Effects of isovolemic resuscitation with hemoglobin-based oxygen carrier Hemoglobin glutamer-200 (bovine) on systemic and mesenteric perfusion and oxygenation in a canine model of hemorrhagic shock: a comparison with 6% hetastarch solution and shed blood

OBJECTIVE: To study Hemoglobin glutamer-200 bovine (Hb-200), 6% hetastarch (HES) and shed whole blood (WB) resuscitation in canine hemorrhagic shock. STUDY DESIGN: Prospective laboratory investigation. Animals Twelve adult dogs [29 +/- 1 kg (mean +/- SD)]. METHODS: Anesthetized dogs were instrumented for recording systemic and mesenteric hemodynamic parameters and withdrawal of arterial, mixed and mesenteric venous blood, in which hematological, oxygenation, blood gas and acid-bases variables were determined. Recordings were made before [baseline (BL)], after 1 hour of hypovolemia and immediately and 3 hours post-resuscitation with 30 mL kg(-1) of either Hb-200, HES, or WB. RESULTS: Blood withdrawal (average 34 +/- 2 mL kg(-1)) caused significant hemodynamic changes, metabolic acidosis and hyperlactatemia characteristic for hemorrhagic shock. Only WB transfusion restored all variables. Hemoglobin glutamer-200 bovine infusion returned most hemodynamic parameters including cardiac output and mesenteric arterial blood flow to BL but increased mean arterial pressure above BL (p < 0.05). However, Hb-200 failed to restore total Hb and arterial oxygen content (CaO2), leaving systemic (DO2I) and mesenteric O2 delivery (DO2Im) below BL (p < 0.05). Nevertheless, acid-base variables recovered completely after Hb-200 resuscitation, and met-hemoglobin (Met-Hb) levels increased (p < 0.05). Hetastarch resuscitation returned hemodynamic variables to or above BL but further decreased total Hb and CaO2, preventing recovery of sDO2I and mDO2I (p < 0.05). Thus, systemic and mesenteric O2 extraction stayed above BL (p < 0.05) while acid-base variables recovered to BL, although slower than in Hb-200 and WB groups (p < 0.05). CONCLUSIONS AND CLINICAL RELEVANCE: Resuscitation with Hb-200 seemed to resolve metabolic acidosis and lactatemia more rapidly than HES, but not WB; yet it is not superior to HES in improving DO2I and DO2Im. The hyperoncotic property of solutions like Hb-200 that results in rapid volume expansion with more homogenous microvascular perfusion and the ability to facilitate diffusive O2 transfer accelerating metabolic recovery may be the key mechanisms underlying their beneficial effects as resuscitants.     

Current development and use of hemoglobin-based oxygen-carrying (HBOC) solutions

Objective: To review the human and veterinary literature on the current development and use of hemoglobin‐based oxygen‐carrying solutions. Human data synthesis: Hemoglobin‐based oxygen‐carrying (HBOC) solutions have been developed extensively over the last 3 decades. Early problems associated with pure hemoglobin and cytoskeleton residues have been resolved with chemical modification of the hemoglobin tetramer resulting in effective oxygen‐carrying molecules of either human or bovine origin. The limited availability of human red blood cells and concerns of disease transmission, the difficulty in mass production of genetically produced hemoglobin solutions (recombinant hemoglobin), and the wide availability of bovine blood have resulted in the development of bovine‐derived HBOC solutions. Research efforts have been directed toward determining the effects of HBOC solutions on tissue perfusion as the target uses of HBOC solutions in human medicine are the perioperative period, shock, and trauma fluid resuscitation. The most controversial issues regarding the cardiovascular effects of HBOC solutions surround increased vasoactivity. Some HBOC formulations have been removed from advanced clinical trials due to intense vasoactivity resulting in increased morbidity. There are currently 3 HBOC solutions in the latter stages of phase III clinical trials: Hemolink®, ^a Hemopure®, ^b and PolyHeme®. ^c The hemoglobin source of Hemopure® is bovine, and the hemoglobin source for Hemolink® and Polyheme® is human. Veterinary data synthesis: The only HBOC solution that has gained approval from the FDA is the veterinary product Oxyglobin®. ^d Oxyglobin® is 13 g/dL of ultrapurified, polymerized hemoglobin solution of bovine origin in a modified lactated Ringer's solution. There is a significant colloid effect and it also provides a plasma source of oxygen‐carrying capacity. The solution is stable at room temperature for 3 years; there is no special preparation required prior to use and no cross‐match is required prior to administration (contains no cell membranes). Veterinary publications on the use of Oxyglobin® include laboratory investigations in dogs, cats, and horses for use as a resuscitation fluid and for the treatment of anemia. Clinical use of Oxyglobin® in dogs, cats, birds, horses, and other mammalian species has been reported in several publications. Conclusion: The search for a safe, effective HBOC solution for use in human medicine is ongoing. Soon, there will be one or several products approved for use in the perioperative period and/or for the treatment of shock and trauma. The practice of veterinary emergency and critical care has been provided a unique opportunity to apply the use of an HBOC solution (Oxyglobin®) to various aspects of perfusion and oxygen‐carrying needs. Continued clinical experience and research is essential in understanding the use of HBOC solutions in veterinary medicine.     

Comparison of fluid types for resuscitation after acute blood loss in mallard ducks (Anas platyrhynchos)

Objective – The purpose of this study was to determine the LD₅₀ for acute blood loss in mallard ducks ( Anas platyrhynchos ), compare the mortality rate among 3 fluid resuscitation groups, and determine the time required for a regenerative RBC response.
Design – Prospective study.
Setting – Medical College of Wisconsin Research facility.
Animals – Eighteen mallard ducks were included for the LD₅₀ study and 28 for the fluid resuscitation study.
Interventions – Phlebotomy was performed during both the LD₅₀ and fluid resuscitation studies. Ducks in the fluid resuscitation study received a 5 mL/kg intravenous bolus of crystalloids, hetastarch (HES), or a hemoglobin-based oxygen-carrying solution (HBOCS).
Measurements and Main Results – The LD₅₀ for acute blood loss was 60% of total blood volume. This blood volume was removed in the fluid resuscitation study to create a model of acute blood loss. Following fluid administration, 6 birds in the crystalloid group (66%), 4 birds in the HES group (40%), and 2 birds in the HBOCS group (20%) died. No statistical difference in mortality rate was seen among the 3 fluid resuscitation groups. Relative polychromasia evaluated post-phlebotomy demonstrated regeneration starting at 24 hours and continuing through 48 hours.
Conclusions – The LD₅₀ for acute blood loss in mallard ducks was 60% of their total blood volume. Although no statistical difference in mortality rate was appreciated among the 3 fluid resuscitation groups, a trend of decreased mortality rate was observed in the HBOCS group. An early regenerative response was apparent following acute blood loss.     

家蚕耐氟与敏感品种乙酰胆碱酯酶的比较研究

用浸叶法添氟以检测氟对家蚕乙酰胆碱酯酶的影响。实验结果显示,添氟后蚕体乙酰胆碱酯酶活性降低,耐氟品种添氟组与对照组差距小于敏感品种;耐氟品种添氟后酶原蛋白含量高于对照组,敏感品种酶原蛋白含量始终低于对照组。研究结果表明,耐氟品种通过乙酰胆碱酯酶基因表达量的增加弥补了氟对乙酰胆碱酯酶活性的影响,使乙酰胆碱酯酶活性总体持平,从而使家蚕产生耐氟性。     

Effect of epidermal growth factor (EGF) on the phosphorylation of mitogen-activated protein kinase (MAPK) in the bovine oviduct in vitro: Alteration by heat stress

Epidermal growth factor (EGF) has been shown to be involved in control of the oviductal microenvironment. To elucidate the potential mechanisms responsible for the detrimental effect of heat stress and to identify the relation with the endocrine status, the effects of EGF on the level of phosphorylated mitogen-activated-protein kinase (MAPK) and proliferation of bovine oviductal epithelial cells (OECs) exposed to different cyclic ovarian steroidal environments (luteal phase (LP), follicular phase (FP) and postovulatory phase (PO)) and temperatures (mild heat stress (40 C) and severe heat stress (43 C)) were investigated. Western blot was performed to evaluate phosphorylated MAPK, while proliferation was analyzed by MTT assay. Stimulation of OECs with EGF alone or with EGF in the PO and FP environments significantly increased the amount of phosphorylated MAPK, with MAPK 44 phosphorylation being highest during exposure to PO conditions. These effects were not observed in the LP. Heat treatment completely blocked effects of EGF on phosphorylated MAPK. Additionally, severe heat stress led to a significantly lower basal level of phosphorylated MAPK. PD98059 (MAPK inhibitor) completely abolished EGF-stimulated MAPK phosphorylation and OECs proliferation. Overall the results indicate that EGF has the potential to increase the amount of phosphorylated MAPK in OECs and therefore could be involved in regulation of the bovine oviductal microenvironment. However, these regulatory mechanisms may be compromised in the presence of heat stress (high ambient temperature), leading to low fertility rates and impaired embryo survival.     

莲花花粉营养成分分析

对莲花花粉的主要营养成分进行了分析测定,结果发现,莲花花粉的含水量7.88%、灰分4.09%、脂肪5.59%、蛋白质15.26%、还原糖7.05%;维生素含量较高的有:VC102mg/100g,VE1.21mg/100g,VB10.6mg/100g,其它维生素未检测到;钾和镁的含量高于大多数花粉;17种氨基酸的含量为15.81%,7种人体必需氨基酸占44.23%,其中以谷氨酸和天门冬氨酸的含量最高,分别为2.24%和2.15%,胱氨酸含量最低,为0.14%;脂肪酸中以棕榈酸含量最高,相对含量为42.23%,亚麻酸、油酸和亚油酸的相对含量分别为25.17%、12.83%和9.90%,PUFA/SFA比值为0.75。本文还首次测定了莲花花粉的水浸率和醇浸率,分别为49.70%和47.35%。建议结合抗氧化能力和测定主要活性成分含量,作为花粉质量控制的指标。     

Retrospective analysis of the clinical utility of ambulatory electrocardiographic (Holter) recordings in syncopal dogs: 44 cases (1991-1995)

The objective of this study was to evaluate retrospectively the clinical utility of ambulatory (Holter) electrocardiographic monitoring in syncopal dogs and to compare the Holter recording with the clinic electrocardiogram (ECG) in these animals. Fifty Holter reports and 44 medical records from 44 dogs were evaluated. A syncopcal episode occurred during monitoring in 24% of the recordings. No obvious relationship was found between the frequency of syncope occurring before Holter recording and the likelihood of a dog having an episode during recording. Holter recordings were helpful in establishing a diagnosis 42% of the time, but no relationship was detected between the frequency of episodes occurring before Holter recording and the likelihood of a diagnostically useful Holter. An arrhythmia was ruled out as the cause of syncope in 12% of the recordings and was implicated as the cause of syncope in 30% of recordings. Of these, 20% were ventricular tachyarrhythmias and 10% were bradyarrhythmias including pacemaker failure. Ambulatory electrocardiographic recordings led to a therapeutic change in 38% of cases. A comparison of the Holter recordings and clinic ECGs documented the expected increased sensitivity for Holter detection of arrhythmias. The average clinic ECG heart rate consistently exceeded the average Holter heart rate with a mean difference between the average heart rates recorded by the two techniques of 31 bpm (range -8-87 bpm).     

Inhibitory effect of insulin-like growth factor-binding protein-7 (IGFBP7) on in vitro angiogenesis of vascular endothelial cells in the rat corpus luteum

Angiogenesis in the developing corpus luteum (CL) is a prerequisite for establishment and maintenance of an early pregnancy. To explore the physiological significance of insulin-like growth factor-binding protein-7 (IGFBP7) in the developing CL, the effects of IGFBP7 on vascular endothelial growth factor (VEGFA)- and luteinizing hormone (LH)-induced in vitro tube formation were tested using isolated luteal microvascular endothelial cells (LECs). Capillary-like tube formation of LECs and their proliferation were stimulated by both VEGFA and LH. IGFBP7 treatment suppressed VEGFA- or LH-induced tube formation. The proliferation and migration of LECs, and phosphorylation of mitogen-activated protein kinase kinase and extracellular signal-regulated kinase 1/2 were inhibited by IGFBP7. Furthermore, IGFBP7 attenuated VEGFA-enhanced cyclooxygenase (COX)-2 mRNA expression and prostaglandin E₂ secretion. These findings suggest the possibility that luteal IGFBP7 secretion may suppress the stimulatory effect of VEGFA on angiogenesis in the early CL.     

A Spontaneous Oligodendroglioma in the Lumbar Portion of the Spinal Cord in a Young BrlHan:WIST@Jcl (GALAS) Rat

Oligodendroglioma is a rare tumor originating from oligodendrocytes found mainly in the cerebrum in aged rats. Only a few reports have shown spontaneous occurrence of this tumor in the spinal cord, and no report has mentioned its occurrence in young rats. We encountered a case of spontaneous oligodendroglioma in the lumbar portion of the spinal cord in a young (9 weeks old) female BrlHan:WIST@Jcl (GALAS) rat. Here we report the detailed histopathological and immunohistochemical characteristics of this case. No clinical signs, no gross lesions at necropsy, and no specific changes in hematology or blood biochemistry were observed. The tumor was located in the dorsal funiculus in the lumbar portion of the spinal cord and widely spread to the dorsal root nerve. The neoplastic cells showed a sheet-like growth pattern and had small round nuclei, clear cytoplasm and distinct cell borders that resulted in a honeycomb pattern. No mitotic figures or other histological lesions were observed. The neoplastic cells were positively stained for Olig2 and PCNA. The present case was considered to be a low-grade oligodendroglioma based on the histological and immunohistochemical features. To our knowledge, our case is considered to be extremely rare and the first report in a young rat.     

Carrier rate of the c.235G>C mutation in the bovine isoleucyl-tRNA synthetase (IARS) gene of Japanese Black cows at Kagoshima prefecture, Japan,and analysis of the metabolic profiling and reproductive performance of heterozygous cows

Bovine isoleucyl-tRNA synthetase (IARS) disorder, a major cause of weak calf syndrome, is caused by a homozygous missense (c.235G>C) mutation in the bovine IARS gene of Japanese Black (JB) cattle, which was identified in 2013. However, the extent to which the carrier rate has changed at Kagoshima prefecture, Japan, and whether the carrier status is associated with any clinical or reproductive problems, have yet to be ascertained. In this study, using a real-time polymerase chain reaction-based genotyping assay, we determined the carrier rate in a regional JB cow population at Kagoshima prefecture. Comparative analyses were performed on the metabolic profile test (MPT) results and reproductive performance data obtained for heterozygous carrier and homozygous wild-type cows. In 2009 and 2018, DNA samples were collected from 130 and 462 clinically healthy JB cows, respectively, in Kagoshima prefecture. MPT results and reproductive performance data were evaluated for 62 cows, comprising four heterozygous carriers and 58 wild-type cows. Genotyping revealed that the carrier rate was 6.9% in 2009 and 1.5% in 2018, the difference of which was statistically significant (P<0.005). There were no statistically significant differences between the carrier and wild-type cows with respect to either MPT results or reproductive performance, indicating that the carrier cows have necessary IARS activity to maintain minimal health and reproductive potential.     

Vasculature of the ophthalmic rete in night herons (Nycticorax nycticorax): scanning electron microscopy of corrosion casts

Vasculature of the ophthalmic rete (rete ophthalmicum) in the night heron (Nycticorax nycticorax) was studied using scanning electron microscopy of vascular corrosion casts and light microscopy on tissue sections. Most blood to the eyeball and a lesser volume of blood to the brain passed through the ophthalmic rete via the external ophthalmic artery. The collateral retial arterioles originated from the external ophthalmic artery forming a flat and fusiform-shaped arterial network at the ventrotemporal region of the eyeball. The arterial network was intermixed with a similar complex of the veins from the eye. The ophthalmotemporal artery, which supplied the eyeball posteriorly, and supraorbital and infraorbital arteries, which supplied the eyeball anteriorly, originated from the rete. Blood from the eye, which is a site of potential heat loss, drained into the ophthalmic rete via the ophthalmotemporal vein. On the casts of retial arterioles, slit-like cleavages at branching sites representing flap valves, which might play a role as sluice valves, were seen. In addition, marks of circularly running grooves, which might represent tufts of smooth muscle cells and might contribute to a sphincter activity, were observed. These anatomical specializations of the avian ophthalmic rete, involving parallel arrangement of arteries and veins, may function to facilitate counter-current heat exchange and to regulate blood pressure and volume to the eye and the brain.     

Malignant Mesothelioma in the Thoracic Cavity of a Crj:CD(SD) Rat Characterized by Round Hyalinous Stroma

Spontaneous malignant mesothelioma was found in a 104-week-old male Crj:CD(SD) rat. The tumor was scattered on the surface of the lung, heart, mediastinal pleura and thoracic wall and metastasized to the alveolar septa. Histopathologically, small flattened or cuboidal tumor cells proliferated with stroma, formed almost normal papillary structures and reacted positively to colloidal iron stain and immunohistochemical staining for mesothelin. Round hyalinous stromata were pronounced, which is a characteristic feature, and the possible reason for this is as follows; at first, a small amount of collagen fibers was formed in the center of the clusters of several tumor cells, and then the cell clusters expanded like balloons with an increase in the collagen fibers.     

Changes in the risk management of Salmonella enterica subspecies diarizonae serovar 61:(k):1, 5, (7) in Swedish sheep herds and sheep meat due to the results of a prevalence study 2012

Background

The prevalence of Salmonella in food producing animals is very low in Sweden due to rigorous control programmes. However, no active surveillance is in place in sheep. The authorities decided to perform a prevalence study in sheep herds because findings at slaughter indicated that sheep associated S. diarizonae (S. enterica subspecies diarizonae serovar 61:(k):1, 5, (7)) might be common in sheep. Sampling was stratified by herd size in two groups, small herds with ≤ 30 animals and large herds with > 30 animals. In each stratum, 237 herds were selected at random. Faecal samples received from 244 out of the 474 randomly selected herds were analysed.

Results

A total of 40 of 100 (40%) of large herds and 17 of 144 (12%) of small herds were positive. The overall adjusted prevalence was 17.6% (95% CI, 12.9-22.2). Sheep associated S. diarizonae was detected in all counties (n = 21). Scientific opinions and an evaluation of on-farm control measures performed concluded that the impact of sheep associated S. diarizonae on human health is very low, and that risk management measures applied in response to findings of sheep associated S. diarizonae in sheep or sheep meat can be expected to have very little impact on reducing risks to human health. As a result, Swedish authorities decided to make an exemption for sheep associated Salmonella diarizonae in sheep and sheep meat in the current Salmonella control measures.

Conclusions

Sheep associated S. diarizonae is endemic in Swedish sheep herds. It is more common in large herds and not limited to certain parts of the country. The responsible authorities concluded that current risk management actions regarding sheep associated S. diarizonae in sheep and sheep meat are not proportional to the risk. This is the first time in the history of the Swedish Salmonella control programme that an exemption from the legislation has been made for a specific serovar. If there is any future indication of an increasing risk, due to e.g. change in the pathogenicity or development of antimicrobial resistance, the risk assessment will be re-evaluated and control measures reinforced if needed.