Immunohistochemical subtypes predict the clinical outcome in high-risk node-negative breast cancer patients treated with adjuvant FEC regimen: results of a single-center retrospective study.

BACKGROUND: Anthracycline-based adjuvant chemotherapy improves survival in patients with high-risk node-negative breast cancer (BC). In this setting, prognostic factors predicting for treatment failure might help selecting among the different available cytotoxic combinations. METHODS: Between 1998 and 2008, 757 consecutive patients with node-negative BC treated in our institution with adjuvant FEC (5FU, epirubicin, cyclophosphamide) chemotherapy were identified. Data collection included demographic, clinico-pathological characteristics and treatment information. Molecular subtypes were derived from estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor 2 (HER2) status and Scarff-Bloom-Richardson (SBR) grade. Disease-free survival (DFS), distant disease-free survival (DDFS) and overall survival (OS) were estimated using the Kaplan-Meier Method, and prognostic factors were examined by multivariate Cox analysis. RESULTS: After a median follow-up of 70 months, the 5-year DFS, DDFS and OS were 90.6 % (95 % confidence interval (CI): 88.2-93.1), 92.8 % (95 % CI: 90.7-95) and 95.1 % (95 % CI, 93.3-96.9), respectively. In the multivariate analysis including classical clinico-pathological parameters, only grade 3 maintained a significant and independent adverse prognostic impact. In an alternative multivariate model where ER, PR and grade were replaced by molecular subtypes, only luminal B/HER2-negative and triple-negative subtypes were associated with reduced DFS and DDFS. CONCLUSIONS: Node-negative BC patients receiving adjuvant FEC regimen have a favorable outcome. Luminal B/HER2-negative and triple-negative subtypes identify patients with a higher risk of treatment failure, which might warrant more aggressive systemic treatment.

Hematological markers and biochemical profiles in terms of gender and age of captive collared peccaries (Tayassu tajacu) in eastern Amazon.

Complete blood counts and blood biochemical analyses are laboratory tests that allow the monitoring of physiological condition, nutrition, and health in free-living or captive wild animals. When interpreting these tests, it is essential to compare the results with reference ranges that are suitable for the species. Few studies have been conducted on the hematological and biochemical characteristics of Tayassu tajacu, particularly for animals raised in the Amazon biome. The objectives of this study were to evaluate the influence of age and gender on the hematological and biochemical profiles of captive T. tajacu, and to establish reference intervals for these parameters. Complete blood counts and biochemical analyses were performed using manual methods and semi-automatic equipment, respectively. There were significant differences in relation to age in hematocrit and hemoglobin levels, and mean cell volumes, in captive T. tajacu. No basophils were observed, and the neutrophil:lymphocyte ratio was less than 1. Levels of total protein, urea, phosphorus, and alkaline phosphatase were significantly affected by age (P < 0.05). Gender did not affect any of the results. The hematological and biochemical parameters for this species were determined, and may be used as reference ranges for captive T. tajacu.

Qualitative analysis of preputial and vaginal bacterial microbiota in owl monkeys (Aotus azarai infulatus) raised in captivity.

BACKGROUND: The aim of this study was to identify the aerobic bacteria of the preputial and vaginal microbiota in owl monkeys that have been raised in captivity and to evaluate the antimicrobial susceptibility of these bacteria by gender and social organization. METHODS: Thirty clinically healthy Aotus azarai infulatus were used. A total of 134 samples were collected, 60 from the preputial mucosa and 74 from the vaginal mucosa. An automated system of bacterial identification was used. RESULTS AND CONCLUSIONS: Staphylococcus intermedius and Proteus mirabilis were the microorganisms that were most frequently identified according to gender and social organization. The antimicrobial susceptibility of the isolated gram-positive bacteria was similar in both sexes. However, the gram-negative strains had some differences. The aerobic bacterial population of the vaginal and preputial microbiota is similar in owl monkeys, and there are no differences in the number and bacterial species according to sex and social organization.

Kinematic analysis of Labrador Retrievers and Rottweilers trotting on a treadmill.

OBJECTIVES: The purpose of the study was to evaluate kinematic patterns in clinically normal Labrador and Rottweiler dogs trotting on a treadmill at a constant velocity. METHODS: Ten Labrador Retrievers aged from 2.2 to 5.1 years, and 10 Rottweilers aged from two to 5.9 years were used. A three-dimensional capture system was used to perform analysis of joint kinematics. Kinematic data were collected by use of a triple-camera system. The kinematic study was performed first on the right side of the dog, and then on the left side. Data were analysed by use of a motion-analysis program. Flexion and extension joint angles, angular velocity and angular acceleration were determined for the shoulder, elbow, carpal, hip, stifle, and tarsal joints. RESULTS: Within each group, the differences between the right and left limbs in all variables were not significant. Significant differences occurred between Labradors and Rottweilers in the following categories: angular displacement and minimum angular acceleration of the stifle (Rottweiler >Labrador); angular displacement and maximum angular velocity of the tarsus (Rottweiler >Labrador); minimum angular velocity of the shoulder (Labrador >Rottweiler); angular displacement, maximum angular acceleration, maximum angular velocity, and minimum angular velocity of the elbow (Labrador>Rottweiler); and maximum angle and maximum angular velocity of the carpus (Labrador>Rottweiler). CLINICAL SIGNIFICANCE: Both breeds had similar kinematic patterns, but there were magnitude differences, especially of the elbow and stifle joints. Therefore, each breed should have a specific database.

Imaging studies of the hindlimbs of pacas (Cuniculus paca) bred in captivity.

OBJECTIVE: To evaluate the hindlimbs of pacas bred in captivity using radiographic and computed tomography (CT) studies. ANIMALS: Nine mature pacas (Cuniculus paca) 5.9-8.2 kg in body weight. METHODS: Radiographical aspects of the bones of the hindlimbs were evaluated, and the Norberg angle and inclination angle were measured for each hindlimb. Anteversion angle were measured in CT examination. RESULTS: The bone anatomy of the hindlimb of the paca was similar to that of the guinea pig, apart from two lunulae and a single fabella (lateral) which were observed. The Norberg angle had mean value of 130.56º ± 3.81 without any significant difference between testers. Inclination angles ranged from 142.44º ± 4.82 to 145.44º ± 4.09 by Hauptman's method, and from 144.94º ± 3.13 to 148.22º ± 3.25 by Montavon's method, for right and left hindlimbs respectively. Average values for the anteversion angles measured with CT ranged from 28.56º ± 5.56 to 32.91º ± 2.62. CLINICAL SIGNIFICANCE: The data may be used in future studies comparing the paca to other rodent species. In addition, the paca could be used as an animal model in orthopaedic research.

Radiographic measurement of tibial joint angles in sheep.

The aim of this study was to establish normal reference values of anatomic and mechanical joint angles of the tibia in sheep at different age groups. Eighteen clinically healthy Santa Ines sheep were used. The animals were divided into three equal groups according to age: Group I - from six- to eight-months-old, Group II - 2-years-old, Group III - from three- to five-years-old. Anatomic medial proximal and lateral distal tibial angles, mechanical proximal and distal tibial angles, and anatomic caudal proximal and anatomic cranial distal tibial angles were measured from tibiae radiographs (n = 36). In the craniocaudal view, the mean values of the anatomic medial proximal, anatomic lateral distal, mechanical medial proximal, and mechanical lateral distal tibial joint angles were 89.6 masculine, 86.6 masculine, 91.4 masculine, and 85.19 masculine respectively. In mediolateral view, the mean values of the anatomic caudal proximal and anatomic cranial distal tibial angles were 64.55 masculine and 105.69 masculine, respectively. The joint orientation angles of the tibia in sheep showed similar values regardless of animal age for both anatomic and mechanical axes.

Evaluation of parameters obtained from two systems of gait analysis.

BACKGROUND: The technical difficulties in utilising the force platform have stimulated the use and development of other gait systems. Therefore, this study aimed to compare the values of gait parameters obtained from a pressure-sensitive walkway and from a treadmill in healthy dogs during walking. METHODS: Twelve healthy, privately owned, Labrador retriever dogs were used. During each trial, each dog was led across the pressure-sensitive walkway utilising a loose leash to the right of the handler. The velocity was restricted to the range of 0.9 to 1.1 m/s and the acceleration between -0.15 and 0.15 m/s2 . For the treadmill, each dog also walked with leash loose on the treadmill. The treadmill speed was maintained at 0.9m/s. The temporospatial variables, and percentage of body weight distribution/percentage of pressure were evaluated between the two gait systems. RESULTS: For both forelimbs and hind limbs, significant differences were found between stance percentage, which was higher on treadmill, and swing percentage and stride length/stance distance, which were higher on the pressure-sensitive walkway. The duty factor value was 0.57 for the pressure-sensitive walkway and 0.60 for treadmill. CLINICAL RELEVANCE: Each gait system has limitations, but also advantages that must be considered depending upon the variable and animal to be evaluated. The gait parameters obtained from the Tekscan pressure-sensitive walkway and Gait4Dog treadmill revealed differences in the temporospatial parameters between systems, but similarity in body-weight distribution/pressure percentage.

Use of extensible internal device in the femur of young dogs.

An extensible internal device (EID) was developed to preserve growth plate during the treatment of fracture complications or segmental bone loss from tumour resection in children. Since this type of extensible, transphyseal, internal fixation device has only been used in a few paediatric cases; the aim of this study was to evaluate an in vivo canine study, a surgical application of this device, and its interference with longitudinal growth of the non-fractured distal femur. Ten clinically healthy two- to three-month-old poodles weighing 1.5-2.3 kg were used. Following a medial approach to the right distal femur, one extremity of the EID, similar to a T-plate, was fixed in the femoral condyle with two cortical screws placed below the growth plate. The other extremity, consisting of an adaptable brim with two screw holes and a plate guide, was fixed in the third distal of the femoral diaphysis with two cortical screws. The EID was removed 180 days after application. All of the dogs demonstrated full weight-bearing after surgery. The values of thigh and stifle circumferences, and stifle joint motion range did not show any difference between operated and control hindlimbs. The plate slid in the device according to longitudinal bone growth, in all but one dog. In this dog, a 10.5% shortening of the femoral shaft was observed due to a lack of EID sliding. The other dogs had the same longitudinal lengths in both femurs. The EID permits longitudinal bone growth without blocking the distal femur growth plate if appropriately placed.

Sonographic Evaluation of Liver Hemodynamic Indices in Overweight and Obese Dogs.

BACKGROUND: Hepatic circulatory disturbances have been associated with obesity and fatty liver in humans. In the veterinary literature, however, there is limited information regarding the effects of different body condition scores (BCS) on liver hemodynamic indices in dogs. OBJECTIVES: To investigate the influence of BCS on liver hemodynamic indices. ANIMALS: Fifty-three client-owned dogs of various breeds were included. METHODS: Prospective observational study. Dogs were divided into 3 BCS groups using a 5-point scale: G1 - 12 ideal dogs, G2 - 21 overweight dogs, G3 - 20 obese dogs. Mean portal velocity (MPV), portal blood flow volume (PBFV), portal congestion index (PCI), hepatic artery resistivity index (HARI), and hepatic vein (HV) spectral wave were obtained by pulsed Doppler sonography. Alkaline phosphatase (ALP), gamma-glutamyl transferase (GGT), and alanine aminotransferase (ALT) activities were determined. Liver enzymes activities and liver hemodynamic indices were compared among groups. RESULTS: Obese dogs had lower MPV, higher percentage of abnormal hepatic vein spectral wave and higher median ALP activity than did ideal dogs (P < 0.05). Overweight and obese dogs had lower PBFV than ideal dogs (P < 0.01). Overweight dogs had higher median GGT activity than ideal dogs (P < 0.05). No difference was observed for PCI, HARI and median ALT activity among the groups. CONCLUSIONS AND CLINICAL IMPORTANCE: Obesity was associated with changes in portal vein indices and in HV spectral wave. These changes were accompanied by significant differences in some liver enzymes activities and could be a sign of early liver disease.

Radiological and osteological study of the pelvic limbs in free-ranging capybaras (Hydrochoerus hydrochaeris).

This study aimed to describe the radiographic anatomy and osteology and to evaluate angular radiographic measurements-Norberg angle, inclination angle and anteversion angle-of the pelvic limbs in free-ranging capybaras. Twenty cadavers of free-ranging capybaras (Hydrochoerus hydrochaeris), including five adults and 15 subadults, were studied. Ventrodorsal, craniocaudal, dorsoplantar and mediolateral radiographic views of the pelvic limbs were obtained. The radiographic features were described together with bone samples. The hip bone (os coxae), shaped like an isosceles trapezoid, was elongated and narrow with the presence of an oblong obturator foramen, sagittal ilial wing and rectilinear ilial body. The femoral shaft was relatively straight, while the greater trochanter was projected above the femoral head. No sesamoid bones of the gastrocnemius and popliteus muscles were observed radiographically or for those animals used in gross macroscopy. The fibula was located lateral and parallel to the tibia. Eight tarsal bones, four metatarsal bones and three digits were identified. The mean radiographic measurements included Norberg angle of 125.9°; respective angles of femoral inclination by the Hauptman B and Tomlinson methods of 139.9 and 141°; anteversion angle of the femoral head and neck of 29.80°. The bones of the pelvic limbs in capybaras have several anatomical characters and radiological features that are shared with members of the caviomorph superfamily Cavioidea. The radiographic angles measured in this study help characterize the functional morphology of this species.

Radiographic measurements of the hindlimbs in crab-eating foxes (Cerdocyon thous, Linnaeus, 1766).

Life expectancy of crab-eating foxes in captivity is approximately 11 years, which favours the development of diseases including orthopaedic disorders. However, to understand disorders that may affect these animals, it is worth determining a normal range of measurements. Therefore, this study aimed to evaluate radiographic measurements of joint angles of the hindlimbs and the ratio of patellar ligament length to patellar length in healthy crab-eating foxes. Fifteen captive crab-eating foxes (Cerdocyon thous), eight males and seven females, aged more than 1 year old, weighing 5.5-7.9 kg were used. Anatomic and mechanical femoral joint angles were assessed in ventrodorsal radiographic views, and mediolateral views were taken to measure patellar ligament length and patellar length, and the tibial plateau angle. The right and left hindlimbs were evaluated. All measurements were conducted in triplicate by the same investigator. No statistically significant differences were observed between sides in the radiographic measurements. The anatomic lateral proximal femoral angle and the anatomic lateral distal femoral angle recorded mean values of 95.43° and 92.75°, respectively. The mechanical lateral proximal femoral angle and the mechanical lateral distal femoral angle recorded mean values of 93.39° and 96.75°, respectively. Inclination angles measured according to the Tomlinson, Hauptman A and Hauptman B methods were 133.80°, 147.32° and 128.63°, respectively. The tibial plateau recorded 18.77°, and the ratio of the patellar ligament length to the patellar length was 1.99. In conclusion, the collected data are important to characterize the normal values of crab-eating fox limbs.

Tibial segmental bone defect treated with bone plate and cage filled with either xenogeneic composite or autologous cortical bone graft. An experimental study in sheep.

Tibia segmental defect healing in sheep were clinically, radiographically and histologically evaluated. Twelve young sheep aged four to five months were divided into two groups, G1 and G2. A 3.5 cm long segmental defect was created in the right tibial diaphysis with maintenance of the periosteum. The bone defects in both groups were stabilized with a bone plate combined with a titanium cage. In G1 the cage was filled with pieces of autologous cortical bone graft. In G2 it was filled with a composite biomaterial which consisted of inorganic bovine bone, demineralized bovine bone, a pool of bovine bone morphogenetic proteins bound to absorbable ultra-thin powdered hydroxyapatiteand bone-derived denaturized collagen. Except for one G1 animal, all of them showed normal limb function 60 days after surgery. Radiographic examination showed initial formation of periosteal callus in both groups at osteo-tomy sites, over the plate or cage 15 days postoperatively. At 60 and 90 days callus remodeling occurred. Histological and morphometric analysis at 90 days after surgery showed that the quantity of implanted materials in G1 and G2 were similar, and the quantity of new bone formation was less (p = 0.0048) and more immature in G1 than G2, occupying 51 +/- 3.46% and 62 +/- 6.26% of the cage space, respectively. These results suggest that the composite biomaterial tested was a good alternative to autologous cortical bone graft in this experimental ovine tibial defect. However, additional evaluation is warranted prior to its clinical usage.

Short-term effects of Whole-Body Vibration on clinical, cardiac, and ambulatory electrocardiographic (Holter) parameters of healthy younger and older adult male non-athletic crossbreed dogs / [Efeitos agudos da Vibração de Corpo Inteiro nos parêmetros clínico, cardíaco e eletrocardiografia ambulatorial (Holter) em cães jovens e idosos sem raça definida, hígidos e não atletas]

This study investigated the effects of WBV in clinical, cardiac, and ambulatory electrocardiographic (Holter) parameters of healthy young and aged male non-athletic dogs. Fourteen dogs were divided into two groups of seven animals: Group I (GI) - young dogs (12.0 and 84.0 months old); Group II (GII) - aged dogs (above 84.0 months old). Dogs were submitted to a single session of WBV (frequencies of 30 and 50 Hz), for 15-min. Variations were identified in the thickness of the interventricular septum and thickness of the left ventricle-free wall values: GI < GII at 5-min before the session. The diameter of the left atrium values showed a difference: GI < GII at 5-min before and 1-min after the session; and a decrease in GII between 5-min before and 1 min after the WBV. Several ambulatory electrocardiography (Holter) parameters demonstrated significant differences between both groups and time-points. A single session of WBV at frequencies of 30 and 50 Hz during 15-min by using a vibrating platform that delivered a vortex wave circulation did not induce significant changes in clinical, cardiac, and ambulatory electrocardiographic (Holter) parameters in healthy young and aged dogs.

O estudo teve como objetivo avaliar os efeitos agudos da vibração de corpo inteiro (VCI) nos parâmetros clínicos, cardíacos e eletrocardiográficos ambulatoriais (Holter) de cães jovens e adultos hígidos sem raça definida e não atletas. Quatorze cães foram divididos em dois grupos de sete cães, de acordo com a idade: Grupo I (GI) - entre 12,0 e 84,0 meses; Grupo II (GII) - acima de 84,0 meses. Os cães foram submetidos à única sessão de VCI com frequências de 30 e 50 Hz, durante 15 minutos. Foram identificadas variações significativas na espessura do septo interventricular e da espessura da parede do ventrículo esquerdo: GI

Osteology and radiology of the Maned Wolf (Chrysocyon brachyurus) pelvic limb.

This study describes the osteology and radiology of the pelvic limb in maned wolves. Ten (five live and five dead) maned wolves (Chrysocyon brachyurus), five males and five females, aged from 2 to 7 years old were used. Digital radiographs were taken and recorded for both pelvic limbs in all animals. Osteology was correlated with the radiographic images. The pelvis had a rectangular shape, and the obturator foramen (foramen obturatum) was oval. The femoral neck (collum femoris) was short and thick. The greater trochanter (trochanter major) extended proximally to near the dorsum of the femoral head (caput ossis femoris). The lateral femoral condyle (condylus lateralis) was larger than the medial condyle (condylus medialis), and the intercondylar fossa (fossa intercondylaris) had a slightly oblique orientation. The proximal tibia displayed medial and lateral condyles with the medial larger. The femur was slightly shorter than the tibia. Seven tarsal bones (ossa tarsi) were present, four long metatarsal bones (ossa metatarsalia II - V) and a short first metatarsal bone (os metatarsal I).

The French Randomized Optimal Stenting Trial: a prospective evaluation of provisional stenting guided by coronary velocity reserve and quantitative coronary angiography. F.R.O.S.T. Study Group.

OBJECTIVES: We sought to make a prospective comparison of systematic stenting with provisional stenting guided by Doppler measurements of coronary velocity reserve and quantitative coronary angiography. BACKGROUND: Despite the increasing use of stents during percutaneous transluminal coronary angioplasty, it is unclear whether systematic stenting is superior to a strategy of provisional stenting in which stents are placed only in patients with unsatisfactory results or as a bail-out procedure. METHODS: Two hundred fifty-one patients undergoing elective coronary angioplasty were randomly assigned either to provisional stenting (group 1, in which stenting was performed if postangioplasty coronary velocity reserve was <2.2 and/or residual stenosis > or =35% or as bail-out) or to systematic stenting (group 2). The primary end point was the six-month angiographic minimal lumen diameter (MLD). Major adverse cardiac events were secondary end points (death, acute myocardial infarction and target lesion revascularization). RESULTS: Stenting was performed in 48.4% of patients in group 1 and 100% of patients in group 2 (p<0.01). Six months after angioplasty, the MLD did not differ between groups (1.90+/-0.79 mm vs. 1.99+/-0.70 mm, p = 0.39), as was the rate of binary restenosis (27.1% vs. 21.4%, p = 0.37). Among patients with restenosis, 13/32 (40.6%) in group 1 but 100% (25/25) in group 2 had in-stent restenosis (p<0.01). Target lesion revascularization (15.1% vs. 14.4% in groups 1 and 2 respectively, p = 0.89) and major adverse cardiac events (15.1% vs. 16.0%, p = 0.85) were not significantly different. CONCLUSIONS: Systematic stenting does not provide superior angiographic results at six months as compared with provisional stenting.

Influence of calibration protocols for a pressure-sensing walkway on kinetic and temporospatial parameters.

OBJECTIVES: To evaluate the influence on the kinetic and temporospatial parameters of calibration protocols with point and step techniques for a pressure-sensing walkway. METHODS: Nine Labrador dogs were used. Two protocols of point calibration technique (C1 and C2) and eight protocols of step calibration technique (C3 to C10) were performed. In C1, weight was added to a stool to match the body mass of each dog. In C2, weight was added to the stool to match a 46.1 kg person. The other eight calibration protocols represented combinations of the following factors: 46.1 kg and 96.1 kg persons, barefoot or wearing sneakers, and stepping onto the platform with one or two feet. RESULTS: The calibration protocols did not affect the temporospatial variables or percentages of body weight (%BW) distribution. Significant differences were found in both PVI (peak vertical force) and VI (vertical impulse) between barefoot versus wearing sneakers, 46.1 kg versus 96.1 kg person, and stepping onto the platform with one foot versus two feet. When comparing C1 with other protocols, significant differences were observed in PVF and VI for both forelimbs and hindlimbs. When comparing C2 with other protocols, significant differences were observed in PVF and VI for both forelimbs and hindlimbs in all protocols. CLINICAL SIGNIFICANCE: The PVF and VI were influenced by the calibration protocol used, but the %BW distribution and temporospatial parameters were not. Using the same calibration protocol for all dogs within the same group eliminated the variability of the kinetic data caused by the calibration.

Evaluation of the marsh deer stifle joint by imaging studies and gross anatomy.

This study aimed to evaluate the stifle joint of marsh deer using imaging studies and in comparison with gross anatomy. Ten hindlimbs from 5 marsh deer (Blastocerus dichotomus) were used. Radiography, computed tomography (CT) and magnetic resonance imaging (MRI) were performed in each stifle joint. Two hindlimbs were dissected to describe stifle gross anatomy. The other limbs were sectioned in sagittal, dorsal or transverse planes. In the craniocaudal radiographic view, the lateral femoral condyle was broader than the medial femoral condyle. The femoral trochlea was asymmetrical. Subsequent multiplanar reconstruction revealed in the cranial view that the external surface of the patella was roughened, the medial trochlea ridge was larger than the lateral one, and the extensor fossa at the lateral condyle was next to the lateral ridge. The popliteal fossa was better visualized via the lateral view. Sagittal MRI images identified lateral and medial menisci, caudolateral and craniomedial bundles of cranial cruciate ligament, caudal cruciate ligament, patellar ligament and common extensor tendon. In conclusion, the marsh deer stifle presents some anatomical characteristics of the ovine stifle joint.

Ketoconazole inhibition of progesterone oxidation by the rabbit.

Ketoconazole, a known cytochrome P-450 inhibitor, inhibited both progesterone ring hydroxylation and side-chain oxidation to steroidal acids. Progesterone 21 6 beta- and 16 alpha-hydroxylase activities of rabbit liver microsomes were inhibited 50% by ketoconazole at concentrations between 10(-5) and 10(-4) M. Steroid acid formation was similarly inhibited at a 10(-5) M concentration. Ketoconazole administration to rabbits produced a significant reduction in the urinary excretion of acidic metabolites of [3H]deoxycorticosterone and [14C]progesterone by approximately 50 and 75% respectively. The differential effect of ketoconazole in vivo may indicate that more than one acidic metabolite pathway may be operative.

Corticosteroid side chain oxidations--3. Evidence for isomerization and direct oxidation reactions in the formation of steroid 21-oic acids by rabbit liver cytosol.

Isomerase complexes that oxidize the alpha-ketol side chain of deoxycorticosterone (DOC) to pregnolic and pregnenoic acids without the addition of cofactors have been purified from rabbit and hamster liver cytosols. The isomerase complex in rabbit liver cytosol was partially resolved from a NAD-dependent dehydrogenase that oxidized the glycol side chain of 20 beta-dihydro DOC to the 20 beta-hydroxy-21-oic acid. Corticosterone (B) and 20 beta-dihydro B were less active substrates than DOC or 20 beta-dihydro DOC with the corresponding preparations. The rabbit resembles other rodent and human species in that isomerization and oxidation at C21 is the major pathway of acid formation whereas direct oxidation at C21 may only be of significance with metabolites that have the glycol side chain.

Corticosteroid side-chain oxidations--I. Structural effects on the excreted isotope ratios of 4-14C- and 21-3H-labelled corticosteroid metabolites in rabbit urine.

The metabolic fates of 4-14C- and 21-3H-labelled corticosteroids have been investigated in the rabbit by analysis of the normalized isotope ratios of neutral and acidic metabolites excreted in the urine. Isotope ratios of excreted radioactivity declined in the order cortisol (F) greater than corticosterone (B) greater than 11-desoxycortisol (S) greater than deoxycorticosterone (DOC). Steroid acids, isolated in alumina fraction C, represented 19.0, 15.0, 9.7 and 2.7% of the doses of DOC, B, S and F, respectively, and the isotope ratios declined in the order F greater than B greater than S greater than DOC. HPLC of steroid acid methyl ester derivatives indicated generally low isotope ratios for DOC and S steroid acids, consistent with complete side-chain oxidation to 20-oxo-21-oic acids and/or 17-carboxylic acids. Several B metabolite methyl esters peaks also exhibited low isotope ratios, but both B and F metabolites gave methyl esters that retained significant tritium consistent with the presence of 20-hydroxysteroid acids. The 21-hydroxy-steroid metabolite fractions had isotope ratios of F = S greater than B greater than DOC. HPLC showed that 20-oxo (tetrahydro) metabolites of B and F had reduced isotope ratios unlike the C-20 reduced (hexahydro) metabolites of DOC and S. It may be concluded that the metabolic fate of the corticoid side-chain in the rabbit is dependent on the steroid structure and may result in the excretion of both 20-oxo and 20-hydroxysteroid acids.