Assessment of MMP-9 and clinical characteristics in dogs with tracheal collapse based on cough severity and fluoroscopic findings: a cross-sectional study.

BACKGROUND: Tracheal collapse (TC), a common disease in dogs, is characterized by cough; however, little is known about the serum biomarkers that can objectively evaluate the severity of cough in canine TC. Furthermore, studies elucidating the relationship of fluoroscopic characteristics with the severity of cough are lacking. Therefore, this study aimed to evaluate the relationship between cough severity and clinical characteristics, fluoroscopic images, and new serum biomarkers in canine TC. RESULTS: Fifty-one client-owned dogs diagnosed with TC based on fluoroscopic and clinical signs were enrolled in this study and divided into three groups according to the severity of cough (grade of cough: 0, 1, and 2). Signalments, comorbidities, and fluoroscopic characteristics were compared among the groups retrospectively. The serum matrix metalloproteinase-9 (MMP-9), interleukin-6 (IL-6), surfactant protein-A (SP-A), and syndecan-1 (SDC-1) levels were measured in all groups. No significant differences in age, breed, sex, or clinical history were observed among the groups. Concomitant pharyngeal collapse increased significantly with the severity of cough (p = .031). Based on the fluoroscopic characteristics, the TC grade of the carinal region increased significantly and consistently with the grade of cough (p = .03). The serum MMP-9 level was significantly higher in the grade 2 group than that in the grade 0 group (p = .014). The serum IL-6 level was significantly lower in the grade 1 group than that in the grade 0 group (p = .020). The serum SP-A and SDC-1 levels did not differ significantly among the groups. CONCLUSIONS: The severity of cough with the progression of TC can be predicted with the fluoroscopic TC grade at the carinal region. MMP-9 may be used as an objective serum biomarker that represents cough severity to understand the pathogenesis.

Pamidronate-induced irreversible symptomatic hypocalcemia in a dog with hypercalcemia after glucocorticoid withdrawal: a case report.

BACKGROUND: Pamidronate is used for the treatment of hypercalcemia. However, a rare but potential adverse event of pamidronate treatment is hypocalcemia. This report describes an unusual case of severe, irreversible hypocalcemia after a single injection of pamidronate for the treatment of hypercalcemia due to glucocorticoid withdrawal in a dog. CASE PRESENTATION: An 11-year-old castrated male Maltese dog presented with anorexia, vomiting, and diarrhea (day 0). The patient had calcinosis cutis throughout the body, calcification of intraabdominal organs, mild azotemia, and severe hypercalcemia. The severe calcification was attributed to long-term glucocorticoid administration, which was discontinued 1 month before presentation. Fluid therapy, diuretics, calcitonin, and a single intravenous injection of pamidronate were used for the treatment of hypercalcemia. On day 14, normocalcemia was achieved, but renal failure occurred. On day 20, severe and irreversible hypocalcemia occurred, and on day 42, the patient was euthanized at the owner's request because of worsened hypocalcemia and renal failure. CONCLUSIONS: Although hypocalcemia is an extremely rare adverse event of bisphosphonate treatment, bisphosphonates like pamidronate can result in potentially life-threatening conditions according to the patient's underlying conditions. Therefore, the patient's condition should be closely monitored and any underlying conditions should be carefully evaluated before initiating the treatment for hypercalcemia using pamidronate.

Anti-cancer effects of DHP107 on canine mammary gland cancer examined through in-vitro and in-vivo mouse xenograft models.

BACKGROUND: Canine mammary gland cancer (CMGC) is a common neoplasm in intact bitches. However, the benefit of adjuvant chemotherapy is unclear. The aim of this study was to investigate the anti-proliferative effects of paclitaxel on CMGC in in-vitro and in-vivo settings. RESULTS: Paclitaxel dose-dependently inhibited viability and induced G2/M phase cell cycle arrest and apoptosis in both primary and metastatic CMGC cell lines (CIPp and CIPm). In animal experiments, the average tumour volume decreased significantly in proportion to the administered oral paclitaxel dose. By examining tumour tissue using a TUNEL assay and immunohistochemical staining with anti-CD31 as a marker of endothelial differentiation, respectively, it was confirmed that oral paclitaxel induced apoptosis and exerted an anti-angiogenetic effect in tumour tissues. Further, downregulation of cyclin D1 in tumour tissues suggested that oral paclitaxel induced cell cycle arrest in tumour tissues in-vivo. CONCLUSIONS: Our results suggest that paclitaxel may have anti-cancer effects on CMGC through cell cycle arrest, induction of apoptosis, and anti-angiogenesis. This study could provide a novel approach to treat CMGC.

Subcutaneous emphysema and pneumomediastinum following orbital blowout pathological fracture in a cat with nasal lymphoma: a case report.

BACKGROUND: Subcutaneous emphysema and pneumomediastinum are rare complications associated with orbital blowout pathological fracture. CASE PRESENTATION: A 7-year old, castrated male Abbysinian cat presented with anorexia, lethargy, nausea, eyelid swelling, nasal discharge, and sneezing. Based on the clinical and diagnostic work-up, the cat was diagnosed with T cell high-grade nasal lymphoma associated with orbital pathological fracture due to the tumour invasion. After chemotherapy, the cat showed massive subcutaneous emphysema from frontal region to abdomen and pneumomediastinum due to orbital blowout pathological fracture. As the nasal mass decreased in volume; the air had moved from the maxillary sinus to the subcutaneous region and the mediastinum through fascial planes in the head and neck region. CONCLUSIONS: This is a first case report of a massive subcutaneous emphysema and pneumomediastinum due to an orbital blowout pathological fracture following chemotherapy in feline nasal lymphoma in veterinary medicine.

Retrospective evaluation of prognosis and survival with various immunosuppressants in 82 dogs diagnosed with meningoencephalitis of unknown etiology (2010-2021).

BACKGROUND: Meningoencephalomyelitis of unknown etiology (MUE) is a comprehensive term for non-infectious inflammatory brain diseases of the central nervous system (CNS) caused by abnormal autoimmune responses. This study aims to compare the differences in survival and clinical response of MUE according to the adjuvant immunosuppressant use. Medical records of 82 dogs diagnosed with MUE were reviewed retrospectively. RESULTS: The overall survival time was 769 days (range 14-2687 days). The median survival time for each adjunctive was: leflunomide 1035 days (range 126-2163 days), mycophenolate mofetil 865 days (range 39-2191 days), cyclosporin 441 days (range 11-2176 days), cytosine arabinoside 754 days (range 6-1898 days) and a combination of mycophenolate mofetil and cytosine arabinoside 132 days (range 23-1227 days). There was no significant difference in the incidence rate of adverse events according to the immunosuppressants, but moderate to severe anemia was confirmed in 3 patients (18.7%) in the leflunomide group. CONCLUSIONS: The survival time and response rate of MUE dogs differed depending on which adjunctive immunosuppressants were used. Leflunomide showed a long survival time and a relatively good response rate in dogs with MUE. However, a large-scale further study with standardized doses of immunosuppressants and supportive treatment and constant monitoring interval is needed.

Clinical infection of Brucella canis in a companion dog with discospondylitis in the Republic of Korea.

A 2-year-old, spayed female, Bichon Frise dog was presented with reluctance to exercise, back pain, and frequent sitting down. Multiple osteolysis, periosteal proliferation, and sclerosis of the vertebral endplates of T11-13 were observed in the radiography, computed tomography, and magnetic resonance imaging. The bacterial culture of the urine specimen, the polymerase chain reaction (PCR) of the blood, and the antibody tests were positive for Brucella canis. Accordingly, discospondylitis caused by B. canis was diagnosed and doxycycline was administered. The clinical signs resolved and the culture and PCR results were negative afterwards. Doxycycline was discontinued after 6 months. The clinical signs recurred 2 weeks later, and the combination treatment of doxycycline and enrofloxacin was initiated. Though no clinical signs were observed after 9 months and the bacterial cultures and PCR were negative, the antibody titre remained at 1 : 200 or more. The dog will continue taking antibiotics until the antibody titre drops. To the best of our knowledge, this is the first case report of a clinical infection of B. canis associated with canine discospondylitis in the Republic of Korea. Although the clinical signs of brucellosis might improve with antibiotic treatment, the disease cannot be cured due to Brucella's various strategies to evade host immune systems. Specifically, it can proliferate and replicate within the host cells, resulting in an environment that makes treatment less effective. Furthermore, owing to its zoonotic potential, owners and veterinarians should consider lifelong management or euthanasia.

Assessment of salivary alpha-amylase and cortisol as a pain related stress biomarker in dogs pre-and post-operation.

BACKGROUND: The use of salivary biomarkers has garnered attention because the composition of saliva reflects the body's physiological state. Saliva contains a wide range of components, including peptides, nucleic acids, electrolytes, enzymes, and hormones. It has been reported that salivary alpha-amylase and cortisol are biomarkers of stress related biomarker in diseased dogs; however, evaluation of salivary alpha-amylase and cortisol pre- and post- operation has not been studied yet. The aim of this study was to evaluate salivary alpha-amylase and cortisol levels in dogs before and after they underwent surgery and investigate the association between the salivary alpha-amylase and cortisol activity and pain intensity. For this purpose, a total of 35 dogs with disease-related pain undergoing orthopedic and soft tissue surgeries were recruited. Alpha-amylase and cortisol levels in the dogs' saliva and serum were measured for each using a commercially available canine-specific enzyme-linked immunosorbent assay kit, and physical examinations (measurement of heart rate and blood pressure) were performed. In addition, the dogs' pre- and post-operative pain scores determined using the short form of the Glasgow Composite Measure Pain Scale (CMPS-SF) were evaluated. RESULTS: After surgery, there was a significant decrease in the dogs' pain scores (0.4-fold for the CMPS-SF, p < 0.001) and serum cortisol levels (0.73-fold, p < 0.01). Based on their pre-operative CMPS-SF scores, the dogs were included in either a high-pain-score group or a low-pain-score group. After the dogs in the high-pain-score group underwent surgical intervention, there was a significant decrease in their CMPS-SF scores and levels of salivary alpha-amylase, serum alpha-amylase, and serum cortisol. Additionally, there was a positive correlation between salivary alpha-amylase levels and CMPS-SF scores in both the high- and low-pain-score groups. CONCLUSIONS: The measurement of salivary alpha amylase can be considered an important non-invasive tool for the evaluation of pain-related stress in dogs.

Evaluation of endothelial cell-specific molecule-1 as a biomarker of glycocalyx damage in canine myxomatous mitral valve disease.

BACKGROUND: Endothelial cell-specific molecule-1 (ESM-1) has emerged as a potential biomarker for cardiovascular disease in humans. Myxomatous mitral valve disease (MMVD) is the most common heart disease in dogs, and we hypothesized that MMVD causes chronic inflammation that increases susceptibility to endothelial glycocalyx (eGCX) damage. In this study, we measured the concentration of ESM-1 in a group of dogs with MMVD and evaluated factors affecting eGCX damage. RESULTS: Sixty-four dogs (control, n = 6; MMVD, n = 58) were enrolled in this study. There was no significant difference in serum ESM-1 concentrations among the MMVD stages. The serum ESM-1 concentration was significantly higher in the death group than in the alive group in MMVD dogs. (p = 0.006). In five dogs with MMVD, serum ESM-1 concentrations tended to decrease when the cardiac drug (pimobendan, furosemide, and digoxin) dose was increased. CONCLUSIONS: In cases where MMVD progressed to decompensated heart failure with clinical symptoms and resulted in death, the concentration of serum ESM-1 increased significantly. Therefore, ESM-1 could be utilized as a new potential negative prognostic factor in patients with MMVD.

Prevalence, co-infection and seasonality of fecal enteropathogens from diarrheic cats in the Republic of Korea (2016-2019): a retrospective study.

BACKGROUND: Diarrhea is one of the most common clinical symptoms in cats and can be caused by infectious pathogens and investigation of the prevalence, co-infection and seasonality of enteropathogens are not well-established in diarrheic cats. RESULTS: Fecal samples of 1620 diarrheic cats were collected and enteropathogens were detected using real-time PCR. We retrospectively investigated the clinical features, total/seasonal prevalence, and infection patterns of enteropathogens. The positive infection rate was 82.59%. Bacterial, viral, and protozoal infections accounted for 49.3, 37.57, and 13.13% of cases, respectively. Feline enteric coronavirus (FECV) was the most common pathogen (29.37%), followed by Clostridium (C.) perfringens, Campylobacter (C.) coli, feline parvovirus, and Tritrichomonas foetus. The seasonality of enteropathogens was observed with peaks as follows: bacterial infections peaked in October, viral infections peaked in November, and protozoal infections peaked in August. Viral and protozoal infections showed differences in prevalence according to patient age. In the infection patterns, the ratios of single infections, mixed infections, and co-infections were 35.72, 9.87, and 54.41%, respectively. FECV was predominant in single infections. The most common patterns of multiple infections were C. perfringens and C. coli in mixed infections and C. perfringens and FECV in co-infections. CONCLUSIONS: Infection patterns differed according to the enteropathogen species, seasonality, and age distribution in cats. The results of this study might be helpful to understand in clinical characteristics of feline infectious diarrhea. In addition, continued monitoring of feline enteropathogens is required.

Pharmacokinetics and diuretic effect of furosemide after single intravenous, oral tablet, and newly developed oral disintegrating film administration in healthy beagle dogs.

BACKGROUND: Furosemide, a diuretic that acts on the loop of Henle, is commonly used to treat congestive heart failure in veterinary medicine. Some owners have difficulty in administering oral tablet medication to animal patients, which leads to noncompliance, especially during long-term administration. Oral disintegrating film (ODF) has the advantages of easy administration via a non-invasive route, rapid dissolution, and low suffocating risk. The objective of this study was to research the pharmacokinetic (PK) profiles and diuretic effect of furosemide after intravenous (IV), orally uncoated tablet (OUT), and newly developed ODF administration in healthy beagle dogs. In this study, a furosemide-loaded ODF (FS-ODF) formulation was developed and five beagle dogs were administered a single dose (2 mg/kg) of furosemide via each route using a cross-over design. RESULTS: The most suitable film-forming agent was sodium alginate; thus, this was used to develop an ODF for easy drug administration. No significant differences were detected in the PK profiles between OUT and FS-ODF. In the blood profiles, the concentration of total protein was significantly increased compared to the baseline (0 h), whereas no significant difference was detected in the concentration of creatinine and hematocrit compared to the baseline. FS-ODF resulted in a similar hourly urinary output to OUT during the initial 2 h after administration. The urine specific gravity was significantly decreased compared to the baseline in each group. The peak times of urine electrolyte (sodium and chloride) excretion per hour were 1 h (IV), 2 h (OUT), and 2 h (FS-ODF). CONCLUSIONS: These results suggest that the PK/PD of furosemide after administration of newly developed FS-ODF are similar to those of OUT in healthy dogs. Therefore, the ODF formulation has the benefits of ease and convenience, which would be helpful to owners of companion animals, such as small dogs (< 10 kg), for the management of congestive heart failure.

Evaluation of salivary vasopressin as an acute stress biomarker in healthy dogs with stress due to noise and environmental challenges.

BACKGROUND: Stress is associated with various detrimental changes in physiological health that affect an animal's quality of life. The hypothalamus-pituitary-adrenal (HPA) axis and the sympathetic-adreno-medullar (SAM) axis are two main physiological pathways that constitute the stress response of an organism. Arginine vasopressin (AVP) is a mediator of the HPA axis and is known to be related to social behaviours and stress. The serum concentration of AVP is higher in more aggressive dogs and humans with post-traumatic stress disorder. Salivary biomarker analysis is a non-invasive method to assess stress. The purpose of this study was to evaluate the possibility of using salivary AVP as an acute stress biomarker in dogs. Salivary AVP concentration was measured before and after exposure to all relevant environmental stimuli (i.e. car trip to the lab, physical examination by the veterinarian, and sampling procedure,) and then after 30 min of vacuum noise exposure. Behavioural assessments, physiologic parameter assessments, and serum cortisol analysis were conducted in combination. Statistical analysis was conducted separately in the total study population, the less stressed group, and the more stressed group, respectively. RESULTS: Based on stress behaviour analysis scores, 28 dogs were classified into less or more stressed groups. All four physiologic parameters (blood pressure, body temperature, heart rate, and respiratory rate) were significantly increased after noise and environmental challenges, in the more stressed group. Serum cortisol did not show any significant change. Salivary AVP significantly decreased after noise and environmental stimulation in the more stressed group but not in the less stressed group. Salivary AVP and blood pressure changes were negatively correlated in the more stressed group. CONCLUSION: Salivary AVP may be a potential acute stress biomarker in dogs.

Investigation on urinary and serum alpha klotho in dogs with chronic kidney disease.

BACKGROUND: As a co-receptor for fibroblast growth factor 23, klotho plays a pivotal role in phosphate metabolism. The kidney is known to be the main source of soluble alpha-klotho and the principal regulator of its concentration. Previous studies in human participants showed that the concentration of soluble alpha-klotho in serum and urine decreased in chronic kidney disease (CKD) patients. However, no previous study has assessed soluble alpha-klotho levels in dogs. This study aimed to measure serum and urinary alpha-klotho levels in CKD dogs and identify their associations with International Renal Interest Society (IRIS) CKD stages and other parameters known to be associated with CKD. RESULTS: Serum and urinary alpha klotho concentrations were measured by a commercially available canine-specific sandwich enzyme-linked immunosorbent assay kit and compared between groups by a nonparametric Kruskal-Wallis test. Spearman's correlation coefficient was used to evaluate the relationships between variables. A stepwise multiple regression analysis was performed to estimate the effects of independent predictors on klotho concentrations. The urine klotho-to-creatinine ratio (UrKl/Cr) was significantly lower in stage 3 dogs than the control group and was significantly lower in dogs with stage 3 and 4 CKD than in those with stage 1 and 2 disease. UrKl/Cr was negatively correlated with serum symmetric dimethylarginine (sSDMA), blood urea nitrogen (BUN), creatinine, and phosphorus concentration. Serum alpha-klotho concentration in dogs with stages 2 and 3 CKD was significantly lower than those in the control group. There was no significant correlation between serum alpha-klotho and BUN, creatinine, and phosphorus concentrations. No statistically significant differences were observed in UrKl/Cr and serum alpha-klotho concentration between groups based on sex, age, urine protein-to-creatinine ratio (UPC), or blood pressure. CONCLUSIONS: UrKl/Cr decreased in dogs with advanced CKD, and it was negatively correlated with sSDMA, BUN, creatinine, and phosphorus concentrations. Thus, klotho is associated with CKD and its clinical consequences, including CKD-mineral bone disorder, in dogs. Although serum klotho concentration was negatively correlated with sSDMA levels, it was not apparently related to IRIS CKD stage or other parameters known to be associated with CKD.

Comparative single-dose pharmacokinetics of sildenafil after oral and rectal administration in healthy beagle dogs.

BACKGROUND: Sildenafil citrate, a highly selective phosphodiesterase type 5 inhibitor, is used to treat pulmonary hypertension (PH) in veterinary medicine. The objective of this study was to investigate pharmacokinetic profiles by oral administration of orally disintegrating film (ODF) and film coated tablet (FCT) formulations and rectal administration of ODF formulation in healthy dogs. Twelve healthy beagle dogs were administered four separate doses of sildenafil: FCT formulation 2 mg/kg orally, ODF formulation 2 mg/kg orally, ODF formulation 2 mg/kg rectally, and ODF formulation 10 mg/kg rectally. For 24 hours following administration, blood samples were collected and the plasma concentrations of sildenafil were assayed by liquid chromatography-tandem mass spectrometry. RESULTS: There were no significant differences in all the pharmacokinetic parameters between FCT and ODF formulations when administrated orally. Cmax at the time of rectal administration was lower when the same dose was given as that orally administered. No serious systemic adverse events (AEs) were observed. CONCLUSIONS: These findings suggest that sildenafil ODF formulation can be used as an alternative to FCT formulation in the treatment of canine PH patients; additionally, rectal administration of sildenafil ODF may be a beneficial treatment option for canine patients who are unable to receive medication orally.

Secondary inappropriate polycythemia with splenic hemangiosarcoma in a young adult cat.

A 20-month-old castrated male Korean shorthair cat was presented with a 3-week history of intermittent vomiting and anorexia, absolute erythrocytosis, and elevated erythropoietin levels. A diagnosis of splenic hemangiosarcoma was made by histopathology and immunohistochemical identification of factor VIII. Paraneoplastic erythrocytosis caused by a splenic hemangiosarcoma in a cat is described.

Polycythémie secondaire inappropriée et hémangiosarcome splénique chez un jeune chat adulte. Un chat commun coréen mâle castré âgé de 20 mois a été présenté avec une anamnèse de 3 semaines de vomissements intermittents et d'anorexie, d'érythrocytose absolue et des taux élevés d'érythropoïétine. Un diagnostic d'hémangiosarcome splénique a été posé par histopathologie et l'identification immunochimique du facteur VIII. L'érythrocytose paranéoplastique causée par un hémangiosarcorme splénique chez un chat est décrite.(Traduit par Isabelle Vallières).

Comparison of Fecal Microbiota between German Holstein Dairy Cows with and without Left-Sided Displacement of the Abomasum.

One of the most common diseases in high-performance German Holstein dairy cows is left-sided displacement of the abomasum (LDA). Hypomotility of the abomasum is detrimental during the pathogenesis of LDA. It is known that improper interactions between the gut microbiota and the enteric nervous system contribute to dysfunctions of gastrointestinal motility. Therefore, we hypothesized that the gut microbial composition will be different between German Holstein dairy cows with and without LDA. We used 16S rRNA gene analysis to evaluate whether there are any differences in bacterial composition between German Holstein dairy cows with and without LDA. Even though our data are limited to being used to correlate compositional changes with corresponding functional aspects in the pathogenesis of LDA, results from this study show that the fecal microbial compositions of German Holstein dairy cows with LDA shifted and were less diverse than those in normal cows. In particular,Spirochaeteswere absent in cows with LDA.

CTLA4 overexpressing adipose tissue-derived mesenchymal stem cell therapy in a dog with steroid-refractory pemphigus foliaceus.

BACKGROUND: Canine pemphigus foliaceus is an autoimmune antibody-mediated skin disease characterized by acantholysis. The objective of this case report is to present the successful management of steroid refractory pemphigus foliaceus with cytotoxic T-lymphocyte antigen 4 (CTLA4)-overexpressing adipose tissue mesenchymal stem cells (ATMSCs). CASE PRESENTATION: A 10-year-old, 12.3-kg, castrated male Shih Tzu presented with severe pruritus and anorexia. The diagnosis of pemphigus foliaceus was made based on its history, physical examination, and histopathology results of a skin biopsy. Treatment with prednisolone and combination therapy of other immunosuppressive drugs had failed; therefore, immunosuppressive gene, CTLA4 overexpressing ATMSCs (CTLA4-ATMSCs) and/or naive ATMSCs administration was performed with the consent of the owner. ATMSCs were administered 21 times over a period of 20 months with intervals of 2 to 8 week. Prednisolone was gradually tapered concurrently and no relapse of the clinical signs was observed. After the termination of CTLA4-ATMSCs and/or naive ATMSCs treatment, the skin lesions had improved and could be managed with a low dose of prednisolone for 12 months. CONCLUSION: CTLA4-ATMSCs or naive ATMSCs transplantation may be beneficial as adjunctive therapy to initiate and maintain the remission of skin lesions caused by pemphigus foliaceus in veterinary medicine.

Molecular Detection of Giardia intestinalis from Stray Dogs in Animal Shelters of Gyeongsangbuk-do (Province) and Daejeon, Korea.

Giardia is a major public health concern and considered as reemerging in industrialized countries. The present study investigated the prevalence of giardiosis in 202 sheltered dogs using PCR. The infection rate was 33.2% (67/202); Gyeongsangbuk-do and Daejeon showed 25.7% (39/152, P<0.0001) and 56% (28/50), respectively. The prevalence of infected female dogs (46.7%, P<0.001) was higher than in male dogs (21.8%). A higher prevalence (43.5%, P<0.0001) was observed in mixed breed dogs than purebred (14.1%). Although most of the fecal samples collected were from dogs of ≥1 year of age which showed only 27.4% positive rate, 61.8% (P<0.001) of the total samples collected from young animals (<1 year of age) were positive for G. intestinalis. A significantly higher prevalence in symptomatic dogs (60.8%, P<0.0001) was observed than in asymptomatic dogs (23.8%). Furthermore, the analysis of nucleotide sequences of the samples revealed that G. intestinalis Assemblages A and C were found in the feces of dogs from Gyeongsangbuk-do and Daejeon. Since G. intestinalis Assemblage A has been known to infect humans, our results suggest that dogs can act as an important reservoir of giardiosis in Korea. Hence, hygienic management should be given to prevent possible transmission to humans.

Therapeutic effects of hepatocyte growth factor-overexpressing human umbilical cord blood-derived mesenchymal stem cells on liver fibrosis in rats.

Fibrosis is a common end stage for a variety of liver diseases, including most chronic liver diseases, and results from an imbalance between collagen deposition and degradation. Mesenchymal stem cells (MSCs) have the ability to migrate into fibrotic livers and differentiate into hepatocytes. Hepatocyte growth factor (HGF) has potent anti-apoptotic and mitogenic effects on hepatocytes during liver injury and plays an essential role in the development and regeneration of the liver. In this study, human HGF-overexpressing human umbilical cord blood-derived MSCs (hHGF-HUCB-MSCs) were prepared using the pMEX Expression System, and the upregulation of hHGF expression was confirmed by RT-PCR and ELISA. HGF expressed by hHGF-HUCB-MSCs exerted a stimulatory effect on hepatocyte proliferation in vitro. hHGF-HUCB-MSCs were transplanted to investigate the therapeutic effects of these cells on carbon tetrachloride (CCL4)-induced liver fibrosis in a rat model. After 4 weeks of cell treatment once per week with 2 × 10(6) cells, biochemical analysis of the serum and histopathological analysis of the liver tissue were performed. The results of the biochemical analysis of the serum show that the hHGF-HUCB-MSC-treated group had higher levels of alanine aminotransferase, aspartate aminotransferase and alkaline phosphatase, indicating the improvement of liver function. Histopathology showed that the hHGF-HUCB-MSC-treated group had reduction in the density of collagen fibres. Thus hHGF-HUCB-MSCs can enhance liver regeneration and could be useful for the treatment of patients with liver fibrosis or cirrhosis.

Stimulatory effect of HGF-overexpressing adipose tissue-derived mesenchymal stem cells on thymus regeneration in a rat thymus involution model.

The thymus is the central lymphoid organ providing a unique and essential microenvironment for T-cell precursor development into mature functionally competent T-lymphocytes. Thus, it is important to develop the strategies for enhancing thymic regeneration from involution induced by a variety of clinical treatments and conditions. Hepatocyte growth factor (HGF) promotes proliferation in a variety of cell types. We have used stem cell-based HGF gene therapy to enhance regeneration from acute thymic involution. HGF-overexpressing human adipose tissue-derived mesenchymal stem cells (HGF-hATMSCs) were generated by liposomal transfection with the pMEX expression vector, constructed by inserting the HGF gene. Significantly increased HGF expression in these cells was confirmed by reverse transcription-polymerase chain reaction and an enzyme-linked immunosorbent assay. HGF produced by HGF-hATMSCs enhanced the proliferation of a mouse thymic epithelial cell line and the expression of interleukin-7 in vitro. We also examined the effect of HGF-hATMSCs on thymic regeneration in rats with acute thymic involution. Significant increases in thymus size and weight, as well as the number of thymocytes (especially, early thymocyte progenitors), were seen in the HGF-hATMSCs-treated rats compared to saline-treated control animals. A stimulatory effect of HGF-hATMSCs on thymic regeneration has therefore been shown, highlighting the clinical value of HGF-hATMSCs for treating thymic involution.

Leptin, adiponectin and serotonin levels in lean and obese dogs.

BACKGROUND: Serotonin (5-hydroytryptamine or 5HT) is associated with numerous behavioral and psychological factors and is a biochemical marker of mood. 5HT is involved in the hypothalamic regulation of energy consumption. 5HT controls appetite in the central nerve system (CNS) and stimulates intestinal mobility. There are few studies looking at the role of 5HT and the relationship between peripheral circulating serotonin and obesity. The aim of this study was to find any differences in leptin, adiponectin, and 5HT between lean and obese dogs and to identify correlations among these factors. RESULTS: Leptin, triglyceride (TG) and cholesterol levels were higher in the obese group (all p < 0.01). Adiponectin and 5HT levels were higher in the lean group compared to the obese group (p < 0.01). Leptin (r = 0.628, p < 0.01), TG (r = 0.491, p < 0.01) and cholesterol (r = 0.419, p < 0.01) were positively correlated with body condition score (BCS), and adiponectin (r = -0.446, p < 0.01) and 5HT (r = -0.490, p < 0.01) were negatively correlated with BCS. Leptin was negatively correlated with adiponectin (r = -0.294, p < 0.01) and 5HT (r = -0.343, p < 0.01). 5HT was negatively correlated with leptin (r = -0.343, p < 0.01), TG (r = -0.268, p < 0.05) and cholesterol (r = -0.357, p < 0.05). CONCLUSIONS: 5HT is an important appetite control neurotransmitter, but there are limited studies for 5HT levels related to obesity in dogs. To the best of our knowledge, this is the first study to evaluate peripheral 5HT levels in obese dogs. From this research, we can assume that 5HT may be correlated with canine obesity. Further studies will be needed to further elucidate the role of low serum 5HT levels in canine obesity.