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1.
Biol Reprod ; 105(6): 1521-1532, 2021 12 20.
Article in English | MEDLINE | ID: mdl-34554181

ABSTRACT

Certain chemotherapeutic drugs are toxic to ovarian follicles. The corpus luteum (CL) is normally developed from an ovulated follicle for producing progesterone (P4) to support early pregnancy. To fill in the knowledge gap about effects of chemotherapy on the CL, we tested the hypothesis that chemotherapy may target endothelial cells and/or luteal cells in the CL to impair CL function in P4 steroidogenesis using doxorubicin (DOX) as a representative chemotherapeutic drug in mice. In both mixed background mice and C57BL/6 mice, a single intraperitoneal injection of DOX (10 mg/kg) on 0.5-day postcoitum (D0.5, postovulation) led to ~58% D3.5 mice with serum P4 levels lower than the serum P4 range in the phosphate buffer saline-treated control mice. Further studies in the C57BL/6 ovaries revealed that CLs from DOX-treated mice with low P4 levels had less defined luteal cords and disrupted collagen IV expression pattern, indicating disrupted capillary, accompanied with less differentiated luteal cells that had smaller cytoplasm and reduced StAR expression. DOX-treated ovaries had increased granulosa cell death in the growing follicles, reduced proliferating cell nuclear antigen-positive endothelial cells in the CLs, enlarged lipid droplets, and disrupted F-actin in the luteal cells. These novel data suggest that the proliferating endothelial cells in the developing CL may be the primary target of DOX to impair the vascular support for luteal cell differentiation and subsequently P4 steroidogenesis. This study fills in the knowledge gap about the toxic effects of chemotherapy on the CL and provides critical information for risk assessment of chemotherapy in premenopausal patients.


Subject(s)
Antibiotics, Antineoplastic/toxicity , Corpus Luteum/drug effects , Doxorubicin/toxicity , Animals , Female , Injections, Intraperitoneal , Mice , Mice, Inbred C57BL , Pregnancy , Pregnancy, Animal
2.
J Vet Diagn Invest ; 36(4): 579-582, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38561905

ABSTRACT

Most canine gliomas occur in adult and aged dogs, and reports in puppies < 12-mo-old are exceedingly rare. Here we describe the occurrence of gliomas in 5 dogs ≤ 12-mo-old. The affected patients (4 males, 1 female) were 3-12-mo-old (x̄ = 6.6-mo-old). None of the dogs were brachycephalic. Clinical signs consisted of dullness (2 cases), seizures (2 cases), vestibular signs, and deafness (1 case each). All patients were euthanized. Grossly, neoplasms were pale-tan or red, soft masses in the telencephalon (4 cases) or gelatinous leptomeningeal thickening in the brain and spinal cord (1 case). Neoplasms were classified as astrocytomas (3 cases) and oligodendrogliomas (2 cases) based on histology or histology and IHC. Our findings confirm that, while exceptionally rare, canine gliomas occur in the first year of life, and are clinically, morphologically, and immunohistochemically similar to gliomas in adult and aged dogs.


Subject(s)
Brain Neoplasms , Dog Diseases , Glioma , Dogs , Animals , Dog Diseases/pathology , Dog Diseases/diagnosis , Female , Male , Glioma/veterinary , Glioma/pathology , Brain Neoplasms/veterinary , Brain Neoplasms/pathology
3.
J Vet Diagn Invest ; 35(1): 87-91, 2023 Jan.
Article in English | MEDLINE | ID: mdl-36366728

ABSTRACT

Here we characterize 6 cases (4 autopsies and 2 biopsies) of histiocytic sarcoma in the CNS of cats. All affected cats had chronic, progressive clinical signs. Three autopsied cats were euthanized because of a poor prognosis, and one died. The clinical outcome for the biopsy cases remains unknown. Tumors occurred in the brain (4 cases), spinal cord (1 case), and brain and spinal cord (1 case). Neoplasms were restricted to the CNS in 3 cases. Reported gross changes in the 4 autopsy cases consisted of neuroparenchymal swelling with or without tissue pallor or gray discoloration (2 cases) and a yellow or dark-gray mass (2 cases). Histologically, pleomorphic, round-to-elongate neoplastic cells with typical histiocytic morphology effaced the neuroparenchyma and leptomeninges. Multinucleate neoplastic cells were observed in all cases. The mitotic count was 1-24 in 2.37 mm2 (10 FN22 40× fields). Neoplastic cells in all cases had positive immunolabeling for Iba1; immunolabeling was negative for E-cadherin, CD3, CD79, and MUM1, confirming their histiocytic origin.


Subject(s)
Histiocytic Sarcoma , Neoplasms , Animals , Autopsy/veterinary , Brain/pathology , Histiocytic Sarcoma/pathology , Histiocytic Sarcoma/veterinary , Neoplasms/pathology , Neoplasms/veterinary
4.
J Vet Diagn Invest ; 35(5): 581-584, 2023 Sep.
Article in English | MEDLINE | ID: mdl-37329122

ABSTRACT

Clinical signs in 4 cases of salmonellosis in cats included vomiting, diarrhea (2 cases each), fever, dystocia, icterus, and seizures (1 case each). Three cats died, and one was euthanized. Grossly, all cats were in poor body condition and had yellow-to-dark-red perianal feces (3 cases), oral and ocular pallor (2 cases) or icterus (1 case), fluid or pasty yellow intestinal contents (4 cases), white or dark-red-to-black depressed areas on the hepatic surface (2 cases), yellow abdominal fluid with swollen abdominal lymph nodes (1 case), and fibrin strands on the placental chorionic surface (1 case). Histologically, all cats had necrotizing enterocolitis and random hepatocellular necrosis. Other histologic findings included mesenteric (4 cases) or splenic (2 cases) lymphoid necrosis, and endometrial and chorioallantoic necrosis (1 case). Gram-negative bacilli were observed within neutrophils and macrophages in the intestinal lamina propria (4 cases), liver, spleen, lymph node, endometrium, and placenta (1 case each). Aerobic bacterial culture on frozen samples of small intestine, mesenteric lymph node, lung, and liver yielded Salmonella enterica subsp. enterica. Serotyping was consistent with S. Enteritidis (cases 1, 3) and S. Typhimurium (cases 2, 4).


Subject(s)
Cat Diseases , Salmonella Infections, Animal , Salmonella enterica , Pregnancy , Cats , Female , Animals , Salmonella Infections, Animal/pathology , Placenta/pathology , Salmonella , Necrosis/veterinary
5.
J Am Vet Med Assoc ; 237(9): 1056-9, 2010 Nov 01.
Article in English | MEDLINE | ID: mdl-21034345

ABSTRACT

CASE DESCRIPTION: A 5-year-old 38.3-kg (84.5-lb) mixed-breed dog was examined because of acute onset of lethargy and anorexia. Four days later, a raised, firm, warm 15 × 10-cm lesion was detected in the right caudal paralumbar area. CLINICAL FINDINGS: Cephalexin treatment yielded a poor response. Formalin-fixed tissue and fluid samples from the cystic areas of the lesion were submitted for cytologic and histologic examinations, routine bacterial and mycobacterial culture, and genus identification and 16S partial sequencing via PCR assays. Cytologic examination revealed chronic pyogranulomatous inflammation. Histologic examination by use of routine, Giemsa, silver, acid-fast, and modified acid-fast stains revealed multifocal nodular granulomatous panniculitis without identifiable organisms. Mycobacteria were initially identified via PCR assay and mycobacterial culture within 3 days. Mycobaterium goodii was speciated by use of partial 16S RNA sequence analysis. TREATMENT AND OUTCOME: The lesion resolved after long-term treatment with a combination of rifampin and clarithromycin and insertion of a Penrose drain. There has been no recurrence of the condition. CLINICAL RELEVANCE: M goodii is an environmental rapidly growing mycobacterium and is a zoonotic pathogen. Infections have not been previously reported in domestic animals in North America, although there are rare reports of infection in humans associated with surgery, especially surgical implants. Domestic animals are a potential sentinel for this non-tuberculous mycobacterial infection in humans, although lack of speciation in infections of domestic animals likely underestimates the potential public health importance of this pathogenic organism. Current microbiological molecular methods allow for a rapid and inexpensive diagnosis.


Subject(s)
Dog Diseases/etiology , Mycobacterium Infections, Nontuberculous/veterinary , Mycobacterium/classification , Panniculitis/veterinary , Animals , Anti-Bacterial Agents/therapeutic use , Clarithromycin/therapeutic use , Dog Diseases/epidemiology , Dog Diseases/microbiology , Dog Diseases/therapy , Dogs , Female , Georgia/epidemiology , Immunocompetence , Mycobacterium Infections, Nontuberculous/epidemiology , Mycobacterium Infections, Nontuberculous/therapy , Panniculitis/epidemiology , Panniculitis/microbiology , Panniculitis/therapy , Rifampin/therapeutic use
6.
J Vet Diagn Invest ; 19(5): 525-31, 2007 Sep.
Article in English | MEDLINE | ID: mdl-17823396

ABSTRACT

Sixteen animals affected in 2 outbreaks of pet food-associated renal failure (2 dogs in 2004; 10 cats and 4 dogs in 2007) were evaluated for histopathologic, toxicologic, and clinicopathologic changes. All 16 animals had clinical and laboratory evidence of uremia, including anorexia, vomiting, lethargy, polyuria, azotemia, and hyperphosphatemia. Where measured, serum hepatic enzyme concentrations were normal in animals from both outbreaks. All animals died or were euthanized because of severe uremia. Distal tubular lesions were present in all 16 animals, and unique polarizable crystals with striations were present in distal tubules or collecting ducts in all animals. The proximal tubules were largely unaffected. Crystals and histologic appearance were identical in both outbreaks. A chronic pattern of histologic change, characterized by interstitial fibrosis and inflammation, was observed in some affected animals. Melamine and cyanuric acid were present in renal tissue from both outbreaks. These results indicate that the pet food-associated renal failure outbreaks in 2004 and 2007 share identical clinical, histologic, and toxicologic findings, providing compelling evidence that they share the same causation.


Subject(s)
Cat Diseases/chemically induced , Cat Diseases/epidemiology , Disease Outbreaks/veterinary , Dog Diseases/chemically induced , Dog Diseases/epidemiology , Renal Insufficiency/veterinary , Triazines/toxicity , Animal Feed , Animals , Asia/epidemiology , Cat Diseases/pathology , Cats , Dog Diseases/pathology , Dogs , Food Contamination , Kidney/pathology , North America/epidemiology , Renal Insufficiency/chemically induced , Renal Insufficiency/pathology , Time Factors
7.
Fertil Steril ; 83 Suppl 1: 1180-7, 2005 Apr.
Article in English | MEDLINE | ID: mdl-15831291

ABSTRACT

OBJECTIVE: The aim of this study was to determine, with a bovine model, the appropriate interval for xenografted adult and newborn ovarian tissue to develop gonadotropin-responsive follicles. DESIGN: Controlled experiment. SETTING: Academic research laboratory. ANIMAL(S): Male non-obese diabetic (NOD) severe combined immunodeficient (SCID) mice (n = 20) were hosts of bovine ovarian tissue. Two dairy calves and one adult beef cow were donors of ovarian tissue. INTERVENTION(S): Newborn and adult bovine ovarian cortical pieces were transplanted to the SC space of intact male NOD SCID mice. Grafts were recovered after euthanasia at intervals after transplantation. MAIN OUTCOME MEASURE(S): Microscopic examination of histologic sections to determine proportions of growing follicles. RESULT(S): There was an increase in the proportion of primary and secondary follicles on day 55 after surgery for the cow and on day 124 after surgery for calf tissue compared with nongrafted and xenografted ovarian tissues recovered at previous intervals. These observed increases were accompanied by decreases in proportions of primordial follicles. Results suggest a sudden increase in the proportion of primary and secondary follicles due to progressive development of primordial follicles. CONCLUSION(S): In the NOD SCID mouse, bovine follicles survived xenotransplantation and underwent development. A longer interval was required for ovarian follicular development in calf tissues compared with that in adult cow ovarian tissues after xenotransplantation.


Subject(s)
Ovarian Follicle/physiology , Ovarian Follicle/transplantation , Transplantation, Heterologous/methods , Animals , Cattle , Female , Graft Survival/physiology , Male , Mice , Mice, Inbred NOD , Mice, SCID , Oogenesis/physiology , Ovarian Follicle/growth & development , Subcutaneous Tissue/surgery
8.
Theriogenology ; 61(2-3): 581-94, 2004 Jan 15.
Article in English | MEDLINE | ID: mdl-14662154

ABSTRACT

Ovarian cortex cryopreservation and xenotransplantation into immunodeficient mice represents a potential means for female germplasm conservation and an immediate model for investigation of folliculogenesis. The objectives of this study were to: (1) assess follicle survival after cryopreservation and transplantation of cat ovarian tissue into non-obese diabetic severely combined immunodeficient (NOD SCID) mice; and (2) evaluate the effects of gonadotropin treatments on follicular development in the transplanted tissue. Slices from the cat ovarian cortex were frozen and after thawing, transplanted under each kidney capsule of castrated male NOD SCID mice (eight xenografts in four mice). Sixty-two days after surgery, mice were randomly assigned (two per group) to gonadotropin-treated (eCG and hCG 88 h later) or control (saline-treated) groups. Twenty-four hours after the last injection, ovarian tissue was recovered and processed for histology. Fresh ovarian tissue from the same original source was similarly processed. Follicles were counted, measured, and classified as primordial, primary, secondary, or antral. Immunoreactive proliferating cell nuclear antigen (PCNA) stain was used to assess follicle viability. Microscopic examination revealed no evidence of necrosis or fibrosis. The grafts were well-vascularized, with follicles at all stages of development. Numbers of follicles in the transplanted tissue were markedly reduced compared to fresh tissue, with approximately 10% of follicles surviving freezing and transplantation procedures. Growing follicles positive for PCNA were found in all xenografts. Gonadotropin treatment did not alter the proportion of resting to growing follicles or mean follicle diameter by comparison with controls from untreated mice. By contrast, luteinization, but not ovulation, of antral follicles was observed only in grafts from treated mice. In summary, frozen-thawed cat ovarian cortex tissue not only survived xenotransplantation, it also contained follicles able to grow to antral stages. Exogenous gonadotropin treatment in this model resulted in luteinization of antral follicles but enhancement of follicular growth and ovulation did not occur.


Subject(s)
Cryopreservation/veterinary , Ovarian Follicle/growth & development , Ovary/transplantation , Transplantation, Heterologous , Animals , Cats , Female , Granulocytes/ultrastructure , Immunohistochemistry , Male , Mice , Mice, Inbred NOD , Mice, SCID , Oocytes/chemistry , Ovarian Follicle/chemistry , Ovarian Follicle/ultrastructure , Ovary/physiology , Progesterone/blood , Proliferating Cell Nuclear Antigen/analysis
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