Prekallikrein deficiency in a family of Belgian horses

A 7-year-old Belgian stallion hemorrhaged excessively after castration; the hemostatic mechanism was investigated. The horse had normal one-stage prothrombin time and markedly prolonged activated partial thromboplastin time (APTT). Results of intrinsic coagulation factor assays were all normal with the exception of prekallikrein activity, which was markedly reduced (less than 1% activity; value for control population, 63 to 150%). Two of this horse's full siblings, a brother and sister, had markedly prolonged APTT and low prekallikrein values (2.5% and less than 1%, respectively). The addition of plasma from a normal equine plasma pool corrected the prolonged APTT in the 3 Belgian sibling with low prekallikrein activity. Prekallikrein activity in 10 other closely related Belgian horses ranged between 12.5 and 64% (mean, 29.3%), compared with 63 to 150% (mean, 91%) in 10 mixed-breed horses. In the 3 Belgian siblings with low prekallikrein activity, the APTT approached normal after prolonged incubation (15 minutes) with the contact activator and in response to addition of an ellagic acid activator. The 3 Belgian siblings with low prekallikrein activity may be homozygous for prekallikrein deficiency, whereas the other close relatives may be heterozygous for the genetic defect.     

Prekallikrein deficiency in a family of miniature horses

Two sibling miniature horses, a male and a female, had a normal 1-stage prothrombin time and a prolonged activated-partial thromboplastin time (APTT). The addition of as little as 5% of a normal equine plasma pool to the plasma samples of both horses shortened their prolonged APTT to within normal limits. Coagulation factor analysis revealed deficiencies in factor XII (12 and 13 U/dl, control population 77 to 128 U/dl), when determined with a feline factor XII-deficient plasma substrate, but normal concentrations (119 and 96 U/dl) when a human factor XII-deficient plasma substrate was used. Deficiencies of another factor, prekallikrein, were detected with a human prekallikrein-deficient plasma substrate (16 and 6 U/dl, control population 70 to 173 U/dl). Other intrinsic coagulation factors were present in normal concentrations. The APTT was measured with plasma from the 2 horses after various incubation periods (1 to 15 minutes) with a contact activator before the addition of Ca ions. With incubation times of greater than or equal to 10 minutes, the APTT of both horses were essentially the same as that of the normal equine plasma pool. Several family members of the 2 prekallikrein-deficient miniature horses appeared to be heterozygous carriers of the prekallikrein deficiency.     

Factor XII and partial prekallikrein deficiencies in a dog with recurrent gastrointestinal hemorrhage

Factor XII deficiency and impaired prekallikrein activity were diagnosed in a 1-year-old Chinese Shar Pei. The dog experienced repeated episodes of intestinal hemorrhage and diarrhea. Laboratory findings were compatible with blood loss (iron deficiency anemia and hypoproteinemia). Necropsy findings suggested mild infiltrative bowel disease that could have been responsible for the dog's diarrhea, but no explanation for the severe recurrent gastrointestinal hemorrhage could be found. Factor XII deficiency is uncommon in the dog and is not associated with hemorrhagic tendencies. The factor XII deficiency in this case may have contributed to the gastrointestinal hemorrhage.     

Genetics of equine bleeding disorders

Genetic bleeding disorders can have a profound impact on a horse's health and athletic career. As such, it is important to understand the mechanisms of these diseases and how they are diagnosed. These diseases include haemophilia A, von Willebrand disease, prekallikrein deficiency, Glanzmann's Thrombasthenia and Atypical Equine Thrombasthenia. Exercise-induced pulmonary haemorrhage also has a proposed genetic component. Genetic mutations have been identified for haemophilia A and Glanzmann's Thrombasthenia in the horse. Mutations are known for von Willebrand disease and prekallikrein deficiency in other species. In the absence of genetic tests, bleeding disorders are typically diagnosed by measuring platelet function, von Willebrand factor, and other coagulation protein levels and activities. For autosomal recessive diseases, genetic testing can prevent the breeding of two carriers.     

Vitamin E deficiency in dogs with retinal pigment epithelial dystrophy

The role of vitamin E deficiency in the development of retinal pigment epithelial dystrophy was investigated in 11 cocker spaniels and four other dogs. The concentration of alpha-tocopherol was measured by high performance liquid chromatography in plasma samples obtained from the affected dogs and from 28 ophthalmoscopically normal, healthy control dogs. The mean (sd) plasma alpha-tocopherol concentration in the normal dogs was 20.2 (7.1) microg/ml, compared with 1.14 (0.67) microg/ml in the 11 affected cocker spaniels. The difference between the two groups remained highly significant when the alpha-tocopherol concentrations were expressed relative to the concentrations of the plasma lipids cholesterol and triglycerides. Low plasma concentrations of alpha-tocopherol were observed in the four affected dogs of other breeds, but the finding was not so consistent. The plasma lipid concentrations were normal in the affected dogs. The deficiency of alpha-tocopherol in the affected dogs appeared to be primary, because there was no clinical, biochemical or pathological evidence of underlying disease, or any indication of a dietary deficiency which might have contributed to the low concentrations of alpha-tocopherol.     

Soluble parasite antigens from Babesia canis do not directly activate the kallikrein system in dogs infected with Babesia canis

Soluble parasite antigens (SPA) from Babesia canis have been shown to induce protective immunity when used as vaccine. In order to explain the immune mechanisms of vaccination, the precise role of SPA in the pathogenesis of canine babesiosis is under investigation. Earlier studies suggested that the plasma kallikrein system is central in the pathogenesis of babesiosis, malaria and trypanosomosis, and significant plasma kallikrein activation during acute B. bovis and P. knowlesi infections has been described. In the studies presented here dogs were experimentally infected with B. canis to investigate whether the plasma kallikrein system is activated during babesiosis infection. Results showed that prekallikrein levels decreased during episodes of peak parasitaemia. No effect was found on the kallikrein levels. In order to determine whether B. canis SPA could activate plasma kallikrein, dogs were infused with variable amounts of B. canis SPA and plasma samples were taken for (pre-) kallikrein determination. The results indicated that B. canis SPA did not affect plasma (pre-) kallikrein levels. In addition, the effect of B. canis SPA on (pre-) kallikrein levels in normal dog plasma was determined in vitro. Again, no effect on (pre-) kallikrein levels was found. The results suggest that, although the kallikrein pathway may be involved in B. canis-associated pathology, the system is not directly activated by B. canis SPA. Furthermore, infusion of B. canis SPA as well as stroma of normal dog erythrocytes triggered the production of the acute phase reactant, C-reactive protein. This suggests that the inflammatory response that is triggered during B. canis infection could be in part due to the release and exposure of self molecules. The implications of these findings are discussed.     

The probable role of Babesia argentina esterase in the in vitro activation of plasma prekallikrein

The purification of an esterase from B. argentina parasites, using affinity chromatography is described. Two fractions were obtained from crude “L” and “S” parasite extracts. The second fraction from each extract obtained after desorption of the column had a greatly enhanced esterase specific activity. When added to normal plasma and incubated at 37°C for 60 min, the second L₁ fraction activated between 12.1% and 72.3% of bovine plasma prekallikrein and the second S₁ fraction, 76.3% and 87.1%. Only slight activation occurred with fraction 1 of L₁ and S₁, and none with normal red cell components. The active fractions were associated with a fibrinogen-like substance and caused fibrin formation in vitro. The implications of these findings are discussed.     

Idiopathic hematuria of unilateral renal origin in a dog

Idiopathic hematuria of unilateral renal origin was diagnosed in a 3-month-old male Weimaraner. The hematuria had been visible grossly for 6 weeks. Extensive clinicopathologic, radiographic, and histologic evaluations localized the source of the hematuria to the right kidney, but could not identify a cause. Nephrectomy of the right kidney resolved the problem. This case report supports a previous article comparing canine idiopathic hematuria of renal origin with benign essential hematuria of human beings.     

Association between plasma vitamin E concentration and the risk of equine motor neuron disease

Equine motor neuron disease (EMND) is a neurodegenerative disorder of the somatic lower motorneurons that results in a syndrome of diffuse neuromuscular disease in the adult horse. The aetiology of this disorder is unknown, although prior studies have suggested that a deficiency in the lipid antioxidant vitamin E (α-tocopherol) contributes to the development of EMND. This paper describes a case-control study designed to investigate the association between plasma vitamin E levels and the risk of EMND for horses. Signalment, plasma vitamin E levels at the time of referral, and information relative to dietary and management practices were collected from 53 horses diagnosed with EMND and 69 controls. The mean plasma vitamin E concentration in EMND cases was significantly lower than that of control horses. After controlling for other risk factors of EMND, there was a statistically significant association between plasma vitamin E levels and EMND, with the likelihood of the disease increasing as the vitamin E concentration decreased. These findings support the reported role of vitamin E deficiency as one of the risk factors for EMND.     

Massive hematuria of nontraumatic renal origin in dogs

Massive hematuria of renal origin was diagnosed in 4 dogs. In all dogs, blood and blood clots were clearly visible in the urine. Serum urea nitrogen and urine concentrating ability were normal. All dogs were anemic, and results of coagulation and platelet function tests were within normal limits. Excretory urography indicated hydroureter and hydronephrosis in all dogs, with filling defects in the bladder attributable to large blood clots in 2 dogs. Cystotomy and catheterization of the ureters enabled identification of one kidney as the source of bleeding in 3 dogs. Unilateral nephrectomy and ureterectomy resolved their hematuria. The results of histologic examination were normal in 2 dogs. The 3rd dog had evidence of pyelitis. Cystoscopy of the 4th dog did not reveal hematuria from either ureter. The dog was not operated on and it continued to have intermittent hematuria.     

日粮不同有效磷水平对蛋雏鸡生长及组织钙磷含量的影响

选择 96只 1日龄健康的罗曼商品蛋鸡 ,随机分成 4个组 ,分别饲喂含有效磷为 0 1 1 %、0 2 %、0 4 %和 0 6 %的日粮。试验 30天。结果表明 ,低磷、高磷日粮显著降低增重和耗料量 (P <0 0 5) ;低磷日粮 ( 0 1 1 % )可导致雏鸡磷缺乏症及高死亡率 ,以生长迟缓、胸骨弯曲为早期的临床指征 ;试验至 1 0天 ,2、3组ACP活性显著高于 1、4组 (P <0 0 5)。试验至 30天 ,低磷日粮显著降低血浆磷含量(P <0 0 5)。试验至 1 0、2 0天 ,低磷日粮显著降低胫骨磷含量 (P <0 0 5)。血浆、胫骨磷水平可作为雏鸡磷缺乏症的早期实验室诊断指标。低磷日粮显著降低肾脏和胫骨钙含量 (P <0 0 5) ,表明低磷日粮对钙的代谢有不利的影响     

Plasma diamine oxidase: a biomarker of copper deficiency in the bovine

This study was designed to test the efficacy of plasma diamine oxidase (DAO) activity as a biomarker of Cu deficiency in the bovine. Angus steers (n = 11) and heifers (n = 17) were assigned to 1 of 3 treatments: 1) control (adequate dietary Cu), 2) Cu-deficient (-Cu), and 3) Cu-deficient plus high dietary Mn (-Cu+Mn), and fed from weaning through finishing. Molybdenum (2 mg/kg of DM) was supplemented to treatments -Cu and -Cu+Mn to induce Cu deficiency via the formation of ruminal thiomolybdates. Samples were collected on 2 sampling dates (d 160 and 190) to determine the efficacy of plasma DAO activity as a biomarker of Cu deficiency. For both sampling dates, liver Cu, plasma Cu, and plasma ceruloplasmin activity indicated that cattle receiving diets designed to induce Cu deficiency (-Cu and -Cu+Mn) were Cu-deficient, with all indices of Cu status lower (P < 0.001) than the control animals. In addition to these traditional indices of Cu status, plasma DAO activity also effectively identified Cu-deficient animals because plasma DAO levels were reduced (P < 0.001) by 2- to 3-fold compared with controls. Correlation analysis indicated that plasma DAO activity was highly correlated to all other indices of Cu status (Pearson R = 0.73 to 0.87). During the growing phase, ADG (P = 0.09) and G:F (P = 0.002) were depressed in Cu-deficient animals compared with controls, whereas cattle performed equally well across all treatments in the finishing phase. The plasma DAO activity assay was precise and reliable based on an intraassay CV of 4.4% and interassay CV of 11.1%. Due to increased variability, freezing and thawing of plasma samples resulted in significant changes in DAO activity relative to fresh plasma DAO activity values. Thus, fresh plasma DAO activity, a relatively simple assay, may serve as an effective tool to diagnose Cu deficiency in the bovine.     

Taurine deficiency in Newfoundlands fed commercially available complete and balanced diets

OBJECTIVE: To determine taurine status in a large group of Newfoundlands related by environment, diet, or breeding to a dog with dilated cardiomyopathy and taurine deficiency. DESIGN: Prospective study. ANIMALS: 19 privately owned Newfoundlands between 5 months and 11.5 years old that had been fed commercial dry diets meeting established nutrient recommendations. PROCEDURE: Diet histories were obtained, and blood, plasma, and urine taurine concentrations and plasma methionine and cysteine concentrations were measured. In 8 dogs, taurine concentrations were measured before and after supplementation with methionine for 30 days. Ophthalmic examinations were performed in 16 dogs; echocardiography was performed in 6 dogs that were taurine deficient. RESULTS: Plasma taurine concentrations ranged from 3 to 228 nmol/mL. Twelve dogs had concentrations < 40 nmol/mL and were considered taurine deficient. For dogs with plasma concentrations < 40 nmol/mL, there was a significant linear correlation between plasma and blood taurine concentrations. For dogs with plasma concentrations > 40 nmol/mL, blood taurine concentrations did not vary substantially. Taurine-deficient dogs had been fed lamb meal and rice diets. Retinal degeneration, dilated cardiomyopathy, and cystinuria were not found in any dog examined for these conditions. The taurine deficiency was reversed by a change in diet or methionine supplementation. CONCLUSIONS AND CLINICAL RELEVANCE: Results indicate a high prevalence of taurine deficiency among an environmentally and genetically related cohort of Newfoundlands fed apparently complete and balanced diets. Blood taurine concentrations indicative of taurine deficiency in Newfoundlands may be substantially less than concentrations indicative of a deficiency in cats.     

Persistent Hematuria as a Result of Chronic Renal Hypertension Secondary to Nephritis in a Stallion

A 13-year-old Lusitano stallion was referred to our institution with a history of severe hematuria for 8.5 months. The origin of the hematuria was determined to be the left kidney. The diagnostic workup failed to identify obstructive, infectious, or neoplastic conditions. The history and ultrasonographic examination suggested a chronic condition. The stallion was subjected to left nephrectomy because of the persistent hematuria and anemia. A histopathological examination detected lesions, which were compatible with chronic nephritis and vascular renal hypertension. It is hypothesized that changes in the normal parenchymal architecture produced a vascular aberration that led to renal hypertension, with subsequent blood extravasation and hematuria. The horse recovered completely after nephrectomy.     

Polyglandular deficiency syndrome in a boxer dog: Thyroid hormone and glucocorticoid deficiency

Summary

Primary hypothyroidism and partial primary adrenocortical deficiency (isolated glucocorticoid deficiency) were diagnosed in an 8‐year‐old spayed female boxer dog, presented because of progressive symmetrical truncal alopecia, lethargy, and intolerance to cold. The diagnosis was based upon the combination of low, non‐TSH‐responsive concentrations of plasma thyroxine and low urinary excretion of corticoids together with high plasma concentrations of ACTH. Normal suppressibility of ACTH concentrations by a low dose of dexamethasone indicated an intact feedback system. Plasma growth hormone levels were elevated, most probably because somatostatin release was depressed by the glucocorticoid deficiency.

The dog improved during oral replacement therapy with thyroxine until death ensued after 9 months as a result of intercurrent disease. Autopsy revealed thyroid atrophy and lymphocytic adrenalitis with complete destruction of the zona fasciculata and zona reticularis of the adrenal cortex.

The combination of primary hypothyroidism and primary adrenocortical deficiency in this dog is identical to the entity known as type II polyglandular autoimmunity or Schmidt's syndrome in humans. The adrenocortical insufficiency remained confined to glucocorticoid deficiency during the observation period; on no occasion did electrolyte concentrations in the plasma reach values suggestive of mineralocorticoid deficiency.     

Early phase components of the kallikrein kinin system in hemorrhagic ascitic fluid and plasma in the rat with induced acute pancreatitis

Acute hemorrhagic pancreatitis (AHP) was induced in 43 anesthetized rats by retrograde injection of sodium taurodeoxycholic acid into the common pancreatic biliary duct. At postinjection hours 1, 3, 6, 12, and 18, samples of plasma and hemorrhagic ascitic fluid (HAF) were obtained from rats in which AHP was induced and from rats that were sham operated. Early phase components of the kallikrein kinin system, including kallikrein-like (KK) activity and prekallikrein (PKK) and kallikrein inhibitor (KKI) concentrations, were measured in plasma and HAF samples. In the rats with induced AHP, PKK concentrations were decreased significantly in 18-hour plasma samples (P less than 0.05) and in all HAF samples (P less than 0.001) from 1 to 18 hours after induction of AHP. The KK activity was significantly increased (P less than 0.001) in the 6- and 12-hour plasma samples. In the 1-hour HAF samples, KK activity was increased greater than 10 times over that in the plasma pool of rats and remained increased for 18 hours. The KKI concentrations were markedly decreased in all HAF samples. In the sham-operated group, no significant change was observed. Histopathologic changes included edema, extensive hemorrhage, focal necrosis of many acinar cells around the head of the pancreas, slight inflammatory cell infiltration, vascular thrombosis, and partial lysis of pancreatic ducts. The extent of the changes of PKK, KK, and KKI values in HAF was greater than the extent of those in plasma. Increasing KK activity in plasma and HAF is indicative of bradykinin generation and the participation of this system in local and systemic pathologic change.(ABSTRACT TRUNCATED AT 250 WORDS)     

Canine specific ELISA for coagulation factor VII

Canine coagulation factor VII (FVII) deficiency can be hereditary or acquired and may cause life threatening bleeding episodes if untreated. FVII procoagulant activity can be measured by FVII activity (FVII:C), but assays for measurement of canine specific FVII antigen (FVII:Ag) have not been available to date. In this study, a canine specific ELISA for measurement of FVII:Ag in plasma was developed and validated. The FVII:Ag ELISA correctly diagnosed homozygous and heterozygous hereditary FVII deficiency. Together with activity based assays, such as FVII:C, the FVII:Ag ELISA should be valuable in the diagnosis of hereditary canine FVII deficiency.     

Epidemiology and diagnosis of subclinical iodine deficiency in crossbred cattle of Punjab.

OBJECTIVE: To determine the prevalence of iodine deficiency in crossbred cows (taurus x indicus) of Punjab and to assess the diagnostic value of the plasma concentrations of thyroid hormones, total cholesterol and free fatty acids in iodine deficiency. The efficacy of ethiodised oil, as a long-term supplement of iodine, was also evaluated. PROCEDURES: Base-line survey of iodine status was conducted by measuring plasma inorganic iodine (PII) concentration in 48 crossbred cows from 31 dairy units. Concentrations of plasma triiodothyronine (T3), thyroxine (T4), total cholesterol and free fatty acids were compared between iodine deficient and normal cows. Circulating T4 and T3 concentrations were also determined before and after injection of ethiodised oil in cows with low PII levels. RESULTS: The mean prevalence of iodine deficiency was 35.9% and showed considerable geographical variation from 0 to 86% within Punjab. Cardinal clinical signs of iodine deficiency were absent and basal plasma T3 and T4 concentrations and their ratio did not differ between deficient and control cows. Activity of circulating T4 and T4:T3 ratio increased in response to ethiodised oil injection and persisted beyond 70 days after injection. CONCLUSION: Asymptomatic iodine deficiency is prevalent in crossbred cows of Punjab and response to iodine supplementation is the most reliable index of thyroid dysfunction associated with iodine deprivation. The results of this study also support the view that injection of 1 mL of 78% ethiodised oil can prevent iodine deficiency for more than 70 days.     

Variations in the response of sheep to experimental magnesium deficiency.

Hypomagnesaemia was induced in adult sheep by changing their diet from chaff given orally to a milk diet, low in Mg, infused via the abomasum. All sheep given the milk diet developed hypomagnesaemia and four out of 19 developed nervous convulsions similar to the natural disease grass tetany. Analysis of the sequential changes in plasma Ca, P and Mg revealed a striking positive correlation between Ca and Mg and hypocalcaemia thus appeared to be a general response to Mg deficiency. Many sheep appeared to adapt to the deficiency since after a period of about 11 days the decline in plasma Mg (and Ca) was either alleviated or reversed. However the four sheep which developed convulsions all showed a rapid and substantial decline in plasma Mg associated with a decline in plasma Ca.     

Hematuria and transitional cell papilloma of the renal pelvis treated via unilateral nephrectomy in an alpaca

CASE DESCRIPTION: An 11-year-old 72-kg (158-lb) sexually intact female alpaca was examined for diagnosis and treatment of hematuria of 4 months' duration. CLINICAL FINDINGS: Pigmenturia was detected by the owner when the alpaca was 8 months pregnant. Radiographic, ultrasonographic, vaginal speculum, and cystoscopic evaluation of the urinary tract revealed normal vaginal and urethral epithelia and increased bladder vessel tortuosity, with pulses of hemorrhage from the left ureter. Regenerative anemia and mild leukopenia were detected and serum urea nitrogen and creatinine concentrations were within reference ranges. TREATMENT AND OUTCOME: Chronic hematuria resolved after unilateral nephrectomy of the left kidney, and no dysfunction was detected in the remaining kidney. Histologic evaluation of the kidney revealed a transitional cell tumor in the renal pelvis. CLINICAL RELEVANCE: Although anemia is common in South American camelids, hematuria is an uncommon sign of this condition. Chronic urinary tract infection, toxin ingestion, and neoplasia causing hematuria or hemoglobinuria should be considered in South American camelids with pigmenturia. Thorough and systematic evaluation of the urinary tract should be performed to locate the site of hemorrhage to treat hematuria appropriately.