Uterine issues in infertile queens: Nine cases.

This prospective case series investigated potential uterine causes of infertility in queens. Purebred queens with infertility (failure to conceive, embryonic death, or failure to maintain pregnancy and produce viable kittens), but no other reproductive disorders were examined approximately 1-8 weeks before mating (Visit 1), 21 days after mating (Visit 2), and 45 days after mating (Visit 3) if pregnant at Visit 2. Investigations included vaginal cytology and bacteriology, urine bacteriology, and ultrasonography. At Visit 2 or 3, uterine biopsy or ovariohysterectomy was performed for histology. Of nine eligible queens, seven were non-pregnant by ultrasound at Visit 2 and two had lost pregnancies by Visit 3. Ovulation was confirmed by serum progesterone concentration in all queens. Ultrasonic appearance of the ovaries and uterus was compatible with a healthy status except for one queen with signs of cystic endometrial hyperplasia (CEH) and pyometra, a follicular cyst in another, and fetal resorptions in two queens. Six cats had histologic lesions of endometrial hyperplasia, including CEH (n=1). Only one cat had no histologic uterine lesions. Bacteria were cultured from vaginal samples in seven queens at Visit 1, (two were non-evaluable), and in five of seven queens sampled at Visit 2. Uterine cultures were negative except for the cat with pyometra. All urine cultures were negative. In summary, the most frequent pathology observed in these infertile queens was histologic endometrial hyperplasia, which can potentially inhibit embryo implantation and healthy placental development. This suggests that uterine disease might contribute substantially to infertility in purebred queens.

Evaluation of surface plasmon field-enhanced fluorescence spectroscopy for rapid measurement of progesterone concentration in bitches.

OBJECTIVE: To compare progesterone (P4) concentrations measured with surface plasmon field-enhanced fluorescence spectroscopy (SPFS) and chemiluminescence immunoassay (CLIA) in serum and plasma samples of client-owned bitches of various ages and breeds and to determine reference ranges for P4 concentrations at various stages of the estrous cycle. SAMPLES: 102 serum samples and 104 plasma samples. PROCEDURES: In experiment 1, 1 aliquot each of serum and plasma was analyzed for P4 concentration by use of SPFS incorporated in a veterinary-specific point-of-care immunologic analyzer and CLIA. In experiment 2, serum collected from bitches in various stages of the estrous cycle was analyzed for P4 concentration by use of SPFS to establish reference ranges for each stage. RESULTS: In experiment 1, P4 concentrations measured by SPFS and CLIA were highly correlated (serum, r = 0.966; plasma, r = 0.968). In experiment 2, ranges of serum basal (proestrous) P4 concentrations (n = 114) and P4 concentrations at the estimated time of ovulation (76), during pregnancy or diestrus (107), and during the prepartum period (50) measured with SPFS were 0.42 to 1.46 ng/mL, 3.69 to 7.85 ng/mL, 11.73 to 28.24 ng/mL, and 1.54 to 3.22 ng/mL, respectively. CONCLUSIONS AND CLINICAL RELEVANCE: Because serum and plasma P4 concentrations measured with SPFS were highly correlated with those measured with CLIA and ranges of serum P4 concentrations measured with SPFS for each of phase of the estrous cycle were well-defined for the large sample size, veterinarians may be able to accurately use this veterinary-specific point-of-care immunologic analyzer with SPFS methodology to determine P4 concentrations of bitches in their daily practice.

Role of Cadherins in Cancer-A Review.

Cadherins play an important role in tissue homeostasis, as they are responsible for cell-cell adhesion during embryogenesis, tissue morphogenesis, differentiation and carcinogenesis. Cadherins are inseparably connected with catenins, forming cadherin-catenin complexes, which are crucial for cell-to-cell adherence. Any dysfunction or destabilization of cadherin-catenin complex may result in tumor progression. Epithelial mesenchymal transition (EMT) is a mechanism in which epithelial cadherin (E-cadherin) expression is lost during tumor progression. However, during tumorigenesis, many processes take place, and downregulation of E-cadherin, nuclear ß-catenin and p120 catenin (p120) signaling are among the most critical. Additional signaling pathways, such as Receptor tyrosine kinase (RTK), Rho GTPases, phosphoinositide 3-kinase (PI3K) and Hippo affect cadherin cell-cell adhesion and also contribute to tumor progression and metastasis. Many signaling pathways may be activated during tumorigenesis; thus, cadherin-targeting drugs seem to limit the progression of malignant tumor. This review discusses the role of cadherins in selected signaling mechanisms involved in tumor growth. The clinical importance of cadherin will be discussed in cases of human and animal cancers.

Infertility in purebred cats - A review of the potential causes.

Although purebred cat breeding is growing in popularity in European countries, most research and publications concern dog reproduction. Infertility in queens has been poorly studied. It may not come as a surprise as common domestic shorthair cats are well known for their excellent fertility. However, even in the latter, the infertility rate is around 20%. Only recently, published articles have analyzed the reproductive performances in different breeds, for example in UK, Sweden, France and Italy, and found similar figures. In cats, infertility may arise from many factors such as mismating, prolonged anestrus or silent heats, hormonal, nutritional, genetical or chromosomal causes. Also, infectious diseases, probably frequent in breeding facilities, include pathological agents that are well recognized as having a negative effect on pregnancy or other pathogens for which the involvement in fertility problems is unclear. However, analyzing the literature, it appears that the most prevalent causes of infertility in pedigree cats may well be, in females, uterine pathology (sub-clinical endometritis, cystic endometrial hyperplasia, or mucometra), and in males, teratospermia, which may be "permanent" and linked to reduced heterozygosity or "transient" in tomcats that present normal quantitative spermatogenic parameters. The influence of the breed is unknown. There is an urgent need to study the origin of infertility in purebred cats in order to improve the diagnosis and to develop treatments that may restore normal fertility in subfertile or infertile animals.

Contraceptive implants used by cat breeders in France: a study of 140 purebred cats.

OBJECTIVES: Deslorelin 4.7 mg and melatonin 18 mg subcutaneous implants were studied in purebred male and female cats, via questionnaires sent to French cat breeders, to assess breed, age, duration of the contraceptive effect, fertility after use, changes in behaviour and side effects. METHODS: Reproductive data were collected in 57 tom cats and 41 queens implanted with deslorelin 4.7 mg, and 42 queens implanted with melatonin 18 mg, for a total of 140 purebred cats, from 38 different catteries, representing 18 breeds. RESULTS: Using deslorelin (Suprelorin 4.7 mg; Virbac), sexual behaviour in males was inhibited for a mean ± SD of 13.4 ± 3.2 (range 8-21) months in 37/57 cats. Of these, 24/37 mated successfully and produced litters at a mean of 15.5 ± 3.6 (range 9-20) months. Inhibition lasted 11 ± 1.1 (range 9-12; n = 6), 13.2 ± 2.4 (range 12-18; n = 6) and 15 ± 3.5 (range 9-18; n = 6) months in Norwegian Forest Cat, Singapura and Ragdoll males, respectively. In 26/41 females implanted with deslorelin 4.7 mg, oestrus was inhibited for a mean of 16.0 ± 5.7 (8-38) months; 12/26 went on to produce a litter. Of the side effects specific to females: two presented persistent oestrus, leading to the removal of the implant; two developed lactation; one had fibroadenomatosis; and one was sterilised owing to cystic endometrial hyperplasia. Using melatonin (Melovine 18 mg; Ceva), 33/42 females had oestrus inhibited for a mean of 86 ± 50 (range 21-277) days after implantation with a peak return to oestrus in March, and 12/33 had a subsequent litter. No side effects were reported. CONCLUSIONS AND RELEVANCE: This study is the first to collect a large amount of field data, in 140 purebred male and female cats where a deslorelin 4.7 mg or a melatonin 18 mg implant was used. These field results may allow for more accurate clinical advice and open up new avenues of research.

Neonatal puppy survival after planned caesarean section in the bitch using aglepristone as a primer: A retrospective study on 74 cases.

Since most of dystocia end up in caesarean sections (C-sections), the history of any problem during whelping is a good reason to plan in advance a further C-section. Our aim was to confirm that on a large sample and over an extended period of time, mortality in puppies <2 weeks of age was low, born after a planned C-section using aglepristone as a primer. Seventy-four C-sections on 59 different bitches were included. Bitches were monitored during oestrus to estimate the day of ovulation by progesterone assays; 60, 61 or 62 days after ovulation, foetal viability was checked by ultrasonography and progesterone plasma level was measured. None of the bitches was at term (progesterone plasma level >2 ng/ml). An injection of aglepristone was performed in late afternoon to block the effect of progesterone, mimicking its drop at the end of pregnancy. The C-section was conducted the following morning. Twenty-one breeds were represented most of which were bulldogs (26%, 21/74) and Great Danes (16%, 13/74). Four hundred and thirty-five puppies were born. A total of 43/435 puppies died within the first 2 weeks (9.89%). None of the puppies showed any external signs of prematurity. The average number of deaths per litter relative to the date after ovulation was similar (0.5 pups per litter at day 60, 0.7 at day 61, 0.4 at day 62). This study shows that planned C-section after an accurate determination of ovulation and using aglepristone as a primer is a safe procedure for bitches and their offspring. It may be offered to owners if a pregnant bitch is "at risk" of dystocia.

Acinar cell injury induced by inadequate unfolded protein response in acute pancreatitis.

Acute pancreatitis (AP) is an inflammatory disorder of pancreatic tissue initiated in injured acinar cells. Severe AP remains a significant challenge due to the lack of effective treatment. The widely-accepted autodigestion theory of AP is now facing challenges, since inhibiting protease activation has negligible effectiveness for AP treatment despite numerous efforts. Furthermore, accumulating evidence supports a new concept that malfunction of a self-protective mechanism, the unfolded protein response (UPR), is the driving force behind the pathogenesis of AP. The UPR is induced by endoplasmic reticulum (ER) stress, a disturbance frequently found in acinar cells, to prevent the aggravation of ER stress that can otherwise lead to cell injury. In addition, the UPR's signaling pathways control NFκB activation and autophagy flux, and these dysregulations cause acinar cell inflammatory injury in AP, but with poorly understood mechanisms. We therefore summarize the protective role of the UPR in AP, propose mechanistic models of how inadequate UPR could promote NFκB's pro-inflammatory activity and impair autophagy's protective function in acinar cells, and discuss its relevance to current AP treatment. We hope that insight provided in this review will help facilitate the research and management of AP.