differences in inflammatory responses during liver regeneration in a murine model of acute liver injury.

A sexual dimorphism in liver inflammation and repair was previously demonstrated. Its cellular dissection in the course of acute liver injury (ALI) was explored. BALB/c mice were treated with carbon tetrachloride (CCl4) by intraperitoneal injection and killed after 3, 5, and 8 days. Histological and hepatic cell population analyses were performed. The correlation between androgen receptor (AR) expression and liver recruited inflammatory cells was investigated by treatment with the AR antagonist flutamide. Additionally, patients with a diagnosis of drug induced liver injury (DILI) were included in the study, with a particular focus on gender dimorphism in circulating monocytes. A delayed resolution of necrotic damage and a higher expression of proinflammatory cytokines were apparent in male mice along with a slower recruitment of inflammatory monocytes. F4/80+CD11b+ macrophages and CD11bhighGr-1high monocytes expressed AR and were recruited later in male compared with female livers after CCl4 treatment. Moreover, CD11bhighAR+Gr-1high recruitment was negatively modulated by flutamide in males. Analysis of DILI patients showed overall a significant reduction in circulating mature monocytes compared with healthy subjects. More interestingly, male patients had higher numbers of immature monocytes compared with female patients.A stronger cytotoxic tissue response was correlated with an impaired recruitment of CD11bhighAR+Gr-1high cells and F4/80+CD11b+ macrophages in the early inflammatory phase under AR signaling. During DILI, a dimorphic immune response was apparent, characterized by a massive recruitment of monocytes to the liver both in males and females, but only in males was this recruitment sustained by a turnover of immature monocytes.

Metabolic signature of Mycobacterium avium subsp. paratuberculosis infected and infectious dairy cattle by integrating nuclear magnetic resonance analysis and blood indices.

The early diagnosis of Mycobacterium avium subsp. paratuberculosis (MAP) is one of the current challenges of farmers and veterinarians. This work aimed to investigate the changes in metabolic levels associated with natural MAP infection in infected and infectious dairy cattle. The study included sera from 23 infectious/seropositive, 10 infected but non-infectious/seronegative, and 26 negative Holstein Fresian cattle. The samples were selected from a collection of samples gathered during a prospective study. The samples were analyzed by quantitative nuclear magnetic resonance (NMR) spectroscopy and routine blood chemistry. The blood indices and the 1H NMR data were concatenated by low-level data fusion, resulting in a unique global fingerprint. Afterwards, the merged dataset was statistically analyzed by the least absolute shrinkage and selection operator (LASSO), which is a shrinkage and selection method for supervised learning. Finally, pathways analysis was performed to get more insights on the possible dysregulated metabolic pathways. The LASSO model achieved, in a 10 time repeated 5-fold cross-validation, an overall accuracy of 91.5% with high values of sensitivity and specificity in classifying correctly the negative, infected, and infectious animals. The pathway analysis revealed MAP-infected cattle have increased tyrosine metabolism and enhanced phenylalanine, tyrosine and tryptophan biosynthesis. The enhanced synthesis and degradation of ketone bodies was observed both in infected and infectious cattle. In conclusion, fusing data from multiple sources has proved to be useful in exploring the altered metabolic pathways in MAP infection and potentially diagnosing negative animals within paratuberculosis-infected herds.

Hematological Parameters from the Feline Blood Donor to the Blood Unit: What Changes Are to Be Expected?

Feline blood donation requires sedation to allow for good blood collection, avoiding venous damage and unnecessary donor stress. In the present study, we describe the variation of hematological parameters in a population of 74 healthy blood-donor cats that underwent the same sedation protocol, including medetomidine, alfaxalone, and butorphanol. Changes in hematological parameters were evaluated in blood samples collected from conscious cats (group A), sedated cats (group B), and feline whole-blood units (FBUs) (group C). Significant differences were observed between unsedated and sedated cats: the mean RBC count, HGB, HCT, and RDW were significantly lower in sedated cats than in conscious ones, with a difference of 17.95%, 18.42%, 28.21%, and 10.00%, respectively. In accordance with previously reported data, our results confirm that sedation is a critical procedure in cats that can affect most of the hematological parameters. The second finding of our study is that no significant differences for the main hematological parameters were observed between sedated cats and FBUs, thus suggesting that the dilution with the conservative-anticoagulant solution exert negligible effects on these parameters with respect to samples of sedated animals. This hematological change must be taken into consideration since such parameters are important to define the quality of FBUs.

Effects of leukoreduction on storage lesions in whole blood and blood components of dogs.

BACKGROUND: Leukoreduction is a routine procedure in human transfusion medicine but is uncommon in veterinary. OBJECTIVES: To evaluate the effect of leukoreduction on the quality of canine whole blood (WB) and blood products during storage. ANIMALS: Ten canine blood donors. METHODS: This is a case series study. An amount of 450 mL of blood was collected from each dog. Five WB and 5 packed red blood cells (pRBC) bags were divided into 2 units each: leukoreduced (LR) and non-leukoreduced (nLR). RBC count, erythrocytes' mean osmotic fragility (MOF), 2,3-diphosphoglycerate (2,3-DPG), adenosine triphosphate (ATP), percentage of hemolysis, potassium (K), lactate, glucose, and cytokines were measured weekly from day of donation (T0) to day 35 (T35); pH, coagulation times, and clotting factors were evaluated at T0 and T35 from WB and in fresh frozen plasma after 1 year of storage. RESULTS: Leukoreduction showed positive effects on lactate (T35: LR WB 14.42 mmol/L SD 2.71, nLR WB 22.42 mmol/L SD 1.86, LR pRBC 20.88 mmol/L SD 2.65, nLR pRBC 36.81 mmol/L SD 2.34; P < .0001), pH (T35: LR WB 6.88 SD 0.16, nLR WB 6.69 SD 0.20, P = .02; LR pRBC 6.57 SD 0.23, nLR pRBC 6.22 SD 0.11; P < .001), and K (LR pRBC 4.08 mmol/L SD 0.88, nLR pRBC 5.48 mmol/L SD 0.90; P < .001). Increasing values of IL8 were observed in nLR units during storage (T0: 4167 ± 11 888 pg/mL; T35: 6367 ± 11 612 pg/mL). CONCLUSION AND CLINICAL IMPORTANCE: LR blood units are recommended to critically ill dogs with marked inflammatory conditions.