Effect of an Injectable Cabergoline Formulation on Serum Prolactin (PRL) and Milk Secretion in Early Postpartum Beagle Bitches

This study was conducted in order to evaluate effects on prolactin (PRL) concentration and mammary milk secretion of an injectable cabergoline formulation administered to five lactating Beagle bitches during early postpartum (PP). Bitches were bled twice daily (from PP day 3 to PP day 12) and then daily (from PP day 13 to PP day 16) to assay serum PRL. On PP day 6, a subcutaneous (SC) injection of 0.1 ml/kg of placebo was administered. On PP day 9, a SC 0.1 ml/kg dose of injectable cabergoline was administered. All bitches were checked for milk production, using a clinical scoring in order to quantify milk expression from each teat. A circadian variation of serum PRL was evident during the 6 days of pre-treatment monitoring. The day after cabergoline injection, an 80% decrease of PRL serum concentration was observed (p < 0.05). The circadian oscillatory pattern of PRL secretion disappeared after administration of cabergoline, and PRL values remained significantly lower than in the previous days for the first 60 h following treatment (p < 0.001). Milk production was drastically reduced when comparing pre-treatment to post-treatment scores (p < 0.001). A single dose of injectable cabergoline caused a significant reduction in serum PRL concentration and a significant reduction in milk flow. The injectable formulation of cabergoline appeared to be safe and well tolerated.     

Effect of Short-Term Restricted Food Intake on Canine Pseudopregnancy

A non-pharmaceutical, dietary option may be useful to manage clinical pseudopregnancy (PSP). To describe the effect of short-term food restriction on canine PSP, 16 privately owned, overtly pseudopregnant bitches were randomly assigned to one of the following groups: Limit-fed (increasing amounts of a restricted maintenance: 50%, 40%, 30% restriction for 2, 3 and 2 days respectively) during 7 days (n = 8) or Maintenance-fed of the same food and period (n = 8). The bitches were physically examined and blood samples were taken for prolactin and progesterone determinations on days 2, 5 and 8. By day 8, none of the bitches had completely regressed the condition although all (8/8) the animals of the Limit-fed and two (25%) of the Maintenance-fed group improved in condition decreasing mammary size and secretion (p < 0.05). No day or group effects were observed for serum prolactin and progesterone concentrations (>0.05). It is concluded that although an 8-day food restriction did not cure PSP, it seemed to hasten PSP signs involution in these bitches. No endocrine change was related to these clinical findings.     

Influence of E‐cadherin genetic variation in canine mammary tumour risk,clinicopathological features and prognosis

E‐cadherin is a cell adhesion molecule that participates in several cellular processes that guarantee the maintenance of structural and functional integrity of epithelial tissues. E‐cadherin plays an important role in mammary carcinogenesis, and various studies have demonstrated the effect of CDH1 genetic variation in risk, progression and biological behaviour of human breast cancer. Although there are some recognized genetic variations in canine CDH1 gene, their influence in canine mammary tumour development and progression has not been previously evaluated. In this study, we aim to assess the influence of CDH1 SNPs rs850805755, rs852280880 and rs852639930 in the risk, clinicopathological features and clinical outcome of canine mammary tumours. A case‐control study was conducted involving 206 bitches with mammary tumours and 161 bitches free of mammary neoplasia. CDH1 SNPs rs850805755 and rs852280880 were associated with a decreased risk and a later onset of mammary tumour development. Furthermore, these SNPs were related to the development of small size carcinomas, of low histological grade and low nuclear pleomorphism. SNP rs852639930 was associated with the development of small size tumours with a non‐infiltrative, non‐invasive growth pattern. Data from the present investigation demonstrate that these CDH1 genetic variants could have a protective role in canine mammary tumours, by being associated with low risk of tumour development, delayed onset of the disease and less aggressive clinicopathological features.     

Aglepristone decreases proliferation in progesterone receptor-positive canine mammary carcinomas

Background: Progesterone receptor (PR) antagonist aglepristone (RU534) has been used successfully for pregnancy termination and therapy of pyometra, vaginal tumors, and mammary hyperplasia in bitches and queens. All of these conditions share with canine mammary carcinomas the expression of PR. Objectives: To study the effect of RU534 on proliferation and apoptosis in canine mammary carcinomas in relation to PR expression. Animals: Twenty‐seven nonspayed bitches with mammary carcinomas were treated with either 2 doses of 20 mg/kg RU534 (n = 22, RU534‐treated group) or oil placebo (n = 5, control group) on days 1 and 8. Methods: Tumor samples were collected before (day 1) and after (day 15) treatment for immunohistochemistry. PR expression, proliferation index (PI), and apoptotic index (AI) were determined using antibodies against PR, Ki67, and cleaved lamin A/C antigens, respectively. The effect of treatment on these parameters was analyzed. Results: Differential expression of PR between day 1 (59.1% PR‐positive tumors) and day 15 (36.4% PR‐positive tumors) was observed in RU534‐treated tumors exclusively. After RU534 treatment, mean PI was significantly decreased in PR‐positive but unchanged in PR‐negative RU534‐treated tumors. A reduction of ≥20% in PI was found in 61.5% of RU534‐treated tumors with PR expression. Conversely, no effect on AI was observed after RU534 treatment. Conclusions and Clinical Importance: Neoadjuvant RU534 treatment had PR expression‐related inhibiting effects on proliferation of canine mammary carcinoma cells.     

Twenty-four-hour Profiles of Serum Prolactin and Luteinizing Hormone in Anoestrous Crossbred Bitches

The dynamics of prolactin (PRL) and luteinizing hormone (LH) secretion in the anoestrous bitch is poorly known. Therefore, the objective of this study was to characterize the 24 h profiles of serum PRL and LH in crossbred anoestrous bitches and to assess whether a relationship exists between the secretory patterns of these two hormones. Serum PRL and LH concentrations were measured in 10 healthy anoestrous crossbred bitches at 145 min intervals for 24 h. During the experiment the animals received continuous artificial illumination and remained undisturbed except at the time of blood sampling. Serum PRL was measured by a homologous enzyme‐linked immunosorbent assay, whereas LH and progesterone (P₄) were determined by radioimmunoassay. The anoestrous state of the bitches was assessed by vaginal cytology, vaginoscopy and physical examination. Two groups of animals were identified according to their PRL levels: a high PRL group (n=3, mean ± SEM 12.3 ± 2.7 ng/ml) and a low PRL group (n=7, mean ± SEM: 2.5 ± 0.9 ng/ml). In the low PRL group, the PRL profiles were flat and did not show any significant circadian pattern. Nevertheless, occasional single‐point peaks were detected in some of the bitches. In the high PRL group the individual PRL profiles were variable. To detect the presence of a circadian change of PRL concentrations, two different sets of time windows (TW) of sampling were studied. The first set was: day [TW1A, samples 1–5 (0900–1840 h)] and night [TW1B, samples 6–10 (2105–0645 h)]. The second set was chosen after visual inspection of the average PRL profiles for both (high and low) groups: [TW2A, samples 3–7 (1350–2330 h) and TW2B, samples 1–2 and 8–10 (0155–1125 h)]. PRL concentrations were not significantly different between day and night. In the high PRL group, but not in the low PRL group, average serum PRL was significantly (p < 0.01) higher in TW2A than TW2B. In both groups serum LH levels were more homogeneous than PRL levels. Neither TW showed circadian changes in LH patterns of secretion (TW1A versus TW1B, p < 0.69; TW2A versus TW2B, p < 0.88). On the other hand, bitches in the high PRL group showed significantly (p < 0.01) lower serum LH levels than those in the low PRL group of animals. Serum PRL concentrations presented a significant inverse correlation with LH concentrations (r=?0.21, p < 0.03) and a significant positive correlation with P₄ concentrations across the study (0.92, p < 0.01). It is concluded that in anoestrous crossbred bitches serum PRL is highly variable and inversely related to LH. No circadian rhythm of PRL secretion appears to exist in most anoestrous bitches.     

Clinical value of carcinoembryonic antigen in mammary neoplasms of bitches

This study aimed at evaluating the behaviour and understanding the diagnostic value of the carcinoembryonic antigen (CEA) in bitches with mammary carcinoma as a tool for monitoring and prognosis of canine cancer patients. Serum samples from 77 bitches were divided into four groups, G1 (n = 21), control group (healthy/neoplasia free bitches); G2 (n = 31), bitches with non‐metastatic mammary carcinoma less than 3 cm; G3 (n = 12), bitches with non‐metastatic mammary carcinoma greater than 3 cm; and, G4 (n = 13) bitches with mammary carcinoma and lymph node metastasis. The marker was dosed once in G1, whereas in G2, G3 and G4, CEA levels were determined before (M0) and 15 days after (M1) mastectomy, using the ELISA kit for humans while reading used ELISYS ONE human. A group of 11 bitches was followed up 45 days after mastectomy (M2). The results for the concentration of markers in blood serum samples at the evaluated times and their relationship with neoplasia biological behaviour and observed clinicopathological changes were evaluated by the Tukey test at 5% significance. The ROC curve was established to find the cut‐off value and calculate the test sensitivity and specificity, the multivariate matching analysis was performed to confirm the association between CEA values and clinicopathological variables. CEA values increased significantly in bitches with mammary carcinoma, metastatic tumours with a diameter larger than 3.0 cm and high grade, compared with healthy ones. In addition, mastectomy reduced the CEA concentration in the blood (P < .05) whereas high CEA levels were associated with unfavourable prognostic factors (P < .05). The biomarker presented good diagnostic value, especially for more aggressive tumours. In conclusion, CEA serum concentrations allowed to follow efficiently the evolution of mammary tumours in bitches, since CEA values increased in bitches with mammary gland tumour and decreased after mastectomy while correlating with prognostic factors such as tumour size, nodal metastasis and histological grade. Further studies are still needed to confirm its diagnostic value for follow‐up of relapse and early metastasis.     

Evaluation of Cabergoline and Buserelin Efficacy for Oestrous Induction in the Bitch

The purpose of this work was to compare two different protocols of oestrous induction, using either a dopamine agonist (cabergoline) or a GnRH agonist (buserelin) in anoestrus bitches. The clinical trial involved 22 Beagle bitches, randomly allotted to two treatment groups: group A (n = 12) was orally administered cabergoline (Galastop^®; Centralvet‐Vetem, Milan, Italy; 5 μg/kg SID), until the onset of cytological oestrus or for a maximum of 30 days and group B (n = 10) was treated with buserelin acetate, (Suprefact^®; Aventis Pharma, Milan, Italy), administered subcutaneously t.i.d., at 1.5 μg/kg for 11 days and 0.75 μg/kg for the following 3 days. Blood samples were collected twice a week to measure progesterone and prolactin concentration. Both cabergoline and buserelin produced a significant early decline in prolactin concentration (p < 0.01), but the effect of cabergoline lasted longer. Progesterone concentration was significantly affected by buserelin administration, showing a significant increase (p < 0.01) from day 3 to day 6 of treatment. Cabergoline confirmed its effectiveness in inducing oestrus as 10 of 12 bitches responded to the treatment, were mated and whelped. On the contrary, oestrus was observed in only three of 10 buserelin‐treated bitches and in two of them 7 and 13 days after the end of treatment. These same two bitches accepted mating and conceived. The results suggest that in a clinical setting, dopaminergic treatment is the treatment of choice as it yields more consistent results and involves a much easier administration protocol.     

Protection of puppies against canine herpesvirus by vaccination of the dams.

Six bitches free of canine herpesvirus 1 (CHV-1) were vaccinated against the virus; a first injection was given 10 days after the presumed date of mating and a second six weeks later. Six similar bitches were left unvaccinated as controls, and all the pups were challenged oronasally with a virulent strain of CHV-1 at three days of age. All the vaccinated bitches seroconverted and had high antibody titres when the puppies were challenged, but the control bitches remained seronegative. In the control group, 62 per cent (18 of 29) of the pups died of CHV-1-induced disease; most of them showed typical clinical signs and macroscopic lesions, and CHV-1 infection was confirmed by the isolation of the virus or by PCR. None of the puppies in the vaccinated group died of CHV-1 infection. The efficacy of the vaccine was confirmed in CHV-1-positive breeding units. The rate of pregnancy tended to be higher in vaccinated bitches and the mortality of pups before weaning was significantly reduced in the litters born to vaccinated bitches.     

Equine Chorionic Gonadotropin and Human Chorionic Gonadotropin Stimulation Increase the Number of Luteinized Follicles and the Progesterone Level Compared with Cabergoline Stimulation in Anoestrus Bitches

In this study, ovarian morphologies and blood progesterone concentrations following oestrous induction in bitches were examined. Fifty‐three clinically healthy anoestrus bitches received cabergoline at a daily dose of 5 μg/kg of body weight per os for 21 days (group I) or subcutaneous equine chorionic gonadotropin at a dose of 20 IU/kg of body weight for five consecutive days with an additional 500 IU s.c. per bitch of human chorionic gonadotropin on the last day of treatment (group II). Twenty bitches that spontaneously displayed oestrous signs were left untreated and served as controls (group III). The induced oestrous rates and ovulation rates in groups I and II were 60.0% vs 64.3% and 86.7% vs 83.3%, respectively. Morphological assessments of the ovarian structures after ovariohysterectomy revealed an increase in the number of luteinized follicles and cysts in group II compared with the two other groups (p < 0.001). In contrast, the numbers of corpora lutea and follicles were similar in all groups. In accordance with the above‐mentioned alteration, the progesterone concentration in the gonadotropin group (II) was increased (p < 0.001) in the periovulatory period compared with the other two groups. During the entire sampling period, the progesterone profiles in the cabergoline (I) and control (III) groups were similar and typical of normally cycling bitches. In conclusion, gonadotropin treatment is associated with an increased progesterone level during the periovulatory period that probably originates from luteinized follicles, whereas cabergoline treatment induces cycles with both physiological progesterone concentrations and ovarian morphologies.     

Comparison of the use of cabergoline and gonadotrophin to treat primary and secondary anoestrus in bitches

Objective To determine the efficacy and reliability of cabergoline and pregnant mare's serum gonadotrophin (PMSG) for induction of oestrus in bitches with primary or secondary anoestrus. Procedures We studied 39 healthy bitches of various breeds aged 2–6 years and in primary or secondary anoestrus: 20 bitches were administered 5 µg/kg/day cabergoline orally until day 2 after the onset of pro‐oestrus or for a maximum of 42 days, and 19 bitches were administered 20 IU/kg/day PMSG intramuscularly for 5 consecutive days, followed by an additional single injection of 25 IU/kg of human chorionic gonadotrophin on the fifth day. Results The rates of oestrus induction in the primary and secondary anoestrous bitches treated with cabergoline and PMSG were found to be similar. Pregnancy and whelping rates in the cabergoline group were statistically different from the rates in the PMSG group (P < 0.001). Conclusion Cabergoline is more effective and reliable for the induction of a fertile oestrus in bitches with primary or secondary anoestrous.     

Vascular Endothelial (VEGF) and Epithelial Growth Factor (EGF) as Well as Platelet‐Activating Factor (PAF) and Receptors are Expressed in the Early Pregnant Canine Uterus

The aim of this study was to investigate the course of expression of platelet‐activating factor (PAF), PAF‐receptor (PAF‐R), epidermal growth factor (EGF), EGF‐R, vascular endothelial growth factor (VEGF), VEGF‐R1 and VEGF‐R2 in uterine tissue during canine pregnancy. For this purpose, 20 bitches were ovariohysterectomized at days 10–12 (n = 10), 18–25 (n = 5) and 28–45 (n = 5) days after mating, respectively. The pre‐implantation group was proven pregnant by embryo flushing of the uterus after the operation, the others by sonography. Five embryo negative, that is, non‐pregnant, bitches in diestrus (day 10–12) served as controls. Tissue samples from the uterus (placentation sites and horn width, respectively) were excised and snap‐frozen in liquid nitrogen after embedding in Tissue Tec^®. Extraction of mRNA for RT‐PCR was performed with Tri‐Reagent. In the embryos, mRNA from all factors except VEGF was detected. In the course of pregnancy, significantly higher expression of PAF and PAFR as well as VEGF and VEGFR2 during the pre‐implantation stage than in all other stages and a strong upregulation of EGF during implantation were characteristic. The course of EGF was in diametrical opposition to the course of the receptor. These results point towards an increased demand for VEGF, EGF and PAF during the earliest stages of canine pregnancy.     

Prognostic impact of neoadjuvant aglepristone treatment in clinicopathological parameters of progesterone receptor‐positive canine mammary carcinomas

Neoadjuvant treatment of canine mammary carcinomas with the progesterone receptor (PR) antagonist aglepristone has a PR expression‐related inhibiting effect on proliferation index (PI). The aim of this study was to evaluate the effect of the treatment in the disease‐free period (DFP) and overall survival (OS) of canine mammary carcinomas. Fifty female dogs with mammary carcinomas were treated with aglepristone (n = 34) or oil vehicle (n = 16) before surgery (day 15). PR expression and PI were analysed by immunohistochemistry in samples taken at days 1 and 15. Epidemiological and clinicopathological data were assessed. DFP and OS data were retrieved every 4–6 months for at least 24 months after surgery. Aglepristone treatment increased DFP of animals bearing PR+ tumours with size smaller than 3 cm, complex and mixed tumours, with histologic grades I and II, and with PI ≤ 10%. Although further studies are necessary, current evidence points to treatment with aglepristone as useful for the management of canine mammary tumours.     

Treatment of pseudopregnancy in the bitch with cabergoline, an ergoline derivative

Cabergoline, a new prolactin inhibitor, was evaluated clinically in 143 bitches with pseudopregnancy and, or, false lactation, 14 cases of lactation after ovariohysterectomy for the removal of dead fetuses, 12 cases of persisting lactation after early weaning, and five cases of eclampsia. The drug was administered as a once-daily oral treatment (on food) in 139 cases or as subcutaneous injections at 48 hour intervals (maximum four injections) at a dose of 5, 2–5 or 1–5 μg/kg bodyweight in 35 cases. Improvement was evident within three to four days, and in 80 per cent of the cases clinical signs (abnormal behaviour, mammary gland swelling. milk secretion) had been significantly reduced or had disappeared within seven days. Treatment was successful in 95 per cent of the cases. Emesis was the only objectionable clinical side effect, being seen in 3 per cent of orally treated animals and necessitated withdrawal of one dog from the study. Vomiting occurred after the first (65-7 per cent) and second (22-9 per cent) injection only.     

Experimental staphylococcal mastitis in bitches: clinical, bacteriological, cytological, haematological and pathological features

The objectives of the work were to study the features of experimentally induced canine mastitis and to present hypotheses regarding the pathogenesis of the disease. The right caudal abdominal mammary gland of six bitches was inoculated on day 8 after whelping with Staphylococcus intermedius to induce mastitis; adjacent mammary glands were used as controls. Clinical examination, bacteriological and cytological (whiteside test, Giemsa) examination of mammary secretion, as well as haematological tests were performed from 5 days before until 34 days after challenge. Mastectomy was sequentially performed 1, 2, 4, 18, 26 and 34 days after challenge in each of the bitches, in order to carry out a pathological examination of mammary glands. All animals developed clinical mastitis: challenged glands became painful, hot, enlarged and oedematous; secretion was brownish, purulent, with flakes or clots, subsequently becoming yellowish and thick. Staphylococci were isolated from all inoculated glands (up to 22 days). WST was positive in 41/46 samples from inoculated glands and 66/138 samples from control glands; neutrophils predominated during the acute stage. Blood leukocyte counts increased, whilst platelet counts decreased. Gross pathological findings initially included congestion, purulent discharge and subcutaneous oedema; then abscesses, brownish areas and size decrease were seen. Salient histopathological features were initially neutrophilic infiltration, haemorrhages, destruction of mammary epithelial cells and alveoli, and then infiltration by lymphocytes, shrunken alveoli, loss of glandular architecture and fibrous tissue proliferation. We conclude that in bitches, intrammamary inoculation of Staphylococcus intermedius can induce clinical mastitis, followed by subclinical disease. The disorder is characterized by bacterial isolation and leukocyte influx in challenged glands, by leukocyte presence in adjacent mammary glands, by increased blood leukocyte counts and by destruction of mammary parenchyma.     

Treatment of spontaneous pyometra in 22 bitches with a combination of cabergoline and cloprostenol

Twenty-two bitches with ultrasonographically diagnosed spontaneous pyometra were treated with a combination of 5 microg/kg cabergoline per day and 5 mug/kg cloprostenol every third day, and potentiated sulphonamide twice a day. Bitches with either open-cervix or closed-cervix pyometra showed a rapid clinical improvement, associated with a reduction in plasma progesterone concentration, increased vulval discharge and a reduction in the diameter of the uterus. The haematological profiles of 21 of the bitches returned to normal within six days of treatment, and their biochemical profiles returned to normal within nine days; 19 of the bitches were managed successfully by a 10-day period of treatment. Two bitches required a further three days of treatment, and in one bitch with a partial uterine torsion the treatment was not successful. Adverse effects of the treatment were limited to the 60 minutes immediately after the administration of prostaglandin, and included retching, vomiting, mild abdominal straining, diarrhoea and panting. The incidence of adverse effects was reduced after each successive dose of prostaglandin. Eleven of the 21 successfully treated bitches were mated at the next oestrus, and seven became pregnant; their litters were smaller than the published breed averages. In four of the bitches the pyometra recurred after the next oestrus.     

Successful treatment of canine necrolytic migratory erythema (superficial necrolytic dermatitis) due to metastatic glucagonoma with octreotide

Necrolytic migratory erythema (NME; also known as superficial necrolytic dermatitis) is a syndrome most often associated with certain chronic liver diseases or pancreatic glucagonomas. In humans with glucaconoma‐associated NME, skin lesions usually respond to octreotide, a somatostatin analogue that inhibits glucagon release. In this report an 11‐year‐old golden retriever dog with pancreatic glucononoma and metastasis to the regional lymph nodes, spleen and liver was diagnosed with NME. The dog exhibited erosions, ulcers and crusts on the paws, pressure points, muzzle, periocular area and prepuce. The dog was also anorexic and had difficulty walking. Because metastasis precluded surgery, treatment was initiated with subcutaneous octreotide (2 μg/kg twice daily). Skin lesions and systemic clinical signs improved markedly within 5 days. The dosage was increased to nearly 3 μg/kg twice daily and signs almost completely resolved within 10 days. Anorexia was the major adverse effect observed. During the following month, both dosage (1–3.7 μg/kg) and frequency (two to four times daily) of the octreotide injections were adjusted to permit control of clinical signs while maintaining adequate appetite. Temporary cessation of octreotide administration resulted in the rapid recurrence of skin lesions. Resuming injections led to improvement of clinical signs within 48 h. The dog was later euthanized because of progressive metastatic disease. In conclusion, subcutaneous octreotide injections were beneficial in this dog with glucagonoma‐associated NME. This somatostatin analogue could be a valuable option to treat canine patients with non‐resectable or relapsing pancreatic glucagonoma‐associated NME.     

Relationship between receptors for epidermal growth factor and steroid hormones in normal, dysplastic and neoplastic canine mammary tissues

The concentrations of receptors for epidermal growth factor (EGF-R), oestrogen (ER) and progesterone (PR) were measured in 108 samples from canine mammary tumours and 132 samples of normal mammary tissue removed surgically from 84 bitches. The history and clinical signs were also recorded. Binding sites of high affinity were detected in 70 per cent of both types of tissue and no significant variations in EGF-R concentrations or positivity were observed with the histology, location, size or number of mammary tumours or the age of the animal. A significant direct correlation (P=0002) was observed between the concentrations of ER and EGF-R only in malignant tumours. The concentrations of EGF-R were significantly correlated (P=0.04) in normal mammary tissues adjacent to and distant from the lesions, but not between normal tissue and tumour tissue. No significant differences were observed in the expression of EGF-R in normal and neoplastic tissues from the same bitches. The direct correlation between the concentrations of EGF-R and ER in malignant tumours could be related to an oestrogen-dependent expression of EGF-R or to a similar pattern of regulation of the receptors.     

Megestrol acetate for estrus postponement in the bitch.

Megestrol acetate was given orally to 389 bitches in early proestrus, at a dosage of 2.2 mg/kg (1 mg/lb) per day for 8 days. Estrus was suppressed in 357 (92%) of the bitches. Additionally, 119 bitches in anestrus were given the drug at the rate of 0.55 mg/kg (0.25 mg/lb) per day for 32 days. Estrus was suppressed in 115 (98%) of these bitches. Adverse effects were minimal. Pyometra developed in 3 (0.8%) of the 389 bitches treated in early proestrus. The drug also was given to 19 bitches at the rate of 0.55 mg/kg/day for 32 days, regardless of the stage ofting at the 1st posttreatment estrus and 4 after mating at the 2nd posttreatment estrus. Litter size, success in rearing pups, and sex ratios were not significantly different from these factors in 53 litters from untreated bitches.     

Comparison of once-daily versus twice-weekly terbinafine administration for the treatment of canine Malassezia dermatitis - a pilot study

Background – Terbinafine, an allylamine antifungal, is used in pulsatile dose regimens for superficial mycoses in human medicine. Objectives – To compare the clinical efficacy of twice‐weekly versus once‐daily terbinafine administration to determine whether preliminary proof‐of‐concept evidence exists for pulsatile administration of terbinafine in the treatment of canine Malassezia dermatitis and to determine whether twice‐weekly treatment results in fewer clinical and owner‐perceived adverse events. Animals – Twenty client‐owned dogs with Malassezia dermatitis. Methods – In this randomized, single‐blinded clinical trial, dogs were randomly assigned to receive terbinafine (30 mg/kg) either once daily for 21 days (n = 10) or once daily on two consecutive days per week for six doses (n = 10). On day 0 and day 21, a mean yeast count was calculated from eight anatomical locations via adhesive tape‐strip cytology, clinical lesion scores were assigned to the same locations, and owners assessed pruritus using a visual analog scale. Results – There was no significant difference between treatment groups with respect to the reduction in mean yeast count (P = 0.343) and clinical lesion scores (P = 0.887). Pruritus measured by visual analog scale was significantly decreased in the twice‐weekly treatment group compared with the daily treatment group (P = 0.047). Seven of 20 dogs had a clinically measurable or owner‐reported adverse event during treatment that included gastrointestinal disturbances, excessive panting and elevated hepatic enzymes, with no significant difference noted between treatment groups. Conclusions and clinical importance – This pilot study indicates that twice‐weekly terbinafine administration may be an effective alternative treatment for canine Malassezia dermatitis and merits further investigation.     

Common germline haplotypes and genotypes identified in BRCA2 exon 11 of dogs with mammary tumours and histopathological analyses

The canine BRCA2 is a tumor supressor gene which encodes the BRCA2 protein, involved in DNA repair through interaction with the RAD51 recombinase. This process is mediated by eigth BRC repeats that are encoded by BRCA2 exon 11. Two variants corresponding to human mutations in human BRC3 repeat have been reported in canine BRC3 repeat. In addition, other variants have also been described in canine BRCA2 exon 11. Considering the importance of polymorphisms in human BRCA2 to breast cancer development, this study aimed to investigate the frequency of variants in BRCA2 exon 11 in 48 blood and tissue DNA samples from bitches with canine mammary tumors (CMT), as well as, to analyze tumor stage and histopathological features. Seven Single Nucleotide Polymorphisms (SNPs) were identified, three of which were evaluated as possibily or probably deleterious variant. Interestingly, almost all the 22 mammary tumors (except one) which presented a clinical staging equal to or greater than III carried at least one mutant allele of these three variants. Besides that, no statistically significant correlation was observed between any of the reported SNPs in heterozygosis or homozygosis and either dogs data (such as breed, age or disease stage) or mammary tumors histopathological characteristics. A total of 97.9% of bitches had one to three polymorphisms of the seven identified in this study, which suggests a possibly correlation between the canine BRCA2 exon 11 polymorphisms and mammary carcinogenesis.