Acute AD Research Articles

Evaluation of Artemisia dubia folium extract-mediated immune efficacy through developing a murine model for acute and chronic stages of atopic dermatitis

BackgroundAtopic dermatitis (AD) is a biphasic type of skin inflammation characterized by a predominance of type-2 (TH2) and type-1 (TH1) helper T cell-biased immune responses at the acute and persistent chronic phases, respectively. The present study was aimed to evaluate the efficacy of Artemisia dubia folium extract (ADFE) on AD-like skin lesions through developing a murine model for acute and chronic stages of AD. To induce acute phase AD, the dorsal skin of BALB/c mice was sensitized twice a week with 1% 2, 4-dinitrochlorobenzene (DNCB), followed by challenge (twice) in the following week with 0.2% DNCB. To induce persistent chronic AD, some mice were challenged twice a week for 4 more weeks. After the second challenge, the dorsal skin was exposed to 3% ADFE (five times per week) for 2 weeks (acute phase) or 4 weeks (persistent chronic phase).ResultsThe paradigm of TH2 or TH1 predominance at the acute and chronic phase, respectively, was observed in this mouse model. During the acute phase, we observed an increased IL-4/IFN-γ ratio in splenic culture supernatants, an increased IgG1/IgG2a ratio in serum, and elevated serum IgE levels; however, the skew toward TH2 responses was diminished during the chronic stage. Compared with vehicle controls, ADFE reduced the IL-4/IFN-γ and IgG1/IgG2a ratios in acute AD, but both ratios increased during the chronic stage.ConclusionsOur results suggest that ADFE concomitantly suppresses the TH2 predominant response in acute AD, as well as the TH1 predominant response in chronic AD. Thus, ADFE is a candidate therapeutic for AD.

Role of YAP-related T cell imbalance and epidermal keratinocyte dysfunction in the pathogenesis of atopic dermatitis

BackgroundAtopic dermatitis (AD) is characterized by impaired skin barrier function and immune system dysfunction. The expression and role of Yes-associated protein (YAP) in AD are unclear. ObjectiveTo characterize the role of the YAP in T cell imbalance and epidermal keratinocyte dysfunction in the pathogenesis of AD. MethodsWe included 35 patients with AD (21 acute and 14 chronic). An AD mouse model was constructed using 2,4-dinitrofluorobenzene, and AD-like inflammatory cell model was constructed using TNF-α/IFN-γ-activated HaCaT cells. The proportion of Th1/Th2/Th17/Treg cells was detected using flow cytometry. After mononuclear cells were obtained from human peripheral blood or mouse spleen and induced to differentiate into different T cell subsets, YAP mRNA and protein expression were analyzed. Up-regulation of YAP was induced by lentivirus and down-regulation of YAP was induced by its specific inhibitor verteporfin (VP). The expression of YAP in skin lesions and infiltrating T cell subsets was detected using immunohistochemistry and double immunofluorescence staining, respectively. ResultsWe found differing degrees of Th1/Th2/Th17/Treg imbalance in acute and chronic AD. YAP expression was downregulated in Treg cells and upregulated in Th17 cells; YAP expression was downregulated in the AD epidermis. After YAP overexpression, the proportion of both Th17 and the Treg cells differentiated from mouse spleen mononuclear cells increased. There was an opposite trend after YAP inhibition. The proliferation and migration decreased and apoptosis increased after YAP inhibition in HaCaT cells. ConclusionChange of YAP expression may cause T cell imbalance and hamper the healing of the epidermis in AD.

Quantitative proteomics of acutely-isolated mouse microglia identifies novel immune Alzheimer\u2019s disease-related proteins

BackgroundMicroglia are innate immune cells of the brain that perform phagocytic and inflammatory functions in disease conditions. Transcriptomic studies of acutely-isolated microglia have provided novel insights into their molecular and functional diversity in homeostatic and neurodegenerative disease states. State-of-the-art mass spectrometry methods can comprehensively characterize proteomic alterations in microglia in neurodegenerative disorders, potentially providing novel functionally relevant molecular insights that are not provided by transcriptomics. However, comprehensive proteomic profiling of adult primary microglia in neurodegenerative disease conditions has not been performed.MethodsWe performed quantitative mass spectrometry based proteomic analyses of purified CD11b+ acutely-isolated microglia from adult (6 mo) mice in normal, acute neuroinflammatory (LPS-treatment) and chronic neurodegenerative states (5xFAD model of Alzheimer’s disease [AD]). Differential expression analyses were performed to characterize specific microglial proteomic changes in 5xFAD mice and identify overlap with LPS-induced pro-inflammatory changes. Our results were also contrasted with existing proteomic data from wild-type mouse microglia and from existing microglial transcriptomic data from wild-type and 5xFAD mice. Neuropathological validation studies of select proteins were performed in human AD and 5xFAD brains.ResultsOf 4133 proteins identified, 187 microglial proteins were differentially expressed in the 5xFAD mouse model of AD pathology, including proteins with previously known (Apoe, Clu and Htra1) as well as previously unreported relevance to AD biology (Cotl1 and Hexb). Proteins upregulated in 5xFAD microglia shared significant overlap with pro-inflammatory changes observed in LPS-treated mice. Several proteins increased in human AD brain were also upregulated by 5xFAD microglia (Aβ peptide, Apoe, Htra1, Cotl1 and Clu). Cotl1 was identified as a novel microglia-specific marker with increased expression and strong association with AD neuropathology. Apoe protein was also detected within plaque-associated microglia in which Apoe and Aβ were highly co-localized, suggesting a role for Apoe in phagocytic clearance of Aβ.ConclusionsWe report a comprehensive proteomic study of adult mouse microglia derived from acute neuroinflammation and AD models, representing a valuable resource to the neuroscience research community. We highlight shared and unique microglial proteomic changes in acute neuroinflammation aging and AD mouse models and identify novel roles for microglial proteins in human neurodegeneration.

Infrarenal aortic repair with or without false lumen intentional placement of endografts for hybrid management of complex aortic dissection

ObjectiveAortic dissection (AD) often involves the infrarenal aorta. We review our experience with open infrarenal aortic repair with or without false lumen intentional placement (FLIP) of endografts in the proximal dissected aorta as part of a hybrid strategy to treat complex AD. MethodsA prospectively maintained database of patients undergoing intervention for AD was reviewed. Data regarding diagnosis, imaging features, nature of the infrarenal repair (one- vs two-stage procedure), endoleaks, need for additional interventions, morbidity, and mortality were collected. ResultsBetween 2006 and 2017, there were 16 patients with AD with thoracoabdominal aortic aneurysm (TAAA), malperfusion, or both who underwent open infrarenal aortic repair or replacement combined with endovascular repair in a single- or multiple-stage procedure. Fifteen patients had a chronic AD and one patient had an acute AD. The most common indication for intervention was absolute size or rapid growth of the abdominal, thoracic, or thoracoabdominal aortic aneurysm (65%). In four patients with AD, the infrarenal replacement surgical graft was used as a common distal seal zone, allowing FLIP of an endograft to treat the proximal AD. Ten (62%) cases were done in two or more stages. Three patients had infrarenal aortic replacement with debranching only. In two of these patients, the proximal dissected aorta has remained stable without aneurysmal degeneration. One patient died as a result of rupture of his aneurysm while awaiting the second stage (perioperative mortality, 6%). Patients were observed from 1 month to 7 years. One patient had a stable type II endoleak, and one patient required subsequent replacement of ascending aortic arch for aneurysmal disease. One patient died of unrelated causes on follow-up. ConclusionsHybrid infrarenal aortic repair for treatment of complex AD can be performed with low morbidity and mortality and excellent medium-term results. This strategy can resolve malperfusion while simultaneously creating a landing zone using the false lumen as the conduit for the stent graft (FLIP) in selected patients. The FLIP technique allows full expansion of the endograft, potential preservation of lumbar and intercostal artery flow, and exclusion of the weaker false lumen while, in some cases, decompressing and thus stabilizing the proximal dissected aorta.

Evaluation of Anti-Inflammatory Activities of Qingre-Qushi Recipe (QRQS) against Atopic Dermatitis: Potential Mechanism of Inhibition of IL-33/ST2 Signal Transduction.

To evaluate the anti-inflammatory activities of QRQS against AD and the inhibitory molecular mechanisms of IL-33/ST2 signal transduction, BALB/c mice were divided into six groups (normal control, OVA control, low-dose of QRQS, middle-dose of QRQS, high-dose of QRQS, and cetirizine) and epicutaneously exposed to ovalbumin or PBS for 3 weeks and treated with QRQS for 2 weeks. Skin biopsies and blood samples were obtained for histological study, antibody analysis, and RNA isolation. HaCaT cells, stimulated by TNF-α and IFN-γ, were treated with QRQS to evaluate mRNA and protein expression by RT-PCR and ELISA. QRQS decreased both epidermal and dermal thickness, alleviated dermatitis, and reduced IL-33 and ST2 positive cell numbers. The concentration of specific IgE, IgG, IgG1, and IgG2a antibodies in serum and the expression of IL-33, ST2, IL-1RAcP, IL-4, and IL-13 mRNA in the skin were suppressed. No significant difference exists in TNF-α or IFN-γ. QRQS decreased IL-33 mRNA and protein secretion in HaCaT cells exposed to TNF-α and IFN-γ in a time- and concentration-dependent manner. QRQS regulates related molecule expression of ovalbumin-induced dermatitis involved in the IL-33/ST2 signaling axis in the treatment of acute AD.

Effect of synchronous perfusion of NaN3 in changes in content of cholinergic neurotransmitter in medial prefrontal cortex and hippocampal extra-cellular fluid

To observe the effect of synchronous perfusion of specific respiratory chain complex IV inhibitor sodium azide (NaN3) in brain on rat ventromedial prefrontal cortex (mPFC) and acetylcholine (ACh) and choline (Ch) contents in hippocampal extra-cellular fluid, and establish the AD rat model induced by mitochondrial acute injury. The synchronous dual-probe dual-channel brain microdialysis sampling technology was applied to synchronously perfuse modified Ringer's solution containing NaN3 (50 micro mol L-1) and neostigmine (2 micro mol L-1) into mPFC and hippocampus of conscious, freely moving normal rats, and continuously collect dialysates from different encephalic areas. Dynamic contents of ACh and Ch were determined by high performance liquid chromatography-post-column immobilized enzyme reactor-electrochemical process. ACh and Ch contents in mPFC extracellular fluid of normal rats were higher than that in hippocampus. During the process of perfusion, NaN3 could significantly reduce ACh in mPFC/hippocampal extra-cellular fluid, but remarkably increase Ch, and constantly inhibit the recovery of ACh and Ch contents in mPFC/hippocampus. The synchronous perfusion of NaN3in rat mPFC and hippocampus can injure functions of the cholinergic nerve projection area, and cause the acute AD model with ACh and Ch metabolic disorders. This model can be used in pathogenetic and pharmacological studies.

Therapeutic and pharmacokinetic characterizations of an anti-amyloidogenic bis-styrylbenzene derivative for Alzheimer’s disease treatment

Alzheimer’s disease drug discovery regarding exploration into the molecules and processes has focused on the intrinsic causes of the brain disorder correlated with the accumulation of amyloid-β. An anti-amyloidogenic bis-styrylbenzene derivative, KMS80013, showed excellent oral bioavailability (F=46.2%), facilitated brain penetration (26%, iv) in mouse and target specific in vivo efficacy in acute AD mouse model attenuating the cognitive deficiency in Y-maze test. Acute toxicity (LD50 >2000mg/kg) and hERG channel inhibition (14% at 10μM) results indicated safety of KMS80013.

Sexual function and autonomic dysreflexia in men with spinal cord injuries: how should we treat?

Systematic review. Review the literature on the acute or prophylactic treatment of autonomic dysreflexia in the context of sexual activities. International. Medline search using AD and spinal cord injury and all years of publication. Thirty-seven papers on the specific treatment of AD showed that nifedipine, prazosin, captopril and clonidine are candidates in the context of sexual activities. Prazosin, however, has an initial hypotensive effect requiring to begin treatment 12 h before intercourse, which makes it less ideal for spontaneous sexual activities. Captopril has an initial hypotensive effect and was only studied in acute AD. Its usefulness in prophylaxis remains to be demonstrated. Clonidine has successfully been used clinically for decades, but never studied in randomized control trials. Nifedipine remains the most widely studied and significant treatment of AD whether in acute or prophylactic conditions. Recent concerns suggest increased cardiovascular risks with sublingual nifedipine in non-SCI populations, but negative long-term effects have not been reported in the SCI population. Sexual function is a priority for men with SCI. As sexual activities, in particular ejaculation, can be a source of AD, adequate treatments and prophylaxis must be considered in the context of sexual activities. Experts must meet and conclude on the thresholds, parameters and treatments that should be considered in the long-term management of AD in the context of sexual function in men with SCI.

Induction of GITRL expression in human keratinocytes by Th2 cytokines and TNF‐α: implications for atopic dermatitis

Glucocorticoid-induced TNF receptor-related protein ligand (GITRL), a ligand for the T cell co-stimulatory molecule GITR, is expressed by keratinocytes and involved in chemokine production. The expression of GITRL in skin inflammation remains unknown. This study investigated cytokine regulation of keratinocyte GITRL expression. Glucocorticoid-induced TNF receptor expression was evaluated in cytokine-treated human epidermal keratinocytes (HEK)s, murine PAM 212 cell line, murine and human skin explants by real time PCR, flow cytometry and immunostaining. Functional responses to GITR fusion protein were examined by real time PCR and ELISA. GITRL expression in AD and psoriasis was studied by immunohistochemistry. Skin biopsies from STAT6VT transgenic mice, which develop spontaneous atopic skin inflammation, were found by immunofluoresence, to have increased keratinocyte GITRL expression. Exposure to Th2 cytokines augmented GITRL mRNA expression in the murine PAM 212 keratinocytic cell line and murine skin explants. In contrast, GITRL mRNA and protein expression was only increased in HEKs and human skin explants in the presence of the combination of TNF-α and Th2 cytokines. A synergistic effect of Th2 cytokines and GITR fusion protein on production of CCL17, the Th2 chemokine, by murine keratinocytes was demonstrated. Immunohistochemical staining showed that acute AD lesions have increased expression of GITRL compared with normal skin, chronic AD lesions and psoriatic plaques. Our studies demonstrate that GITRL expression is augmented by Th2 cytokines and TNF-α in keratinocytes. Increased GITRL expression in acute AD skin lesions is shown. This observation suggests a link between cytokine-regulated keratinocyte GITRL expression and its role in inflammatory responses in AD.

Assessment of left ventricular twist mechanics in Tako-tsubo cardiomyopathy by two-dimensional speckle-tracking echocardiography

To assess left ventricular (LV) twist mechanics in patients with Tako-tsubo cardiomyopathy (TTC). Two-dimensional strain and LV twist by speckle-tracking echocardiography was performed in 17 consecutive patients with typical TTC according to the Mayo clinic criteria [78 ± 8 years, 88% women, and mean left ventricular ejection fraction (LVEF) 45 ± 10%], at the acute phase (within 24 h after admission) and after recovery (1 month later). Seventeen control (C) patients matched for age and sex (mean LVEF 70 ± 7%), and 17 patients with acute anterior myocardial infarction (MI) treated by successful primary angioplasty 24 h before, matched for LVEF, age, and sex, were compared with TTC patients. LV twist was assessed using the parasternal basal and apical short-axis planes, and defined as the net difference in degrees of apical (Ar) and basal rotation (Br). Peak systolic and early diastolic, apical (As and Ad) and basal (Bs and Bd) rotation rate, and LV twisting rate (TR) and untwisting rate (UR) (in °/s) were derived from rotational and twist curves. The time sequences were normalized to the percentage of systolic duration. At the acute phase, Ar, As, Ad, Bs, LV twist (10 ± 9° vs. 23 ± 6°), LV TR, and LV UR were significantly impaired in patients with TTC when compared with controls (all, P < 0.05). Patients with MI displayed intermediate values (P = NS vs. TTC, and P < 0.05 vs. C). However, in the subgroup of patients with electrocardiogram ST-segment elevation at presentation (n = 12 TTC and 17 MI), several LV twist mechanics parameters were significantly reduced in TTC patients when compared with MI patients, LV twist, and LV TR being the most significant factors (all, P≤ 0.01). Abnormal reversed Ar (clockwise when seen from the apex) was seen in three patients (18%) with TTC vs. none in the other groups. A significant correlation between LV twist and LVEF, LV volumes, wall motion score index, and plasma NT-pro BNP was observed in the TTC group (all, P < 0.05). At follow-up, LV twist mechanics improved significantly in TTC patients (all, P < 0.05 vs. acute phase), who had final values similar to C (all, P = NS), whereas the magnitude of improvement was lower in MI patients (P ≤ 0.05 vs. TTC). LV twist mechanics is significantly impaired in patients with TTC mainly due to a severe reduction in apical function and is entirely reversible. Furthermore, in the subgroup of patients with ST-segment elevation, the early post-admission evaluation of LV twist mechanics is more severely impaired in TTC when compared with MI.

Efficacy of Topical Immunoglobulins against Experimental Adenoviral Ocular Infection

Presently, there is no U.S. Federal Drug Administration (FDA)-approved antiviral therapy for the treatment of adenoviral (Ad) ocular infections. The goal of the present study was to determine the antiviral efficacy of human immunoglobulin (Ig), a preparation of highly purified and concentrated immunoglobulin (IgG) antibodies isolated from a large pool of human plasma donors, in vitro and on acute Ad replication in the Ad5 New Zealand White (NZW) rabbit ocular model. The antiviral activity of human Ig against multiple wild-type and human ocular isolates of adenovirus serotypes was investigated in vitro by using neutralizing assays in different human epithelial cell lines. In vivo bilateral topical ocular toxicity and antiviral efficacy were evaluated with established Ad5/NZW rabbit ocular models. In vivo Ig antiviral results were compared with those obtained with topical 0.5% cidofovir and saline. In three different epithelial cell lines, <or=6.25 mg/mL of the Ig neutralized several wild-type adenoviral serotypes that cause ocular infections. A dose of <or=10 mg/mL neutralized 88% of ocular isolates of the adenovirus serotypes. After treatment of infected animals, adenovirus-positive cultures per total cultures (days 1-14; P = 0.021), the duration of Ad5 shedding, (P = 0.008), and the mean combined ocular viral titer during the early (days 1-5; P = 0.0001) and the late (days 7-14; P = 0.013) phases of infection were significantly lower in Ig-treated animals than in saline-treated animals and were similar to those in cidofovir-treated animals. Ig demonstrated antiviral properties against multiple adenoviral serotypes in vitro and in the Ad5/NZW rabbit ocular model. Further studies are needed to advance topical immunoglobulin for treatment and prophylaxis of ocular infections.

Bone Contusion Distribution In A Cohort Of Patients With Acute Ad Disruption

Bone Contusion Distribution In A Cohort Of Patients With Acute Ad Disruption

Oral Prednisone Has Niche Role for Acute AD

Oral Prednisone Has Niche Role for Acute AD

Endovascular stent-graft treatment of aortic dissection: determinants of post-interventional outcome

To investigate the results of endovascular stent-graft placement for the treatment of patients with type B aortic dissection (B-AD). A total of 38 patients (62+/-10 years, 32 male) with acute (n=10) and chronic (n=28) type B-AD were treated with endovascular stent-grafts. The implantation procedure was successful in all patients. Peri-procedural non-fatal complications occurred in four (11%) patients. Overall, 4/38 (11%) patients died during the in-hospital period. Patients undergoing stent-graft placement for acute AD had a significantly higher in-hospital mortality than patients with chronic AD (40 vs. 0%, P=0.001). During a median follow-up of 18 (1-57) months, there were six additional deaths. Overall survival rates were 97.4+/-2.6% at 30 days, 80.4+/-6.7% at 1 year, 73.2+/-7.8% at 2 years, and 54.9+/-16.9% at 4 years. Patients with a poor clinical health status (ASA class > 3) had a significantly reduced life expectancy compared with patients with only moderate co-morbidities (ASA class </= 3) (1-year survival rate 28.6+/-17.1 vs. 92.6+/-6.7%, P=0.0001). Multivariable analysis revealed that a poor clinical health status (ASA>3) pre-operatively (HR=29.5, 95% CI 1.5-581.9, P=0.026) and increased age (HR=1.1, 95% CI 0.9-1.2, P=0.084) were independent determinants of post-interventional mortality. Endovascular stent-graft treatment is a safe alternative for patients with AD. The pre-operative clinical health status of the patient is the most important determinant of post-interventional outcome. Careful patient selection is thus of particular importance.

Intracranial Pressure, High Altitude and Acute Mountain Sickness

Conference Abstract| February 01 1995 Intracranial Pressure, High Altitude and Acute Mountain Sickness AD Wright, FRCP; AD Wright, FRCP 1Birmingham Medical Research Expeditionary Society, The Medical School, Edgbaston, Birmingham. B15 2TJ and Audiology Centre, The Royal National Throat, Nose and Ear Hospital, London. WC1X 8DA Search for other works by this author on: This Site PubMed Google Scholar CHE Imray, FRCS; CHE Imray, FRCS 1Birmingham Medical Research Expeditionary Society, The Medical School, Edgbaston, Birmingham. B15 2TJ and Audiology Centre, The Royal National Throat, Nose and Ear Hospital, London. WC1X 8DA Search for other works by this author on: This Site PubMed Google Scholar MSC Morrissey, FRCS otol; MSC Morrissey, FRCS otol 1Birmingham Medical Research Expeditionary Society, The Medical School, Edgbaston, Birmingham. B15 2TJ and Audiology Centre, The Royal National Throat, Nose and Ear Hospital, London. WC1X 8DA Search for other works by this author on: This Site PubMed Google Scholar RJ Marchbanks, Phd; RJ Marchbanks, Phd 1Birmingham Medical Research Expeditionary Society, The Medical School, Edgbaston, Birmingham. B15 2TJ and Audiology Centre, The Royal National Throat, Nose and Ear Hospital, London. WC1X 8DA Search for other works by this author on: This Site PubMed Google Scholar AR Bradwell AR Bradwell 1Birmingham Medical Research Expeditionary Society, The Medical School, Edgbaston, Birmingham. B15 2TJ and Audiology Centre, The Royal National Throat, Nose and Ear Hospital, London. WC1X 8DA Search for other works by this author on: This Site PubMed Google Scholar Clin Sci (Lond) (1995) 88 (s32): 26P. https://doi.org/10.1042/cs088026Pb Views Icon Views Article contents Figures & tables Video Audio Supplementary Data Peer Review Share Icon Share Facebook Twitter LinkedIn MailTo Cite Icon Cite Get Permissions Citation AD Wright, CHE Imray, MSC Morrissey, RJ Marchbanks, AR Bradwell; Intracranial Pressure, High Altitude and Acute Mountain Sickness. Clin Sci (Lond) 1 February 1995; 88 (s32): 26P. doi: https://doi.org/10.1042/cs088026Pb Download citation file: Ris (Zotero) Reference Manager EasyBib Bookends Mendeley Papers EndNote RefWorks BibTex toolbar search Search Dropdown Menu toolbar search search input Search input auto suggest filter your search All ContentAll JournalsClinical Science Search Advanced Search This content is only available as a PDF. © 1995 The Biochemical Society and the Medical Research Society1995 Article PDF first page preview Close Modal You do not currently have access to this content.

Enzyme-linked immunosorbent assay (ELISA) for detecting antibodies in sera of patients with adenovirus infection

The 41 distinct antigenic types of adenoviruses (Ads) are responsible for a broad spectrum of diseases in humans. We have developed an enzyme-linked immunosorbent assay (ELISA) using adenovirus (Ad) infected MRC-5 cells for detecting IgG and IgM antibodies to Ads. Using the ELISA, we detected IgG antibodies in 100% ( 20 20 ) of sera from normal adults (geometric mean titer, GMT = 1840.8, range = 40−20,480) and IgM antibodies in 3 of 20 sera (15%) with a GMT of 25.1. Our indirect immunofluorescence (IF) technique also detected IgG antibodies in 100%) of these sera (GMT = 248.3, range = 40−5,120) and IgM antibodies in the 3 samples reactive in ELISA (GMT = 20.0, range = < 5−40). In contrast, the complement fixation (CF) test detected antibodies to Ads in only 65% ( 13 20 ) of these sera (GMT = 10.9, range = < 4−32). Moreover, IgG and IgM responses could not be distinguished using CF. Thus the sensitivity of these three techniques is greatest for ELISA. Additionally, a study of sequential sera from 3 patients with acute Ad infection disclosed seroconversion using all three methods. Both the ELISA and IF techniques permit the detection of transition from IgM to IgG, whereas CF only detects conversion from seronegativity to seropositivity. Finally, preliminary data suggest that the IgM response as measured by ELISA is specific for subgroups or types of Ad. This newly devised ELISA may be useful for detecting Ad infections.