The effect of medetomidine on the regional cerebral blood flow in dogs measured using Technetium-99m-Ethyl Cysteinate Dimer SPECT

Sedatives and anaesthetics are known to cause changes in the regional cerebral blood flow. In dogs intramuscular sedation with medetomidine, a potent sedative frequently used in veterinary medicine, is sometimes indicated prior to intravenous injection of ^99mTechnetium-Ethyl Cysteinate Dimer (^99mTc-ECD) in brain perfusion studies using Single Photon Emission Computed Tomography (SPECT). Based on the knowledge of the distribution of alpha₂-receptors in the brain, we hypothesized altered regional brain perfusion in dogs receiving medetomidine prior to ^99mTc-ECD. Two conditions were compared in 10 dogs; tracer injection before and after intramuscular sedation with medetomidine. In our study, medetomidine caused a significantly higher tracer uptake in all brain regions. Semi-quantification of brain perfusion rendered a lower perfusion index in the subcortical region and an imbalance between left and right cortical perfusion induced by medetomidine. This study shows that caution is needed when quantifying the brain perfusion indices under medetomidine sedation.     

REGIONAL BRAIN PERFUSION IN 10 NORMAL DOGS MEASURED USING TECHNETIUM-99m ETHYL CYSTEINATE DIMER SPECT

Single photon emission computed tomography (SPECT) of the brain using perfusion tracers allows estimation of regional brain perfusion. This allows in vivo examination of brain function in the setting of neuropsychologic and pathophysiologic changes. However functional imaging data on brain perfusion in dogs are limited. Hence, the aim of this study was to determine the scintigraphic regional perfusion pattern of the normal canine brain. Ten healthy shepherd type dogs were injected with 925 MBq Technetium-99m ethyl cysteinate (ECD) 20 minutes before the examination. Acquisition was performed using a triple head gamma camera equipped with fanbeam collimators. Uniform attenuation correction and triple energy window correction were applied. Computed tomographic images were obtained from the same dogs, reoriented along the orbito-meatal axis and SPECT perfusion data were coregistered to the CT-volume data. Based on morphological and suggested brain divisions, regions-of-interest (ROIs) were defined for the bilateral frontocerebral, temporocerebral, parietocerebral, occipitocerebral, cerebellar, thalamic, and striatal area. Regional count density was normalized on total counts. All dogs had the highest uptake in the thalamic/striatal area compared to a rather homogeneous cerebral uptake. No significant left/right count differences were found, but a rostro-caudal gradient (+12-13%) was present. In this group, age and gender did not influence the perfusion pattern.     

The use of nuclear imaging for a mixed C cell microfollicular carcinoma of the thyroid gland in a mature horse

A 15‐year‐old Boerperd stallion presented for thyroid enlargement associated with inappetance. Ultrasonographic examination of the thyroid gland revealed an enlarged left lobe, which, on cytological examination, contained numerous anaplastic cells. A mixed C cell microfollicular thyroid carcinoma was diagnosed following histopathological examination of the excisional biopsy specimen. In order to determine metastasis, pulmonary radiographs revealed a poorly‐marginated soft tissue opacity caudo‐dorsal to the cardiac silhouette. Thyroid and pulmonary scintigraphy was performed comparing ^99mTc‐sestamibi with ^99mTc‐pertechnetate and no metastasis was detectable. Following hemithyroidectomy, the stallion made a full recovery without the need for neoadjuvant chemotherapy. Six months later, repeated thyroid and pulmonary scintigraphy using ^99mTc‐sestamibi was normal.     

Regional distribution of technetium-99m-ECD in the canine brain: Optimal injection–acquisition interval in adult beagles

Changes in the regional cerebral blood flow (rCBF), a measure for regional cerebral metabolism, have been reported in dogs suffering from behavioral problems like shadow chasing, anxiety, and compulsive disorders. The rCBF can be measured with single-photon emission computed tomography. Although the acquisition is performed afterward under general anesthesia, the distribution of technetium-99m-ethylene-diylbis-l-cysteine diethyl ester or ^99mTc-ECD, a tracer which becomes trapped in the brain, represents the rCBF at the moment the tracer was administered to the awake dog (fixed or frozen image). The aim of this study was to examine the in vivo stability and the duration of the fixed distribution of this tracer in the canine brain. Three acquisitions were performed 15, 40, and 65 minutes after tracer injection. Total counts and perfusion indices, normalized to the total brain counts and to the cerebellum, were calculated (semiquantification). At T65, significant differences in the perfusion indices occurred compared with at T15. This study shows that in dogs, regional differences in the clearance of ^99mTc-ECD result in significant alterations of the perfusion indices from 65 minutes onward after tracer injection. Therefore, it is recommended to start the acquisition between 15 and 40 minutes postinjection in dogs when this technique is used for studying rCBF alterations in dogs with behavioral problems.     

The influence of the tracer injection–acquisition interval on the distribution of 99mTc-ECD in the brain of laboratory cats

Single-photon emission computed tomography (SPECT) can be used to study the regional distribution of the cerebral blood flow in the feline brain without interference of anesthetics. When the tracer, ^99mtechnetium-ethyl cysteinate dimer (^99mTc-ECD), is injected in the awake animal, the acquisition can be performed afterward under general anesthesia, whereas the tracer distribution still represents the regional cerebral blood flow (rCBF) in the awake animal. The aim of this study was to look at the in vivo stability of ^99mTc-ECD in the feline brain. For this purpose, 6 cats (n = 6) were used, and 3 serial acquisitions were performed starting at 40 (T40), 60 (T60), and 85 (T85) minutes after tracer injection. Total counts and perfusion indices (PIs), normalized to the total brain and to the cerebellum, were calculated. When T85 was compared with T40, total counts decreased, depending on the brain region, with 29% (left thalamus) to 51% (bulbus olfactorius). These regional differences in tracer clearance resulted in significantly altered PIs at T85 as compared with T40. This study shows that ^99mTc-ECD SPECT can be used in cats for studying the rCBF and that the clearance of ^99mTc-ECD in the feline brain is region dependent. As a result, the acquisition should be started between 40 and 60 minutes after tracer injection.     

FOCAL SKELETAL MUSCLE UPTAKE OF 99mTECHNETIUM‐HYDROXYMETHYLENE Diphosphonate FOLLOWING PERONEAL NERVE BLOCKS IN HORSES

We have observed focal skeletal muscle uptake of ^99mTechnetium‐hydroxymethylene diphosphonate (Tc‐HDP), which could mimic a tibial lesion, in horses following peroneal nerve blocks. To characterize this observation further, 45 bone phase scintigrams were performed in 12 horses undergoing peroneal nerve blocks. Scans were performed before, and 1, 3, 7, and 14 days postblock. The superficial and deep branches of the peroneal nerve were blocked by injecting 10 ml of 2% mepivacaine in one limb and 20 ml in the other. Images were evaluated for uptake at the block site and uptake likely to mimic a tibial lesion. Regions of interest were placed over the block site and distal tibia. Count density ratios were used to estimate change in uptake intensity over time. The overall proportion affected was 0.52 (95% confidence interval [CI], 0.36–0.68; P<0.001) 1 day postblock and 0.24 (95% CI, 0.13–0.40; P=0.005) 3 days postblock. The overall proportion likely to mimic a tibial lesion was 0.19 (95% CI, 0.09–0.33; P<0.001) 1 day postblock and 0.21 (95% CI, 0.09–0.40; P=0.005) 3 days postblock. Focal skeletal muscle uptake was seen in only one horse 7 days postblock. Increased uptake intensity was associated with higher local anesthetic dose (P=0.042). Peroneal nerve blocks cause focal skeletal muscle uptake of ^99mTc‐HDP on bone phase scintigraphy. This occurs in approximately 50% of blocked limbs and can mimic a tibial lesion on the lateral view in approximately 20% of blocked limbs.     

Furosemide administration onehour before bone scintigraphy examination in horses does not improve the image quality or reduce the radiation dose rate

This prospective, cross‐sectional, pilot study aimed to investigate the effects of furosemide as a diuretic on the image quality of bone scintigraphy performed using ^99mTc‐HDP and to investigate the impact of furosemide on the radiation dose rate. Thirty‐one horses undergoing bone scintigraphy were included. The horses were divided into the control (n = 14) and furosemide group (n = 17), which received 1 mg/kg furosemide intravenously 1 h post ^99mTc‐HDP administration. The image quality was assessed subjectively and semi‐quantitatively. The bone‐to‐soft tissue (B:S) ratio was calculated from the counts per pixel of regions of interest (ROI) positioned over the left radial diaphysis (bone ROI) and its caudal soft tissue area (soft tissue ROI). The radiation rate dose (μSv/h) of both groups was measured at 0, 3, 6, 12, 18, and 24 h post ^99mTc‐HDP administration at a distance of 0, 30, and 100 cm from the head, kidney, and pelvis. The results showed no significant differences in the B:S ratio or the radiation dose rate observed between the groups. However, the radiation dose rate decreased by 56% at 3 h post ^99mTc‐HDP administration and keeping a distance of 30 cm reduced the radiation dose rate by 65%. Administering furosemide does not improve the image quality or reduce the radiation dose rate. The authors recommend commencing with bone scintigraphy 3 h post ^99mTc‐HDP administration and keeping at least a distance of 30 cm from the horse to reduce the staff radiation dose.     

Single‐voxel and multi‐voxel spectroscopy yield comparable results in the normal juvenile canine brain when using 3 Tesla magnetic resonance imaging

Conventional magnetic resonance imaging (MRI) characteristics of canine brain diseases are often nonspecific. Single‐ and multi‐voxel spectroscopy techniques allow quantification of chemical biomarkers for tissues of interest and may help to improve diagnostic specificity. However, published information is currently lacking for the in vivo performance of these two techniques in dogs. The aim of this prospective, methods comparison study was to compare the performance of single‐ and multi‐voxel spectroscopy in the brains of eight healthy, juvenile dogs using 3 Tesla MRI. Ipsilateral regions of single‐ and multi‐voxel spectroscopy were performed in symmetric regions of interest of each brain in the parietal (n = 3), thalamic (n = 2), and piriform lobes (n = 3). In vivo single‐voxel spectroscopy and multi‐voxel spectroscopy metabolite ratios from the same size and multi‐voxel spectroscopy ratios from different sized regions of interest were compared. No significant difference was seen between single‐voxel spectroscopy and multi‐voxel spectroscopy metabolite ratios for any lobe when regions of interest were similar in size and shape. Significant lobar single‐voxel spectroscopy and multi‐voxel spectroscopy differences were seen between the parietal lobe and thalamus (P = 0.047) for the choline to N‐acetyl aspartase ratios when large multi‐voxel spectroscopy regions of interest were compared to very small multi‐voxel spectroscopy regions of interest within the same lobe; and for the N‐acetyl aspartase to creatine ratios in all lobes when single‐voxel spectroscopy was compared to combined (pooled) multi‐voxel spectroscopy datasets. Findings from this preliminary study indicated that single‐ and multi‐voxel spectroscopy techniques using 3T MRI yield comparable results for similar sized regions of interest in the normal canine brain. Findings also supported using the contralateral side as an internal control for dogs with brain lesions.     

Radionuclides in lung diagnostics: A new approach

Summary

With a ^99mTc‐labelled aerosol an inhalation (ventilation) image of the lungs was obtained. A lung perfusion image was obtained with ^99mTc‐labelled macro‐aggregates. The data from the gamma camera were stored in a computer and the inhalation‐perfusion (I/P) ratio was calculated for the total lung as well as for one half another selected region, and a local (pixel) area. In the anaesthetised dog in sternal recumbency, the I/P ratio decreased from the cranial to the caudal lung regions. Hence in the dog gravity is not the only determinant of the I/P ratio distribution, as it is assumed to be in man. Position and anaesthesia appeared to influence the distribution of I/P ratios within the lung.     

REGIONAL BRAIN PERFUSION IN EPILEPTIC DOGS EVALUATED BY TECHNETIUM-99m-ETHYL CYSTEINATE DIMER SPECT

We evaluated the feasibility of interictal single photon emission computed tomography (SPECT) to detect alterations in regional cerebral blood flow and neuronal activity in dogs with idiopathic epilepsy. Twelve dogs with idiopathic epilepsy underwent interictal technetium-99m-ethyl cysteinate dimer SPECT of the brain. Different cortical regions of interest (ROIs), 1 ROI at the cerebellum and 1 ROI at the subcortical area were evaluated by semiquantitative analysis and compared with a control group (18 dogs). Significant hypoperfusion ( P =0.02) was present in the subcortical area of epileptic dogs. This hypoperfusion was not associated with seizure frequency, age at onset of seizures, duration of epilepsy, or time since the last seizure. Interictal SPECT did not reveal cortical or cerebellar perfusion alterations. The subcortical area may play an important role in the pathophysiology of canine idiopathic epilepsy.     

Canine reference intervals for the Sysmex XT-2000iV hematology analyzer

Background: The laser‐based Sysmex XT‐2000iV hematology analyzer is increasingly used in veterinary clinical pathology laboratories, and instrument‐specific reference intervals for dogs are not available. Objective: The purpose of this study was to establish canine hematologic reference intervals according to International Federation of Clinical Chemistry and Clinical and Laboratory Standards Institute guidelines using the Sysmex XT‐2000iV hematology analyzer. Methods: Blood samples from 132 healthy purebred dogs from France, selected to represent the most prevalent canine breeds in France, were analyzed. Blood smears were scored for platelet (PLT) aggregates. Reference intervals were established using the nonparametric method. PLT and RBC counts obtained by impedance and optical methods were compared. Effects of sex and age on reference intervals were determined. Results: The correlation between impedance (I) and optical (O) measurements of RBC and PLT counts was excellent (Pearson r=.99 and .98, respectively); however, there were significant differences between the 2 methods (Student's paired t‐test, P<.0001). Differences between sexes were not significant except for HCT, PLT‐I, and PLT‐O. WBC, lymphocyte, and neutrophil counts decreased significantly with age (ANOVA, P<.05). Median eosinophil counts were higher in Brittany Spaniels (1.87 × 10⁹/L), Rottweilers (1.41 × 10⁹/L), and German Shepherd dogs (1.38 × 10⁹/L) than in the overall population (0.9 × 10⁹/L). PLT aggregates were responsible for lower PLT counts by the impedance, but not the optical, method. Conclusion: Reference intervals for hematologic analytes and indices were determined under controlled preanalytical and analytical conditions for a well‐characterized population of dogs according to international recommendations.     

DIURETIC RENAL SCINTIGRAPHY IN NORMAL CATS

The purpose of this study was to develop a protocol for diuretic renal scintigraphy (renography) in cats and describe normal findings. ^99mTc‐DTPA renal scintigraphy was performed twice in 10 healthy cats. Furosemide or saline were injected 4.5 min after radiopharmaceutical administration for the diuretic or control scan, respectively. A dynamic acquisition was performed for 8 min. The following parameters were evaluated: (1) global and individual glomerular filtration rate (GFR); (2) shape of the time–activity curve (TAC); (3) time of peak (TOP); (4) individual kidney excretion half‐time (T_1/2) of the radiopharmaceutical; (5) percentage of maximum activity measured at the end of the study. Global GFR in the control studies (2.79±0.83 ml/min/kg, mean±SD) did not differ significantly from the diuretic scans (2.34±0.51 ml/min/kg). The shape of most (16/20) TAC of diuretic renograms was similar to those of control renograms. The TOP of the diuretic renogram curves was 3.06±0.58 min, and did not differ from that of the control scans (3.01±0.61 min). T_1/2 of the diuretic renograms was significantly shorter (5.15±0.83 min) than that of the control renograms (6.31±1.50 min). A significantly lower percentage of maximum activity was present at the end of the study in diuretic renograms (median: 47.25%; range: 33.60–59.60%) compared with control renograms (63.40%; 30.00–69.40%). Diuretic renal scintigraphy is a noninvasive and fast procedure to perform in cats. The applicability of this technique needs to be investigated in patients with significantly impaired renal function and obstructive uropathies.     

EFFECT OF SEDATION ON CONTRAST‐ENHANCED ULTRASONOGRAPHY OF THE SPLEEN IN HEALTHY DOGS

Contrast‐enhanced ultrasound of the spleen enables the dynamic assessment of the perfusion of this organ, however, both subjective and quantitative evaluation can be strongly influenced by sedative agent administration. The purpose of this prospective, experimental study was to test effects of two sedative agents on splenic perfusion during contrast‐enhanced ultrasound of the spleen in a sample of healthy dogs. Contrast‐enhanced ultrasound of the spleen was repeated in six healthy Beagles following a cross‐over study design comparing three protocols: awake, butorphanol 0.2 mg/Kg intramuscular (IM), and dexmedetomidine 500 μg/m² IM. After intravenous injection of a phospholipid stabilized sulfur hexafluoride microbubble solution (SonoVue®, Bracco Imaging, Milano, Italy), the enhancement intensity and perfusion pattern of the splenic parenchyma were assessed and perfusion parameters were calculated. Normal spleen was slightly heterogeneous in the early phase, but the parenchyma was homogeneous at a later phase. Sedation with butorphanol did not modify perfusion of the spleen. Dexmedetomidine significantly reduced splenic enhancement, providing diffuse parenchymal hypoechogenicity during the entire examination. Measured parameters were significantly modified, with increased arrival time (AT; (< 0.0001) and time to peak (TTP; P < 0.0001), and decreased peak intensity (PI; P = 0.0108), wash‐in (P = 0.0014), and area under the curve (AUC; P = 0.0421). Findings supported the use of butorphanol and contraindicated the use of dexmedetomidine as sedatives for splenic contrast ultrasound procedures in dogs. Short‐term and diffuse heterogeneity of the spleen in the early venous phase was determined to be a normal finding.     

Photodynamic detection of canine mammary gland tumours after oral administration of 5‐aminolevulinic acid

5‐Aminolevulinic acid (5‐ALA) is widely used in photodynamic detection (PDD) and therapy. We evaluated the pharmacokinetics of 5‐ALA‐induced porphyrins and its effectiveness in PDD in dogs with mammary gland tumours (MGTs) following oral administration. Healthy dogs and those with MGTs (nine each) were orally administered 4 mg kg^?1 5‐ALA. Protoporphyrin IX (PpIX) was not detected in the plasma of healthy dogs but it peaked in dogs with MGT at 2 h after 5‐ALA administration. In the PDD study, 16 dogs with MGT were orally administered 40 mg kg^?1 5‐ALA, and MGT but not normal tissue showed red fluorescence after 2–4 h. Photon counts were 6635–63 890 and 59–4011 (median, 19 943 and 919) for MGT and non‐tumour tissues, respectively. Cell density strongly correlated with PpIX photon counts of MGT tissue of the dogs (R = 0.743, P = 0.0009). We suggest that 5‐ALA‐PDD might be an effective diagnostic tool for MGTs.     

Measurements of hypoxia ([18F]‐FMISO, [18F]‐EF5) with positron emission tomography (PET) and perfusion using PET ([15O]‐H2O) and power Doppler ultrasonography in feline fibrosarcomas*

The aim of this study was to evaluate if hypoxia in feline fibrosarcomas can be detected. This was done using positron emission tomography (PET), two hypoxia tracers and polarographic pO₂ measurements. Of the seven cats included, five received [¹⁸F]‐fluoromisonidazole and two 2‐(2‐nitro‐1H‐imidazol‐1‐yl)‐N‐(2,2,3,3,3‐pentafluoropropyl) acetamide. Perfusion was evaluated with [¹⁵O]‐H₂O (n = 4) and with contrast‐enhanced power Doppler ultrasonography (n = 5). Hypoxia was detected in three cats. Polarographic pO₂ measurements did not confirm PET results. In the ultrasonographic evaluation, low vascularity and low perfusion were seen with a peripheral vascular pattern and no perfusion in the centre of the tumour. This was in contrast to the [¹⁵O]‐H₂O scans, where central perfusion of the tumour was also found. In conclusion, it appears that hypoxia exists in this tumour type. The presence of tumour necrosis and heterogeneous hypoxia patterns in these tumours may explain the found discrepancies between the applied techniques.     

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.     

DIFFUSION‐WEIGHTED MAGNETIC RESONANCE IMAGING OF THE NORMAL CANINE BRAIN

Diffusion‐weighted imaging (DWI) MRI has been primarily reported as a method for diagnosing cerebrovascular disease in veterinary patients. In humans, clinical applications for diffusion‐weighted MRI have also included epilepsy, Alzheimer's, and Creutzfeld–Jakob disease. Before these applications can be developed in veterinary patients, more data on brain diffusion characteristics are needed. Therefore, the aim of this study was to evaluate the distribution of diffusion in the normal canine brain. Magnetic resonance imaging of the brain was performed in ten, clinically normal, purpose‐bred beagle dogs. On apparent diffusion coefficient maps, regions of interest were drawn around the caudate nucleus, thalamus, piriform lobe, hippocampus, semioval center, and cerebral cortex. Statistically significant differences in mean apparent diffusion coefficient were found for the internal capsule, hippocampus, and thalamus. The highest apparent diffusion coefficient (1044.29 ± 165.21 μm²/s (mean ± SD (standard deviation)) was detected in the hippocampus. The lowest apparent diffusion coefficient was measured in the semioval center (721.39 ± 126.28 μm²/s (mean ± SD)). Significant differences in mean apparent diffusion coefficients of the caudate nucleus, thalamus, and piriform lobe were found by comparing right and left sides. Differences between brain regions may occur due to differences in myelination, neural density, or fiber orientation. The reason for the differences between right and left sides remains unclear. Data from the current study provide background for further studies of diffusion changes in dogs with brain disease.     

Intraarticular injection of a Tin‐117 m radiosynoviorthesis agent in normal canine elbows causes no adverse effects

This longitudinal prospective exploratory study used serial measurements in five dogs to evaluate safety and retention of a tin‐117 m (^117mSn) colloid after intra‐articular injection in normal elbow joints. Each dog was deemed healthy based on physical examination, laboratory results, and radiographic evaluation of both elbows. While anesthetized, each received an MRI of both elbows, followed by fluorine‐18 fluorodeoxyglucose positron emission tomography scans of both elbow joints and associated lymph nodes. Joint fluid (0.5‐1.0 mL) was withdrawn aseptically from the left elbow joint, followed by intra‐articular injection of ^117mSn colloid (92.5 MBq; 1‐1.5 ml). Post‐injection assessments included blood counts, serum chemistry panels, urinalyses, radiographs, joint fluid analyses, MRI/positron emission tomography scans, scintigraphy, and biodistribution scans. On day 45‐47, each dog was euthanized and a complete postmortem examination was performed. Tissue samples were submitted for histopathology and radioisotope retention studies. Left elbow joints were decalcified and sectioned for future autoradiography. Scintigraphy, 1 day after injection, indicated slight radioisotope escape from the joint to regional lymph nodes. Serial blood, urine, feces, and organ counts indicated >99.1% of the ^117mSn activity was retained in the joint for 45‐47 days. Radiation output levels were below patient release levels the day following injection. Maximum standard uptake value for the injected joint decreased. Joint fluid cytology was unchanged. No dog exhibited lameness during the study. Absence of joint damage and lack of systemic effects after injection of the ^117mSn colloid in normal canine elbow joints indicate that this agent may be safely used for radiosynoviorthesis in dogs with osteoarthritis.     

Intestinal microbiota of broilers submitted to feeding restriction and its relationship to hepatic metabolism and fat mass: Fast‐growing strain

The present study was conducted to verify how feed restriction affects gut microbiota and gene hepatic expression in broiler chickens and how these variables are related to body weight gain. For the experiment, 21‐d‐old Cobb500^TM birds were distributed in a completely randomized experimental design with three treatments: T1. Control (ad libitum—3.176 Mcal/kg ME—metabolizable energy—and 19% CP—crude protein); T2. Energetic restriction (2.224 Mcal/kg ME and 19% CP) from 22 to 42 days with consumption equivalent to control; T3. Quantitative restriction (70% restriction, i.e., restricted broilers ingested only 30% of the quantity consumed by the control group—3.176 Mcal/kg ME and 19% CP) for 7 days, followed by refeeding ad libitum from 28 to 42 days. Ileum and caecum microbiota collections were made at 21, 28 and 42 days of age. Hepatic tissue was collected at 28 and 42 days old for relative gene expression analyses. At 43‐d‐old, body composition was quantified by DXA (Dual‐energy X‐ray Absorptiometry). Both feed restriction programmes decreased Lactobacillus and increased Enterococcus and Enterobacteriaceae counts. No differences were found in the refeeding period. Energetic restriction induced the expression of CPT1‐A (Carnitine palmitoyltransferase 1A) gene, and decreased body fat mass. Quantitative feed restriction increased lipogenic and decreased lipolytic gene expression. In the refeeding period, CPT1‐A gene expression was induced, without changing the broilers body composition. Positive associations were found between BWG (Body Weight Gain) and Lactobacillus and Clostridium cluster IV groups, and negatively associations with Enterobacteriaceae and Enterococcus bacterial groups. In conclusion, differences found in microbiota were similar between the two feed restriction programmes, however, hepatic gene expression differences were only found in quantitative restriction. Higher counts of Lactobacillus and Clostridium cluster IV groups in ileum are likely to be related to better broiler performance and low expression of lipogenic genes.     

Evaluation of dexamethasone as a chemoprotectant for CCNU‐induced bone marrow suppression in dogs*

In mice and people, administering corticosteroids before chemotherapy can reduce the severity of myelosuppression without reducing antitumour effects. This study investigated whether pretreatment with dexamethasone would reduce the incidence of grade 4 neutropenia in dogs receiving CCNU. Twenty‐five dogs received dexamethasone [0.1 mg kg^?1 per os (PO) every 12 h] for 5 days and on the sixth day received CCNU (90 mg m^?2 PO). Historical dogs (n = 67) received CCNU alone (90 mg m^?2 PO). Forty‐five percent of historical dogs had grade 4 neutropenia, while 64% of dogs pretreated with dexamethasone had grade 4 neutropenia (P = 0.16). Dexamethasone plasma levels were quantified by enzyme‐linked immunosorbent assay in three healthy dogs. Peak plasma concentrations after a single oral 0.1‐mg kg^?1 dose were <80 ng mL^?1, the minimum level associated with chemoprotective effects of dexamethasone in people. Pretreatment with dexamethasone did not reduce the incidence of grade 4 neutropenia in dogs receiving CCNU.