Mhan-Pyo Yang

Trans -10, cis -12-conjugated linoleic acid modulates NF-κB activation and TNF-α production in porcine peripheral blood mononuclear cells via a PPARγ-dependent pathway

The activation of PPARγ by ligands, including conjugated linoleic acid (CLA) isomers, plays an important role in the immune response. Among CLA isomers, trans-10, cis-12 (t10c12)-CLA is known to participate in the modulation of pro-inflammatory cytokine secretion. The aim of the present study was to assess the effect of t10c12-CLA on PPARγ activation, NF-κB activation and TNF-α expression in lipopolysaccharide (LPS)-naive and LPS-stimulated porcine peripheral blood mononuclear cells (PBMC). In addition, the effect of PPARγ inhibition on NF-κB activation and TNF-α expression in porcine PBMC was examined. t10c12-CLA was found to increase TNF-α expression and NF-κB activity in LPS-naive porcine PBMC. In contrast, t10c12-CLA decreased TNF-α expression and NF-κB activity in LPS-stimulated porcine PBMC. t10c12-CLA up-regulated PPARγ activity and mRNA expression in both LPS-naive and LPS-stimulated porcine PBMC. GW9662, a PPARγ antagonist, completely negated the modulating effects of t10c12-CLA on TNF-α expression and NF-κB activity in both LPS-naive and LPS-stimulated porcine PBMC. These results suggest that t10c12-CLA can modulate TNF-α production and NF-κB activation by a PPARγ-dependent pathway in porcine PBMC.

Ethanol Extract of Magnolia officinalis Prevents Lipopolysaccharide-Induced Memory Deficiency via Its Antineuroinflammatory and Antiamyloidogenic Effects

Magnolia bark contains several compounds such as magnolol, honokiol, 4‐O‐methylhonokiol, obovatol, and other neolignan compounds. These compounds have been reported to have various beneficial effects in various diseases. There is sufficient possibility that ethanol extract of Magnolia officinalis is more effective in amyloidogenesis via synergism of these ingredients. Neuroinflammation has been known to play a critical role in the pathogenesis of Alzheimers disease (AD). We investigated whether the ethanol extract of M. officinalis (10 mg/ kg in 0.05% ethanol) prevents memory dysfunction and amyloidogenesis in AD mouse model by intraperitoneal lipopolysaccharide (LPS, 250 µg/ kg/day for seven times) injection. We found that ethanol extract of M. officinalis prevented LPS‐induced memory deficiency as well as inhibited the LPS‐induced elevation of inflammatory proteins, such as inducible nitric oxide synthase and cyclooxygenase 2, and activation of astrocytes and microglia. In particular, administration of M. officinalis ethanol extract inhibited LPS‐induced amyloidogenesis, which resulted in the inhibition of amyloid precursor protein, beta‐site amyloid‐precursor‐protein‐cleaving enzyme 1 and C99. Thus, this study shows that ethanol extract of M. officinalis prevents LPS‐induced memory impairment as well as amyloidogenesis via inhibition of neuroinflammation and suggests that ethanol extract of M. officinalis might be a useful intervention for neuroinflammation‐associated diseases such as AD. Copyright

Trans-10, cis-12-conjugated linoleic acid attenuates tumor necrosis factor-α production by lipopolysaccharide-stimulated porcine peripheral blood mononuclear cells through induction of interleukin-10

Conjugated linoleic acid (CLA) can stimulate or inhibit immune cell function, and among CLA isomers, trans-10, cis-12 (t10c12)-CLA was shown to participate in the modulation of pro- or anti-inflammatory cytokine secretion. The objective of this study was to examine the effect of t10c12-CLA on tumor necrosis factor (TNF)-α production by lipopolysaccharide (LPS)-stimulated porcine peripheral blood mononuclear cells (PBMCs). In addition, we determined whether these effects were associated with the induction of interleukin (IL)-10. Treatment of LPS-unstimulated porcine PBMCs with t10c12-CLA increased both TNF-α expression and IL-10 production. However, treatment of LPS-stimulated porcine PBMCs with t10c12-CLA suppressed TNF-α production and increased the levels of IL-10. Furthermore, treatment of LPS-stimulated porcine PBMCs with IL-10 suppressed the production of TNF-α. The effects of t10c12-CLA on TNF-α expression by both LPS-naïve and LPS-stimulated PBMCs were inhibited by IL-10 treatment. The suppressive effects of t10c12-CLA on TNF-α production by LPS-stimulated porcine PBMCs were inhibited by an anti-IL-10 polyclonal antibody. These findings suggest that t10c12-CLA has an immunostimulatory effect on porcine PBMCs mediated via the up-regulation of TNF-α production, and an anti-inflammatory effect in LPS-stimulated PBMCs mediated via the down-regulation of TNF-α production, and that both is likely to be associated with the induction of IL-10.

Serum adipokine concentrations in dogs with naturally occurring pituitary-dependent hyperadrenocorticism.

Background An excess of intra‐abdominal fat is observed frequently in dogs with hyperadrenocorticism (HAC). Adipokine dysregulation is a possible cause of complications related to visceral obesity, but little information is available on adipokine in dogs with naturally occurring HAC. Objectives To examine the differences in the circulating adipokines concentrations in overweight dogs with and without pituitary‐dependent HAC (PDH). Animals Thirty healthy dogs and 15 client‐owned dogs with PDH. Methods Case–controlled observational study, which enrolled 15 overweight dogs diagnosed with PDH and 30 otherwise healthy dogs of similar body condition score. Nine of 15 dogs with PDH were treated with low‐dose trilostane twice daily and reassessed after treatment. Results The serum leptin (P < .0001) and insulin (P < .0001) concentrations were significantly higher in the PDH group (leptin, 22.8 ± 8.8 [mean ± SD]; insulin, 9.1 ± 6.1) than the healthy group (leptin, 4.9 ± 3.7; insulin, 1.9 ± 0.9). However, there were no significant differences in the adiponectin, resistin, tumor necrosis factor (TNF)‐α, interleukin (IL)‐1β, IL‐6, IL‐10, and IL‐18 levels between the 2 groups. In the PDH group, the serum cortisol concentrations had a linear association with the leptin concentrations, and there were significant decreases in the leptin (P = .0039) and insulin (P = .0039) levels after trilostane treatment. However, the leptin and insulin levels remained higher after trilostane treatment than in healthy control dogs with similar body condition score. Conclusions and Clinical Importance Hypercortisolemia in dogs with PDH might upregulate the circulating leptin levels. However, a large population‐based study will be necessary to determine whether the upregulation of leptin is involved directly with the complications caused by HAC.

Efficacy of Low- and High-Dose Trilostane Treatment in Dogs (< 5 kg) with Pituitary-Dependent Hyperadrenocorticism

BACKGROUND Trilostane is commonly used to treat pituitary-dependent hyperadrenocorticism (PDH) in dogs. There are differing opinions regarding the dose and frequency of trilostane administration in dogs with PDH. OBJECTIVES To compare the efficacy of 2 trilostane protocols in the treatment of dogs with PDH. ANIMALS Sixteen client-owned dogs with PDH and a body weight <5 kg. METHODS Prospective observational study. Group A (n=9; low-dose treatment group) received 0.78 ± 0.26 mg of trilostane/kg PO every 12 h and group B (n = 7; high-dose treatment group) 30 mg of trilostane/dog PO every 24 h. All of the dogs were reassessed at 2, 4, 8, 12, 16, and 24 weeks after the initiation of treatment. RESULTS An improvement in both ACTH-stimulated serum cortisol concentrations and clinical signs occurred more slowly in group A than in group B; however, after 20 weeks of treatment, 2/7 dog in group B had clinical signs and abnormal laboratory findings consistent with hypoadrenocorticism. At 24 weeks, an improvement in the clinical findings of all of the dogs in both groups was detected. CONCLUSIONS AND CLINICAL IMPORTANCE In dogs with PDH, twice-daily administration of low-dose trilostane is an effective approach to the management of PDH. In addition, our results suggest fewer potential adverse effects if trilostane is administered twice daily in the lower dose.

In vitro evaluation of the effect of trans-10, cis-12 conjugated linoleic acid on phagocytosis by canine peripheral blood polymorphonuclear neutrophilic leukocytes exposed to methylprednisolone sodium succinate

OBJECTIVE To examine whether in vitro treatment with trans-10, cis-12 conjugated linoleic acid (t10c12-CLA) restores the phagocytic capacity and oxidative burst activity (OBA) of canine polymorphonuclear neutrophilic leukocytes (PMNs) exposed to methylprednisolone sodium succinate (MPSS). SAMPLE POPULATION Peripheral blood PMNs obtained from 12 healthy Beagles. PROCEDURES The experimental design involved administration of a high dose of MPSS, which is the recommended protocol for dogs with acute spinal cord injury. To evaluate PMN function, blood samples were collected from dogs before IV injections of doses of MPSS or saline (0.9% NaCl) solution (time 0) and 2, 12, and 24 hours after injections ceased. Polymorphonuclear neutrophilic leukocytes were isolated from blood samples and incubated with t10c12-CLA alone or t10c12-CLA in combination with N-acetylcysteine (an antioxidant agent). Phagocytic capacity and OBA were measured simultaneously by use of flow cytometry. RESULTS The phagocytic capacity and OBA of PMNs were suppressed by IV injection of MPSS and restored 12 hours after injection ceased. In vitro treatment with t10c12-CLA enhanced the phagocytic capacity and OBA of PMNs, regardless of whether dogs had been treated with MPSS. Effects of t10c12-CLA on OBA were detected only when phagocytosis was stimulated by microspheres. Use of N-acetylcysteine attenuated the stimulatory effects of t10c12-CLA. CONCLUSIONS AND CLINICAL RELEVANCE Exposure to t10c12-CLA enhanced the phagocytic capacity and OBA of canine PMNs, and this effect may have involved t10c12-CLA-induced generation of reactive oxygen species.

Evaluation of partial cranial cruciate ligament rupture with positive contrast computed tomographic arthrography in dogs

Computed tomographic arthrography (CTA) of four cadaveric canine stifles was performed before and after partial cranial cruciate ligament rupture in order to verify the usefulness of CTA examination for the diagnosis of partial cranial cruciate ligament rupture. To obtain the sequential true transverse image of a cranial cruciate ligament, the computed tomography gantry was angled such that the scanning plane was parallel to the fibula. True transverse images of cranial cruciate ligaments were identified on every sequential image, beginning just proximal to the origin of the cranial cruciate ligament distal to the tibial attachment, after the administration of iodinated contrast medium. A significant decrease in the area of the cranial cruciate ligament was identified on CTA imaging after partial surgical rupture of the cranial cruciate ligament. This finding implies that CTA can be used for assessing partial cranial cruciate ligament ruptures in dogs.

Immunoenhancing effect of trans-10, cis-12 conjugated linoleic acid on the phagocytic capacity and oxidative burst activity of canine peripheral blood phagocytes

The effect of trans-10, cis-12 conjugated linoleic acid (t10c12-CLA) on the phagocytic capacity and oxidative burst activity (OBA) of canine peripheral blood phagocytes was examined. t10c12-CLA did not directly affect the phagocytic capacity and OBA of peripheral blood mononuclear cells (PBMC), monocytes or polymorphonuclear cells (PMN). However, the phagocytic capacity of PMN and monocytes was enhanced by the culture supernatant from t10c12-CLA-treated PBMC. This supernatant enhanced the latex bead-induced OBA of PMN and monocytes. t10c12-CLA also increased TNF-alpha production by PBMC. Recombinant canine (rc) TNF-alpha also increased the phagocytic capacity and OBA of PMN and monocytes. The ability of the culture supernatant from t10c12-CLA-treated PBMC to stimulate the phagocytic capacity and OBA of phagocytes was inhibited by anti-rcTNF-alpha pAb. These results suggest that t10c12-CLA has an immunoenhancing effect on the phagocytic capacity and OBA of phagocytes, and this effect may be mediated by TNF-alpha released from t10c12-CLA-treated PBMC.

Serum adipokine concentrations in dogs with diabetes mellitus: a pilot study

This study was conducted to determine whether serum adipokine concentrations differed between healthy dogs and dogs with diabetes mellitus (DM). To accomplish this, 19 dogs with newly diagnosed DM were compared to 20 otherwise healthy dogs. The serum concentrations of visfatin, leptin, IL-1β, IL-6, IL-18, and TNF-α were significantly higher in diabetic dogs than in healthy dogs, whereas the serum adiponectin concentrations were lower in diabetic dogs. However, there were no significant differences in the IL-10 and resistin levels between groups. The serum leptin concentrations in diabetic dogs with and without concurrent disorders differed significantly. Treatment with insulin induced a significant decrease in IL-6 in diabetic dogs without concurrent disorders. These results show that the clinical diabetic state of dogs could modulate the circulating visfatin and adiponectin concentrations directly, while upregulation of leptin was probably a result of concurrent disorders rather than an effect of persistent hyperglycemia as a result of DM.

Serum adipokine concentrations in dogs with acute pancreatitis.

Background Limited information is available about the role of adipokines in the development and progression of acute pancreatitis (AP) in dogs. Objectives To determine whether the circulating concentrations of adipokines differed between healthy dogs and dogs with AP, and whether the circulating concentrations differed between AP survivors and AP nonsurvivors. Animals Twenty‐eight healthy dogs and 25 client‐owned dogs with AP. Methods Prospective observational cohort study of 25 client‐owned dogs with newly diagnosed AP and 28 otherwise healthy dogs with similar body condition scores. The serum concentrations of leptin, adiponectin, resistin, visfatin, interleukin (IL)‐1β, IL‐6, IL‐10, IL‐18, and tumor necrosis factor (TNF)‐α were measured. Results The serum concentrations of leptin (P = .0021), resistin (P = .0010), visfatin (P < .0001), IL‐1β (P < .0001), IL‐6 (P = .0002), IL‐10 (P < .0001), and IL‐18 (P < .0001) were significantly higher in dogs with AP than healthy dogs, whereas the adiponectin concentration (P = .0011) was significantly lower. There were significant differences in the serum concentrations of leptin (P = .028) and adiponectin (P = .046) in survivors and nonsurvivors. After the disappearance of clinical signs, the concentrations of resistin (P = .037) and IL‐1β (P = .027) decreased significantly, whereas the serum concentrations of leptin (P > .999), adiponectin (P = .11), visfatin (P = .83), IL‐6 (P = .82), IL‐10 (P = .82), IL‐18 (P = .56), and TNF‐α (P = .94) did not differ significantly. Conclusion and Clinical Importance This study showed that dysregulation of adipokines might be involved in the pathogenesis of AP. In addition, leptin and adiponectin are likely to be associated with mortality rate in AP.