Histopathological evaluation of the lungs in experimental autoimmune encephalomyelitis.

IMPORTANCE: Experimental autoimmune encephalomyelitis (EAE) is an animal model of multiple sclerosis characterized by inflammation within the central nervous system. However, inflammation in non-neuronal tissues, including the lungs, has not been fully evaluated. OBJECTIVE: This study evaluated the inflammatory response in lungs of EAE mice by immunohistochemistry and histochemistry. METHODS: Eight adult C57BL/6 mice were injected with myelin oligodendrocyte glycoprotein35-55 to induce the EAE. Lungs and spinal cords were sampled from the experimental mice at the time of sacrifice and used for the western blotting, histochemistry, and immunohistochemistry. RESULTS: Histopathological examination revealed inflammatory lesions in the lungs of EAE mice, characterized by infiltration of myeloperoxidase (MPO)- and galectin-3-positive cells, as determined by immunohistochemistry. Increased numbers of collagen fibers in the lungs of EAE mice were confirmed by histopathological analysis. Western blotting revealed significantly elevated level of osteopontin (OPN), cluster of differentiation 44 (CD44), MPO and galectin-3 in the lungs of EAE mice compared with normal controls (p < 0.05). Immunohistochemical analysis revealed both OPN and CD44 in ionized calcium-binding adapter molecule 1-positive macrophages within the lungs of EAE mice. CONCLUSIONS AND RELEVANCE: Taken together, these findings suggest that the increased OPN level in lungs of EAE mice led to inflammation; concurrent increases in proinflammatory factors (OPN and galectin-3) caused pulmonary impairment.

Glycoconjugate-Specific Developmental Changes in the Horse Vomeronasal Organ.

The vomeronasal organ (VNO) is a tubular pheromone-sensing organ in which the lumen is covered with sensory and non-sensory epithelia. This study used immunohistochemistry and lectin histochemistry techniques to evaluate developmental changes, specifically of the glycoconjugate profile, in the horse VNO epithelium. Immunostaining analysis revealed PGP9.5 expression in some vomeronasal non-sensory epithelium (VNSE) cells and in the vomeronasal receptor cells of the vomeronasal sensory epithelium (VSE) in fetuses, young foals, and adult horses. Olfactory marker protein expression was exclusively localized in receptor cells of the VSE in fetuses, young foals, and adult horses and absent in VNSE. To identify the glycoconjugate type, lectin histochemistry was performed using 21 lectins. Semi-quantitative analysis revealed that the intensities of glycoconjugates labeled with WGA, DSL, LEL, and RCA120 were significantly higher in adult horse VSE than those in foal VSE, whereas the intensities of glycoconjugates labeled with LCA and PSA were significantly lower in adult horse VSE. The intensities of glycoconjugates labeled with s-WGA, WGA, BSL-II, DSL, LEL, STL, ConA, LCA, PSA, DBA, SBA, SJA, RCA120, jacalin, and ECL were significantly higher in adult horse VNSE than those in foal VNSE, whereas the intensity of glycoconjugates labeled with UEA-I was lower in adult horse VNSE. Histochemical analysis of each lectin revealed that various glycoconjugates in the VSE were present in the receptor, supporting, and basal cells of foals and adult horses. A similar pattern of lectin histochemistry was also observed in the VNSE of foals and adult horses. In conclusion, these results suggest that there is an increase in the level of N-acetylglucosamine (labeled by WGA, DSL, LEL) and galactose (labeled by RCA120) in horse VSE during postnatal development, implying that they may influence the function of VNO in adult horses.

Off-Label Use of Crisdesalazine (GedaCure) in Meningoencephalitis in Two Dogs.

An 8-year-old, castrated male Shih-tzu dog (Case 1) showing ataxia and gait disorder was referred for neurological examination and magnetic resonance imaging. Through comprehensive examinations, the patient was tentatively diagnosed with meningoencephalitis of unknown origin (MUO) and treatment with prednisolone and cytosine arabinoside was started. The symptoms were improving with immunosuppressive treatment. However, severe bacterial cystitis occurred and we could not avoid tapering off prednisolone. Then, neurological signs recurred. Therefore, we added crisdesalazine, which allowed us to reduce the daily dosage of immunosuppressants easily. In another case, a 4-year-old, spayed female Yorkshire terrier dog (Case 2) was referred to our hospital showing a head tilt, circling, and loss of the menace reflex. The patient was tentatively diagnosed with MUO and treatment with some immunosuppressants was attempted. The clinical symptoms improved, but the alleviation was inadequate. Thus, we added crisdesalazine. The neurological signs then markedly improved. Moreover, the drugs could be tapered off more easily than before. Crisdesalazine is a novel drug that has antioxidant and anti-inflammatory action in brain disease and is used particularly for dementia. In this paper, we tried an off-label use of this drug in canine MUO patients, and found that it had, in these two patients, additional therapeutic effects on the MUO.

Primary pyomyositis and uveitis in a cat.

A 6-year-old neutered male Siamese cat was referred for investigation of hindlimb ataxia and blindness of 2 weeks' duration. A swollen right hind limb, with no history of trauma, and no evidence of an external wound, was observed on physical examination. Ophthalmic examination revealed bilateral absence of the menace response and changes consistent with uveitis. Blood tests identified changes consistent with inflammation including serum amyloid A elevation. Infectious disease testing was negative. Degenerate neutrophils and bacterial cocci were detected on fine needle aspiration cytology of the affected limb. Thoracic radiography and abdominal ultrasonography identified no abnormalities. Primary pyomyositis was suspected and clindamycin was prescribed following Penrose drain tube placement. In addition, eye drops containing tobramycin, atropine, and prednisolone were administered. The clinical signs and serum amyloid A level were markedly improved after 5 days of treatment. Based on the medical history and lack of other findings, the uveitis was suspected to be secondary to the pyomyositis. The clinical signs resolved completely, and no recurrence was reported within a 6-month follow-up period. To the best of our knowledge, primary pyomyositis with uveitis has not been previously reported in cats.

Veratramine Inhibits the Cell Cycle Progression, Migration, and Invasion via ATM/ATR Pathway in Androgen-Independent Prostate Cancer.

Prostate cancer (PC) is the second leading cause of cancer-related death among men. Treatment of PC becomes difficult after progression because PC that used to be androgen-dependent becomes androgen-independent prostate cancer (AIPC). Veratramine, an alkaloid extracted from the root of the Veratrum genus, has recently been reported to have anticancer effects that work against various cancers; however, its anticancer effects and the underlying mechanism of action in PC remain unknown. We investigated the anticancer effects of veratramine on AIPC using PC3 and DU145 cell lines, as well as a xenograft mouse model. The antitumor effects of veratramine were evaluated using the CCK-8, anchorage-independent colony formation, trans-well, wound healing assays, and flow cytometry in AIPC cell lines. Microarray and proteomics analyses were performed to investigate the differentially expressed genes and proteins induced by veratramine in AIPC cells. A xenograft mouse model was used to confirm the therapeutic response and in vivo efficacy of veratramine. Veratramine dose dependently reduced the proliferation of cancer cells both in vitro and in vivo. Moreover, veratramine treatment effectively suppressed the migration and invasion of PC cells. The immunoblot analysis revealed that veratramine significantly downregulated Cdk4/6 and cyclin D1 via the ATM/ATR and Akt pathways, both of which induce a DNA damage response that eventually leads to G1 phase arrest. In this study, we discovered that veratramine exerted antitumor effects on AIPC cells. We demonstrated that veratramine significantly inhibited the proliferation of cancer cells via G0/G1 phase arrest induced by the ATM/ATR and Akt pathways. These results suggest that veratramine is a promising natural therapeutic agent for AIPC.

NOLC1 knockdown suppresses prostate cancer progressions by reducing AKT phosphorylation and ß-catenin accumulation.

Although several studies have focused on cancer diagnosis and therapy, prostate cancer (PC) remains an intractable disease. Androgen deprivation therapy (ADT), which is used to treat early stage PC can lead to the development of castration-resistant prostate cancer (CRPC), which is highly associated with androgen receptor (AR) mutations. Nucleolar and coiled-body phosphoprotein 1 (NOLC1) is a chaperone that shuttles between the nucleus and the cytoplasm. Studies suggest that NOLC1 regulates PC progression; however, the underlying mechanisms remain unclear. Herein, we showed that NOLC1 knockdown suppresses PC cell proliferation by altering the signaling pathways and the expression of various proteins involved in DNA replication, amino acid metabolism, and RNA processing. Mechanistically, NOLC1 knockdown suppressed cell cycle progression by inhibiting AKT phosphorylation and ß-catenin accumulation. Finally, we showed that NOLC1 expression is higher in human PC than in human hyperplastic prostate tissues. Altogether, we demonstrated that NOLC1 knockdown suppresses the progression of both AR-positive and AR-negative PC cells by inducing changes in the expression of several genes leading to cell cycle arrest. Thus, NOLC1 might be a novel and promising therapeutic target for PC.

A rare case of cecal malignant peripheral nerve sheath tumor in a dog.

A 12-year-old mixed-breed dog presented with a 2-month history of abdominal distension. Radiographic examination, abdominal ultrasonography, and computed tomography revealed a mass in the cecum (15.0 × 11.9 × 4.5 cm). The cecal mass was surgically removed and examined histopathologically. Immunohistochemically, the neoplastic cells expressed S-100 and neuron specific enolase but not α-smooth muscle actin and CD117 (c-kit). These histologic and immunohistochemical features indicated that the mass was consistent with a malignant peripheral nerve sheath tumor (MPNST). In dogs, most MPNSTs arise from the brachial plexus, spinal nerve root, and skin of the extremities. However, gastrointestinal MPNSTs in dogs have not been described previously. To the best of our knowledge, this is the first report to describe cecal MPNST in a dog.

Computed tomographic features of the temporomandibular joint in 10 Jeju horses.

BACKGROUND: The equine temporomandibular joint (TMJ) has a complex anatomical structure that makes diagnosis of TMJ disorders difficult. Computed tomography (CT) is now available in equine medicine; hence, TMJ evaluation has become more convenient. OBJECTIVES: The objectives of this study were to describe the CT features of the TMJ in Jeju horses and to compare these features with those of Thoroughbreds. METHODS: In this report, the TMJs of 10 Jeju horses (mean age: 4.5 ± 1.9 yr; mean body weight: 282.6 ± 40.3 kg) and 6 Thoroughbreds (mean age: 7.3 ± 1.6 yr; mean body weight: 479.7 ± 44.0 kg) were examined using CT. After CT scanning, the Hounsfield units (HU) and height to width ratio (H:W) of the mandibular condyle were measured. RESULTS: The mean H:W in Jeju horses was significantly lower than that in Thoroughbreds. The mean HU in Jeju horses was lower than that in Thoroughbreds; however, the difference was not significant. The most frequent CT finding was an irregular medial margin of the mandibular condyle in both breeds. CONCLUSIONS: In this study, the shape of the mandibular condyle in Jeju horses was flatter than that in Thoroughbreds. This report could be useful in evaluating the TMJ in Jeju horses. Moreover, CT could be a pragmatic choice for the examination of the TMJ in horses.