Treatment of fibroepithelial hyperplasia (FEH) of the mammary gland in the cat with the progesterone antagonist Aglépristone (Alizine)

Three cases of fibroepithelial hyperplasia (FEH) of the mammary gland in the cat are reported. A one year old female cat had a distinct enlargement of the middle mammary glands, one on each side, 5 days after the first estrus. One week later the cat was treated with medroxyprogesterone acetate (Depo-Promone). The affected glands, along with the remaining glands, increased further in size. A five year old female cat was treated with Proligeston (Covinan) for the suppression of estrus. Two weeks later fibroepithelial hyperplasia occurred in two glands, one with a well demarcated ulceration. A seven months old male cat was treated with delmadinon acetate (Tarden) because of urine spraying. Two months later he had enlargement of all mammary glands. All three cats were treated with the progesterone antagonist Aglépristone (Alizine). Within 5 to 11 weeks the mammary glands had regressed to normal.     

Immunohistochemistry with keratin,vimentin, desmin,and α‐smooth muscle actin monoclonal antibodies in canine mammary gland: Normal mammary tissue

Summary

Normal canine mammary gland tissue was studied immunohistochemically with monoclonal antibodies (MoAbs) directed against various human keratin types, vimentin, desmin, and α‐smooth muscle actin. Both ductal and alveolar luminal cells were immunoreactive with MoAbs recognizing respectively human keratins no. 7, 8, 18 and 19. In addition, some ductal luminal cells were labelled with a keratin 4 and a keratin 10 MoAb. Basal/myoepithelial cells were immunoreactive only with MoAbs directed against keratin 14, keratins 14 and 17, and a‐smooth muscle actin. The vimentin MoAb merely labelled solitary loose intraluminal cells representing macro‐phages or sloughed epithelial cells. These findings correspond largely to observations made in human breast tissue.     

Immunohistochemistry with keratin,vimentin, desmin,and α‐smooth muscle actin monoclonal antibodies in canine mammary gland: Malignant mammary tumours

Summary

Ten malignant canine mammary gland tumours and five metastases from three of these tumours were studied immunohistochemically with monoclonal antibodies (MoAbs) directed against different human keratin types (K), α‐smooth muscle actin, vimentin, and desmin.

In all tumours the neoplastic epithelium was rather homogeneously labelled with the keratin MoAbs RCK 102 (K 5 and 8) and CAM 5.2 (K 8). The adenocarcinomas (n=5), the solid carcinomas (n=2), and the carcinosarcoma (n=1) showed heterogeneous labelling with the MoAbs specific for luminal cell antigens in the normal canine mammary gland, i.e., K 18, K 7 and K 19 MoAbs. These cells were also immunoreactive with K 4 and K 10 MoAbs. The spindle cell carcinomas (n=2), however, did not react with these MoAbs.

All tumours except one adenocarcinoma were characterized by the absence of immunoreactive labelling with the α‐smooth muscle actin MoAb. In the solid carcinomas this was associated with the absence of labelling with one or both basal cell specific keratin MoAbs, i.e., 8.7 (K 14 and 17) and RCK 107 (K 14), respectively. In contrast, the other malignant tumours showed marked labelling of neoplastic epithelium with these MoAbs. Another remarkable finding was the labelling of a limited to moderate number of neoplastic epithelial cells with the vimentin MoAb. The presence of such labelling patterns in canine mammary gland tumours may be indicative of malignancy. Metastatic tumour tissues had a labelling pattern largely similar to that of the primary tumour, although also loss of reactivity for some keratin MoAbs was seen.     

Expression of 14-3-3 σ protein in normal and neoplastic canine mammary gland

14-3-3 σ protein is a negative cell cycle regulator, with both reduced and elevated levels associated with cancer in humans. This study assessed the expression of this protein in canine mammary tissues using immunohistochemistry and Western blotting. 14-3-3 σ was detected in 97% of the mammary tissue samples examined and was found in both myoepithelial (MECs) and epithelial (ECs) cells. Expression levels were elevated and reduced in neoplastic ECs and MECs, respectively (P < 0.001). Intense expression of 14-3-3 σ was detected in neoplastic ECs infiltrating blood vessels and lymph nodes and suggests a possible role for this protein in the malignant transformation of mammary neoplasms. Moreover, double immunostaining for 14-3-3 σ and the MEC – specific marker p63, confirmed that 14-3-3 σ is a highly sensitive marker of MECs since all p63 – positive cells were also positive for 14-3-3 σ. However, this protein is not exclusive to MECs as ECs also labelled positively.     

Involvement of TNF-α and MAPK pathway in the intramammary MMP-9 release via degranulation of cow neutrophils during acute mammary gland involution

Neutrophil-derived MMP-9 activity is regulated more promptly and efficiently at the level of degranulation than at other levels of regulation. In human neutrophils, degranulation is one of the earliest responses to TNF-α stimulation, which involves protein kinase C and mitogen-activating protein kinase (MAPK) pathways. The level of MMP-9 in mammary secretion of cows increases drastically following milk-stasis, which is partially explained by increases of both neutrophil infiltration and neutrophil degranulation per se. Since MMP-9 represents one of the major remodeling capacities in the mammary gland of cows during early dry period, the current study attempted to explore the involved intracellular mechanisms in the up-regulated MMP-9 secretion. We repeatedly measured on the somatic cells of mammary secretion along the early dry period of cows the expression of TNF-α protein and the phosphorylation of p38 MAPK, ERK, and JNK. Also, cultures of bovine peripheral neutrophils were conducted to examine the mode of short-term MMP-9 secretion in response to TNF-α stimulation and the blocking effects of TNF-α antibody and inhibitors of MAPK pathways. Ex vivo measurements show that conventional cow milk has fully transformed into a neutrophil-abundant, lactoferrin-rich, and high-MMP-9 mammary secretion by d 7 in milk-stasis. No significant (P>0.05) change, however, was found in the expression of TNF-α or the phosphorylation extent of MAPK pathway intermediates on the somatic cells of mammary secretion during the first 3 weeks in milk-stasis. In vitro studies indicate linear increase of short-term MMP-9 release in response to TNF-α stimulation in dosages between 0.1 and 10 ng/ml. In the presence of preparations of d 7-dry secretion of cows, the short-term release of MMP-9 from bovine peripheral neutrophils was significantly (P<0.05) blocked by inhibitor of p38 MAPK but was significantly (P<0.05) promoted by ERK inhibitor while TNF-α antibody or JNK inhibitor exerted no effect. In conclusion, the current ex vivo measurements suggest no apparent association of TNF-α and MAPK pathway with long term intramammary accumulation of MMP-9 during the early dry period of cows, whereas cultures of bovine peripheral neutrophils under a simulated acute involution intramammary environment of cows suggest a role played by TNF-α and MAPK pathways in the short-term MMP-9 release via degranulation.     

Immunohistochemistry with keratin,vimentin, desmin,and α‐smooth muscle actin monoclonal antibodies in canine mammary gland: Benign mammary tumours and duct ectasias

Summary

Duct ectasias (n=2) and different types of benign canine mammary tumours (n=19) were studied immunohistochemically with monoclonal antibodies (MoAbs) directed against various human keratin types (K), α‐smooth muscle actin, vimentin, and desmin. In the duct ectasias and in most tumours the epithelial structures revealed an inner and outer cell layer. The inner cell layer was characterized by labelling with K 7, 8, 18, 19 and mostly also with K 4 and/or K 10 MoAbs. The outer cell layer was almost invariably labelled by K 14, K 14 and 17, and a‐smooth muscle actin MoAbs. The labelling patterns of both duct ectasias and tumours corresponded largely to the patterns observed in normal mammary gland tissue, although a more distinct heterogeneity was seen. Tumours histomorphologically assumed to be of a myoepithelial origin did not show immunohistochemical features of myoepithelial cells. The myoepithelial nature of the vast majority of spindle‐shaped cells present in the adenomas of the complex type and in the fibroadenomas of the benign mixed type could not be confirmed immunohistochemically. These cells, however, unequivocally expressed vimentin, suggesting proliferation of stromal cells in these tumours, which in the fibroadenomas of the benign mixed type may show metaplasia to bone or cartilage.

In the duct ectasias and in some tumours, a fraction of elongated stromal cells, probably representing myofibroblasts, was labelled with the α‐smooth muscle actin MoAb.     

Are complex carcinoma of the feline mammary gland and other invasive mammary carcinoma identical tumours? Comparison of clinicopathologic features,DNA ploidy and follow up

Feline mammary carcinomas are known for their unfavourable prognosis due to a strong tendency to local recurrence and metastasis. We studied 73 spontaneous primary mammary carcinomas and identified eight cases presenting a biphasic nature, with neoplastic epithelial and myoepithelial cells (complex carcinoma). These cases presented histopathologic features associated with a better prognosis; they were also associated with higher overall survival and disease-free survival rates compared to other common invasive mammary carcinomas of non-specified type. Complex carcinoma appears to be a low-grade malignancy.     

Endothelial cells and angiogenesis in the horse in health and disease—A review

The cardiovascular system is the first functional organ in the embryo, and its blood vessels form a widespread conductive network within the organism. Blood vessels develop de novo, by the differentiation of endothelial progenitor cells (vasculogenesis) or by angiogenesis, which is the formation of new blood vessels from existing ones. This review presents an overview of the current knowledge on physiological and pathological angiogenesis in the horse including studies on equine endothelial cells. Principal study fields in equine angiogenesis research were identified: equine endothelial progenitor cells; equine endothelial cells and angiogenesis (heterogeneity, markers and assessment); endothelial regulatory molecules in equine angiogenesis; angiogenesis research in equine reproduction (ovary, uterus, placenta and conceptus, testis); angiogenesis research in pathological conditions (tumours, ocular pathologies, equine wound healing, musculoskeletal system and laminitis). The review also includes a table that summarizes in vitro studies on equine endothelial cells, either describing the isolation procedure or using previously isolated endothelial cells. A particular challenge of the review was that results published are fragmentary and sometimes even contradictory, raising more questions than they answer. In conclusion, angiogenesis is a major factor in several diseases frequently occurring in horses, but relatively few studies focus on angiogenesis in the horse. The challenge for the future is therefore to continue exploring new therapeutic angiogenesis strategies for horses to fill in the missing pieces of the puzzle.     

Coccidiosis in sheep—A review

Extract

Coccidiosis has long been recognized III Europe and the United States as a disease of some importance. As an introduction to the papers that follow in this issue, the authors considered that it would be profitable to review some of the overseas literature dealing with coccidiosis in sheep.     

Scrapie — the risks in perspective

Extract

No-one would deny that there is always an element of risk of introducing an exotic disease with any importation of animals. It must be accepted that the epidemiological features of scrapie pose unique difficulties because of the lengthy incubation period and the uncertainty that can exist in determining if, and when, an imported animal may have been exposed to infection.     

Enterogenic Stenotrophomonas maltophilia migrates to the mammary gland to induce mastitis by activating the calcium-ROS-AMPK-mTOR-autophagy pathwayOA

Background Mastitis is an inflammatory disease of the mammary gland that has serious economic impacts on the dairy industry and endangers food safety. Our previous study found that the body has a gut/rumen-mammary gland axis and that disturbance of the gut/rumen microbiota could result in ‘gastroenterogenic mastitis’. However, the mechanism has not been fully clarified. Recently, we found that long-term feeding of a high-concentrate diet induced mastitis in dairy cows, and the abundance of Steno...     

Steroid hormone receptors ERα and PR characterised by immunohistochemistry in the mare adrenal gland

Background

Sex steroid hormone receptors have been identified in the adrenal gland of rat, sheep and rhesus monkey, indicating a direct effect of sex steroids on adrenal gland function.

Methods

In the present study, immunohistochemistry using two different mouse monoclonal antibodies was employed to determine the presence of oestrogen receptor alpha (ERalpha) and progesterone receptor (PR) in the mare adrenal gland. Adrenal glands from intact (n = 5) and ovariectomised (OVX) (n = 5) mares, as well as uterine tissue (n = 9), were collected after euthanasia. Three of the OVX mares were treated with a single intramuscular injection of oestradiol benzoate (2.5 mg) 18 – 22 hours prior to euthanasia and tissue collection (OVX+Oe). Uterine tissue was used as a positive control and showed positive staining for both ERalpha and PR.

Results

ERalpha staining was detected in the adrenal zona glomerulosa, fasciculata and reticularis of all mare groups. Ovariectomy increased cortical ERalpha staining intensity. In OVX mares and one intact mare, positive ERalpha staining was also detected in adrenal medullary cells. PR staining of weak intensity was present in a low proportion of cells in the zona fasciculata and reticularis of all mare groups. Weak PR staining was also found in a high proportion of adrenal medullary cells. In contrast to staining in the adrenal cortex, which was always located within the cell nuclei, medullary staining for both ERalpha and PR was observed only in the cell cytoplasm.

Conclusion

The present results show the presence of ERalpha in the adrenal cortex, indicating oestradiol may have a direct effect on mare adrenal function. However, further studies are needed to confirm the presence of PR as staining in the present study was only weak and/or minor. Also, any possible effect of oestradiol treatment on the levels of steroid receptors cannot be determined by the present study, as treatment time was of a too short duration.     

Unorthodox procedures and the Guide — A reply

Extract

Madam: — Dr Piper has hit the nail on the head when he says that all practitioners use unorthodox procedures from time to time, and are therefore now obliged to ensure that the client is aware of this and also understands what is being done. This is an extension of Section VII A of the current Guide to Professional Conduct (Responsibilities with Animal Remedies). I do not believe it would be considered unreasonable by the majority of the profession.