Upper airway inflammation in waste handlers exposed to bioaerosols

Aims: To examine work associated upper airway inflammation in 31 waste handlers, and to correlate these findings with personally monitored exposure to different bioaerosol components.

Methods: Cell differentials, interleukin 8 (IL-8), myeloperoxidase (MPO), and eosinophilic cationic protein (ECP) were examined in NAL (nasal lavage), and swelling of the nasal mucosa was determined by acoustic rhinometry before work start on Monday and the following Thursday. Bioaerosol exposure was determined by personal full shift exposure measurements on Monday, Tuesday, and Wednesday and analysed for total bacteria, fungal spores, endotoxin, and ß(1→3)-glucans.

Results: The increased percentage of neutrophils from Monday (28%) to Thursday (46%) correlated with increases in ECP (r_S = 0.71, p < 0.001) and MPO (r_S = 0.38, p < 0.05), and showed a close to significant correlation with nasal swelling (r_S = -0.55, p = 0.07). The Thursday levels of neutrophils, MPO, and IL-8 were associated with the exposure to fungal spores (range 0–2.0 x 10⁶/m³) and endotoxin (range 4–183 EU/m³) measured the day before, and the median exposure to ß(1→3)-glucans (range 3–217 ng/m³), respectively (r_S = 0.47–0.54, p < 0.01). Swelling of the nasal mucosa was associated with the fungal spore and ß(1→3)-glucan exposure (r_S = 0.58–0.59, p < 0.05).

Conclusion: These results are based on a relatively small population, and conclusions must be drawn with care. The results suggested that a moderate exposure to fungal spores, endotoxins, and ß(1→3)-glucans during waste handling induced upper airway inflammation dominated by neutrophil infiltration and swelling of the nasal mucosa.

     

丹皮酚联合甲氨蝶呤对大鼠佐剂性关节炎的治疗作用

目的：研究丹皮酚联合甲爨蝶呤对佐剂性关节炎（从）大鼠的治疗作用。方法：弗氏完全佐剂免疫诱导大鼠AA,随机分为正常组,模型组,丹皮酚（200mg／kg,ig）组,甲氨蝶呤（0．75mg／kg,ig）组和丹皮酚联合甲氨蝶呤（200mg±0．75mg／kg,ig）组。给药后对AA大鼠做整体观察,足爪肿胀度和关节炎指数评分测定,血清中TNF-α IL-1β水平测定。结果：与正常组比较,模型组大鼠足爪肿胀度和关节炎指数评分明显升高,血清中TNF-α和 IL-1β水平显著升高;联合给药组相较于单独给药组,明显抑制大鼠足爪肿胀度和关节炎指数评分,降低血清中TNF-α 和 IL-1β 水平。结论：丹皮酚联合甲氨蝶呤显著改善AA大鼠多发性关节炎病变症状,降低血清中TNF-α和IL-1β 水平,提示丹皮酚联合甲氨蝶吟可能时娄风湿关节炎具有治疗作用．     

Immunomodulatory and Anti-inflammatory Effects of Asiatic Acid in a DNCB-Induced Atopic Dermatitis Animal Model

We examined the immunomodulatory and anti-inflammatory effects of asiatic acid (AA) in atopic dermatitis (AD). AA treatment (5–20 µg/mL) dose-dependently suppressed the tumor necrosis factor (TNF)-α level and interleukin (IL)-6 protein expression in interferon (IFN)-γ + TNF-α-treated HaCaT cells. The 2,4-dinitrocholrlbenzene (DNCB)-induced AD animal model was developed by administering two AA concentrations (30 and 75 mg/kg/d: AD + AA-L and AD + AA-H groups, respectively) for 18 days. Interestingly, AA treatment decreased AD skin lesions formation and affected other AD characteristics, such as increased ear thickness, lymph node and spleen size, dermal and epidermal thickness, collagen deposition, and mast cell infiltration in dorsal skin. In addition, in the DNCB-induced AD animal model, AA treatment downregulated the mRNA expression level of AD-related cytokines, such as Th1- (TNF-α and IL-1β and -12) and Th2 (IL-4, -5, -6, -13, and -31)-related cytokines as well as that of cyclooxygenase-2 and CXCL9. Moreover, in the AA treatment group, the protein level of inflammatory cytokines, including COX-2, IL-6, TNF-α, and IL-8, as well as the NF-κB and MAPK signaling pathways, were decreased. Overall, our study confirmed that AA administration inhibited AD skin lesion formation via enhancing immunomodulation and inhibiting inflammation. Thus, AA can be used as palliative medication for regulating AD symptoms.     

内毒素对新生大鼠CXCL12表达影响的研究

目的:研究内毒素作用于新生大鼠后,肺组织趋化因子-基质细胞衍生因子(CXCL 12)表达的变化及可能作用。方法:腹腔注射内毒素诱发7日龄新生大鼠急性肺损伤,免疫组织化学法检测肺组织中CXCL 12及白细胞介素-18(IL-18)蛋白水平的表达情况。结果:正常新生大鼠肺组织中CXCL 12呈阴性表达,IL-18蛋白阴性/弱阳性表达;内毒素作用后,CXCL 12及IL-18蛋白的表达随着损伤严重程度的增加而增强。结论:CXCL 12可能在新生大鼠急性肺损伤的发病中发挥一定的作用。     

A priori dietary omega-3 lipid supplementation results in local pancreatic macrophage and pulmonary inflammatory response attenuation in a model of experimental acute edematous pancreatitis (AEP)

BACKGROUND: Acute pancreatitis is often complicated by multiorgan dysfunction, which is postulated to occur in part by macrophage infiltration into the pancreas. Eicosapentaenoic acid (EPA), an omega-3 fatty acid, is the principal biologic component of fish oil and has clinically and experimentally been demonstrated to be anti-inflammatory. We hypothesized that dietary EPA supplementation before the induction of pancreatitis would attenuate both M-mediated local pancreatic and systemic pulmonary inflammatory response in an in vivo model of acute edematous pancreatitis (AEP). METHODS: Male Sprague-Dawley (SD) rats were pretreated 2 times per day with oral gavage with EPA (omega-3 fatty acid; 5 mg/kg/dose) or omega-6 fatty acid control (5 mg/kg/dose) or saline (equal volume) for 2 weeks. AEP was induced in omega-3, omega-6, and saline pretreated rats by 5 hourly subcutaneous (SC) injections of cerulein. Pancreas, lung, and serum were harvested 3 hours after the last cerulein injection. Severity of pancreatitis was confirmed by serum amylase and by histopathologic score. Pancreatic macrophage infiltration was assessed by confocal fluorescent microscopy, and pulmonary leukocyte respiratory burst (LRB) analysis was performed on mononuclear cells obtained from bronchioalveolar lavage (BAL). RESULTS: All animals demonstrated acute pancreatitis through hyperamylasemia and histopathologic examination. Confocal analysis demonstrated significantly lower macrophage infiltration, and BAL analysis by flow cytometry demonstrated significantly lower (p < .05) LRB in the omega-3-treated group compared with the omega-6 and the saline pancreatitis group. CONCLUSIONS: Attenuation of both pancreatic MPhi inflammatory response and pulmonary leukocyte respiratory burst in AEP by EPA supports further investigation into the potential role for EPA dietary supplementation in the progression of pancreatitis-associated sequelae.     

Phosphatidylserine inhibits inflammatory responses in interleukin-1β–stimulated fibroblast-like synoviocytes and alleviates carrageenan-induced arthritis in rat

Recently, phosphatidylserine (PS) has received attention for its anti-inflammatory effect; however, the molecular mechanisms of its action have not been fully understood. Thus, we hypothesized that PS might have antiarthritic and anti-inflammatory effects. To test this hypothesis, the in vitro anti-inflammatory effect of soybean-derived PS was tested on interleukin (IL)-1β–stimulated fibroblast-like synoviocytes from rheumatoid arthritis patients (RA-FLS) by measuring the levels of IL-6, IL-8, prostaglandin E₂, and vascular endothelial growth factor by enzyme-linked immunosorbent assay. The analgesic and antiarthritic activities of PS were investigated in rat models of carrageenan-induced acute paw pain and arthritis. The former was evaluated with a paw pressure test; the latter, by measuring paw volume and weight distribution ratio. In addition, the participation of mitogen-activated protein kinase signaling in the anti-inflammatory and antiarthritic effects of PS was investigated in RA-FLS. Phosphatidylserine inhibited the production of inflammatory mediators IL-6; IL-8; vascular endothelial growth factor; and, in particular, prostaglandin E₂ in IL-1β–stimulated RA-FLS. These effects were associated with abrogation of inhibitor of nuclear factor–κBα phosphorylation and suppression of p38 and c-jun amino terminal kinase but not extracellular signal–regulated kinase 1/2 phosphorylation. In rats, PS also showed a significant inhibitory effect on arthritic and nociceptive symptoms induced by carrageenan. These findings suggest that PS has anti-inflammatory and antiarthritic effects in vitro and in in vivo animal models; thus, PS should be further studied to determine its potential use as either a pharmaceutical or dietary supplement for alleviating arthritic symptoms.     

Acute alcohol intake impairs lung inflammation by changing pro- and anti-inflammatory mediator balance.

Previous studies have shown that alcohol (ethanol [EtOH]) intoxication impairs lung immunity by affecting cytokines pivotal to the inflammatory process. The objective of this study was to test the hypothesis that acute alcohol intoxication impairs lung innate immunity by downregulating the expression of proinflammatory mediators while simultaneously upregulating anti-inflammatory mediators. EtOH was administered to the mice 0.5h prior to an intratracheal injection of Escherichia coli lipopolysaccharide (LPS). The animals were killed either 4 or 24h after LPS to recover plasma, lungs, and bronchoalveolar lavage fluid. Lung inflammatory cytokines tumor necrosis factor-alpha (TNF-alpha), interleukin-1 beta (IL-1beta), IL-6, macrophage inhibitory factor (MIF), IL-10, TGF-beta, and receptors for TNF-alpha, IL-1beta, IL-6, and TGF-beta as well as glycoprotein (gp)130 and corticosterone (CS) levels were evaluated at mRNA and protein level. While the mRNA expression and the soluble TNF-Rp55 levels were significantly upregulated by EtOH, LPS-induced TNF-alpha activity, TNF-Rp55 mRNA expression, and soluble TNF-Rp55 levels were significantly suppressed. The LPS-induced expression of IL-1beta, IL-6, MIF, gp130, and receptors IL-1RI, IL-1RII, and IL-6Ralpha were also significantly impaired by EtOH. EtOH increased significantly the basal IL-10 activity at 3h, which continued to remain elevated even at 24h. The EtOH effect on IL-10 activity persisted even in LPS-challenged mice. EtOH and LPS augmented lung CS levels independently of each other. EtOH suppressed upregulation of TGF-beta1 mRNA expression by LPS and blocked completely LPS-induced TGF-beta1 secretion. In conclusion, the data suggest that the suppression of acute lung inflammation by EtOH intoxication is largely due to impairment by EtOH of proinflammatory cytokine signaling at the levels of cytokine expression and secretion as well as receptor expression and soluble receptor activity. The augmentation by EtOH of anti-inflammatory mediators' secretion most likely shifts the cytokine balance in the anti-inflammatory direction.     

Discriminating between Lyme neuroborreliosis and other central nervous system infections by use of biomarkers CXCL13 and IL-6

CXCL13 in cerebrospinal fluid has gradually become an established biomarker for Lyme neuroborreliosis (LNB), however the diagnostic performance of CXCL13 may be improved by the addition of IL-6, a non-specific infection biomarker. The aim of this study was to measure the concentrations of CXCL13 and IL-6 in cerebrospinal fluid, in the attempt to evaluate the diagnostic performance of these two biomarkers, in the differentiation between definite and possible LNB, as well as between LNB and other neuroinfections. This study used a cross-sectional design to quantify the levels of CXCL13 and IL-6 in cerebrospinal fluid (CSF) specimens from consecutive patients examined for central nervous system (CNS) infections at Lillebaelt Hospital in the Region of Southern Denmark. CXCL13 and IL-6 were measured simultaneously using the Bio-Plex 200 multiplex Cytokine Immunoassay System (Bio-Rad). Based on clinical and paraclinical findings, we grouped patients into six separate groups: definite LNB, possible LNB, Viral CNS infection, non-Borrelia Bacterial CNS infection, Other CNS disease (with pleocytosis) and Negative (without pleocytosis). A combined interpretation of four variables (leukocyte cell counts, protein concentration, CXCL13 and IL-6 concentrations in CSF) is presented using principal component cluster analysis. We included by chart review 390 patients discharged with definite LNB (n = 31), possible LNB (n = 10), confirmed Viral or non-Borrelia Bacterial CNS infection (n = 34), Other CNS disease (n = 58), and Negative (n = 257) for CXCL13 and IL-6 analysis. Principal component analysis (PCA) revealed three distinct clusters based on leukocyte cell counts, protein concentration, CXCL13 and IL-6 concentrations in CSF from 380 included patients (10 possible LNB patients excluded). The clusters clearly differentiate the groups: definite LNB, non-Borrelia Bacterial CNS infection and Negative (without pleocytosis). A receiver operating characteristic (ROC) curve comparing LNB patients (n = 31) and all non-LNB conditions with CSF pleocytosis (n = 99) indicated an optimal CXCL13 cut-off value of 50.7 pg/mL, resulting in a sensitivity and a specificity of 93.6 and 91.1%, respectively. The ROC analysis comparing patients with confirmed non-LNB CNS infection (n = 34) and all others with CSF pleocytosis (n = 97) resulted in an optimal IL-6 cut-off value of 111.5 pg/mL, yielding a sensitivity and a specificity of 78.8% and 82.5% respectively. Of the ten possible LNB patients, three cases (with CXCL13 levels above cut-off) fall within the LNB cluster, and one case is just outside, providing some laboratory support for the diagnosis of LNB. The remaining six possible LNB patients (with CXCL13 levels below the 50.7 cut-off) had little support for the diagnosis of LNB in the PCA-plot. The results of this study confirm that CXCL13 is a valuable supplement for diagnosis of LNB, and that the combination of CXCL13 and IL-6 may be used to differentiate cases of LNB from other CNS infections. Furthermore, IL-6 can be of differential diagnostic value when evaluating patients with possible LNB.     

Inflammation as well as angiogenesis may participate in the pathophysiology of brain radiation necrosis

Radiation necrosis (RN) after intensive radiation therapy is a serious problem. Using human RN specimens, we recently proved that leaky angiogenesis is a major cause of brain edema in RN. In the present study, we investigated the same specimens to speculate on inflammation''s effect on the pathophysiology of RN. Surgical specimens of symptomatic RN in the brain were retrospectively reviewed by histological and immunohistochemical analyses using hematoxylin and eosin (H&E) staining as well as immunohistochemical staining for VEGF, HIF-1α, CXCL12, CXCR4, GFAP, CD68, hGLUT5, CD45, IL-1α, IL-6 TNF-α and NF-kB. H&E staining demonstrated marked angiogenesis and cell infiltration in the perinecrotic area. The most prominent vasculature was identified as thin-walled leaky angiogenesis, i.e. telangiectasis surrounded by prominent interstitial edema. Two major cell phenotypes infiltrated the perinecrotic area: GFAP-positive reactive astrocytes and CD68/hGLUT5-positive cells (mainly microglias). Immunohistochemistry revealed that CD68/hGLUT5-positive cells and GFAP-positive cells expressed HIF-1α and VEGF, respectively. GFAP-positive cells expressed chemokine CXCL12, and CD68/hGLUT5-positive cells expressed receptor CXCR4. The CD68/hGLUT5-positive cells expressed pro-inflammatory cytokines IL-1α, IL-6 and TNF-α in the perinecrotic area. VEGF caused leaky angiogenesis followed by perilesional edema in RN. GFAP-positive cells expressing CXCL12 might attract CXCR4-expressing CD68/hGLUT5-positive cells into the perinecrotic area. These accumulated CD68/hGLUT5-positive cells expressing pro-inflammatory cytokines seemed to aggravate the RN edema. Both angiogenesis and inflammation might be caused by the regulation of HIF-1α, which is well known as a transactivator of VEGF and of the CXCL12/CXCR4 chemokine axis.     

Transgenic Overexpression of Aryl Hydrocarbon Receptor Repressor (AhRR) and AhR-Mediated Induction of CYP1A1, Cytokines,and Acute Toxicity

Background:

The aryl hydrocarbon receptor repressor (AhRR) is known to repress aryl hydrocarbon receptor (AhR) signaling, but very little is known regarding the role of the AhRR in vivo.

Objective:

This study tested the role of AhRR in vivo in AhRR overexpressing mice on molecular and toxic end points mediated through a prototypical AhR ligand.

Methods:

We generated AhRR-transgenic mice (AhRR Tg) based on the genetic background of C57BL/6J wild type (wt) mice. We tested the effect of the prototypical AhR ligand 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) on the expression of cytochrome P450 (CYP)1A1 and cytokines in various tissues of mice. We next analyzed the infiltration of immune cells in adipose tissue of mice after treatment with TCDD using flow cytometry.

Results:

AhRR Tg mice express significantly higher levels of AhRR compared to wt mice. Activation of AhR by TCDD caused a significant increase of the inflammatory cytokines Interleukin (IL)-1β, IL-6 and IL-10, and CXCL chemokines in white epididymal adipose tissue from both wt and AhRR Tg mice. However, the expression of IL-1β, CXCL2 and CXCL3 were significantly lower in AhRR Tg versus wt mice following TCDD treatment. Exposure to TCDD caused a rapid accumulation of neutrophils and macrophages in white adipose tissue of wt and AhRR Tg mice. Furthermore we found that male AhRR Tg mice were protected from high-dose TCDD-induced lethality associated with a reduced inflammatory response and liver damage as indicated by lower levels of TCDD-induced alanine aminotransferase and hepatic triglycerides. Females from both wt and AhRR Tg mice were less sensitive than male mice to acute toxicity induced by TCDD.

Conclusion:

In conclusion, the current study identifies AhRR as a previously uncharacterized regulator of specific inflammatory cytokines, which may protect from acute toxicity induced by TCDD.

Citation:

Vogel CF, Chang WL, Kado S, McCulloh K, Vogel H, Wu D, Haarmann-Stemmann T, Yang GX, Leung PS, Matsumura F, Gershwin ME. 2016. Transgenic overexpression of aryl hydrocarbon receptor repressor (AhRR) and AhR-mediated induction of CYP1A1, cytokines, and acute toxicity. Environ Health Perspect 124:1071–1083; http://dx.doi.org/10.1289/ehp.1510194     

Arthropathies associated with calcium-containing crystals

Monosodium urate crystals are clearly related to acute attacks of gout and to the hard tissue destruction of chronic tophaceous gout. Fortunately, the acute attacks are readily treated with anti-inflammatory drugs, and destructive changes due to tophi may be prevented or reversed, at least in part, by the intelligent control of serum urate levels. Control of gout is one of the premier success stories of modern medicine. In contrast, the number of patients who have arthritis associated with crystals that contain calcium appears to be rising--perhaps a function of better recognition, perhaps related to the aging of the population. CPPD and BCP crystals can be associated with acute or subacute inflammation, but as in acute gout, it is easily controlled with anti-inflammatory drugs or by local injections of corticosteroids. A direct relationship of BCP and CPPD crystals to the associated destructive arthropathies has been hypothesized and is supported by clinical observations, animal studies, and in vivo experiments. Unlike gout, which is usually associated with a systemic metabolic abnormality (i.e., hyperuricemia), calcium crystals deposition seem to be a localized phenomenon, although numerous local sites in several joints are often involved in a given patient. Tissue degeneration in gout clearly follows (tophaceous) crystal deposition. Calcium crystal deposition may follow, rather than precede, destructive joint changes. Alternatively, both destructive changes and crystal deposition may derive independently from a common, still obscure, biochemical abnormality of joint tissues. P. A. Dieppe and colleagues believe that calcium crystal deposition follows either primary or secondary tissue degeneration but that the crystals exert a positive feedback effect (amplification loop) that accelerates degeneration. Each of those formulations of a pathogenetic role for crystals may be true in a given case, analogous to the etiology of primary and secondary forms of hyperuricemia and to sodium urate crystal deposition coexistent with osteoarthritis (tophus formation in Heberden's nodes). Conclusive proof of a significant role for BCP or CPPD crystals in the pathogenesis of human joint tissue damage depends on interrupting the postulated disease mechanism and showing that this prevents joint deterioration and leads to significant repair of existing damage. Our current position is somewhat analogous to that of our colleagues who had to contend with management of gouty arthritis before the advent of effective drugs for control of hyperuricemia.     

Daily Oral Supplementation with 60 mg of Elemental Iron for 12 Weeks Alters Blood Mitochondrial DNA Content,but Not Leukocyte Telomere Length in Cambodian Women

There is limited evidence regarding the potential risk of untargeted iron supplementation, especially among individuals who are iron-replete or have genetic hemoglobinopathies. Excess iron exposure can increase the production of reactive oxygen species, which can lead to cellular damage. We evaluated the effect of daily oral supplementation on relative leukocyte telomere length (rLTL) and blood mitochondrial DNA (mtDNA) content in non-pregnant Cambodian women (18–45 years) who received 60 mg of elemental iron as ferrous sulfate (n = 190) or a placebo (n = 186) for 12 weeks. Buffy coat rLTL and mtDNA content were quantified by monochrome multiplex quantitative polymerase chain reaction. Generalized linear mixed-effects models were used to predict the absolute and percent change in rLTL and mtDNA content after 12 weeks. Iron supplementation was not associated with an absolute or percent change in rLTL after 12 weeks compared with placebo (ß-coefficient: −0.04 [95% CI: −0.16, 0.08]; p = 0.50 and ß-coefficient: −0.96 [95% CI: −2.69, 0.77]; p = 0.28, respectively). However, iron supplementation was associated with a smaller absolute and percent increase in mtDNA content after 12 weeks compared with placebo (ß-coefficient: −11 [95% CI: −20, −2]; p = 0.02 and ß-coefficient: −11 [95% CI: −20, −1]; p= 0.02, respectively). Thus, daily oral iron supplementation for 12 weeks was associated with altered mitochondrial homeostasis in our study sample. More research is needed to understand the risk of iron exposure and the biological consequences of altered mitochondrial homeostasis in order to inform the safety of the current global supplementation policy.     

Acute Encephalopathy Associated with Influenza A Infection in Adults

We report acute encephalopathy associated with influenza A infection in 3 adults. We detected high cerebrospinal fluid (CSF) and plasma concentrations of CXCL8/IL-8 and CCL2/MCP-1 (CSF/plasma ratios >3), and interleukin-6, CXCL10/IP-10, but no evidence of viral neuroinvasion. Patients recovered without sequelae. Hyperactivated cytokine response may play a role in pathogenesis.     

克淋通方抑菌及抗炎作用的实验研究

目的观察克淋通方的抑菌及抗炎作用。方法采用体外混合培养法观察克淋通方对各种常见细菌的抑菌作用;并用在大鼠足趾部皮下注射1%琼脂0.05 ml/只致其肿胀以计算肿胀率,观察克淋通方的抗炎作用。结果克淋通胶囊各个剂量组对各种细菌均有抑制效应;对各种细菌的最低抑菌浓度分别为淋菌0.0125 g/ml、金黄色葡萄球菌0.00135 g/ml、肺炎双球菌0.025 g/ml、乙型溶血性链球菌及伤寒沙门菌0.05 g/ml、致病大肠埃希菌、弗氏志贺菌及铜绿假单胞菌<0.1 g/ml;克淋通胶囊对琼脂所致大鼠足趾肿胀有一定的抑制作用,其中高剂量组作用较为明显(P<0.01)。结论克淋通方具有较强的抗炎作用和体外抑菌作用。     

Lymphocyte activation in silica-exposed workers

Exposure to silica dust has been examined as a possible risk factor for autoimmune diseases, including systemic sclerosis, rheumatoid arthritis, systemic lupus erythematosus and ANCA-associated vasculitis. However, the underlying cellular and molecular mechanisms resulting in the increased prevalence of autoimmunity remain elusive. To clarify these mechanisms, we studied various markers of immune activation in individuals occupationally exposed to silica dust, i.e., serum levels of soluble IL-2 receptor (sIL-2R), levels of IL-2, other pro- and anti-inflammatory cytokines and lymphoproliferation. Our results demonstrate that silica-exposed individuals present important alterations in their immune response when compared to controls, as shown by increased serum sIL-2R levels, decreased production of IL-2 and increased levels of the pro-inflammatory (IFN-γ, IL-1α, TNF-α, IL-6) as well as anti-inflammatory (IL-10 and TGF-β) cytokines. Furthermore, silica-exposed individuals presented enhanced lymphoproliferative responses. Our findings provide evidence that the maintenance of immune homeostasis may be disturbed in silica-exposed individuals, possibly resulting in autoimmune disorders.     

Possible functions of adrenomedullin from the seminal fluid in the female reproductive tract of the rat

Adrenomedullin (ADM) is found in male accessory sex glands and is part of the seminal secretion. It plays an important role in protecting the sperm in the female reproductive tract. In this study, we investigated the roles of ADM in inflammation and oxidative stress in the endometrium and in leukocyte and macrophage infiltration in the endometrial stroma. The expression of the ADM gene in the ventral prostate, coagulating gland, and seminal vesicle was determined by real time PCR. The peptide levels in the tissue and secretion were measured using an EIA Kit. The highest ADM mRNA and peptide levels were found in the ventral prostate. Most of the ADM in the seminal vesicle was stored in the tissue while little was secreted. The expression of the IL-1β gene and the secretion of TNFα and IL-6 in uterine tissue decreased significantly after treatment with ADM for 4 hours. Using an immunostaining method, the levels of leukocyte and macrophage infiltration were found to be lower at 24 hours post coitus than 1.5 hours post coitus. The infusion of ADM receptor antagonist reduced the infiltration of leukocyte and macrophages in the endometrial stroma at 24 hours post coitus. As to the anti-oxidative effect of ADM in the female tract, the reactive oxygen species (ROS) level in isolated endometrial epithelial cells was significantly decreased after treatment with ADM or seminal fluid. Our findings demonstrated that ADM in the seminal secretion may modify the inflammatory responses, play an anti-oxidative role, and increase leukocyte and macrophage infiltration in the uterus.     

The effect of flurbiprofen in acute ankle distortions

The efficacy of flurbiprofen was studied by means of a double-blind randomized clinical trial involving 50 patients with an acute lateral ankle distortion (grade I). It could not be demonstrated that the NSAID shortened the duration of convalescence after this injury. Neither the pain nor the swelling showed a statistically significant decrease. Side effects were more frequent in patients treated with flurbiprofen. In view of these findings use of flurbiprofen in the treatment of acute ankle distortions is to be regarded as inadvisable.     

Effect of Cone of Pinus densiflora on DNCB-Induced Allergic Contact Dermatitis-Like Skin Lesion in Balb/c Mice

Cone of Pinus densiflora (CP), or Korean red pinecone, is a cluster of Pinus densiflora fruit. CP has also been verified in several studies to have anti-oxidation, anti-fungal, anti-bacterial, and anti-melanogenic effects. However, anti-inflammatory effects have not yet been confirmed in the inflammatory responses of pinecones to allergic contact dermatitis. The purpose of this study is to prove the anti-inflammatory effect of CP on allergic contact dermatitis (ACD) in vitro and in vivo. CP inhibited the expression of TSLP, TARC, MCP-1, TNF-α, and IL-6 in TNF-α/IFN-γ-stimulated HaCaT cells and MCP-1, GM-CSF, TNF-α, IL-6, and IL-8 in PMACI (phorbol-12-myristate-13-acetate plus A23187)-stimulated HMC-1 cells. CP inhibited the phosphorylation of mitogen-activated protein kinase (MAPKs), as well as the translocation of NF-κB on TNF-α/IFN-γ stimulated in HaCaT cells. In vivo, CP decreased major symptoms of ACD, levels of IL-6 in skin lesion, thickening of the epidermis and dermis, infiltration of eosinophils and mast cells, and the infiltration of CD4⁺ T cells and CD8⁺ T cells. This result suggests that CP represents a potential alternative medicine to ACD for diseases such as chronic skin inflammation.     

Effects of ankle sprain in a general clinic population 6 to 18 months after medical evaluation

OBJECTIVE: To assess the 1-year outcome of standard medical care of acute ankle sprains in a general clinic-based population. DESIGN: A self-administered survey was mailed to all adult patients who presented to a health system provider for evaluation of ankle sprain. SETTING: A regional primary care health system. PARTICIPANTS: Four hundred sixty-seven (66.5%) of 702 patients with ankle sprains evaluated by a system physician from April 1, 1995, to March 31, 1996. MAIN OUTCOME MEASURES: Prevalence and severity of self-reported ankle pain, swelling, perceived instability, and perceived weakness 6 to 18 months after medical evaluation. RESULTS: Most patients sought medical evaluation shortly after injury and were immobilized or braced; 32.7% reported formal or home-based physical therapy. Six to 18 months after injury, 72.6% reported residual symptoms. Of these, 40.4% reported at least 1 moderate to severe symptom, most commonly perceived ankle weakness; 40.3% were unable to walk 1 mile; and 43.3% were unable to jump or pivot on the ankle without symptoms. Factors associated with moderate to severe residual symptoms were reinjury of the ankle (odds ratio [OR], 7.21; 95% confidence interval [CI], 4.14-12.68), activity restriction longer than 1 week (OR, 2.04; 95% CI, 1.25-3.32), and limited weight bearing longer than 28 days (OR, 2.16; 95% CI, 1.28-3.63). CONCLUSIONS: Residual lifestyle-limiting symptoms are common 6 to 18 months after an ankle sprain. Ankle sprains may be more problematic than generally thought, or standard medical treatment may be inadequate. Further studies evaluating treatment regimens are needed to identify effective methods to reduce the long-term functional limitations of ankle sprain in general clinic populations.