Mesenchymal Stem Cells and Extracellular Vesicles Derived from Canine Adipose Tissue Ameliorates Inflammation, Skin Barrier Function and Pruritus by Reducing JAK/STAT Signaling in Atopic Dermatitis.

Canine atopic dermatitis (AD) is a common chronic inflammatory skin disorder resulting from imbalance between T lymphocytes. Current canine AD treatments use immunomodulatory drugs, but some of the dogs have limitations that do not respond to standard treatment, or relapse after a period of time. Thus, the purpose of this study was to evaluate the immunomodulatory effect of mesenchymal stem cells derived from canine adipose tissue (cASCs) and cASCs-derived extracellular vesicles (cASC-EVs) on AD. First, we isolated and characterized cASCs and cASCs-EVs to use for the improvement of canine atopic dermatitis. Here, we investigated the effect of cASCs or cASC-EVs on DNCB-induced AD in mice, before using for canine AD. Interestingly, we found that cASCs and cASC-EVs improved AD-like dermatitis, and markedly decreased levels of serum IgE, (49.6%, p = 0.002 and 32.1%, p = 0.016 respectively) epidermal inflammatory cytokines and chemokines, such as IL-4 (32%, p = 0.197 and 44%, p = 0.094 respectively), IL-13 (47.4%, p = 0.163, and 50.0%, p = 0.039 respectively), IL-31 (64.3%, p = 0.030 and 76.2%, p = 0.016 respectively), RANTES (66.7%, p = 0.002 and 55.6%, p = 0.007) and TARC (64%, p = 0.016 and 86%, p = 0.010 respectively). In addition, cASCs or cASC-EVs promoted skin barrier repair by restoring transepidermal water loss, enhancing stratum corneum hydration and upregulating the expression levels of epidermal differentiation proteins. Moreover, cASCs or cASC-EVs reduced IL-31/TRPA1-mediated pruritus and activation of JAK/STAT signaling pathway. Taken together, these results suggest the potential of cASCs or cASC-EVs for the treatment of chronic inflammation and damaged skin barrier in AD or canine AD.

Correlation of Sagittal Imbalance and Recollapse after Percutaneous Vertebroplasty for Thoracolumbar Osteoporotic Vertebral Compression Fracture: A Multivariate Study of Risk Factors.

STUDY DESIGN: A retrospective case control study. PURPOSE: This study aimed to assess the clinical significance of sagittal balance for predicting and managing the recollapse of cemented vertebra following percutaneous vertebroplasty (PVP) in patients with thoracolumbar osteoporotic vertebral fracture (OVF). OVERVIEW OF LITERATURE: Recently, the recollapse of cemented vertebra following PVP for OVF has been reported. Although the risk factors for recollapse have been determined, the association between sagittal spinopelvic parameters and sagittal imbalance with recollapse has not been established. METHODS: Ambulatory patients who underwent single-level PVP for thoracolumbar OVF with a follow-up of at least 24 months were retrospectively reviewed. The patients were divided into two groups depending on the presence of symptomatic recollapse at the cemented vertebra: (1) recollapsed (RC) group and (2) noncollapsed (NC) group. The patient characteristics and radiographic measurements associated with sagittal imbalance were analyzed at each follow-up visit. RESULTS: Overall, 134 patients (RC group, n=28; NC group, n=106) were enrolled. The mean fracture-free interval was 3.2 months (range, 1.2-25.1 months). The multivariate binary logistic regression analysis identified low bone mineral density (p =0.047), degree of dynamic mobility within the vertebra (p =0.025), and sagittal imbalance as significant risk factors for recollapse (p =0.013; odds ratio, 5.405). The progression of sagittal imbalance and thoracolumbar kyphosis (T10-L2) was more significant in the RC and sagittal imbalance groups than in the NC group (both p =0.000). CONCLUSIONS: Sagittal imbalance, lower bone mineral density, and dynamic mobility within the vertebra are associated with the recollapse of cemented vertebrae following PVP. Sagittal imbalance, rather than local kyphosis or thoracolumbar kyphosis, is particularly significant in that it results in more progressive collapse and sagittal deformity and is accompanied by substantial back pain and neurological deficits. Therefore, a stricter and more active management, including anti-osteoporosis medication, is required for the treatment of OVF with sagittal imbalance of the spine.

Anti-Photoaging Effects of Low Molecular-Weight Fucoidan on Ultraviolet B-Irradiated Mice.

Ultraviolet (UV) B exposure induces DNA damage and production of reactive oxygen species (ROS), which causes skin photoaging through signaling pathways of inflammation and modulation of extracellular matrix remodeling proteins, collagens, and matrix metalloproteinase (MMP). As low molecular-weight fucoidan (LMF) has potential antioxidant and anti-inflammatory properties, we examined the protective effects of LMF against UVB-induced photoaging. A UVB-irradiated mouse model was topically treated with myricetin or LMF at 2.0, 1.0 and 0.2 mg/cm² (LMF2.0, LMF1.0 and LMF0.2, respectively) once a day for 15 weeks. Wrinkle formation, inflammation, oxidative stress, MMP expression, and apoptosis in the treated regions were compared with those in a distilled water-treated photoaging model (UVB control). LMF treatments, particularly LMF2.0 and LMF1.0, significantly inhibited the wrinkle formation, skin edema, and neutrophil recruitment into the photo-damaged lesions, compared with those in the UVB control. While LMF decreased interleukin (IL)-1ß release, it increased IL-10. The LMF treatment inhibited the oxidative stresses (malondialdehyde and superoxide anion) and enhanced endogenous antioxidants (glutathione). Additionally, LMF reduced the mRNA expression of MMP-1, 9, and 13. The histopathological analyses revealed the anti-photoaging effects of LMF exerted via its antioxidant, anti-apoptotic, and MMP-9-inhibiting effects. These suggest that LMF can be used as a skin-protective remedy for photoaging.

Antioxidant and hepatoprotective effects of fermented red ginseng against high fat diet-induced hyperlipidemia in rats.

This study was performed to investigate the antioxidant and hepatoprotective effects of fermented red ginseng (Panax ginseng C.A. Meyer; FRG) on high-fat diet-induced hyperlipidemia in rats. Sprague-Dawley rats were divided into four groups of seven: normal control, NC; high-fat diet control, HFC; high-fat diet-0.5% FRG, HF-FRGL; and high-fat diet-1% FRG, HF-FRGH. All rats were fed a high-fat diet for eight weeks, except those in the NC group, while rats in the FRG treatment groups received drinking water containing 0.5% or 1% FRG. After eight weeks of treatment, levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), total cholesterol (TC), triglycerides (TG), low-density lipoprotein-cholesterol (LDL-C), and high-density lipoprotein-cholesterol (HDL-C) in the serum were measured. The concentration of the oxidative stress marker malondialdehyde (MDA), and activity of antioxidant enzymes including superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GSH-Px) in rat liver were evaluated. Histological analysis of the liver was performed using hematoxylin and eosin. The high-fat diet markedly increased serum levels of ALT, AST, TC, TG, and LDL-C and hepatic MDA levels, while administration of FRG to the hyperlipidemic rats resulted in a significant decline in the levels of these parameters. Furthermore, the decline in the levels of serum HDL-C and hepatic SOD, CAT, and GSH-Px induced by the high-fat diet was attenuated by FRG treatment. In addition, histopathological analysis of liver sections suggested that FRG treatment also provided protection against liver damage. These results suggested that FRG improved lipid profiles, inhibited lipid peroxidation, and played a protective role against liver injury in hyperlipidemic rats.

Simultaneous determination of zolazepam and tiletamine in dog plasma by liquid chromatography coupled to a tandem mass spectrometry.

A mixture of tiletamine, a dissociative anesthetic, and zolazepam, a minor tranquilizer, has been widely used as an anesthetic or an immobilizing agent in a variety of animal species. However, interestingly, their pharmacokinetic behaviors have been published only in polar bears and pigs. In this study, we introduce a sensitive liquid chromatography/tandem mass spectrometry (LC/MS/MS) method for determining the two drugs in dog plasma. After simple protein precipitation with acetonitrile including midazolam (internal standard), the analytes were chromatographed on a reversed-phase column with a mobile phase of 10 m m ammonium acetate aqueous solution and acetonitrile (1:4, v/v). The accuracy and precision of the assay were in accordance with FDA regulations for the validation of bioanalytical methods. This method was used to measure the concentrations of zolazepam and tiletamine in plasma after a single intramuscular 10 mg dose of each in beagle dogs.

Mapping of the dog skin based on biophysical measurements.

Trans epidermal water loss (TEWL), skin hydration status and pH were determined in 14 skin regions of five healthy male Beagle dogs (2-4 years) both before and after anaesthesia. Trans epidermal water loss was highest for the footpad and head and lowest for the inguinal region. Skin hydration status was higher in the ear but did not vary significantly in other regions. Skin pH was usually alkaline with the highest values on the lower back and tail. Following anaesthesia, TEWL and skin hydration were significantly lower on the head, upper back and footpad, and upper back and elbow respectively, while skin pH was unaffected by this procedure. While measurement of pH would seem to be valid anywhere on the body in anaesthetized dogs, regional factors should be considered when interpreting TEWL and skin hydration values and when treating regional skin diseases in veterinary practice.

Circadian variations of serum thyroxine, free thyroxine and 3,5,3'triiodothyronine concentrations in healthy dogs.

This study was to determine the daily fluctuation of serum thyroxine (tT4), free thyroxine (fT4), 3,5,3'-triiodothyronine (T3) concentrations in healthy dogs. Thyroid function of these dogs was evaluated on the basis of results of TSH response test. Samples for the measurement of serum tT4, fT4, and T3 concentrations were obtained at 3- hour intervals from 8 : 00 to 20 : 00. Serum tT4, fT4, and T3 concentrations were measured by the enzyme chemiluminescent immunoassay (ECLIA). Mean T3 concentrations had no significant differences according to the sample collection time during the day. Mean tT4 and fT4 concentrations at 11 : 00 were 3.28 +/- 0.86 microg/dl and 1.30 +/- 0.37 ng/dl, respectively and mean tT4 and fT(4) at 14:00 were 3.54 +/- 1.15 microg/dl and 1.35 +/- 0.12 ng/dl, respectively. These concentrations were significantly high compared with tT4 and fT4 concentrations at 8:00, which were 1.75 +/- 0.75 microg/dl and 0.97 +/- 0.25 ng/dl, respectively (p < 0.05). According to the sample collection time, mean tT4 and fT4 concentrations changed with similar fluctuation during the day. Based on these results, it was considered that measurement of serum tT4 and fT4 concentrations from 11 : 00 to 14 : 00 might more easily diagnose the canine hypothyroidism in practice.