Capsular and fascial closure with barbed sutures reduces blood loss compared to traditional interrupted sutures in total hip arthroplasty.

BACKGROUND: STRATAFIX, a recently introduced barbed suture device, incorporates self-anchoring, knotless sutures with higher tensile strength and enhanced tissue-holding capacity compared to traditional braided absorbable sutures. This study aimed to compare the efficacy of barbed sutures and interrupted sutures in capsular and fascial closure during total hip arthroplasty. METHODS: We retrospectively reviewed the records of patients who underwent total hip arthroplasty between April 2017 and March 2021. Overall, 547 patients were evaluated, comprising 77 men and 470 women (mean age: 64.5 years). Among them, 330 patients were in the interrupted suture (control) group, while 217 were in the barbed suture (BS) group. Data on surgical time, perioperative hemoglobin, length of hospital stay, complications such as transfusions and delayed wound healing, and dislocation rates were collected during the latest outpatient follow-up and compared between the two groups. RESULTS: No differences were observed in intraoperative blood loss between the groups. However, the BS group exhibited significantly longer operative time, as well as significantly lower postoperative blood loss, total blood loss, and postoperative hemoglobin drop compared to the control group. Dislocation was reported in two cases within the control group, whereas no instances were recorded in the BS group. CONCLUSION: The use of barbed sutures demonstrated effectiveness in reducing perioperative blood loss for capsular and fascial closure during total hip arthroplasty.

Asian flush is a potential protective factor against COVID-19: a web-based retrospective survey in Japan.

BACKGROUND: Coronavirus disease 2019 (COVID-19), first reported in December 2019, spread worldwide in a short period, resulting in numerous cases and associated deaths; however, the toll was relatively low in East Asia. A genetic polymorphism unique to East Asians, Aldehyde dehydrogenase 2 rs671, has been reported to confer protection against infections. METHOD: We retrospectively investigated the association between the surrogate marker of the rs671 variant, the skin flushing phenomenon after alcohol consumption, and the timing of COVID-19 incidence using a web-based survey tool to test any protective effects of rs671 against COVID-19. RESULTS: A total of 807 valid responses were received from 362 non-flushers and 445 flushers. During the 42 months, from 12/1/2019 to 5/31/2023, 40.6% of non-flushers and 35.7% of flushers experienced COVID-19. Flushers tended to have a later onset (Spearman's partial rank correlation test, p = 0.057, adjusted for sex and age). Similarly, 2.5% of non-flushers and 0.5% of flushers were hospitalized because of COVID-19. Survival analysis estimated lower risks of COVID-19 and associated hospitalization among flushers (p = 0.03 and <0.01, respectively; generalized Wilcoxon test). With the Cox proportional hazards model covering 21 months till 8/31/2021, when approximately half of the Japanese population had received two doses of COVID-19 vaccine, the hazard ratio (95% confidence interval) of COVID-19 incidence was estimated to be 0.21 (0.10-0.46) for flusher versus non-flusher, with adjustment for sex, age, steroid use, and area of residence. CONCLUSIONS: Our study suggests an association between the flushing phenomenon after drinking and a decreased risk of COVID-19 morbidity and hospitalization, suggesting that the rs671 variant is a protective factor. This study provides valuable information for infection control and helps understand the unique constitutional diversity of East Asians.

Molecular Mechanisms of Aggregation of Canine SOD1 E40K Amyloidogenic Mutant Protein.

Canine degenerative myelopathy (DM) is a human amyotrophic lateral sclerosis (ALS)-like neurodegenerative disease. It is a unique, naturally occurring animal model of human ALS. Canine DM is associated with the aggregation of canine superoxide dismutase 1 (cSOD1), which is similar to human ALS. Almost 100% of cases in dogs are familial, and the E40K mutation in cSOD1 is a major causative mutation of DM. Therefore, it is important to understand the molecular mechanisms underlying cSOD1(E40K) aggregation. To address this, we first analyzed the structural model of wild type cSOD1. Interactions were evident between amino acid E40 and K91. Therefore, the mutation at residue E40 causes loss of the interaction and may destabilize the native structure of cSOD1. Differential scanning fluorimetry revealed that the E40K mutant was less stable than the wild type. Moreover, stability could be recovered by the E40K and K91E double mutation. Acceleration of amyloid fibril formation in vitro and aggregate formation in cells of cSOD1(E40K) was also suppressed by the introduction of this double mutation in thioflavin T fluorescence assay results and in transfectant cells, respectively. These results clearly show the importance of the interaction between amino acid residues E40 and K91 in cSOD1 for the stability of the native structure and aggregation.

WT1 peptide-based immunotherapy for advanced thymic epithelial malignancies.

Thymic epithelial tumors are rare malignancies, and no optimal therapeutic regimen has been defined for patients with advanced disease. Patients with advanced thymic epithelial tumors, which were resistant or intolerable to prior therapies, were eligible for this study. Patients received 9 mer-WT1-derived peptide emulsified with Montanide ISA51 adjuvant via intradermal administration once a week as a monotherapy. After the 3-month-protocol treatment, the treatment was continued mostly at intervals of 2-4 weeks until disease progression or intolerable adverse events occurred. Of the 15 patients enrolled, 11 had thymic carcinoma (TC) and 4 had invasive thymoma (IT). Median period from diagnosis to the start of treatment was 13.3 and 65.5 months for TC and IT, respectively. No patients achieved a complete or partial response. Of the 8 evaluable TC patients, 6 (75.0%) had stable disease (SD) and 2 had progressive disease (PD). Of the 4 evaluable IT patients, 3 (75.0%) had SD and 1 (25.0%) had PD. Median period of monotherapy treatment was 133 and 683 days in TC and IT patients, respectively. No severe adverse events occurred during the 3-month-protocol treatment. As adverse events in long responders, thymoma-related autoimmune complications, pure red cell aplasia and myasthenia gravis occurred in two IT patients. Cerebellar hemorrhage developed in a TC patient complicated with Von Willebrand disease. Induction of WT1-specific immune responses was observed in the majority of the patients. WT1 peptide vaccine immunotherapy may have antitumor potential against thymic malignancies.

Response to estrus induction with abortion treatment in microminipigs on different days after insemination.

In microminipigs, estrus induction with abortion treatment, which is typically performed between 25 and 40 days after mating, is not always successful. Thus, the authors hypothesized that it may be more difficult to induce estrus by treating microminipigs approximately 40 days after mating. Accordingly, in this study, estrus induction was performed with abortion treatment in four microminipigs as follows: 0.3 mg of cloprostenol, a prostaglandin F2-alpha analog, was administered (day 0); after 24 h, 0.15 mg of cloprostenol and 250 IU of equine chorionic gonadotrophin were administered intramuscularly and simultaneously (day 1); after 96 h, 120 IU of human chorionic gonadotropin was injected intramuscularly (day 4). These treatments were compared at two different stages of pregnancy: early treatment (26.5 ± 0.7 days) and late treatment (38.3 ± 0.8 days). In the early treatment, all four microminipigs exhibited estrus on day 5, whereas in the late treatment, estrus was observed clearly in only two pigs on day 6 and slightly in 1 pig on day 10, whereas it was unclear in 1 pig. These results suggest that it is difficult to induce estrus with abortion treatment in microminipigs at approximately 40 days after mating.

Genetic association of swine leukocyte antigen class II haplotypes and body weight in Microminipigs.

OBJECTIVE: Microminipigs are a novel animal model with extensive applications in laboratory studies owing, in part, to their extremely small body sizes. In this study, the relationship between swine leukocyte antigen (SLA) class II haplotype and body weight was evaluated in the Microminipig population. METHODS: A total of 1,900 haplotypes, covering SLA class II haplotypes Lr-0.7, Lr-0.23, Lr-0.17, Lr-0.37, Lr-0.16, Lr-0.11, Lr-0.13, and Lr-0.18, were analyzed in 950 piglets. Birth weights and weights on postnatal day 50 were examined in piglets with eight different SLA class II haplotypes. RESULTS: The mean birth weight of piglets with the Lr-0.23 haplotype (0.415 kg, n = 702) was significantly lower than that of piglets with Lr-0.17 (0.445 kg, n = 328) and Lr-0.37 (0.438 kg, n = 383) haplotypes. At postnatal day 50, the mean body weight of piglets with the Lr-0.23 haplotype (3.14 kg) was significantly lower than that of piglets with the Lr-0.13 haplotype (3.46 kg, p<0.01). There were no significant differences in daily gains (DGs) among the eight haplotypes. However, piglets with the Lr-0.11 and -0.18 haplotype combination or any heterozygous haplotype combinations containing Lr-0.23 had significantly lower DGs than those of piglets with the Lr-0.18, 0.37 haplotype combination. CONCLUSION: Piglets with the Lr-0.23 haplotype had relatively low body weights at birth and on postnatal day 50 and slightly lower DGs than those of piglets with other haplotypes. Therefore, the Lr-0.23 SLA class II haplotype may be a suitable marker for the selective breeding of Microminipigs with small body sizes.

Association of WT1 IgG antibody against WT1 peptide with prolonged survival in glioblastoma multiforme patients vaccinated with WT1 peptide.

We previously evaluated Wilms' tumor gene 1 (WT1) peptide vaccination in a large number of patients with leukemia or solid tumors and have reported that HLA-A*24:02 restricted, 9-mer WT1-235 peptide (CYTWNQMNL) vaccine induces cellular immune responses and elicits WT1-235-specific cytotoxic T lymphocytes (CTLs). However, whether this vaccine induces humoral immune responses to produce WT1 antibody remains unknown. Thus, we measured IgG antibody levels against the WT1-235 peptide (WT1-235 IgG antibody) in patients with glioblastoma multiforme (GBM) receiving the WT1 peptide vaccine. The WT1-235 IgG antibody, which was undetectable before vaccination, became detectable in 30 (50.8%) of a total of 59 patients during 3 months of WT1 peptide vaccination. The dominant WT1-235 IgG antibody subclass was Th1-type, IgG1 and IgG3 . WT1-235 IgG antibody production was significantly and positively correlated with both progression-free survival (PFS) and overall survival (OS). Importantly, the combination of WT1-235 IgG antibody production and positive delayed type-hypersensitivity (DTH) to the WT1-235 peptide was a better prognostic marker for long-term OS than either parameter alone. These results suggested that WT1-235 peptide vaccination induces not only WT1-235-specific CTLs as previously described but also WT1-235-specific humoral immune responses associated with antitumor cellular immune response. Our results indicate that the WT1 IgG antibody against the WT1 peptide may be a useful predictive marker, with better predictive performance in combination with DTH to WT1 peptide, and provide a new insight into the antitumor immune response induction in WT1 peptide vaccine-treated patients.

Identification and characterization of two CD4 alleles in Microminipigs.

BACKGROUND: We previously identified two phenotypes of CD4+ cells with and without reactions to anti-pig CD4 monoclonal antibodies by flow cytometry in a herd of Microminipigs. In this study, we analyzed the coding sequences of CD4 and certified the expression of CD4 molecules in order to identify the genetic sequence variants responsible for the positive and negative PBMCs reactivity to anti-pig CD4 monoclonal antibodies. RESULTS: We identified two CD4 alleles, CD4.A and CD4.B, corresponding to antibody positive and negative, respectively, by nucleotide sequencing of PCR products using CD4 specific primer pairs. In comparison with the swine CD4 amino-acid sequence [GenBank: NP_001001908], CD4.A had seven amino-acid substitutions and CD4.B had 15 amino-acid substitutions. The amino-acid sequences within domain 1 of CD4.B were identical to the swine CD4.2 [GenBank: CAA46584] sequence that had been reported previously to be a modified CD4 molecule that had lost reactivity with an anti-pig CD4 antibody in NIH miniature pigs. Homozygous and heterozygous CD4.A and CD4.B alleles in the Microminipigs herd were characterised by using the RFLP technique with the restriction endonuclease, BseRI. The anti-pig CD4 antibody recognized pig PBMCs with CD4.AA and CD4.AB, but did not recognized those with CD4.BB. We transfected HeLa cells with the FLAG-tagged CD4.A or CD4.B vectors, and certified that transfected HeLa cells expressed FLAG in both vectors. The failure of cells to react with anti-CD4 antibodies in CD4.B pigs was associated to ten amino-acid substitutions in domain 1 and/or one amino-acid substitution in joining region 3 of CD4.B. We also found exon 8 was defective in some CD4.A and CD4.B resulting in the loss of the transmembrane domain, which implies that these CD4 proteins are secreted from helper T cells into the circulation. CONCLUSIONS: We identified that amino-acids substitutions of domain 1 in CD4.B gave rise to the failure of some CD4 expressing cells to react with particular anti-pig CD4 monoclonal antibodies. In addition, we developed a PCR-RFLP method that enabled us to simply identify the CD4 sequence variant and the positive and negative PBMCs reactivity to our anti-pig CD4 monoclonal antibodies without the need to use flow cytometric analysis.

Intravenous infusion of amino acids in dogs attenuates hypothermia during anaesthesia and stimulates insulin secretion.

OBJECTIVE: To evaluate the effect of intravenous infusion of amino acids on the prevention of hypothermia during anaesthesia in dogs. STUDY DESIGN: Randomized experimental trial. ANIMALS: Seven healthy Beagle dogs. METHODS: Four concentrations of amino acids were prepared with a 10% amino acid solution and an acetated Ringer's solution, and dogs were infused with each of the solutions at 1 week intervals. Dogs were infused with amino acid solution at 12 mL kg(-1)  hour(-1) for 60 minutes before and for 60 minutes after induction of anaesthesia. Acetated Ringer's solution was infused at the same rate for the remaining 60 minutes of anaesthesia. The infusion treatments were: 1) A0, nutrient-free acetated Ringer's solution; 2) A6, 0.6 g kg(-1)  hour(-1) ; 3) A9, 0.9 g kg(-1)  hour(-1) ; and 4) A12, 1.2 g kg(-1) hour(-1) . Rectal temperature (RT), heart rate (HR), mean arterial pressure (MAP), blood insulin, glucose, urea nitrogen (BUN) and creatinine concentrations, and time to extubation were measured. RESULTS: Before anaesthesia, RT was not affected by amino acid infusion. RT decreased progressively during anaesthesia and the absolute values of RT from 30 to 120 minutes were significantly higher in A12 than in A0 (p < 0.05). Reductions in HR and MAP during anaesthesia were attenuated by amino acid infusion in a dose-dependent manner. Plasma insulin concentration was significantly higher in A12 than in A0 during amino acid infusion and the increase in insulin concentration was greater during than before anaesthesia. BUN increased during amino acid infusion in a dose- and time-dependent fashion. Time until extubation was shorter in A12 than in A0. CONCLUSIONS AND CLINICAL RELEVANCE: Amino acids infused at 1.2 g kg(-1)  hour(-1) in dogs attenuated the decrease in RT, HR, and MAP during anaesthesia, and induced a significant increase in plasma insulin concentration.

Two distinct effector memory cell populations of WT1 (Wilms' tumor gene 1)-specific cytotoxic T lymphocytes in acute myeloid leukemia patients.

Wilms' tumor gene 1 (WT1) protein is a promising tumor-associated antigen for cancer immunotherapy. We have been performing WT1 peptide vaccination with good clinical responses in over 750 patients with leukemia or solid cancers. In this study, we generated single-cell gene-expression profiles of the effector memory (EM) subset of WT1-specific cytotoxic T lymphocytes (CTLs) in peripheral blood of nine acute myeloid leukemia patients treated with WT1 peptide vaccine, in order to discriminate responders (WT1 mRNA levels in peripheral blood decreased to undetectable levels, decreased but stayed at abnormal levels, were stable at undetectable levels, or remained unchanged from the initial abnormal levels more than 6 months after WT1 vaccination) from non-responders (leukemic blast cells and/or WT1 mRNA levels increased relative to the initial state within 6 months of WT1 vaccination) prior to WT1 vaccination. Cluster and principal component analyses performed using 83 genes did not discriminate between responders and non-responders prior to WT1 vaccination. However, these analyses revealed that EM subset of WT1-specific CTLs could be divided into two groups: the "activated" and "quiescent" states; in responders, EM subset of the CTLs shifted to the "quiescent" state, whereas in non-responders, those shifted to the "activated" state following WT1 vaccination. These results demonstrate for the first time the existence of two distinct EM states, each of which was characteristic of responders or non-responders, of WT1-specific CTLs in AML patients, and raises the possibility of using advanced gene-expression profile analysis to clearly discriminate between responders and non-responders prior to WT1 vaccination.

Evaluation of muscle mass and intramuscular fatty infiltration in dogs with hypercortisolism and their association with prognosis.

BACKGROUND: Muscle atrophy and intramuscular fatty infiltration, as well as their association with prognosis, have not been quantified in dogs with spontaneous hypercortisolism (HC). OBJECTIVE: To quantitatively evaluate muscle atrophy and IM fatty infiltration in dogs with HC and determine their prognostic impact. ANIMALS: Fifty-three dogs with HC and 66 control dogs without HC. METHODS: Retrospective cohort study. Medical records and computed tomography images obtained between 2014 and 2021 were evaluated. Kaplan-Meier curves and log-rank tests were used to analyze the effect of muscle atrophy and IM fatty infiltration on the prognosis of dogs with HC. RESULTS: Dogs with HC showed lower visually measured cross-sectional area (VCSA) and cross-sectional area based on attenuation (HCSA) than control dogs (median [interquartile range {IQR}]: 50.3 mm2/mm [36.2-67.8] vs 66.7 mm2/mm [48.0-85.9]; P < .001; 30.4 mm2/mm [13.7-57.2] vs 54.8 mm2/mm [39.7-71.5]; P < .001, respectively). Dogs with HC had lower epaxial muscle attenuation (L3HU) than control dogs (median [IQR]: 21.2 Hounsfield [HU] [12.4-28.2] vs 33.2 HU [22.6-43.6]; P < .001). Dogs with HC with lower HCSA or L3HU had shorter survival (median [IQR]: 670 days [222-673] vs 949 days [788-1074], P < .01; 523 days [132-670] vs 949 days [756-1074], P < .01, respectively) but not lower VCSA (median [IQR]: 673 days [132-788] vs 949 days [523 to not applicable]; P = .30). CONCLUSION AND CLINICAL IMPORTANCE: Hypercortisolism in dogs causes muscle atrophy and IM fatty infiltration and is associated with poor prognosis.

Analyzing lumbar vertebral shape and alignment in female patients with degenerative spondylolisthesis: Comparisons with spinal stenosis and risk factor exploration.

PURPOSE: This study aimed to examine the vertebral body shape characteristics and spondylopelvic alignment in L4 degenerative spondylolisthesis (DS) as well as the risk factors for the development of DS. METHODS: This cross-sectional study compared vertebral morphology and sagittal spinopelvic alignment in female patients with lumbar DS and lumbar spinal stenosis (LSS). The degree of lumbar lordosis (LL), pelvic incidence (PI), cross-sectional area (CSA), and vertebral body height ratio (ha/hp) of the lumbar spine were compared using full-length spine radiographs and computed tomography in 60 females with DS and in 60 women with LSS. RESULTS: No significant differences in age or body mass index were observed between the two groups; however, the DS and LSS groups significantly differed in PI (mean, 58.9±10.8 vs. 47.2±11.6, P < 0.001), L4 CSA (mean, 1,166.2 m2 vs. 1,242.0 m2, P = 0.002) and ha/hp (mean, 1.134 vs. 1.007, P < 0.001). The L4 ha/hp was significantly higher in the DS group than in the LSS group. Additionally, LL values were negatively correlated with vertebral L5 CSA in the DS group (r = -0.28, P < 0.05). The LSS and DS groups demonstrated positive correlations between LL and L2, L3, and L4 ha/hp (r = 0.331, 0.267, and 0.317; P < 0.01, < 0.05, and < 0.05, respectively) and between LL and L4 and L5 ha/hp (r = 0.333, 0.331; P < 0.01, respectively). Multivariate regression analyses revealed that PI and ha/hp ratio may be independent predictors of DS development. CONCLUSION: The DS group had significantly larger LL, PI, and L4 ha/hp and smaller L4 CSA than the LSS group. The lumbar vertebral body shape and sagittal spinopelvic alignment in females might be independent predictors of DS development.

Ovarian dynamics in progesterone tablet-induced superovulation in goats assessed by magnetic resonance imaging.

Controlled internal drug-releasing (CIDR) devices are commonly used for superovulation in goats. However, such devices are unavailable in some countries, including Japan. In this technical note, we aimed to explore the efficacy of an alternative superovulation protocol using progesterone tablets in goats. We employed intravaginal progesterone tablets (LUTINAS® Vaginal Tablet 100 mg) following a standard superovulation protocol. Additionally, we assessed the ovarian dynamics using 3T-magnetic resonance imaging (MRI) 1 day preceding the progesterone treatment (Day "-1") and 3 days before the end of treatment (Days 11-13). The ovarian monitoring was successfully performed in the short tau inversion recovery T2-weighted images of MRI, and ovulation was confirmed by the disappearance of follicles on Day 13 post-administration of the tablets. Immediately after ovulation, oviduct flushing yielded a substantial number of oocytes (13.5 ± 1.8 oocytes per animal). These findings provide evidence that the administration of progesterone tablets can serve as a viable alternative for inducing. Additionally, our findings suggest that 3T-MRI is a promising alternative to conventional ultrasonography for monitoring ovarian dynamics following superovulation in experimental goats.

Trismus due to myotonia associated with hyperadrenocorticism in a dog.

We present the report of trismus due to hyperadrenocorticism-associated myotonia diagnosed by electromyography in a dog. An intact female Miniature Dachshund, 13 years and 9 months old, presented with stiff gait and trismus as well as polyuria and polydipsia. Abdominal ultrasonography showed enlarged adrenal glands. An adrenocorticotropic hormone stimulation test revealed an exaggerated response. Based on these findings, this case was diagnosed with hyperadrenocorticism. Electromyography revealed myotonic discharge in the temporalis muscle and limbs. Therefore, trismus was considered to be caused by hyperadrenocorticism-associated myotonia, and the case was treated with oral trilostane (1.3 mg/kg, once daily). During the 4-month follow-up period, despite the partial improvement in stiff gait, trismus did not recover. Long-term data on more cases are warranted to assess the prognosis and clinical characteristics of trismus due to hyperadrenocorticism-associated myotonia.

Prognostic value of serum cystatin C concentration in dogs with myxomatous mitral valve disease.

BACKGROUND: Impaired renal function is 1 of the poor prognostic factors in dogs with myxomatous mitral valve disease (MMVD). However, the value of cystatin C (Cys-C), a marker of renal function, as a prognostic marker for MMVD in dogs has not yet been explored. OBJECTIVE: This study aims to investigate the prognostic value of Cys-C in dogs with MMVD. ANIMALS: Fifty client-owned small-breed dogs with MMVD were included in this study. METHODS: This is a retrospective, cross-sectional study. The prognostic value of serum Cys-C concentration was assessed using univariable and multivariable Cox hazard regression analyses. Kaplan-Meier survival curves for MMVD-specific survival in dogs stratified into high and low Cys-C groups were generated and analyzed using the log-rank test. RESULTS: Serum Cys-C concentrations were significantly associated with MMVD-related death (P < .01) in both univariable (hazard ratio [HR], 5.086; 95% confidence interval [CI], 1.950-13.270) and multivariable Cox hazard regression analysis (HR, 4.657; 95% CI, 1.767-12.270). The high Cys-C group (n = 14) had a significantly shorter MMVD-specific survival time than the low Cys-C group (n = 36; P < .01). In dogs with normal blood creatinine concentrations, the high Cys-C group (n = 10) had a significantly shorter MMVD-specific survival time than the low Cys-C group (n = 36; P < .01). CONCLUSIONS AND CLINICAL IMPORTANCE: High serum Cys-C concentrations were associated with a worse prognosis of MMVD. Furthermore, serum Cys-C could be a predictor of MMVD prognosis even in dogs with normal blood creatinine concentration.

Quantitative assessment of muscle mass and gene expression analysis in dogs with glucocorticoid-induced muscle atrophy.

The present study aimed to quantitatively evaluate muscle mass and gene expression in dogs with glucocorticoid-induced muscle atrophy. Five healthy beagles received oral prednisolone for 4 weeks (1 mg/kg/day), and muscle mass was then evaluated via computed tomography. Histological and gene expression analyses were performed using biopsy samples from the biceps femoris before and after prednisolone administration. The cross-sectional area of the third lumbar paraspinal and mid-femoral muscles significantly decreased after glucocorticoid administration (from 27.5 ± 1.9 to 22.6 ± 2.0 cm2 and from 55.1 ± 4.7 to 50.7 ± 4.1 cm2, respectively; P<0.01). The fast- and slow-twitch muscle fibers were both atrophied (from 2,779 ± 369 to 1,581 ± 207 µm2 and from 2,871 ± 211 to 1,971 ± 169 µm2, respectively; P<0.05). The expression of the growth factor receptor-bound protein 10 (GRB10) significantly increased after prednisolone administration (P<0.05). Because GRB10 suppresses insulin signaling and the subsequent mammalian target of rapamycin complex 1 activity, increased expression of GRB10 may have resulted in a decrease in protein anabolism. Taken together, 1 mg/kg/day oral prednisolone for 4 weeks induced significant muscle atrophy in dogs, and GRB10 might participate in the pathology of glucocorticoid-induced muscle atrophy in canines.

Urinary liver-type fatty acid-binding protein in two dogs with acquired Fanconi syndrome: A case report.

Background: Fanconi syndrome (FS) is defined as multiple defects of the proximal tubules and is diagnosed by clinical symptoms. However, in dogs with FS, the damage in the proximal tubules that is responsible for the clinical symptoms has not been evaluated. Among FS cases, tubular damage in acquired FS is reversible following the elimination of a causative factor. Liver-type fatty acid-binding protein (L-FABP) is a biomarker of tubular damage in various animals including dogs. Urinary L-FABP measurement may be useful for the diagnosis and follow-up evaluation in canine FS. Case Description: At the first visit, two Toy Poodles that had no remarkable findings on physical examination presented with glycosuria without hyperglycemia, hypokalemia, hyperchloremia, increased levels of plasma alkaline phosphatase, and metabolic acidosis. Considering all the factors involved, the dogs were clinically diagnosed with acquired FS. The owner reported that they routinely fed the dog with chicken jerky, a recently considered cause of acquired FS. Following the withdrawal of the jerky, abnormalities including glycosuria improved in both dogs. Moreover, urinary L-FABP levels, which were high at diagnosis, presented a decreasing trend during the follow-up. However, in one dog, the elevated urinary L-FABP level did not return to normal. Conclusion: Although the clinical symptoms of acquired FS in dogs could be improved by the elimination of a causative factor, the severity of tubular damage described by urinary L-FABP may not be necessarily linked to the degree of functional deterioration. Therefore, the evaluation of proximal tubular damage by L-FABP may be of clinical value during the follow-up of acquired FS in canines.

The inhibitory effects of MIF on accumulation of canine degenerative myelopathy-associated mutant SOD1 aggregation.

Canine degenerative myelopathy (DM) is a progressive neurodegenerative disorder, which is commonly associated with c.118G > A (p. E40K) missense mutation in the superoxide dismutase 1 (SOD1) gene. Mutant SOD1 protein (SOD1E40K) is likely to be misfolded, acquire insolubility, aggregate in the cytoplasm of neural cells, and lead to degeneration of the nervous tissues. Along with a chaperone activity, macrophage migration inhibitory factor (MIF) is a multifunctional protein that has been shown to directly inhibit human mutant SOD1 misfolding and enhance survival of mutant SOD1-expressing motor neurons. The purpose of this study was to determine whether MIF also inhibits DM-related SOD1E40K misfolding and accumulation of SOD1 aggregates. Human embryonic kidney 293A cells were transfected SOD1cWT or SOD1E40K with or without MIF. The percentages of cells containing transfected SOD1 aggregates were measured by immunocytochemistry, and the amount of SOD1E40K in the insoluble fraction was evaluated by immunoblotting. The percentage of cells with SOD1E40K aggregates and the amount of insoluble SOD1E40K protein decreased in the presence of MIF. Because the chaperone activity of MIF assists in SOD1E40K folding and enhances the refolding and degradation of misfolded SOD1E40K, the results of this study suggests that MIF regulates the accumulation of SOD1 aggregates by its chaperone activity. We propose that enhancing intracellular MIF chaperone activity could be an effective therapeutic strategy for DM.

Effect of age, sex, and breed on serum cystatin C and creatinine concentrations in dogs.

This study investigated the effects of age, sex and breed on serum cystatin C (Cys-C) and creatinine in small breed dogs. This retrospective study included 250 dogs weighing less than 15 kg without azotemia. Serum Cys-C and creatinine concentrations were analyzed, along with their correlation with age, and the difference between sexes or dog breeds. Serum Cys-C concentration correlated with age (P < 0.001), and did not differ between sexes or dog breeds. By contrast, serum creatinine concentration did not correlate with age. Serum creatinine concentration was higher in males than females (P < 0.05), and was lower in Miniature Dachshunds and Chihuahuas, and was higher in Shiba Inus compared to the general study population (P < 0.001). Serum Cys-C concentration correlates with age, and might be more sensitive to aging-associated subclinical renal dysfunction than serum creatinine concentration in dogs. Unlike serum creatinine concentration, serum Cys-C concentration is not affected by sex or dog breed.

Human Muse cells reduce myocardial infarct size and improve cardiac function without causing arrythmias in a swine model of acute myocardial infarction.

BACKGROUND: We recently reported that multilineage-differentiating stress enduring (Muse) cells intravenously administered after acute myocardial infarction (AMI), selectively engrafted to the infarct area, spontaneously differentiated into cardiomyocytes and vessels, reduced the infarct size, improved the left ventricular (LV) function and remodeling in rabbits. We aimed to clarify the efficiency of Muse cells in a larger animal AMI model of mini-pigs using a semi-clinical grade human Muse cell product. METHOD AND RESULT: Mini-pigs underwent 30 min of coronary artery occlusion followed by 2 weeks of reperfusion. Semi-clinical grade human Muse cell product (1x107, Muse group, n = 5) or saline (Vehicle group, n = 7) were intravenously administered at 24 h after reperfusion. The infarct size, LV function and remodeling were evaluated by echocardiography. Arrhythmias were evaluated by an implantable loop recorder. The infarct size was significantly smaller in the Muse group (10.5±3.3%) than in the Vehicle group (21.0±2.0%). Both the LV ejection fraction and fractional shortening were significantly greater in the Muse group than in the Vehicle group. The LV end-systolic and end-diastolic dimensions were significantly smaller in the Muse group than in the Vehicle group. Human Muse cells homed into the infarct border area and expressed cardiac troponin I and vascular endothelial CD31. No arrhythmias and no blood test abnormality were observed. CONCLUSION: Muse cell product might be promising for AMI therapy based on the efficiency and safety in a mini-pig AMI.