首页 | 本学科首页   官方微博 | 高级检索  
相似文献
 共查询到20条相似文献，搜索用时 203 毫秒
1.
The pharmacokinetics of dantrolene and its active metabolite, 5‐hydroxydantrolene, after a single oral dose of either 5 or 10 mg/kg of dantrolene was determined. The effects of exposure to dantrolene and 5‐hydroxydantrolene on activated whole‐blood gene expression of the cytokines interleukin‐2 (IL‐2) and interferon‐γ (IFN‐γ) were also investigated. When dantrolene was administered at a 5 mg/kg dose, peak plasma concentration (Cmax) was 0.43 μg/mL, terminal half‐life (t1/2) was 1.26 h, and area under the time–concentration curve (AUC) was 3.87 μg·h/mL. For the 10 mg/kg dose, Cmax was 0.65 μg/mL, t1/2 was 1.21 h, and AUC was 5.94 μg·h/mL. For all calculated parameters, however, there were large standard deviations and wide ranges noted between and within individual dogs: t1/2, for example, ranged from 0.43 to 6.93 h, Cmax ratios ranged from 1.05 to 3.39, and relative bioavailability (rF) values ranged from 0.02 to 1.56. While activated whole‐blood expression of IL‐2 and IFN‐γ as measured by qRT‐PCR was markedly suppressed following exposure to very high concentrations (30 and 50 μg/mL, respectively) of both dantrolene and 5‐hydroxydantrolene, biologically and therapeutically relevant suppression of cytokine expression did not occur at the much lower drug concentrations achieved with oral dantrolene dosing.  相似文献   

2.
Cyclosporine is a powerful T‐cell inhibitor used in the treatment of immune‐mediated and inflammatory diseases in the dog. There is limited information on how to best monitor patients on cyclosporine therapy. Currently, pharmacokinetic and pharmacodynamic assays are available. Pharmacokinetic assays that measure the concentration of cyclosporine in the blood are used to assess if an appropriate drug concentration has been achieved; however, target blood drug concentrations have not been shown to reliably correlate with suppression of T‐cell function in the dog. In human transplant recipients, therapeutic drug monitoring has shifted to include pharmacodynamic‐based monitoring. Our laboratory has validated a RT‐qPCR assay to measure the pharmacodynamic effects of cyclosporine in the dog. In this study, activated T‐cell expression of IL‐2 and IFN‐γ was measured using RT‐qPCR daily for 7 consecutive days in 8 healthy Walker hounds receiving oral cyclosporine at a dosage of 10 mg/kg every 12 hr. Cytokine production was found to be markedly decreased within 24 hr after the initiation of cyclosporine and remained significantly decreased for the duration of the project. Based on these results, cyclosporine causes a rapid drop in T‐cell cytokine production that is sustained with continued dosing in healthy dogs. Although performed in healthy dogs, this study demonstrated a marked decrease in cytokine suppression within 24 hr of drug administration, suggesting that pharmacodynamic monitoring of cyclosporine's effects on T cells could be considered within several days of commencing therapy in dogs suffering from life‐threatening immune‐mediated disorders.  相似文献   

3.
Six dogs were used to determine single and multiple oral dose pharmacokinetics of ABT‐116. Blood was collected for subsequent analysis prior to and at 15, 30 min and 1, 2, 4, 6, 12, 18, and 24 h after administration of a single 30 mg/kg dose of ABT‐116. Results showed a half‐life of 6.9 h, kel of 0.1/h, AUC of 56.5 μg·h/mL, Tmax of 3.7 h, and Cmax of 3.8 μg/mL. Based on data from this initial phase, a dose of 10 mg/kg of ABT‐116 (no placebo control) was selected and administered to the same six dogs once daily for five consecutive days. Behavioral observations, heart rate, respiratory rate, temperature, thermal and mechanical (proximal and distal limb) nociceptive thresholds, and blood collection were performed prior to and 4, 8, and 16 h after drug administration each day. The majority of plasma concentrations were above the efficacious concentration (0.23 μg/mL previously determined for rodents) for analgesia during the 24‐h sampling period. Thermal and distal limb mechanical thresholds were increased at 4 and 8 h, and at 4, 8, and 16 h respectively, postdosing. Body temperature increased on the first day of dosing. Results suggest adequate exposure and antinociceptive effects of 10 mg/kg ABT‐116 following oral delivery in dogs.  相似文献   

4.
Dairy cow mastitis is a detrimental factor in milk quality and food safety. Mastitis generally refers to inflammation caused by infection by pathogenic microorganisms. Our studies in recent years have revealed the role of miRNA regulation in Staphylococcus aureus‐induced mastitis. In the present study, we overexpressed and suppressed miR‐145 to investigate the function of miR‐145 in Mac‐T cells. Flow cytometry, ELISA and EdU staining were used to detect changes in the secretion of several Mac‐T cytokines and in cell proliferation. We found that overexpression of miR‐145 in Mac‐T cells significantly reduced the secretion of IL‐12 and TNF‐α, but increased the secretion of IFN‐γ; the proliferation of bovine mammary epithelial cells was also inhibited. Using quantitative real‐time PCR (qRT‐PCR), Western blotting and luciferase multiplex verification techniques, we found that miR‐145 targeted and regulated FSCN1. Knock‐down of FSCN1 significantly increased the secretion of IL‐12, while the secretion of TNF‐α was significantly downregulated in Mac‐T cells. Upon S. aureus infection of mammary gland tissue, the body initiated inflammatory responses; Bta‐miR‐145 expression was downregulated, which reduced the inhibitory effect on the FSCN1 gene; and upregulation of FSCN1 expression promoted mammary epithelial cell proliferation to allow the recovery of damaged tissue. The results of the present study will aid in understanding the immune mechanism opposing S. aureus infection in dairy cows and will provide a laboratory research basis for the prevention and treatment of mastitis.  相似文献   

5.
The purpose of this study was to evaluate a combination of immunostimulatory bacterial DNA sequences and allergen‐specific immunotherapy for the treatment of canine atopic dermatitis. Seven dogs with nonseasonal atopic dermatitis diagnosed by history, clinical signs and exclusion of differential diagnoses were included. All dogs had been on allergen‐specific immunotherapy for at least 12 months with incomplete responses, were on additional antipruritic therapy and showed residual pruritus. Pruritus was marked by the owner on a visual analogue scale, lesions were determined by a clinician using the Canine Atopic Dermatitis Extent and Severity Index (CADESI), and concurrent medications were recorded before entering the study and after 14 weeks of treatment. Peripheral blood mononuclear cells were isolated and cultured; canine cytokine message for IFNγ, IL‐4, TNF and IL‐10 was quantitated using RT‐PCR. A mixture of allergen extract and liposome‐DNA complexes was injected intradermally at the beginning of the study and after 2, 4, 6, 10 and 14 weeks. CADESI, pruritus and medication scores, and cytokine messages at the beginning and end of the study were compared with a paired t‐test. There were significant improvements in pruritus scores (P = 0.0277). Reductions in medication scores and CADESI were not statistically significant. IL‐4 production decreased significantly (P = 0.0428); decreases in other cytokines were not significant. Although the number of dogs in this pilot study was small, the results warrant further investigation of a combination of immunostimulatory bacterial DNA sequences and allergen‐specific immunotherapy for the treatment of canine atopic dermatitis. Funding: Self‐funded.  相似文献   

6.
IgE‐mediated late‐phase reactions can be induced in the skin of normal and atopic dogs by intradermal injections of anti‐IgE antibody. The histology of these reactions is very similar to that of naturally occurring atopic dermatitis. To characterize the cellular, cytokine and chemokine responses in the skin of placebo‐ and prednisolone‐treated dogs, normal beagles received either placebo or 0.5 mg/kg prednisolone twice daily for three days prior to intradermal injection of polyclonal rabbit anti‐canine IgE. Eight‐millimetre punch biopsy skin samples were taken before injection and at the injection sites after 6, 24 and 48 h. Histological and immunohistochemical examination revealed a rapid cellular influx. Eosinophil and neutrophil numbers increased from <1 to 61.4 ± 14.1, and from 7 to 62.2 ± 10.8 cells/mm2, respectively, within 6 h after injection, and remained moderately elevated 48 h later. The numbers of CD1c+, CD3+ and CD4+ mononuclear cells were also increased by 6 h. Taqman analysis demonstrated 2.5‐ to 72‐fold increases in mRNA expression for IL‐13, IL‐5, MCP (CCL2), RANTES (CCL5) and TARC (CCL17). Levels of mRNA for IL‐2, IL‐4, IL‐6, and IFNγ remained negligible. Prednisolone administration suppressed the influx of neutrophils and eosinophils, and the expression of IL‐13, CCL2, CCL5 and CCL17 (33, 97, 58, 86, 73 and 90%, respectively), as well as the influx of CD1c+ and CD3+ cells. These data document the cytokine and chemokine response to anti‐IgE injection and demonstrate the anti‐inflammatory effect of prednisolone. Funding: Schering‐Plough Animal Health.  相似文献   

7.
Heparin‐binding EGF‐like growth factor (HB‐EGF) regulates several cell functions by binding to its membrane receptor (ErbB1 and ErbB4). Experimental evidences suggest that HB‐EGF, prostaglandins (PGs) and interferon‐τ (IFN‐τ) regulate uterine function for pregnancy establishment in ruminants. In this study, the mRNA expressions of HB‐EGF, ErbB1 and ErbB4 in bovine endometrium and the effects of HB‐EGF and IFN‐τ on PGE2 and PGF2‐α production by endometrial cells were investigated. RT‐PCR analysis revealed that HB‐EGF mRNA was greater at the mid‐luteal stage than at the early and regressed luteal stages (p < 0.05). ErbB1 mRNA expression was greater at the mid‐ and late luteal stages than at the other luteal stages (p < 0.05). IFN‐τ increased the expression of HB‐EGF, ErbB1 and ErbB4 mRNA in epithelial cells (p < 0.05). HB‐EGF did not affect PGF2‐α or PGE2 production by bovine endometrial epithelial cells, but increased PGF2‐α and PGE2 production by bovine endometrial stromal cells (p < 0.05). IFN‐τ significantly decreased HB‐EGF‐stimulated PGF2‐α (p < 0.05), but not PGE2 (p > 0.05) production by stromal cells. These results indicate that HB‐EGF and its receptors expression changed in bovine endometrium throughout the oestrous cycle. IFN‐τ increased their expression in cultured endometrial cells. HB‐EGF and IFN‐τ have the ability to regulate PGs production by stromal cells and therefore may play a role in the local regulation of uterine function at the time of implantation in cattle.  相似文献   

8.
A study was undertaken to investigate the role of in ovo administrated carbohydrates on the expression pattern of growth and immune‐related genes. In ovo injections (n = 400) were carried out on the 14th day of incubation into the yolk sac/amnion of the broiler chicken embryos. Expression of growth‐related genes: chicken growth hormone (cGH), insulin‐like growth factor‐I & II (IGF‐I & II) and mucin were studied in hepatic and jejunum tissues of late‐term embryo and early post‐hatch chicks. Expression of candidate immune genes: Interleukin‐2, 6, 10 and 12 (IL‐2, IL‐6, IL‐10 and IL‐12), Tumour necrosis factor‐alpha (TNF‐α) and Interferon gamma (IFN‐γ) were studied in peripheral blood monocyte cells of in ovo‐injected and control birds following antigenic stimulation with sheep RBC (SRBC) or mitogen concanavalin A (Con‐A). Glucose injection significantly increased the expression of IGF‐II gene during embryonic period and both cGH and IGF‐II in early post‐hatch period, while ribose‐injected chicks had higher expression of IGF‐II gene during embryonic stage. Enhanced mucin gene expression was also observed in fructose‐injected chicks during embryonic age. Glucose‐injected chicks had higher expression of IL‐6 or IL‐10, while those injected with fructose or ribose had higher expression of IL‐2, IL‐12 and IFN gamma. It is concluded that in ovo supplementation of carbohydrates might help in improving the growth of late‐term embryos and chicks. In ovo glucose could modulate humoral‐related immunity, while fructose or ribose might help in improving the cellular immunity in broiler chickens.  相似文献   

9.
This study's objective was to determine the effects in dogs of oral capromorelin, a ghrelin agonist, at different doses for 7 days on food consumption, body weight and serum concentrations of growth hormone (GH), insulin‐like growth factor 1 (IGF‐1), and cortisol. Adult Beagles (n = 6) were dosed with placebo BID, capromorelin at 3.0 mg/kg SID, 4.5 mg/kg SID, or 3.0 mg/kg BID. Food consumption, body weight, serum capromorelin, GH, IGF‐1, and cortisol were measured at intervals on days 1, 4, 7, and 9. Capromorelin increased food consumption and body weight compared to placebo and caused increased serum GH, which returned to the baseline by 8 h postdose. The magnitude of the GH increase was less on days 4 and 7 compared to Day 1. IGF‐1 concentrations increased on Day 1 in capromorelin‐treated dogs and this increase was sustained through Day 7. Serum cortisol increased postdosing and returned to the baseline concentrations by 8 h. The magnitude of the increase was less on days 4 and 7 compared to Day 1. A dose of 3 mg/kg was chosen for further study in dogs based on this dose causing increased food consumption and sustained IGF‐1 serum concentrations that may increase lean muscle mass when administered over extended periods.  相似文献   

10.
  相似文献   

11.
Reasons for performing study: Airway inflammation in recurrent airway obstruction (RAO) is triggered by housing affected horses in stables. It has been suggested that RAO is an allergic condition, but innate immune mechanisms are also involved. Fungal products activate innate immune mechanisms through toll‐like receptor 2 (TLR2). In human airway epithelium, TLR2 activation leads to interleukin (IL)‐8 production. This pathway is negatively regulated by the zinc finger protein A20. This study was performed to enhance understanding of innate immune mechanisms in RAO. Hypothesis: TLR2 and IL‐8 mRNA are elevated in RAO during stabling compared with controls. A20 mRNA is negatively associated with the numbers of airway inflammatory cells. Objectives: To determine TLR 2 , IL‐8 and A20 mRNA expression in lungs of stabled and pastured RAO‐affected and control horses. Methods: Airway obstruction and inflammatory cell counts in bronchoalveolar lavage were measured, and TLR 2 , IL‐8 and A20 mRNA expression quantified by qRT‐PCR in 6 RAO‐affected and 6 control horses, during and after exposure to hay and straw. Results: Airway obstruction and neutrophils were increased in RAO‐affected horses during stabling. While stabling increased IL‐ 8 , TLR2 and A20 mRNA were unaffected. TLR2 and A20 were significantly correlated (r = 0.83) and A20 mRNA was negatively associated with inflammatory cells. Potential relevance: Stabling does not lead to an increase in TLR2 expression. Other molecules or processes in the TLR2 cascade might be important in fungal‐induced airway inflammation. Equine epithelial‐derived A20 may be involved in modulation of airway inflammation.  相似文献   

12.
Cyclosporine is a powerful immunosuppressive drug that is being used with increasing frequency to treat a wide range of immune-mediated diseases in the dog. To date, ideal dosing protocols that will achieve immunosuppression with cyclosporine in dogs remain unclear, and standard methods that can measure effectiveness of immunosuppression have not been established. The aim of our study was to evaluate the effects of in vitro cyclosporine exposure on a panel of molecules expressed by activated T cells to ascertain their potential as biomarkers of immunosuppression in dogs. Blood was drawn from six healthy dogs, and peripheral blood mononuclear cells (PBMC) were isolated and activated. Half of the cells were incubated with 200 ng/mL cyclosporine prior to activation, and the other half were not exposed to cyclosporine. Samples were analyzed using flow cytometry, and the expression of intracellular cytokines IL-2, IL-4, and IFN-γ was evaluated after 6, 12, and 24h of drug exposure. Each cytokine exhibited a time-dependent suppression profile, and all but two samples activated in the presence of cyclosporine showed lower cytokine expression than untreated controls. We also evaluated the expression of the surface T cell activation molecules CD25 and CD95 by flow cytometry after 36 h of drug exposure. Expression of these surface molecules decreased significantly when activated in the presence of cyclosporine. Our results suggest that suppressed expression of the markers related to T cell activation could potentially be utilized as an indicator of the efficacy of cyclosporine therapy in dogs.  相似文献   

13.

Background

Left ventricular torsional motion plays an important role for effective pump function. However, noninvasive clinical assessment of torsional deformations by two‐dimensional speckle‐tracking echocardiography (2D‐STE) in dogs with myxomatous mitral valve disease (MMVD) has not been reported.

Hypothesis

Left ventricular torsion is determined by the native orientation of the helical myocardial fibers, such that it might provide better assessment of myocardial function than conventional methods.

Animals

Sixty‐seven client‐owned dogs with MMVD were classified into 3 classes based on the International Small Animal Cardiac Health Council classification and 16 weight‐ and age‐matched healthy dogs.

Methods

Dogs were examined for myocardial deformations by 2D‐STE and were evaluated for peak systolic rotation and rotation rate at each basal and apical view. Dogs also were evaluated for peak systolic torsion and torsion rate.

Results

Peak systolic torsion was higher in class II than in class I (P < .001) dogs. Peak systolic torsion was lower in class III than in class II (P = .001) dogs and controls (P = .003).

Conclusions and Clinical Importance

Torsional deformations assessed by 2D‐STE differed among clinical classes of MMVD. Myocardial torsional deformations by 2D‐STE may provide more detailed assessment of contractile function in dogs with MMVD.  相似文献   

14.

Background

Measurement of plasma‐free metanephrines is the test of choice to identify pheochromocytoma in human patients.

Objectives

To establish the sensitivity and specificity of plasma‐free metanephrine (fMN) and free normetanephrine (fNMN) concentrations to diagnose pheochromocytoma in dogs.

Animals

Forty‐five client‐owned dogs (8 dogs with pheochromocytoma, 11 dogs with adrenocortical tumors, 15 dogs with nonadrenal disease, and 11 healthy dogs.)

Methods

A prospective study. EDTA plasma was collected from diseased and healthy dogs and submitted for fMN and fNMN measurement by liquid chromatography‐tandem mass spectrometry (LC‐MS/MS).

Results

Free MN concentration (median [range]) was significantly higher in dogs with pheochromocytoma (8.15 [1.73–175.23] nmol/L) than in healthy dogs (0.95 [0.68–3.08] nmol/L; P < .01) and dogs with adrenocortical tumors (0.92 [0.25–2.51] nmol/L; P < .001), but was not different from dogs with nonadrenal disease (1.91 [0.41–6.57] nmol/L; P ≥ .05). Free NMN concentration was significantly higher in dogs with pheochromocytoma (63.89 [10.19–190.31] nmol/L) than in healthy dogs (2.54 [1.59–4.17] nmol/L; P < .001), dogs with nonadrenal disease (3.30 [1.30–10.10] nmol/L; P < .001), and dogs with adrenocortical tumors (2.96 [1.92–5.01] nmol/L); P < 0.01). When used to diagnose pheochromocytoma, a fMN concentration of 4.18 nmol/L had a sensitivity of 62.5% and specificity of 97.3%, and a fNMN concentration of 5.52 nmol/L had a sensitivity of 100% and specificity of 97.6%.

Conclusions and Clinical Importance

Plasma fNMN concentration has excellent sensitivity and specificity for the diagnosis of pheochromocytoma in dogs, whereas fMN concentration has moderate sensitivity and excellent specificity. Measurement of plasma‐free metanephrines provides an effective, noninvasive, means of identifying dogs with pheochromocytoma.  相似文献   

15.
The aim of this study was to determine whether local scrotal heating (42°C, for 1 hr) had an effect on the expression of tight junction (TJ)‐associated molecule Occludin in boar testes. Adult boars (Landrace, n = 6) were used and randomly divided into two groups (n = 3 each). Three boars were given local scrotal exposure to 42°C for approximately 1 h with a home‐made electric blanket of controlled temperature as local scrotal heating group, the other three boars received no heat treatment and were left at standard room temperature as control group. After 6 hr, all boars were castrated and the testes were harvested. qRT‐PCR, Western blotting and immunohistochemistry were used to explore the expression and localization of Occludin. qRT‐PCR and Western blotting showed that the protein and mRNA levels of Occludin significantly decreased in local scrotal heating group as compared to the control. Furthermore, immunoreactivity staining of Occludin was localized at the sites of the blood–testis barrier (BTB) and formed an almost consecutive and strong immunoreactivity strand in the control, while Occludin was limited to Sertoli cells (SCs) and no obvious immunoreactivity strand was present in local scrotal heating group. These data indicated that local scrotal heating decreased the expression of TJ‐associated molecule Occludin, which may be involved in heat‐induced spermatogenesis damage.  相似文献   

16.
Atopic dermatitis (AD) is thought to be caused by immunologic abnormalities expressed as a Th1/Th2 cytokine imbalance in both humans and dogs. Several studies have focused on the therapeutic effects of IFNγ in human AD with successful results; however, the mechanism of action of IFNγ is not fully understood. We investigated the effect of recombinant canine interferon gamma (rCaIFNγ) on 10 dogs with AD and evaluated the ratio of IL‐4 mRNA to IFNγ mRNA in peripheral blood mononuclear cells, serum total IgE levels, and histological changes in skin. After six injections of rCaIFNγ over a span of 2 weeks, seven of the 10 dogs showed improvement, and six of these seven dogs exhibited decreased IL‐4:IFNγ mRNA ratios. Two of the three cases that did not improve had increased IL‐4:IFNγ mRNA ratios. Total serum IgE levels were significantly decreased in nine of 10 cases. The number of IgE‐positive cells detected by immunostaining and the number of mast cells in skin biopsy samples were decreased. A reduction of epidermal cell layers was demonstrated by histopathology after treatment. These results demonstrated that rCaIFNγ may be a novel safe and effective therapeutic option for the treatment of canine AD, and the mechanism of action of rCaIFNγ may be related to the modulation of Th2 cytokines to Th1 cytokines with the reduction of serum IgE production. Funding: Self‐funded.  相似文献   

17.
Gamma interferon (IFN‐γ) production and cross‐breed pregnancy have been attributed a role in protecting dairy cows infected with Neospora caninum against abortion. Plasma levels of pregnancy‐associated glycoproteins‐1 (PAG‐1) are a marker of placental/foetal well‐being and of PAG‐2 is an abortion risk indicator in chronically N. caninum‐infected animals. The present study examines, in cross‐breed pregnancies, interactions between IFN‐γ production and levels of PAG‐1 and PAG‐2 in non‐aborting naturally Neospora‐infected dairy cows. Data were obtained from 60 pregnant Holstein‐Friesian cows: 44 Neospora‐seropositive and 16 Neospora‐seronegative; 12 became pregnant using Holstein‐Friesian semen and 48 using Limousin semen. Blood samples were collected on Days 40, 90, 120, 150, 180 and 210 of gestation. Gamma interferon was only detected in the plasma of nine of the 44 Neospora‐seropositive cows, all of them became pregnant using Limousin semen. Through GLM procedures, in cows inseminated with Limousin semen and Neospora‐seropositive cows showing no IFN‐γ production, PAG‐1 concentrations were high and increased throughout gestation compared to the levels detected in cows inseminated with Holstein‐Friesian semen and Neospora‐seropositive cows producing IFN‐γ, respectively. In Neospora‐seronegative cows and in Neospora‐seropositive cows showing no IFN‐γ production, significantly increased PAG‐2 concentrations were observed on gestation Day 120. Our findings indicate that IFN‐γ production correlates negatively and the production of antibodies against N. caninum is uncorrelated with plasma PAG concentrations during gestation in Neospora‐infected dairy cows. Accordingly, IFN‐γ production could be linked to the transplacental migration of tachyzoites, which may cause a reduction in PAG levels.  相似文献   

18.
Lactobacillus rhamnosus GG (LGG) is increasingly applied in functional food products and acts as a probiotic model in nutritious and clinical studies. Increasing evidences have revealed the immune modulation of LGG on macrophages. The aim of this study is to investigate the effect of LGG on macrophage polarization of murine bone marrow‐derived macrophages (BMDMs). BMDMs were treated with 108 colony‐forming units (CFU)/ml LGG for 1.5, 3, and 6 hr. Results showed that LGG obviously upregulated the mRNA expression of M1‐associated cytokines (p < .05), including interleukin‐1 beta (IL‐1β), IL‐6, tumor necrosis factor‐alpha (TNF‐α), and inducible nitric oxide synthase (iNOS), whereas had no effect on the expression of M2‐associated markers (p > .05), including arginase 1 (Arg1), mannose receptor, and chitinase‐like protein 3 (YM1). Furthermore, LGG markedly increased the expression of pro‐inflammatory cytokines (IL‐12p40, cyclooxygenase‐2 [COX‐2], and interferon‐γ [IFN‐γ]) (p < .05) and anti‐inflammatory cytokines (IL‐10, IL‐4, and transforming growth factor‐β [TGF‐β]) (p < .05). In addition, we also found that TLR2/MyD88/MAPK signaling pathway was required for LGG‐induced M1 macrophage polarization and M1‐related cytokines expression. Together, these findings demonstrate that probiotic LGG facilitates M1 polarization of BMDMs, suggesting that LGG may have an immunotherapeutic potential in regulating the host defense against pathogen invasion.  相似文献   

19.

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.  相似文献   

20.
Expression of programmed cell death receptor ligand 1 (PD‐L1) on tumor cells has been associated with immune escape in human and murine cancers, but little is known regarding the immune regulation of PD‐L1 expression by tumor cells and tumor‐infiltrating macrophages in dogs. Therefore, 14 canine tumor cell lines, as well as primary cultures of canine monocytes and macrophages, were evaluated for constitutive PD‐L1 expression and for responsiveness to immune stimuli. We found that PD‐L1 was expressed constitutively on all canine tumor cell lines evaluated, although the levels of basal expression were very variable. Significant upregulation of PD‐L1 expression by all tumor cell lines was observed following IFN‐γ exposure and by exposure to a TLR3 ligand. Canine monocytes and monocyte‐derived macrophages did not express PD‐L1 constitutively, but did significantly upregulate expression following treatment with IFN‐γ. These findings suggest that most canine tumors express PD‐L1 constitutively and that both innate and adaptive immune stimuli can further upregulate PD‐L1 expression. Therefore the upregulation of PD‐L1 expression by tumor cells and by tumor‐infiltrating macrophages in response to cytokines such as IFN‐γ may represent an important mechanism of tumor‐mediated T‐cell suppression in dogs as well as in humans.  相似文献   

设为首页 | 免责声明 | 关于勤云 | 加入收藏

Copyright©北京勤云科技发展有限公司  京ICP备09084417号