Hypoglycemic effects of vanadium on alloxan monohydrate induced diabetic dogs

The hypoglycemic effects after oral administration of vanadium have been studied previously in many species such as rats, mice and even humans. However, there has been no prior report on the glucose lowering effect of vanadium on diabetic dogs. Therefore, the purpose of this study was to evaluate the hypoglycemic effects of oral vanadium on diabetic dogs. Diabetes mellitus in the dogs studied was induced by alloxan monohydrate intravenous injection. The dogs were divided into two groups, one was the diabetic control (DC) group (n = 4) and the other was the vanadium treated (DV) group (n = 6). Fresh water was supplied to the dogs in the DC group, but sodium metavanadate solution (0.1~0.2 mg/ml) was given to the dogs in DV group from one week after the alloxan injection. The fasting glucose levels, fructosamine and serum chemistry profiles were compared between the two groups weekly for three weeks. The fasting blood glucose levels in DV group were significantly lower than those in the DC group (p < 0.01). Fructosamine levels in the DV group were also lower than those in the DC group (p < 0.05). The serum chemistry profiles were not significantly different in comparisons between the two groups. However, the cholesterol levels were significantly lower in the DV group compared to the DC group (p < 0.05). Our findings showed that oral vanadium administration had a hypoglycemic effect on chemically induced diabetic dogs.     

Hepatotoxicosis in dogs consuming a diet of camel meat contaminated with indospicine

Background Four dogs presented with clinical signs of severe hepatic disease after consuming a commercial camel meat diet. Methods Laboratory investigation revealed evidence of severe liver disease, including markedly increased serum alanine aminotransferase (ALT) activity and total bilirubin concentration, and prolonged clotting times. Results Two dogs deteriorated despite supportive therapy and were euthanased. Histologically, both livers appeared similar, with the main lesion being extensive periacinar necrosis and haemorrhage. Indospicine, a toxic amino acid of plant origin, was detected in the serum and/or plasma from all four dogs, as well as in tissues of a dog that was necropsied and in a sample of the camel meat fed to this animal. Serum biochemistry tests using blood samples collected from 15 additional dogs identified as having eaten the diet detected indospicine was in the serum of 14 and 3 had increased ALT activity. One of the latter dogs subsequently developed clinical signs of severe liver disease and was euthanased. Conclusion To the authors' knowledge, this is the first published report of the detection of indospicine residues in camel meat and the occurrence of severe, sometimes fatal, liver disease in dogs that consumed this contaminated meat.     

双峰驼奶对2型糖尿病大鼠肾组织结构及其细胞凋亡的影响

观察双峰驼奶对2型糖尿病大鼠肾组织结构及其细胞凋亡的影响,为临床预防和治疗糖尿病及其并发症提供理论参考。通过链脲佐菌素（streptozotocin,STZ）结合高糖高脂饮食诱导构建2型糖尿病（type 2diabetes mellitus,T2DM）大鼠模型,糖尿病大鼠随机分为糖尿病模型组（diabetes model control,DMC）、低剂量骆驼奶组（2ml/d）（low camel milk,LCM）、高剂量骆驼奶组（5ml/d）（high camel milk,HCM）和盐酸二甲双胍组（200mg/kg）（metformin hydrochloride,MTH）,每组12只,另设正常对照组（control group,C）。建模成功后,试验组处理4周后检测大鼠空腹血糖（FPG）浓度变化;采用苏木精-伊红（HE）染色方法检查肾脏组织的病理变化;采用荧光定量Real time-PCR法检测Bax（Bcl2-associated X protein,Bax）、Bcl-2（B cell lymphoma/lewkmia-2,Bcl-2）、细胞凋亡蛋白酶3（cysteinyl aspartate specific proteinase 3,Caspase 3）和核转录因子（nuclear factor-kappa B,NF-κB）mRNA的表达丰度;采用免疫组织化学染色法和免疫印迹法观察肾脏组织凋亡相关蛋白Bax和Bcl-2的表达变化。结果显示,与DMC组相比,LCM、HCM、MTH组大鼠FPG浓度均显著下降（P〈0.01）,LCM组大鼠胰岛素敏感性指数（ISI）显著升高（P〈0.01）;HE染色显示DMC组肾小球体积增大,囊腔变小,肾小球内出血严重,而LCM、HCM、MTH组肾小球体积、囊腔间隙较正常,肾小球出血明显减少;Bax mRNA和NF-κB mRNA在DMC组中表达量最高,Bcl-2mRNA和Caspase 3mRNA分别在LCM组和HCM组有较高的表达量;与DMC组相比,LCM、HCM、MTH组大鼠肾脏细胞Bax蛋白表达减低,Bcl-2蛋白表达升高。结果表明,双峰驼奶能显著降低糖尿病大鼠肾脏损伤,抑制其细胞凋亡,对糖尿病及其并发症的治疗发挥有效作用。     

Evaluation of the dose–response relationship of oral robenacoxib in urate crystal‐induced acute stifle synovitis in dogs

The objective of the study was to establish the dose–response relationship for robenacoxib, a selective cyclooxygenase (COX)‐2 inhibitor, in a urate crystal model of acute synovitis. In a randomized partial Latin square design trial, 12 beagle dogs were administered orally single doses of robenacoxib (0.5, 1, 2, 4 and 8 mg/kg), placebo and the positive control meloxicam (0.1 mg/kg), 3 h after injection of sodium urate crystals into a stifle joint. Dogs were assessed for weight bearing on a force plate and by subjective clinical orthopaedic observations. Robenacoxib produced dose‐dependent improvement in weight bearing, and decreased pain on palpation and joint swelling, over the dose range 0.5–2 mg/kg with no further increase in effect over the range 2–8 mg/kg. For weight bearing on the force plate, the ED₅₀ of robenacoxib was 0.6–0.8 mg/kg. The onset of action and time to peak effect of robenacoxib were faster (respectively, 2–2.5 h and 3–5 h) than for meloxicam (respectively, 3 h and 6 h). Robenacoxib significantly inhibited COX‐2 at all doses, with dose‐related activity. Robenacoxib did not inhibit COX‐1 over the dose range 0.5–4 mg/kg, but produced transient inhibition at 8 mg/kg. In conclusion, oral administration of robenacoxib over the dose range 0.5–8 mg/kg demonstrated significant analgesic and anti‐inflammatory efficacy in dogs.     

A dose‐escalation study of combretastatin A4‐phosphate in healthy dogs

Combretastatin A4 ‐Phosphate (CA4P ) is a vascular disrupting agent revealing promising results in cancer treatments for humans. The aim of this study was to investigate the safety and adverse events of CA4P in healthy dogs as a prerequisite to application of CA4P in dogs with cancer. Ten healthy dogs were included. The effects of escalating doses of CA4P on physical, haematological and biochemical parameters, systolic arterial blood pressure, electrocardiogram, echocardiographic variables and general wellbeing were characterised. Three different doses were tested: 50, 75 and 100 mg m^?2. At all 3 CA4P doses, nausea, abdominal discomfort as well as diarrhoea were observed for several hours following administration. Likewise, a low‐grade neutropenia was observed in all dogs. Doses of 75 and 100 mg m^?2 additionally induced vomiting and elevation of serum cardiac troponine I levels. At 100 mg m^?2, low‐grade hypertension and high‐grade neurotoxicity were also observed. In healthy dogs, doses up to 75 mg m^?2 seem to be well tolerated. The severity of the neurotoxicity observed at 100 mg m^?2, although transient, does not invite to use this dose in canine oncology patients.     

Chemotherapy‐induced diarrhoea in dogs and its management with smectite: Results of a monocentric open‐label randomized clinical trial

Chemotherapy‐induced diarrhoea (CID) is a frequent chemotherapy adverse event in dogs. Yet, there is currently no consensus regarding its management. Smectite is a natural medical clay, widely used in the treatment of acute diarrhoea in humans. The objectives of this study were to assess the efficacy of smectite in the management of CID in dogs, and to collect epidemiological data on CID. For each episode of diarrhoea, dogs were randomized into two management groups: Smectite group, receiving smectite at 0.5 g/kg PO per day divided in two to three doses initiated at the start of CID; control group, without initial medication. In both groups, rescue metronidazole was prescribed if CID progressed or was not improved within 48 hours. Sixty dogs were recruited and received 426 chemotherapy administrations between June 2017 and March 2019. The incidence rate of CID was 110/426 (25.8%, 95% CI: 21.7%‐30.2%), and significantly differed between the chemotherapeutic drugs administered (P < .001). Metronidazole was administered in 5/54 events (9.3%, 95% CI: 3.1%‐20.3%) in the smectite group and in 40/56 events (71.4%, 95% CI: 57.5%‐82.3%) in the control group (P < .001). The time to resolution of diarrhoea was shorter (P < .001) in the smectite group (median: 19.5 hours, interquartile range [IQR]: 13.5‐32 hours) compared with the control group (median: 53 hours, IQR: 31.5‐113.5 hours). The results of this study support the administration of smectite in the first‐line management of CID in dogs.     

Outcome and toxicity associated with a dose‐intensified,maintenance‐free CHOP‐based chemotherapy protocol in canine lymphoma: 130 cases

A dose‐intensified/dose‐dense chemotherapy protocol for canine lymphoma was designed and implemented at the Veterinary Hospital of the University of Pennsylvania. In this study, we describe the clinical characteristics, prognostic factors, efficacy and toxicity in 130 dogs treated with this protocol. The majority of the dogs had advanced stage disease (63.1% stage V) and sub‐stage b (58.5%). The median time to progression (TTP) and lymphoma‐specific survival were 219 and 323 days, respectively. These results are similar to previous less dose‐intense protocols. Sub‐stage was a significant negative prognostic factor for survival. The incidence of toxicity was high; 53.9 and 45% of the dogs needed dose reductions and treatment delays, respectively. Dogs that required dose reductions and treatment delays had significantly longer TTP and lymphoma‐specific survival times. These results suggest that dose density is important, but likely relative, and needs to be adjusted according to the individual patient's toxicity for optimal outcome.     

CASE REPORT: Corneal papilloma associated with papillomavirus in a one‐humped camel (Camelus dromedarius)

A 15‐year‐old male dromedary camel with a history of chronic severe keratoconjunctivitis and corneal mass in the left eye of 6 months’ duration was referred to the Veterinary Medical Teaching Hospital at Adnan Menderes University. A superficial keratectomy was performed and biopsy material submitted for histopathology. The diagnosis was corneal papilloma. There has been no recurrence of the neoplasm to date (6 months, 1 year). Corneal papilloma has not been reported previously in camels and seems to be associated with papillomavirus.     

The effect of some cryoprotectants on dromedary camel frozen‐thawed semen

The cryopreserved camel semen is often associated with poor quality and fertility. This study aimed to improve the dromedary frozen semen quality by comparing the efficiency of four cryoprotectant agents (CPAs) on sperm freezability. Semen samples were collected from seven male Maghrabi camels, diluted with Shotor diluent supplemented with glycerol (Sh‐G), dimethyl formamide (DMF, Sh‐DF), dimethyl sulfoxide (DMSO, Sh‐DS) or ethylene glycol (EG, Sh‐EG), all at 6% final concentration, and the samples were subjected to cryopreservation. The results revealed the superiority of Sh‐DF over Sh‐G and Sh‐DS in terms of post‐thaw motility (55.83 ± 2.20 vs. 47.50 ± 4.33 and 45.00 ± 2.89%, respectively), sperm membrane (49.00 ± 0.58, 39.33 ± 3.33 and 42.67 ± 1.45%, respectively) and acrosomal integrities (53.00 ± 0.58, 57.33 ± 0.88 and 52.33 ± 1.45%, respectively). Sh‐EG group showed the lowest post‐thaw motility, plasma membrane and acrosome integrities (12.50 ± 1.44, 22.67 ± 1.45 and 30.67 ± 1.45, respectively). In conclusion, the protocols of dromedary camel semen cryopreservation could be enhanced using 6% DMF as a cryoprotectant agent.     

The dose–response relation for the antinociceptive effect of morphine in a fish,rainbow trout

Jones, S. G., Kamunde, C., Lemke, K., Stevens, E. D. The dose–response relation for the antinociceptive effect of morphine in a fish, rainbow trout. J. vet. Pharmacol. Therap.  35 , 563–570. There have been suggestions that analgesics be used by fish researchers. But in the absence of dose–response data for morphine, this suggestion seems imprudent. The purpose of the present study was to develop a dose–response relationship in fish using six doses of morphine. The response (movement of the fins or tail) to a noxious stimulus (electrical shock to the face region) was monitored before and after a dose of morphine intraperitoneally (i.p.). The i.p. dose of morphine ED₅₀ in rainbow trout was 6.7 ± 0.8 mg/kg (n = 12 at each dose). The plasma morphine concentration EC₅₀ was 4.1 ± 1.5 mg/L. In a second experiment, rainbow trout tested with equal amounts of morphine and naloxone (30 mg/kg) showed that the antinociceptive effect of morphine was blocked by naloxone. It has been suggested that stress‐induced analgesia has been a confounding factor in some fish studies. However, plasma cortisol levels in our study indicated that stress was not a confounding factor in the present experiments. The ED₅₀ for morphine in fish was higher than that reported for humans or other mammals. Our observation showing a dose–response relation for morphine using a noxious stimulus supports arguments for its effectiveness as an antinociceptive drug in fish.     

The effect of experimentally induced hypothyroidism on the isoflurane minimum alveolar concentration in dogs

ObjectiveTo determine the effect of experimentally induced hypothyroidism on isoflurane (ISO) minimum alveolar concentration (MAC) in dogs.Study designProspective experimental study.AnimalsEighteen adult female mongrel dogs, age 2–4 years and weighing 8.2–13.1 kg.MethodsHypothyroidism was induced in nine dogs by the intravenous administration of 1 mCi kg⁻¹ of ¹³¹Iodine. The remaining nine dogs served as controls. Dogs were studied 9–12 months after the induction of hypothyroidism. Anesthesia was induced with ISO in oxygen via a mask. The trachea was intubated, and anesthesia was maintained using ISO in oxygen using a semi-closed rebreathing circle system. The dogs were mechanically ventilated to maintain an end-tidal carbon dioxide concentration between 35 and 45 mmHg. End-tidal ISO concentrations were measured with an infrared gas analyzer. The MAC was determined in duplicate using a tail clamp technique. The mean values for the groups were compared using a two sample t-test.ResultsThe mean ± SD MAC of isoflurane in the hypothyroid and euthyroid dogs was 0.98 ± 0.31% and 1.11 ± 0.26%, respectively. The mean MAC of isoflurane in hypothyroid dogs was not significantly different from the mean MAC of isoflurane in the control dogs (p=0.3553).Conclusion and clinical relevanceThe MAC of ISO in dogs was not significantly affected by experimentally induced hypothyroidism. The dose of ISO in dogs with hypothyroidism does not need to be altered.     

Morphogenesis of lingual papillae of one‐humped camel (Camelus dromedarius) during prenatal life: A light and scanning electron microscopic study

This study was made on 24 camel fetuses of crown‐rump vertebral length (CVRL) ranging from 10.5 cm to 105 cm CVRL (94–352 days old). These camel fetuses were classified into three groups representing the three trimesters of prenatal life. During the first trimester (94–142 days), lingual papillae (circumvallate and lentiform papillae) were demonstrated on the lingual root, but lingual body and the apex were almost free of papillae except for some scattered epithelial projections especially near the lateral borders of the body. In the second trimester (152–229 days), the lentiform papillae covered the entire root of the tongue except for areas occupied by the circumvallate papillae. Taste buds with clear pores were observed for the first time in areas between the circumvallate gustatory furrow and surface epithelium of the tongue. In addition, short numerous filiform papillae were observed on the rostral part of the lingual body and the lateral parts of the apex. Fungiform papillae, however, were demonstrated amidst the filiform papillae. In this trimester, taste buds were also seen on the top of the fungiform papillae. In the third trimester (256–352 days), all lingual papillae were clearly demonstrated on the dorsum of the root, body and apex of the tongue. Both types of gustatory papillae (circumvallate and fungiform) had well‐developed taste buds. Mechanical papillae (filiform and lentiform) were well developed. Lentiform papillae occupied most of the dorsal aspect of the Torus linguae; they were larger in size with semicircular apices. Filiform papillae, however, were numerous and demonstrated heavily on the lateral and rostral parts of the body as well as on the apex of the tongue.     

Romifidine and low doses of tiletamine‐zolazepam in dogs

ObjectiveTo evaluate clinical effects of romifidine and low doses of tiletamine‐zolazepam (TZ) in dogs.Study designRandomized “blinded” cross‐over study.AnimalsSix healthy beagle dogs (two males, four females).MethodsIn separate preliminary experiments dogs received intravenous (IV) tiletamine‐zolazepam (TZ) at 1 and 2 mg kg^?1. For the main trial, dogs received romifidine (R) followed 5 minutes later by IV at six dose regimens: R40TZ1, R60TZ1, R80TZ1 (Romifidine at 40, 60, 80 μg kg^?1 and TZ at 1 mg kg^?1), R40TZ2, R60TZ2 and R80TZ2 (Romifidine at 40, 60, 80 μg kg^?1 and TZ at 2 mg kg^?1). Dogs underwent endotracheal intubation, but breathed room air. Cardiorespiratory variables were measured and arterial blood analyzed. Quality of sedation, duration of anaesthesia and time to recovery (TR) were recorded. Data were analysed by anova or Friedman test as relevant.ResultsEndotracheal intubation was possible with all romifidine/TZ combinations but not with TZ alone. Mean times (minutes) from TZ injection to return of pedal reflex were 1–3 minutes for TZ alone, and 9–17 minutes for romifidine combinations. In the main trial (romifidine combinations) mean time (minutes) to standing increased with increasing dosage (R40TZ1 13; R80TZ2 32). Five minutes after TZ administration, when compared with baseline arterial blood pressures and arterial carbon dioxide had increased, and respiratory rate, pH and arterial oxygen tensions decreased, these changes becoming statistically significant with the higher dose rates. One dog in R60TZ2 and three dogs in R80TZ2 became hypoxaemic.Conclusions and clinical relevanceRomifidine improves the quality and lengthens the duration of anaesthesia induced by TZ. The combination provides a suitable protocol for induction of or short‐term anaesthesia in healthy dogs. However, the higher doses cause cardiovascular stimulation and respiratory depression, and precautions should be taken accordingly.     

Refractometric total plasma protein measurement as a cage‐side indicator of hypoalbuminemia and hypoproteinemia in hospitalized dogs

Objective – To assess the relationship between total plasma protein (TPP) as measured by refractometry and serum hypoalbuminemia and hypoproteinemia in hospitalized dogs. Design – Retrospective, observational study conducted over 6‐month period between March and August 2008. Setting – University teaching hospital. Animals – Four hundred and three hospitalized dogs in an ICU. Interventions – None. Measurements and Main Results – TPP, serum albumin, total protein, glucose, urea, cholesterol was measured from dogs enrolled in study. TPP was evaluated as a predictor for hypoalbuminemia defined both as albumin <25 g/L (<2.5 g/dL) and albumin <20 g/L (<2.0 g/dL), and serum hypoproteinemia, defined as serum total protein <40 g/L (<4.0 g/dL), using logistic regression. Impact of glucose, urea, cholesterol, and total bilirubin on refractometric readings were also assessed. TPP predicted hypoalbuminemia at albumin concentrations of <25 g/L (<2.5 g/dL) and <20 g/L (<2.0 g/dL) (P<0.001). A TPP<60 g/L (<6.0 g/dL) predicted albumin <25 g/L (<2.5 g/dL) with 73% sensitivity and 86% specificity. A TPP<58 g/L (<5.8 g/dL) predicted a serum albumin <20 g/L (<2.0 g/dL) with 70% sensitivity and 80% specificity. For dogs with known risk factors where specificity optimization may be appropriate, refractometer TPP<50 g/L (<5.0 g/dL) and <48 g/L (<4.8 g/dL) predicted hypoalbuminemia at each level with >95% specificity, although sensitivity was poor. Refractometer TPP<58 g/L (<5.8 g/dL) predicted serum total protein of <40 g/L (<40 g/dL) with sensitivity of 82% and specificity of 84%. Hypercholesterolemia and hyperglycemia significantly affected TPP readings; an increase in serum glucose by 10 mmol/L (180 mg/dL) was associated with an average independent increase in refractometer TPP of 2.27 g/L (0.23 g/dL) (P<0.001, 95% confidence interval=1.08–3.47) and an increase in serum cholesterol of 1 mmol/L (38.6 mg/dL) was associated with an average independent increase in refractometer TPP of 1.36 g/L (0.14 g/dL) (P<0.001, 95% confidence interval=1.12–1.59). Conclusion – Suboptimal sensitivity limits the use of refractometric TPP for prediction of hypoalbuminemia in the context of patient screening; a high proportion of false negatives may result. However, identification of a refractometric TPP<58 g/L is strongly indicative of both serum hypoalbuminemia and hypoproteinemia, with high specificity, and warrants further investigation. Refractometric readings may be falsely increased in patients with hyperglycemia or hypercholesterolemia.