Mitochondria in reproduction / 대한생식의학회지

In reproduction, mitochondria produce bioenergy, help to synthesize biomolecules, and support the ovaries, oogenesis, and preimplantation embryos, thereby facilitating healthy live births. However, the regulatory mechanism of mitochondria in oocytes and embryos during oogenesis and embryo development has not been clearly elucidated. The functional activity of mitochondria is crucial for determining the quality of oocytes and embryos; therefore, the underlying mechanism must be better understood. In this review, we summarize the specific role of mitochondria in reproduction in oocytes and embryos. We also briefly discuss the recovery of mitochondrial function in gametes and zygotes. First, we introduce the general characteristics of mitochondria in cells, including their roles in adenosine triphosphate and reactive oxygen species production, calcium homeostasis, and programmed cell death. Second, we present the unique characteristics of mitochondria in female reproduction, covering the bottleneck theory, mitochondrial shape, and mitochondrial metabolic pathways during oogenesis and preimplantation embryo development. Mitochondrial dysfunction is associated with ovarian aging, a diminished ovarian reserve, a poor ovarian response, and several reproduction problems in gametes and zygotes, such as aneuploidy and genetic disorders. Finally, we briefly describe which factors are involved in mitochondrial dysfunction and how mitochondrial function can be recovered in reproduction. We hope to provide a new viewpoint regarding factors that can overcome mitochondrial dysfunction in the field of reproductive medicine.

Challenges of stem cell therapies in companion animal practice

Regenerative medicine using stem cells from various sources are emerging treatment modality in several refractory diseases in veterinary medicine. It is well-known that stem cells can differentiate into specific cell types, self-renew, and regenerate. In addition, the unique immunomodulatory effects of stem cells have made stem cell transplantation a promising option for treating a wide range of disease and injuries. Recently, the medical demands for companion animals have been rapidly increasing, and certain disease conditions require alternative treatment options. In this review, we focused on stem cell application research in companion animals including experimental models, case reports and clinical trials in dogs and cats. The clinical studies and therapeutic protocols were categorized, evaluated and summarized according to the organ systems involved. The results indicate that evidence for the effectiveness of cell-based treatment in specific diseases or organ systems is not yet conclusive. Nonetheless, stem cell therapy may be a realistic treatment option in the near future, therefore, considerable efforts are needed to find optimized cell sources, cell numbers and delivery methods in order to standardize treatment methods and evaluation processes.

Genome-wide association study of degenerative mitral valve disease in Maltese dogs

Genome-wide association study (GWAS) is a powerful tool for identifying the genetic causes of various diseases. This study was conducted to identify genomic variation in Maltese dog genomes associated with degenerative mitral valve disease (DMVD) development and to evaluate the association of each biological condition with DMVD in Maltese dogs. DNA was extracted from blood samples obtained from 48 Maltese dogs (32 with DMVD and 16 controls). Genome-wide single nucleotide polymorphism (SNP) genotyping was performed. The top 30 SNPs from each association of various conditions and genetic variations were mapped to their gene locations. A total of 173,662 loci were successfully genotyped, with an overall genotype completion rate of 99.41%. Quality control analysis excluded 46,610 of these SNPs. Manhattan plots were produced using allelic tests with various candidate clinical conditions. A significant peak of association was observed between mitral valve prolapse (MVP) and SNPs on chromosome 17. The present study revealed significant SNPs in several genes associated with cardiac function, including PDZ2, Armadillo repeat protein detected in velo-cardio-facial syndrome, catenin (cadherin-associated protein) alpha 3, low-density lipoprotein receptor class A domain containing protein 4, and sterile alpha motif domain containing protein 3. To our knowledge, this is the first study of a genetic predisposition to DMVD in Maltese dogs. Although only a limited number of cases were analyzed, these data could be the basis for further research on the genetic predisposition to MVP and DMVD in Maltese dogs.

Polymorphism in the serotonin transporter protein gene in Maltese dogs with degenerative mitral valve disease

Degenerative mitral valve disease (DMVD) is the most commonly acquired cardiac disease in dogs. This study evaluated the relationship between genetic variations in the serotonin transporter (SERT) gene of Maltese dogs and DMVD. Genomic DNA was extracted from blood samples collected from 20 client-owned DMVD Maltese dogs and 10 healthy control dogs, and each exon of the SERT gene was amplified via polymerase chain reaction. The resulting genetic sequences were aligned and analyzed for variations by comparing with reference sequences; the predicted secondary structures of these variations were modeled and cross-verified by applying computational methods. Genetic variations, including five nonsynonymous genetic variations, were detected in five exons. Protein structure and function of the five nonsynonymous genetic variations were predicted. Three of the five polymorphisms were predicted to be probable causes of damage to protein function and confirmed by protein structure model verification. This study identified six polymorphisms of the SERT gene in Maltese dogs with DMVD, suggesting an association between the SERT gene and canine DMVD. This is the first study of SERT mutation in Maltese dogs with DMVD and is considered a pilot study into clinical genetic examination for early DMVD diagnosis.

Prolonged reflex bradycardia after occlusion of patent ductus arteriosus with an Amplatz canine duct occluder in a dog

A 9-month-old intact male Maltese dog (1.52 kg) was diagnosed with a patent ductus arteriosus (PDA). Transcatheter occlusion of the PDA was performed by using the Amplatz canine duct occluder (ACDO). After occlusion, reflex bradycardia occurred and lasted for at least 15 h with normal systolic arterial pressure and slightly increased diastolic arterial pressure. The bradycardia slowly resolved, and the heart rate was normal in re-examinations after 7 and 30 days. This is the first case of reflex bradycardia after ACDO implantation, in which the bradycardia continued for a long time, even after recovery from anesthesia.

Primary intestinal mast cell tumor in a Russian Blue cat: ultrasonographic and histopathological findings

A 11-year-old, female Russian Blue cat was presented with anorexia, vomiting, and diarrhea lasting for 3 days. Abdominal ultrasonography revealed a hypoechoic, non-circumferential, and eccentrically formed intestinal loop with altered wall layering and thickening of the tunica muscularis. After surgical resection, histopathologic examination confirmed an infiltrative, round-cell neoplasm composed of sheets and cords of neoplastic mast cells within a fibrotic, edematous stroma. The cat was alive and healthy 6 months after surgery. To the best of our knowledge, this is the first reported case of an intestinal mast cell tumor in a Russian Blue cat in South Korea.

Combination therapy of cyclosporine and prednisolone in a dog with systemic lupus erythematosus

An 11-year-old, spayed female poodle presented with fever and shifting lameness. Physical examination revealed hyperthermia (40.6℃), and proteinuria was detected upon urinalysis. Increased neutrophils (83%) and decreased viscosity were revealed upon synovial fluid analysis. Serum antinuclear antibody was positive at 1 : 80. Based on these findings, the dog was diagnosed with systemic lupus erythematosus. Immunosuppressive therapy was initiated with prednisolone and cyclosporine, and the condition was markedly improved after the treatments. This case report describes the clinical and laboratory findings, imaging characteristics and successful outcomes after prednisolone plus cyclosporine therapy in a canine systemic lupus erythematosus case.

Acquired myasthenia gravis in a domestic shorthair cat with cranial mediastinal mass

A 7-year-old castrated male domestic short-hair cat presented with anorexia, constipation, depression, and voice alteration. Physical and neurological examinations revealed hyperthermia (40.5℃), ventroflexion of the neck, reduced responses to external stimuli, generalized muscle weakness, and exercise intolerance. Thoracic radiographs revealed the presence of a cranial mediastinal mass. The history, clinical signs, and other examination results were compatible with acquired myasthenia gravis (MG). Acetylcholine receptor (AChR) antibody titers were determined to confirm MG and the serum AChR antibody concentration was 1.24 nmol/L (reference interval, < 0.3 nmol/L). This is the first diagnosis of acquired MG in a cat in Korea.

Characteristic Clinical Features and Survival in Cats with Symptomatic Hypertrophic Cardiomyopathy / 동물의과학연구지

Hypertrophic cardiomyopathy (HCM) is recognized as the most common feline cardiac disease. Several studies have evaluated the population characteristics and survival time of cats with HCM; however, these reports included large numbers of asymptomatic HCM. The purpose of this study was to evaluate the characteristics and survival time of cats with symptomatic HCM admitted to emergency service. Medical records were examined to verify clinical diagnosis of HCM. Asymptomatic cats diagnosed with HCM were also excluded from the study. From a total of 13 cats, eight were classified in the arterial thromboembolism (ATE) group while the other five were in the congestive heart failure (CHF) group. Middle-aged (6 years, range 1.4~7 years) male cats (53.8%) were included in this study. Pelvic limb paralysis, depression, and respiratory distress were common clinical signs found in symptomatic HCM cats. Hematologic evaluation found that enzymes related to muscle damage and tissue necrosis were elevated in both groups and highly elevated in the ATE group. Left atrium was remarkably enlarged in ATE group cats. The median survival time of cats in the ATE group was significantly shorter than that of cats in the CHF group (P=0.002). Prospective investigation based on a large population would be required to clarify the effects of various factors on prognosis of HCM cats.

Identification of Staphylococcus pseudintermedius in canine infective endocarditis using PCR-RFLP analysis / 동물의과학연구지

A 5-year-old, 8.95 kg, female Schnauzer presented anorexia with a 3-day history and increased heart sound intensity. Based on the clinical and echocardiographic findings along with the positive blood culture result, the dog was diagnosed with infective endocarditis (IE). Using proper antibiotics treatment, clinical signs were improved within 3 days and resolved within 1 week. For exact identification of the causative agent, multiplex polymerase chain reaction (PCR) and PCR-restriction fragment length polymorphism (RFLP) methods were performed. The etiological agent was confirmed as Staphylococcus pseudintermedius with antibiotics resistance genes such as beta-lactamase (blaZ) and methicilline resistance (mecA). The bacterial virulence factors included pyogenic toxin genes such as staphylococcal enterotoxins A, B, C, D, and E and toxic shock syndrome toxin 1. Diagnosis of IE is challenging due to a variety of non-specific clinical presentations, rapid disease progression, and lack of a confirmative diagnostic technique. This report demonstrated that such molecular diagnostics could be very useful for diagnosing and identifying characteristics of the causative organism for prediction of prognosis and proper treatment. To our knowledge, this is the first report on the isolation of S. pseudintermedius using molecular diagnostics from a clinical case of canine IE.

Drug-induced blood cell dyscrasia associated with phenobarbital administration in a dog / 대한수의학회지

A 13-year-old, spayed, female Chihuahua dog was referred for evaluation of fever, lethargy, and dyspnea. Hematologic evaluation revealed severe neutropenia, thrombocytopenia, and mild anemia. The dog had been undergoing phenobarbital therapy for the past 7 weeks because of generalized seizures due to meningoencephalomyelitis of unknown etiology. After ruling out other possible causes of cytopenias, a tentative diagnosis was made of drug-induced blood cell dyscrasia. The neutropenia and thrombocytopenia resolved after discontinuation of phenobarbital (8 days and 15 days after discontinuation, respectively). This is the first case report in Korea to demonstrate blood dyscrasia associated with idiosyncratic adverse effects of phenobarbital.

Antibiotic resistance and molecular characterization of ophthalmic Staphylococcus pseudintermedius isolates from dogs

The prevalence, virulence potential, and antibiotic resistance of ophthalmic Staphylococcus pseudintermedius (SP) isolated from dogs were examined. Sixty-seven Staphylococcus species were isolated from ophthalmic samples and surveyed for species-specific sequences in the Staphylococcus intermedius group (SIG) nuclease gene (SInuc), exfoliative toxin gene for SIG (siet), and antibiotic resistance genes (blaZ and mecA). PCR-restriction fragment length polymorphism analysis of the pta gene was also performed. Fifty isolates were identified as SIG strains, all of which were found to be SP. The blaZ gene was detected in 42 of the 50 SP strains and mecA gene was observed in 18 of the 50 SP strains. The 50 SP strains were most susceptible to amoxicillin/clavulanic acid (94%) and chlorampenicol (70%), and highly resistant to tetracycline (94%) and penicillin (92%). It was also found that 16 (88.9%) mecA-positive SP strains were resistant to oxacillin, tetracycline and penicillin. All mecA-positive SP were resistant to more than four of the eight tested antibiotics and therefore considered SP with multi-drug resistance (MDR). Our results indicate a high prevalence of antibiotic resistance genes in ophthalmic SP along with a close relationship between MDR SP strains and the mecA gene. Based on our findings, judicious administration of antibiotics to companion dogs is necessary.

Focal form of acquired myasthenia gravis with megaesophagus in a Yorkshire terrier dog / 대한수의학회지

A 12-year-old, castrated male Yorkshire terrier dog presented with frequent regurgitations that had begun 45 days earlier and become more progressive. Radiographs revealed an air-trap region behind the cranial esophageal sphincter muscle in the esophagus and esophagographies with barium contrast showed mild esophageal dilation with decreased motility. Esophageal motility increased within 5 min of neostigmine methylsulfate administration and acetylcholine receptor antibodies titer increased to beyond the normal range. Based on these findings, acquired myasthenia gravis with focal form was diagnosed, making this the first such case diagnosed by an acetylcholine receptor antibody test in Korea.

Azidothymidine and recombinant human interferon-alpha therapy in a cat with feline immunodeficiency virus / 동물의과학연구지

A 7-year-old, spayed female, domestic short hair cat showed signs of a 2-week history of chronic anorexia, depression, and severe weight loss. Upon physical examination, pyrexia, mild gingivitis, and pale mucus membranes were noted. Laboratory analysis revealed normocytic normochromic non-regenerative anemia, severe thrombocytopenia, and hypergammaglobulinemia. Serum protein electrophoresis revealed the presence of elevated alpha-2 fraction within the globulin concentration. Based on history, clinical signs, and laboratory results, systemic viral infection was strongly suspected. Reverse transcriptase polymerase chain reaction identified the presence of feline immunodeficiency virus (FIV) in the serum. Furthermore, gene sequencing revealed the virus as FIV subtype A. Treatment with anti-retroviral agents, including azidothymidine (AZT) and recombinant human interferon-alpha, was continued for 4 weeks. However, the patient's clinical condition deteriorated, resulting in death 1 month after initiation of treatment due to progressive renal failure. Necropsy and histopathology revealed hepatic and renal necrosis with hyper-cellular bone marrow mainly comprised of myeloid precursor cells. This case report is the first to describe phylogenetic subtyping, anti-retroviral combination treatment, and clinical outcomes in an FIV-infected cat in Korea. In addition, this report suggests that treatment should be initiated during the early phase of infection that could be effective for the virus.

Sensitization rates of causative allergens for dogs with atopic dermatitis: detection of canine allergen-specific IgE

Allergen-specific IgE serology tests became commercially available in the 1980s. Since then these tests have been widely used to diagnose and treat allergic skin diseases. However, the relationship between a positive reaction and disease occurrence has been controversial. The purpose of this study was to evaluate allergens using a serologic allergy test in dogs with atopic dermatitis (AD). Dogs clinically diagnosed with AD (n=101) were tested using an allergen-specific IgE immunoassay. Among the total 92 environmental and food allergens, house dust and house dust mites were the most common. Several allergens including airborne pollens and molds produced positive reactions, and which was considered increasing allergens relating to the climate changes. The presence of antibodies against staphylococci and Malassezia in cases of canine AD was warranted in this study. Additionally, strong (chicken, turkey, brown rice, brewer's yeast, and soybean) and weakly (rabbit, vension, duck, and tuna) positive reactions to food allergens could be used for avoidance and limited-allergen trials.

Prescription Patterns for Patients with Schizophrenia in Korea: A Focus on Antipsychotic Polypharmacy

OBJECTIVE: This study investigated the prescription patterns for Korean patients with schizophrenia with a particular focus on antipsychotic polypharmacy. All data were gathered from patients presenting at 41 tertiary university hospitals and 8 secondary hospitals. METHODS: Data from three multicenter studies conducted in Korea were retrospectively reviewed and integrated to identify patients with schizophrenia who had their antipsychotic medication switched to paliperidone extended-release between 2008 and 2009. The rates for antipsychotic polypharmacy, combined use of different antipsychotic classes with a special focus on atypical antipsychotics, and psychotropic polypharmacy using benzodiazepines, mood stabilizers, and other relevant drugs were identified. RESULTS: Of the 851 Korean patients analyzed in this study, 20.4% (n=173) had been prescribed antipsychotic polypharmacy. Of the 678 patients receiving antipsychotic monotherapy, 6.9% (n=47) were prescribed a typical antipsychotic and 93.1% (n=631) were prescribed an atypical antipsychotic. Of the 173 patients receiving a combination of antipsychotic drugs, only 6.4% (n=11) had been prescribed polypharmacy with typical antipsychotics, while 46.82% (n=81) were prescribed atypical+atypical antipsychotics or typical+atypical antipsychotics. The highest co-prescription rates for other psychotropic drugs in conjunction with antipsychotics included benzodiazepines (30.3%), anticholinergic drugs (28.8%), antidepressants (13.3%), beta-blockers (10.1%), and mood stabilizers (8.7%). CONCLUSION: The present findings demonstrate that the rate of antipsychotic polypharmacy is relatively low in Korea and that Korean clinicians prefer to prescribe atypical, rather than typical, antipsychotic drugs. This suggests that there is a distinct prescription pattern in Korea that is focused on antipsychotic polypharmacy.

Clomipramine treatment of acral lick dermatitis in a dog / 대한수의학회지

An 11-year-old, toy poodle dog was presented with dermatologic lesions and mammary gland tumor (MGT) evaluation. A solitary, lobulated MGT (size 2.5 x 3.5 cm) was affecting the 5th left mammary gland. Firm, oval plaque skin lesions were present on the left dorsal carpal area. The skin lesions were alopecic and salivary staining. The dog had historical separation anxiety and excessive licking of skin lesions were observed. Based on the clinical and histopathologic examinations, MGT was diagnosed with mammary complex adenoma and the skin lesions were diagnosed with acral lick dermatitis. Behavior modification treatment using oral clomipramine was effective.

Sebaceous adenitis in a Jindo dog: Dermatologic and histopathologic findings / 동물의과학연구지

A two-year-old, castrated male Jindo dog presented with a three-week history of non-pruritic alopecia and scales on dorsum. The dermatologic lesions were progressive and did not respond to antibiotics and treatment for ectoparasite. Silver-white scales were adhered to the hair shafts and a follicular cast was marked on a trichogram. Findings on histopathologic examination of the skin lesions were consistent with sebaceous adenitis. Treatment with systemic cyclosporine and topical shampoo treatment was recommended for long term management. This case report is the first to describe a sebaceous adenitis in our country and suggests combination treatment approaches to long term management of this disease.

Cutaneous hemangiopericytoma in a dog : Cytologic and Histopathologic findings / 동물의과학연구지

A 10-year-old, castrated male, English cocker spaniel dog was presented for evaluation of a mass in the left forelimb. Physical examination revealed a solitary subcutaneous mass measuring 2.7 x 2.1 x 1 cm in size. Radiographs and ultrasonography showed a well-circumscribed, focally mineralized, non-invasive to muscle layer mass without signs of further bone invasion and periosteal reaction. Cytologic evaluation of the mass through fine needle aspiration revealed a mesenchymal cell type malignant tumor without distant metastasis. An excisional biopsy was performed for definitive diagnosis and the mass was diagnosed as cutaneous hemangiopericytoma. This case report presents disagreement between fine needle aspiration and histopathology during diagnostic procedures of cutaneous hemangiopericytoma in a dog.

The Influence of Previous Antipsychotic Polypharmacy Versus Monotherapy on the Effectiveness of Antipsychotic after Switching to Paliperidone Extended-release

OBJECTIVE: Although antipsychotic polypharmacy is widely used in the pharmacotherapy of schizophrenia, its effectiveness is controversial. In particular, clinicians tend to avoid switching to monotherapy in patients who have been prescribed polypharmacy. In the present study, the authors investigate whether there is difference in time to discontinuation of antipsychotics between patients on previous monotherapy or polypharmacy. METHODS: Pooled analysis was conducted on two 24-week, multicenter, open-label, non-comparative studies that were originally designed to investigate the effectiveness of switching to paliperidone extended-release (ER) in patients with schizophrenia. Patients were divided into two groups according to previously prescribed antipsychotics, that is, to a polypharmacy group or a monotherapy group. The primary outcome measure was time to discontinuation of paliperidone ER. In addition, the authors sought to identify clinical variables that influence time to discontinuation. RESULTS: Before switching to paliperidone ER, 535 of 673 (79.5%) patients were prescribed antipsychotic monotherapy, and the remaining 138 (20.5%) patients were prescribed antipsychotic polypharmacy. No significant differences in time to discontinuation of paliperidone ER were observed between the polypharmacy and monotherapy groups. Personal and social performance scale score was the only factor found to influence time to discontinuation of paliperidone ER. No differences in psychopathology or adverse effects were found between the monotherapy and polypharmacy groups. CONCLUSION: Our results suggest that number of antipsychotics prescribed before switching to monotherapy does not influence clinical prognosis in patients with schizophrenia.