Estimation of human percutaneous bioavailability for two novel brominated flame retardants, 2-ethylhexyl 2,3,4,5-tetrabromobenzoate (EH-TBB) and bis(2-ethylhexyl) tetrabromophthalate (BEH-TEBP)

DOE Office of Scientific and Technical Information (OSTI.GOV)

Knudsen, Gabriel A., E-mail: gabriel.knudsen@nih.g

2-Ethylhexyl-2,3,4,5-tetrabromobenzoate (EH-TBB) and bis(2-ethylhexyl)tetrabromophthalate (BEH-TEBP) are novel brominated flame retardants used in consumer products. A parallelogram approach was used to predict human dermal absorption and flux for EH-TBB and BEH-TEBP. [{sup 14}C]-EH-TBB or [{sup 14}C]-BEH-TEBP was applied to human or rat skin at 100 nmol/cm{sup 2} using a flow-through system. Intact rats received analogous dermal doses. Treated skin was washed and tape-stripped to remove “unabsorbed” [{sup 14}C]-radioactivity after continuous exposure (24 h). “Absorbed” was quantified using dermally retained [{sup 14}C]-radioactivity; “penetrated” was calculated based on [{sup 14}C]-radioactivity in media (in vitro) or excreta + tissues (in vivo). Human skin absorbedmore » EH-TBB (24 ± 1%) while 0.2 ± 0.1% penetrated skin. Rat skin absorbed more (51 ± 10%) and was more permeable (2 ± 0.5%) to EH-TBB in vitro; maximal EH-TBB flux was 11 ± 7 and 102 ± 24 pmol-eq/cm{sup 2}/h for human and rat skin, respectively. In vivo, 27 ± 5% was absorbed and 13% reached systemic circulation after 24 h (maximum flux was 464 ± 65 pmol-eq/cm{sup 2}/h). BEH-TEBP in vitro penetrance was minimal (< 0.01%) for rat or human skin. BEH-TEBP absorption was 12 ± 11% for human skin and 41 ± 3% for rat skin. In vivo, total absorption was 27 ± 9%; 1.2% reached systemic circulation. In vitro maximal BEH-TEBP flux was 0.3 ± 0.2 and 1 ± 0.3 pmol-eq/cm{sup 2}/h for human and rat skin; in vivo maximum flux for rat skin was 16 ± 7 pmol-eq/cm{sup 2}/h. EH-TBB was metabolized in rat and human skin to tetrabromobenzoic acid. BEH-TEBP-derived [{sup 14}C]-radioactivity in the perfusion media could not be characterized. < 1% of the dose of EH-TBB and BEH-TEHP is estimated to reach the systemic circulation following human dermal exposure under the conditions tested. Chemical compounds studied in this article: 2-Ethylhexyl 2,3,4,5-tetrabromobenzoate (PubChem CID: 71316600; CAS No

Human leukocyte antigen B27 and B51 double-positive Behçet uveitis.

PubMed

Ahn, Jae Kyoun; Park, Yeoung Geol

2007-10-01

To describe the clinical characteristics of human leukocyte antigen (HLA) B27 and B51 double-positive Behçet uveitis and to determine whether the coexistence of HLA-B27 can affect Behçet uveitis. We retrospectively reviewed the medical records of patients with Behçet uveitis and patients with HLA-B27-associated non-Behçet uveitis who underwent HLA-B27 and HLA-B51 typing and were followed up for more than 3 years. We divided the patients into 3 groups according to HLA-B27/B51 status and compared the clinical outcomes. Main outcome measures were demographic features, uveitis characteristics, complications, treatments, and visual prognosis. Fourteen patients with HLA-B27(+)B51(+) Behçet uveitis, 43 patients with HLA-B27(-)B51(+) Behçet uveitis, and 41 patients with HLA-B27(+)B51(-) non-Behçet uveitis were identified. HLA-B27(+)B51(+) Behçet uveitis showed the demographic features similar to HLA-B27(-) counterparts. However, HLA-B27(+)B51(+) Behçet uveitis showed less involvement of posterior segments, a less chronic course, fewer complications in posterior segments, and less use of systemic medication or surgical intervention for inflammatory control, similar to HLA-B27(+)B51(-) non-Behçet uveitis. The long-term vision prognosis of HLA-B27(+)B51(+) Behçet uveitis was more favorable than that of HLA-B27(-)B51(+) Behçet uveitis. Our results indicate that HLA-B27(+)B51(+) Behçet uveitis is a benign subgroup of Behçet uveitis. The positivity of HLA-B27 may be a good prognostic factor in Behçet uveitis.

Behçet disease in Western Algeria.

PubMed

Ghembaza, M E A; Bouabdallah, N; Lounici, A

2017-02-01

The aim of the current study was to describe the epidemiological and clinical features of Behçet disease in western Algeria. This observational retrospective study examined records for patients with Behçet disease seen in our department from 1990 to 2015. Of the 61 patients included in the study, 80.3% were men, for a sex ratio of 4.08. The mean age at onset was 27.2±7 years, and the mean interval between the onset of symptoms and diagnosis was 4.8±6.3 years. Dermatologic manifestations were the most common finding. Oral ulcers were seen in all patients, genital ulcers in 60%, pseudofolliculitis in 56.4%, and erythema nodosum in 13.5%. A pathergy test was positive in 20% of the patients. The frequencies of the remaining manifestations were as follows: joint involvement 50%, ocular involvement 71.2%, vascular complications 29.6%, neurological involvement 19%, and gastrointestinal complications 7.5%. Besides dermatological manifestations, ocular and vascular complications were the most common features observed in our patients.

Differential diagnosis and management of Behçet syndrome.

PubMed

Ambrose, Nicola L; Haskard, Dorian O

2013-02-01

Behçet syndrome (also known as Behçet disease) is a rare condition that is associated with considerable morbidity. Cases of Behçet syndrome have been reported worldwide, but the highest prevalence occurs in countries that border the ancient Silk Route, such as Turkey and Iran. Although oral ulceration, genital ulceration and eye disease are the classic triad of manifestations, the cardiovascular, gastrointestinal, musculoskeletal and central nervous systems can also be affected. The syndrome is chronic and relapsing with some patients having benign episodes whereas others have more serious complications, including blindness or the rupture of a pulmonary arterial aneurysm. Diagnosing Behçet syndrome, particularly outside of endemic regions, often incurs a considerable delay owing to the rarity of this condition. Furthermore, a paucity exists of data from randomized controlled trials on the optimal therapeutic approaches to use in patients, as well as a lack of informative laboratory surrogate markers to monitor disease progression. This Review discusses the issues surrounding the diagnosis and differential diagnosis of Behçet syndrome and presents the current approaches to managing patients with this complex group of disorders.

Behçet's syndrome: facts and controversies.

PubMed

Mat, Cem; Yurdakul, Sebahattin; Sevim, Ayşegül; Özyazgan, Yılmaz; Tüzün, Yalçın

2013-01-01

Behçet's syndrome is a systemic vasculitis of small and large vessels affecting both veins and arteries. Almost all patients with Behçet's syndrome have recurrent oral aphthae, followed by genital ulcers, variable skin lesions, such as erythema nodosum and papulopustuler lesions, arthritis, uveitis, thrombophlebitis, and gastrointestinal and central nervous system involvement. Recent epidemiologic works suggest that genetic factors are more important than environmental factors in its pathogenesis. European League Against Rheumatism guidelines were recently published for the treatment of Behçet's syndrome. Although these are quite useful for the management of mucocutaneous, eye, and joint involvement, treatment of vascular, neurological, and gastrointestinal involvement are still problematic as there are no controlled studies for these manifestations. This contribution addresses the epidemiology, mucocutaneous manifestations, diagnostic criteria, and evidence-based therapies, including biologic agents. Copyright © 2013 Elsevier Inc. All rights reserved.

The role of infections in Behçet disease and neuro-Behçet syndrome.

PubMed

Marta, Monica; Santos, Ernestina; Coutinho, Ester; Silva, Ana Martins; Correia, João; Vasconcelos, Carlos; Giovannoni, Gavin

2015-07-01

Infections are considered an environmental trigger for exacerbations of immune-mediated diseases. We aimed to establish if common viral infections could be identified as a precipitant of Behçet disease (BD) with or without neurological involvement and to assess the variability of the immune response to common viruses. We also investigated whether cytokines and chemokines could be markers of neurological involvement. Finally, we explored if anti-basal ganglia antibodies (ABGAs) would be associated with neurological involvement in BD. Our study included 14 individuals with BD with neurological involvement (neuroBehçet syndrome - NBS), 16 individuals with BD without neurological involvement and 18 healthy controls (HC). Overall we found a tendency for increased levels of anti-viral IgG antibody levels in BD, more evident in NBS patients versus HC. Epstein-Barr viral-capsid antigen IgG titres were increased in NBS patients versus other BD patients (p=0.032). Anti-measles antibody titres induced by vaccination were similarly elevated. ABGAs were not detected in the serum of our cohort. Raised levels of serum IL-8 in some BD patients did not reflect clinical activity or severity. In conclusion, there was evidence for a polyclonal immune activation rather than a specific virus effect in the sera of individuals with BD or NBS. Copyright © 2015 Elsevier B.V. All rights reserved.

Estimation of human percutaneous bioavailability for two novel brominated flame retardants, 2-ethylhexyl 2,3,4,5-tetrabromobenzoate (EH-TBB) and bis(2-ethylhexyl) tetrabromophthalate (BEH-TEBP).

PubMed

Knudsen, Gabriel A; Hughes, Michael F; Sanders, J Michael; Hall, Samantha M; Birnbaum, Linda S

2016-11-15

2-Ethylhexyl-2,3,4,5-tetrabromobenzoate (EH-TBB) and bis(2-ethylhexyl)tetrabromophthalate (BEH-TEBP) are novel brominated flame retardants used in consumer products. A parallelogram approach was used to predict human dermal absorption and flux for EH-TBB and BEH-TEBP. [ 14 C]-EH-TBB or [ 14 C]-BEH-TEBP was applied to human or rat skin at 100nmol/cm 2 using a flow-through system. Intact rats received analogous dermal doses. Treated skin was washed and tape-stripped to remove "unabsorbed" [ 14 C]-radioactivity after continuous exposure (24h). "Absorbed" was quantified using dermally retained [ 14 C]-radioactivity; "penetrated" was calculated based on [ 14 C]-radioactivity in media (in vitro) or excreta+tissues (in vivo). Human skin absorbed EH-TBB (24±1%) while 0.2±0.1% penetrated skin. Rat skin absorbed more (51±10%) and was more permeable (2±0.5%) to EH-TBB in vitro; maximal EH-TBB flux was 11±7 and 102±24pmol-eq/cm 2 /h for human and rat skin, respectively. In vivo, 27±5% was absorbed and 13% reached systemic circulation after 24h (maximum flux was 464±65pmol-eq/cm 2 /h). BEH-TEBP in vitro penetrance was minimal (<0.01%) for rat or human skin. BEH-TEBP absorption was 12±11% for human skin and 41±3% for rat skin. In vivo, total absorption was 27±9%; 1.2% reached systemic circulation. In vitro maximal BEH-TEBP flux was 0.3±0.2 and 1±0.3pmol-eq/cm 2 /h for human and rat skin; in vivo maximum flux for rat skin was 16±7pmol-eq/cm 2 /h. EH-TBB was metabolized in rat and human skin to tetrabromobenzoic acid. BEH-TEBP-derived [ 14 C]-radioactivity in the perfusion media could not be characterized. <1% of the dose of EH-TBB and BEH-TEHP is estimated to reach the systemic circulation following human dermal exposure under the conditions tested. 2-Ethylhexyl 2,3,4,5-tetrabromobenzoate (PubChem CID: 71316600; CAS No. 183658-27-7 FW: 549.92g/mol logP est : 7.73-8.75 (12)) Abdallah et al., 2015a. Other published abbreviations for 2-ethylhexyl-2

Headache in Behçet's disease.

PubMed

Aykutlu, E; Baykan, B; Akman-Demir, G; Topcular, B; Ertas, M

2006-02-01

The aim of this study was to investigate the characteristics of headache in patients with Behçet's disease (BD) seeking neurological consultation. Consecutive patients with BD seen within 1 year at the neuro-Behçet's out-patient clinic were studied using an electronic database according to the classification criteria of the International Headache Society. During a 12-month period 118 BD patients were admitted, and 98 had headaches. Migraine was the most common type of primary headache diagnosed in 45 patients (46.4%) in the whole headache group, followed by tension-type headache (TTH) in 26 cases (26.8%). Thirty-seven patients had secondary headaches mainly due to cerebral venous thrombosis or parenchymal neurological involvement of BD. Of these patients, 15 had both primary and secondary headaches. The primary headaches of 13 patients were exacerbated with systemic BD flare-ups, and four patients had migraine attacks triggered only by systemic BD activation which showed a good response to the treatment of systemic inflammation. The majority of the headaches of patients with BD do not indicate any neurological involvement; they are usually due to migraine or TTH. In a minority of patients, migraine associated with systemic inflammation of BD is notable.

Interferon Alpha-2a Therapy in Patients with Refractory Behçet Uveitis.

PubMed

Hasanreisoglu, Murat; Cubuk, Mehmet Ozgur; Ozdek, Sengul; Gurelik, Gokhan; Aktas, Zeynep; Hasanreisoglu, Berati

2017-02-01

To report the results of IFNα2a therapy in patients with Behçet uveitis refractory to azathioprine-cyclosporine combination treatment. In a retrospective study, 39 patients treated with either azathioprine-cyclosporine combination treatment (group 1, n = 23) or IFNα2a (group 2, n = 16) with a diagnosis of ocular Behçet disease (BD), were included in the study. Group 2 consisted of patients who did not respond to conventional combination therapy, and were therefore treated with IFNα2a. Clinical response and relapse rates were recorded for each group. The mean number of uveitis attacks/year per patient was 0.8 ± 1.6 in Group 1. In Group 2, a significant decrease in the mean number of uveitis attacks/year per patient was observed after initiation of IFNα2a (2.4 ± 1.8 vs 1.3 ± 2.0) (p<0.05). When the two groups were compared after administration of IFNα2a therapy, no statistical difference was found in terms of uveitis attack/year and attack-free intervals, with a partial response to both treatments. IFNα2a therapy is an effective alternative for Behçet uveitis patients where conventional combination therapy fails.

Severe panuveitis in neuro-Behçet's disease in Malaysia: a case series.

PubMed

Othman, Khairuddin; Liza-Sharmini, Ahmad Tajudin; Ibrahim, Mohtar; Tharakan, John; Yanai, Ryoji; Zunaina, Embong

2017-01-01

Behçet's disease (BD) is a multisystemic disease that is very rare in Malaysia. About 5% of patients develop central nervous system involvement, termed neuro-Behçet's. Neuro-Behçet's is one of the most serious causes of long-term morbidity and mortality. We report two cases of neuro-Behçet's associated with uveitis (ocular BD) highlighting the clinical presentation, diagnostic measurement, and therapeutic management of these cases.

Colon perforation and Budd-Chiari syndrome in Behçet's disease.

PubMed

Baş, Yılmaz; Güney, Güven; Uzbay, Pınar; Zobacı, Ethem; Ardalı, Selin; Özkan, Ayşegül Taylan

2015-05-02

Behçet's disease is a chronic inflammatory disease involving multiple systems, with vasculitis being the most important pathological feature. Multiple colon perforations are thought to be secondary to vasculitis and they occur in patients with ulcers. These may be encountered within the entire colon but most commonly in the ileocecal region. Intestinal perforation and Budd-Chiari syndrome are infrequent in Behçet's disease, and are associated with high mortality and morbidity. Budd-Chiari syndrome results from occlusion of either hepatic veins or adjacent inferior vena cava, or both. We report a patient with Behçet's disease having multiple perforations in the transverse colon, descending colon, and sigmoid colon. The patient also had Budd-Chiari syndrome due to inferior vena cava thrombosis extending into the right and middle hepatic vein. Our observations are presented with a review of the literature. In Behçet's disease, treatment of colon perforation necessitates urgent surgery, whereas management of Budd-Chiari syndrome is directed towards the underlying cause. Behçet's disease, as a chronic multisystemic disease with various forms of vasculitis, is resistant to medical and surgical treatment. Prognosis is worse in Behçet's disease with colon perforation than that in Budd-Chiari syndrome alone.

The immunogenetics of Behçet’s disease: A comprehensive review

PubMed Central

Takeuchi, Masaki; Kastner, Daniel L; Remmers, Elaine F

2015-01-01

Behçet’s disease is a chronic multisystem inflammatory disorder characterized mainly by recurrent oral ulcers, ocular involvement, genital ulcers, and skin lesions, presenting with remissions and exacerbations. It is thought that both environmental and genetic factors contribute to its onset and development. Although the etiology of Behçet’s disease remains unclear, recent immunogenetic findings are providing clues to its pathogenesis. In addition to the positive association of HLA-B*51, which was identified more than four decades ago, and which has since been confirmed in multiple populations, recent studies report additional independent associations in the major histocompatibility complex class I region. HLA-B*15, -B*27, -B*57, and -A*26 are independent risk factors for Behçet’s disease, while HLA-B*49 and – A*03 are independent class I alleles that are protective for Behçet’s disease. Genome-wide association studies have identified associations with genome-wide significance (P < 5 × 10−8) in the IL23R–IL12RB2, IL10, STAT4, CCR1-CCR3, KLRC4, ERAP1, TNFAIP3, and FUT2 loci. In addition, targeted next-generation sequencing has revealed the involvement of rare nonsynonymous variants of IL23R, TLR4, NOD2, and MEFV in Behçet’s disease pathogenesis. Significant differences in gene function or mRNA expression associated with the risk alleles of the disease susceptibility loci suggest which genes in a disease-associated locus influence disease pathogenesis. These genes encompass both innate and adaptive immunity and confirm the importance of the predominant polarization towards helper T cell (Th) 1 versus Th2 cells, and the involvement of Th17 cells. In addition, epistasis observed between HLA-B*51 and the risk coding haplotype of the endoplasmic reticulum-associated protease, ERAP1, provides a clue that an HLA class I-peptide presentation-based mechanism contributes to this complex disease. PMID:26347074

Behçet syndrome: a contemporary view.

PubMed

Yazici, Hasan; Seyahi, Emire; Hatemi, Gulen; Yazici, Yusuf

2018-02-01

The presence of symptom clusters, regional differences in disease expression and similarities with, for example, Crohn's disease suggest multiple pathological pathways are involved in Behçet syndrome. These features also make formulating disease criteria difficult. Genetic studies have identified HLA-B*51 to be the important genetic risk factor. However, the low prevalence of HLA-B*51 in many patients with bone fide disease, especially in non-endemic regions, suggests other factors must also be operative in Behçet syndrome. This consideration is also true for the newly proposed 'MHC-I-opathy' concept. Despite lacking a clear aetiological mechanism and definition, management of manifestations that include major vascular disease (such as Budd-Chiari syndrome and pulmonary artery involvement), eye disease and central nervous system involvement has improved with the help of new technology. Furthermore, even with our incomplete understanding of disease mechanisms, the prognoses of patients with Behçet syndrome, including those with eye disease, continue to improve.

Seroprevalence of Borrelia burgdorferi in patients with Behçet's disease.

PubMed

Onen, Fatos; Tuncer, Dilek; Akar, Servet; Birlik, Merih; Akkoc, Nurullah

2003-11-01

Turkey is one of the countries where Behçet's disease is most prevalent. Although its pathogenesis is not defined clearly, infectious agents are thought to play a role in the etiology. In one study of a group of uveitis patients, including those with Behçet's disease, increased seropositivity to B. burgdorferi was reported by enzyme-linked immunosorbent assay (ELISA). The seroprevalence of B. burgdorferi has been found to be as high as 36% in some rural areas of Turkey, although Lyme disease caused by B. burgdorferi is quite rare. In this study, we investigated the seroreactivity to B. burgdorferi antigens in patients with Behçet's disease and compared it with that of healthy and disease controls. This study was conducted in Izmir in western Turkey. B. burgdorferi immunoglobulin (Ig)M and IgG antibodies were tested by ELISA in the sera of patients with Behçet's disease ( n=30), rheumatoid arthritis patients as disease controls ( n=31), and healthy controls ( n=31). Positive results were confirmed by Western blotting. The difference in B. burgdorferi seropositivity between the groups was not significant by any method. Seroreactivity to B. burgdorferi antigens by ELISA was detected in 26.7% of the patients with Behçet's disease, 35.5% of those with rheumatoid arthritis, and 19.4% of the healthy controls. Immunoblots were positive in 13.3% of the Behçet's disease patients, 22.6% of the rheumatoid arthritis patients, and 12.9% of healthy controls. These results suggest no association between Behçet's disease and B. burgdorferi infection.

Behçet's syndrome pathophysiology and potential therapeutic targets.

PubMed

Emmi, Giacomo; Silvestri, Elena; Squatrito, Danilo; D'Elios, Mario Milco; Ciucciarelli, Lucia; Prisco, Domenico; Emmi, Lorenzo

2014-04-01

Behçet syndrome is a systemic inflammatory disorder characterized by multiorgan involvement such as oral and genital ulcers, uveitis, skin lesions as well as by less frequent, but often more severe, central nervous system and vascular manifestations. The pathogenetic mechanisms are still incompletely known; however the interaction between a specific genetic background and environmental or infectious factors certainly contributes to the immune dysregulation that characterizes this disease. The discovery of new immunological pathways in Behçet syndrome pathogenesis may help us to set up new treatments. In this review, we will focus our attention on the possible mechanisms underlying Behçet syndrome pathogenesis and their potential role as novel therapeutic targets.

Update on the therapy of Behçet disease

PubMed Central

Saleh, Zeinab

2014-01-01

Behçet disease is a chronic inflammatory systemic disorder, characterized by a relapsing and remitting course. It manifests with oral and genital ulcerations, skin lesions, uveitis, and vascular, central nervous system and gastrointestinal involvement. The main histopathological finding is a widespread vasculitis of the arteries and veins of any size. The cause of this disease is presumed to be multifactorial involving infectious triggers, genetic predisposition, and dysregulation of the immune system. As the clinical expression of Behçet disease is heterogeneous, pharmacological therapy is variable and depends largely on the severity of the disease and organ involvement. Treatment of Behçet disease continues to be based largely on anecdotal case reports, case series, and a few randomized clinical trials. PMID:24790727

Quality control of modified xiaoyao san through the determination of 22 active components by ultra-performance liquid chromatography.

PubMed

Qin, Feng; Huang, Jun; Qiu, Xinjian; Hu, Sihang; Huang, Xi

2011-01-01

A simple, sensitive, and reliable ultra-performance liquid chromatography (UPLC) method has been developed for simultaneous determination of 22 major constituents in modified xiaoyao san (MXS), a multiherbal formula. The chromatographic separation was performed on an ACQUITY UPLC BEH C18 column (150 x 2.1 mm, 1.7 microm, particle size), with an aqueous 0.5% acetic acid and acetonitrile mobile phase gradient. The method was validated for linearity (r2 >0.9937), intraday and interday precision (RSD <8.51%), recovery (91.18-107.73%), LOD (0.02-4.17 ng/mL), and LOQ (0.05-12.50 ng/mL). The established method was successfully applied to quantify the 22 marker compounds in MXS, which provided a useful basis of overall evaluation of the quality of MXS.

Estimation of human percutaneous bioavailability for two novel brominated flame retardants, 2-ethylhexyl 2,3,4,5-tetrabromobenzoate (EH-TBB) and bis(2-ethylhexyl) tetrabromophthalate (BEH-TEBP)

PubMed Central

Knudsen, Gabriel A.; Hughes, Michael F.; Sanders, J. Michael; Hall, Samantha M.; Birnbaum, Linda S.

2016-01-01

2-ethylhexyl-2,3,4,5-tetrabromobenzoate (EH-TBB) and bis(2-ethylhexyl)tetrabromophthalate (BEH-TEBP) are novel brominated flame retardants used in consumer products. A parallelogram approach was used to predict human dermal absorption and flux for EH-TBB and BEH-TEBP. [14C]-EH-TBB or [14C]-BEH-TEBP was applied to human or rat skin at 100 nmol/cm2 using a flow-through system. Intact rats received analogous dermal doses. Treated skin was washed and tape-stripped to remove “unabsorbed” [14C]-radioactivity after continuous exposure (24h). “Absorbed” was quantified using dermally retained [14C]-radioactivity; “penetrated” was calculated based on [14C]-radioactivity in media (in vitro) or excreta+tissues (in vivo). Human skin absorbed EH-TBB (24±1%) while 0.2±0.1% penetrated skin. Rat skin absorbed more (51±10%) and was more permeable (2±0.5%) to EH-TBB in vitro; maximal EH-TBB flux was 11±7 and 102±24 pmol-eq/cm2/h for human and rat skin, respectively. In vivo, 27±5% was absorbed and 13% reached systemic circulation after 24 h (maximum flux was 464±65 pmol-eq/cm2/h). BEH-TEBP in vitro penetrance was minimal (<0.01%) for rat or human skin. BEH-TEBP absorption was 12±11% for human skin and 41±3% for rat skin. In vivo, total absorption was 27±9%; 1.2% reached systemic circulation. In vitro maximal BEH-TEBP flux was 0.3±0.2 and 1±0.3 pmol-eq/cm2/h for human and rat skin; in vivo maximum flux for rat skin was 16±7 pmol-eq/cm2/h. EH-TBB was metabolized in rat and human skin to tetrabromobenzoic acid. BEH-TEBP-derived [14C]-radioactivity in the perfusion media could not be characterized. Less than 1% of the dose of EH-TBB and BEH-TEHP is estimated to reach the systemic circulation following human dermal exposure under the conditions tested. PMID:27732871

Right Ventricular Thrombus with Behçet's Syndrome

PubMed Central

Dogan, Sait M.; Birdane, Alparslan; Korkmaz, Cengiz; Ata, Necmi; Timuralp, Bilgin

2007-01-01

Behçet's syndrome is a chronic multisystem disease that presents with recurrent oral and genital ulceration and recurrent uveitis. Cardiac involvement is an extremely rare manifestation of this disorder. A 33-year-old man with Behçet's syndrome was admitted to our department with a history of cough, fever, chest pain, hemoptysis, and weight loss. Transthoracic and transesophageal echocardiography revealed a right ventricular thrombus. After 1 month of treatment with warfarin, cyclophosphamide, and corticosteroid, the intracardiac thrombus resolved. PMID:17948088

Life story of Dr. Hulusi Behçet.

PubMed

Saylan, T

1997-12-01

Dr. Hulusi Behçet was born on February 20, 1889 in Istanbul. He graduated from Gülhane Military Medical Academy in 1910 and then he specialized in Dermatology and Venereal Diseases. He served in the Edirne Military Hospital between 1914-1918 and then went to Budapest and Berlin to improve his knowledge. In 1923, he started at the Istanbul Medical Faculty as an academic staff and with university reform in 1933, he was appointed as a professor to Department of Dermatology and Venereal Diseases and continued his career there until his death in 1948. Three patients whom he had consulted for years and who shared similar symptoms made him suspect a new disease and a viral etiology which may play a role in the appearance of this disease. After several discussions and publications, medical literature had accepted Behçet's Disease as a special entity. Dr. Behçet published a total of 196 articles, 53 of which were published in prestigious international journals.

Behçet's disease with endocarditis and the Budd-Chiari syndrome.

PubMed Central

McDonald, G S; Gad-Al-Rab, J

1980-01-01

Endocarditis of the mitral and aortic valves is described for the first time in a patient with Behçet's disease. A second patient had minor changes in the mitral valve similar to that seen in the vasculitis which occurs in this condition. Valvulitis in Behçet's disease probably has the same pathogenesis as the vasculitis. The second patient also had a rare combination of Behçet's disease and the Budd-Chiari syndrome, and the necropsy findings are described. Images Fig. 1 Fig. 2 Fig. 3 Fig. 4 Fig. 5 Fig. 6 PMID:7430372

Behçet's syndrome in Iranian Azari people.

PubMed

Shahneh, Fatemeh Zare; Babaloo, Zohreh; Baradaran, Behzad; Hamzavi, Fatemeh; Bayazi, Babak; Bandehagh, Ali

2012-11-01

Behçet's Syndrome (BS) is a chronic recurrent multisystemic inflammatory disorder characterized by oral and genital ulcers, ocular inflammation. Behçet's syndrome has a complex genetic etiology. However, epidemiological studies recommend that genetic factors have a significant influence to its pathogenesis, alike to other autoinflammatory disorders. Epidemiological statistics, clinical records and HLA typing were studied in Iranian Azari patients with Behçet's syndrome. This investigation considered HLA associations with BS and HLA with certain clinical characteristics, age and sex in the (Tabriz) Iran which has an ethnically homogeneous population. HLA-A and HLA-B typing was performed in 290 BS patients, conforming to International Study Group criteria and in 300 blood donors, as controls. Patient records were retrospectively reviewed and patients reassessed clinically. HLA-B5, HLA-B35, HLA-51, HLA-B52 and HLA-CW4 presented significantly high frequencies in all patients. No other HLA type was associated. There was a significant HLA link with male sex in BS patients and Mean age (34 +/- 1.1) was determined. We present the frequency and correlation between Iranian Azari patients with Behçet's syndrome and particular HLA antigens. Ninety nine percent had mouth ulceration, 64% genital ulceration, 72% skin lesions and 52% ocular involvement. This study supports HLA-B5, HLA-B35, HLA-51, HLA-B52 and HLA-CW4 immunogenetic predisposition in an ethnically homogeneous (Iranian Azari) population.

Double pylorus in a patient with Behçet's syndrome.

PubMed

Hatemi, Ibrahim; Hatemi, Gulen; Erzin, Yusuf Z; Celik, Aykut Ferhat

2015-01-01

We report a patient with Behçet's syndrome who presented with upper gastrointestinal haemorrhage. Gastroduodenoscopy showed a gastroduodenal fistula which caused the appearance of double pylorus in the antrum. The possibility of peptic ulcer disease related to non-steroidal anti-inflammatory drug use or Behçet's syndrome itself, as the cause of this rare condition in this patient is discussed.

A Case of Myelodysplastic Syndrome with Intestinal Behçet's Disease-Like Symptoms Treated by Prednisolone and Azacitidine.

PubMed

Endo, Masatsugu; Sekikawa, Akira; Tsumura, Takehiko; Maruo, Takanori; Osaki, Yukio

2015-11-21

BACKGROUND Intestinal Behçet's disease-like symptoms are rare complications of myelodysplastic syndrome and are often refractory to immunosuppressive therapies. We described a case of myelodysplastic syndrome complicated by Behçet's disease-like symptoms treated with prednisolone and azacitidine. CASE REPORT A 68-year-old Japanese woman was admitted to our hospital because of persistent high fever and lower abdominal pain. Oral ulcerations developed after admission, and multiple ulcers were found in her terminal ileum by endoscopic examination. She was diagnosed with myelodysplastic syndrome with trisomy 8 by bone marrow examination. Her symptoms diminished after administration of prednisolone, but relapsed afterwards. She began azacitidine therapy and her symptoms have been controlled for at least 10 months. CONCLUSIONS This case might suggest the possibility of azacitidine as a treatment option for myelodysplastic syndrome complicated by Behçet's disease-like symptoms.

New Insights in the Clinical Understanding of Behçet's Disease

PubMed Central

Cho, Sung Bin; Cho, Suhyun

2012-01-01

Behçet's disease is a chronic relapsing multisystemic inflammatory disorder characterized by four major symptoms (oral aphthous ulcers, genital ulcers, skin lesions, and ocular lesions) and occasionally by five minor symptoms (arthritis, gastrointestinal ulcers, epididymitis, vascular lesions, and central nervous system symptoms). Although the etiology of Behçet's disease is still unknown, there have been recent advances in immunopathogenic studies, genome-wide association studies, animal models, diagnostic markers, and new biological agents. These advances have improved the clinical understanding of Behçet's disease and have enabled us to develop new treatment strategies for this intractable disease, which remains one of the leading causes of blindness. PMID:22187230

Behçet's disease in the United States: A single center descriptive and comparative study.

PubMed

Kilian, Nathan C; Sawalha, Amr H

2017-12-01

Behçet's disease is heterogeneous with clinical variability across ethnicities and geographic locations. The goal of this study was to analyze the clinical characteristics of our multi-ethnic Behçet's disease cohort at the University of Michigan. A detailed patient characterization was performed. Differences in disease characteristics between men and women, and between patients fulfilling the International Criteria for Behçet's Disease (ICBD) and the International Study Group criteria (ISG) were determined in our cohort. A total of 114 patients with a male to female ratio of ~ 1:4 were included. All patients met the ICBD criteria, including 76 who also met the ISG criteria. Over 95% of patients had recurrent genital ulcers, which is higher than generally reported. Retinitis was 5.3 times more likely in men than in women (p=0.009), and arthralgia was 3.3 times more likely in women than men (p=0.048). When comparing cohorts derived from the two different criteria, the ISG cohort had more skin manifestations (OR=3.3, p=0.0006). Acneiform lesions were associated with ~8 times higher odds of developing retinitis in our patients (p=0.0008), and superficial thrombophlebitis was associated with a trend for higher odds of developing uveitis (OR=4.1, p=0.057). Using the ICBD criteria, 38 additional patients were identified compared to only using the ISG criteria. Of these patients, 28 presented with only mucosal ulceration with or without joint involvement. We characterize Behçet's disease in a multi-ethnic cohort from North America. Using ICBD criteria in the United States significantly increases the likelihood of identifying Behçet's disease, particularly in patients with isolated mucosal involvement who constitute a substantial subset of patients in this region.

Suicidal ideation among patients with Behçet's syndrome.

PubMed

Saygin, Caner; Uzunaslan, Didem; Hatemi, Gulen; Hamuryudan, Vedat

2015-01-01

To evaluate the frequency of suicidal ideation among Behçet's syndrome (BS) patients compared to healthy and diseased controls and to delineate possible factors predicting an increase in suicidal ideation. We included consecutive BS patients attending our outpatient clinic, patients with ankylosing spondylitis (AS) and healthy hospital staff as controls. Suicidal ideation was assessed by a standard questionnaire. Linear regression was used to identify the factors associated with suicidal ideation, such as demographic and clinical features, drugs, disease activity assessed using the Behçet's disease current activity form (BDCAF) for BS patients and BASDAI for AS patients, Behçet's disease quality of life (BDQoL) and Beck depression inventory (BDI) score. We surveyed 303 BS patients, 52 AS patients and 106 healthy controls. Suicidal thoughts, as reflected by a positive response to the first three items of the questionnaire, were higher among BS patients with major organ involvement (42%) than those with mucocutaneous involvement (35%) and the control groups. There were significantly more BS patients with active major organ involvement who had thought to terminate their lives without plans within the last year (25.5%) compared to those with active mucocutaneous involvement (8.7%) and active AS patients (10%) (p=0.012). Patient-reported joint pain (β=-0.155, p=0.046), BDQoL (β=0.176, p=0.032), and BDI (β=0.017, p<0.0001) scores, suicidal thoughts before the onset of BS (β=-0.124, p=0.043), neurologic involvement (β=0.119, p=0.047) and past prednisone use (β=0.212, p=0.005) were independent predictors of suicidal thoughts. BS patients with major organ involvement have increased thoughts of suicide during the active stages of their disease. A number of risk factors could help physicians to identify patients with increased suicidal thoughts.

Behçet's Disease and Intracardiac Thrombosis: A Report of Three Cases

PubMed Central

Düzgün, Nurşen; Küçükşahin, Orhan; Atasoy, Kayhan Çetin; Togay Işıkay, Canan; Gerede, Demet Menekşe; Erden, Ayşe; Şahap, Seda Kaynak; İbiş, Muhammed Arif; Ateş, Aşkın

2013-01-01

We present three patients with Behçet's disease associated with intracardiac thrombus and pulmonary vascular involvement. One of these patients had also Budd-Chiari syndrome. All patients were treated with corticosteroid plus monthly intravenous cyclophosphamide as first line treatment and with no recurrences. Immunosuppressive therapy was successful in the treatment of intracardiac thrombus and also in the regression of pulmonary vascular thromboses in these patients. Intracardiac thrombus in Behçet's disease is rarely seen. Behçet's disease should be remembered in the differential diagnosis of the patients with intracardiac mass, especially in patients from the Mediterranean and Middle East populations. PMID:23936717

Separation analysis of macrolide antibiotics with good performance on a positively charged C18HCE column.

PubMed

Wei, Jie; Shen, Aijin; Yan, Jingyu; Jin, Gaowa; Yang, Bingcheng; Guo, Zhimou; Zhang, Feifang; Liang, Xinmiao

2016-03-01

The separation of basic macrolide antibiotics suffers from peak tailing and poor efficiency on traditional silica-based reversed-phase liquid chromatography columns. In this work, a C18HCE column with positively charged surface was applied to the separation of macrolides. Compared with an Acquity BEH C18 column, the C18HCE column exhibited superior performance in the aspect of peak shape and separation efficiency. The screening of mobile phase additives including formic acid, acetic acid and ammonium formate indicated that formic acid was preferable for providing symmetrical peak shapes. Moreover, the influence of formic acid content was investigated. Analysis speed and mass spectrometry compatibility were also taken into account when optimizing the separation conditions for liquid chromatography coupled with tandem mass spectrometry. The developed method was successfully utilized for the determination of macrolide residues in a honey sample. Azithromycin was chosen as the internal standard for the quantitation of spiramycin and tilmicosin, while roxithromycin was used for erythromycin, tylosin, clarithromycin, josamycin and acetylisovaleryltylosin. Good correlation coefficients (r(2) > 0.9938) for all macrolides were obtained. The intra-day and inter-day recoveries were 73.7-134.7% and 80.7-119.7% with relative standard deviations of 2.5-8.0% and 3.9-16.1%, respectively. Outstanding sensitivity with limits of quantitation (S/N ≥ 10) of 0.02-1 μg/kg and limits of detection (S/N ≥ 3) of 0.01-0.5 μg/kg were achieved. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Genetics Home Reference: Behçet disease

MedlinePlus

... of Behçet disease has been reported in northern Turkey, where the disorder affects up to 420 in ... Updated Pages Reviewed : June 2017 Published : June 19, 2018 The resources on this site should not be ...

Resolution of Behçet's syndrome associated pulmonary arterial aneurysms with infliximab.

PubMed

Schreiber, Benjamin E; Noor, Nadim; Juli, Christoph F; Haskard, Dorian O

2011-12-01

We describe the successful treatment of pulmonary arterial aneurysms in Behçet's syndrome using a tumor necrosis factor (TNF) inhibitor. A case is reported of Behçet's syndrome complicated by pulmonary arterial aneurysms that responded to anti-TNF therapy. This is accompanied by a literature review of previously published cases. We searched the English language medical literature using the PubMed and Medline search terms: "Behçet's," "Pulmonary aneurysms," and "infliximab," "etanercept," or "adalimumab." A 43-year-old man with a 6-month history of oral and genital ulcers, weight loss, and fatigue developed arterial aneurysms in the common carotid and common iliac arteries and thromboses in a femoral vein and pulmonary arteries. Treatment with high-dose oral corticosteroids and pulsed intravenous cyclophosphamide was initiated but while on treatment he developed pulmonary arterial aneurysms with hemoptysis. His treatment was changed to intravenous infliximab with methotrexate to which he showed a good response with marked clinical improvement, reduction in his inflammatory markers, and regression of the pulmonary arterial aneurysms. The review of the literature identified 3 reported cases of treatment of pulmonary arterial aneurysms in Behçet's syndrome with anti-TNF therapy, with good outcomes in each case. Pulmonary artery aneurysms are important complications of Behçet's syndrome. Anti-TNF inhibitors should be considered in patients who do not respond to treatment with corticosteroids and cyclophosphamide. Copyright © 2011 Elsevier Inc. All rights reserved.

State of the art for ab initio vs empirical potentials for HeH+ (2e-), BeH+ (4e-), BeH (5e-), Li2 (6e-) and BH (6e-)

NASA Astrophysics Data System (ADS)

Dattani, Nike

For large internuclear distances, the potential energy between two atoms is known analytically, based on constants that are calculated from atomic ab initio rather than molecular ab initio. This analytic form can be built into models for molecular potentials that are fitted to spectroscopic data. Such empirical potentials constitute the most accurate molecular potentials known. For HeH+, and BeH+, the long-range form of the potential is based only on the polarizabilities for He and H respectively, for which we have included up to 4th order QED corrections. For BeH, the best ab initio potential matches all but one observed vibrational spacing to < 1 cm- accuracy, and for Li2 the discrepancy in the spacings is < 0.08 cm-1 for all vibrational levels. But experimental methods such as photoassociation require the absolute energies, not spacings, and these are still several in several cm-1 disagreement. So empirical potentials are still the only reliable way to predict energies for few-electron systems. We also give predictions for various unobserved ''halo nucleonic molecules'' containing the ''halo'' isotopes: 6,8He, 11Li, 11,14Be and 8 , 17 , 19B.

Adherence to guidelines for the treatment of Behçet's syndrome in New York and Amsterdam.

PubMed

Kerstens, Floor G; Turkstra, Franktien; Atalay, Selma; van Vugt, Richard M; Swearingen, Christopher J; Yazici, Yusuf

2017-01-01

To assess adherence to published guidelines for the treatment of Behçet's syndrome (BS) in two geographic areas. We extracted guideline statements from the 2008 EULAR recommendations. Adherence to these statements was evaluated retrospectively in both New York (USA) and Amsterdam (The Netherlands), by reviewing records from patients fulfilling the ISG criteria. We analysed data per statement and event, and divided data according to the year in which an event occurred. We compared events prior to 2009 to those after publication of the EULAR recommendations (2009 and later). 474 patients were evaluated, 24 of whom were from Amsterdam. Treatment adherence varied substantially across various Behçet's manifestations, ranging from 21% vs. 31% in posterior uveitis, 50% vs. 25% in arterial disease, 29% vs. 29% in arthritis and 38% vs. 55% in erythema nodosum to 65% vs. 67% in deep venous thrombosis (DVT), before and after publication of the guidelines respectively. Topical treatment of mucocutaneous disease was only 2% vs. 8%, whereas adherence in neuro-Behçet was ≥ 94% and 100% in gastrointestinal disease. Adherence to treatment guidelines varies substantially by Behçet's manifestation. Lack of adherence in manifestations such as eye disease and arthritis suggests that current recommendations are not sufficient or other concurrent manifestations require more aggressive treatment. The extensive use of anti-TNF agents might indicate a shift towards more aggressive treatment. Thus, our results suggest the 2008 guidelines were not in line with treatment in clinical practice over the past years and the recent revision of the recommendations was indeed needed.

[Behçet's disease].

PubMed

Wechsler, Bertrand; Du-Boutin, Lê Thi Huong; Amoura, Zahir

2005-02-15

Behçet's disease is a vasculitis of unknown origine. Mucocutaneous manifestations are necessary for diagnosis. Ocular and neurological involvements can lead to severe impairment. Arterial involvement may be lethal. Treatment is only symptomatic using steroids, colchicine and antiaggregant therapy. Immunosuppressive drugs are generally given for severe manifestations resistant to conventional therapy. Alpha interferon and infliximab are interesting in case of failure or relapses despite treatment. As in all chronic diseases, education and good observance are needed to improve prognosis.

Ustekinumab for Behçet's disease.

PubMed

Mirouse, Adrien; Barete, Stéphane; Monfort, Jean-Benoît; Resche-Rigon, Matthieu; Bouyer, Anne-Sophie; Comarmond, Cloé; Sène, Damien; Domont, Fanny; Ferfar, Yasmina; Cacoub, Patrice; Saadoun, David

2017-08-01

To evaluate the efficacy and safety of ustekinumab in the treatment of oral ulcers (OU) in patients with Behçet's disease (BD). Prospective study including 14 patients [median age of 39 (34; 41) years, with 71% of men] fulfilling criteria of the International Study Group for BD and with active OU resistant to colchicine. Patients received ustekinumab 90 mg (n = 11) or 45 mg (n = 3) subcutaneously at inclusion, at week 4, and every 12 weeks. The primary efficacy endpoint was the proportion of patients with complete response (CR), defined as no oral ulcer, at week 12. At week 12, 64% were in CR, 21% in partial response and 14% non-responders. The median number of OU decreased from 2 [2; 4] to 1 [0; 1.25] (p = 0.0005) at week 12. Mean change from baseline to week 12 of Behçet's syndrome activity score (BSAS) was 22.8 ± 0.3 (p = 0.01). The median daily corticosteroids dose decreased from 12.5 (10; 16.3) to 5 [5; 10] mg/day (p = 0.02). Three patients reported headaches, leading to discontinuation of ustekinumab in one case. After a median follow-up of 7 [3; 12] months, 10 (71%) patients were still receiving ustekinumab and four (28%) experienced a relapse. Decreased levels of circulating IL-17 and IL-12 [median [IQR]; 3.9 [1.6; 10.6] vs. 29.2 [25.2; 42.7] pg/ml, and 29.4 [23.1; 33.3] vs. 56.1 [51.1; 64.4] pg/ml, p = 0.008 for both] were observed under ustekinumab, respectively. Ustekinumab seems to be efficient and safe for patient with BD and refractory OU although relapses are frequent. Copyright © 2017 Elsevier Ltd. All rights reserved.

Overlooked Management and Risk Factors for Anemia in Patients with Intestinal Behçet's Disease in Actual Clinical Practice.

PubMed

Kim, Bun; Park, Soo Jung; Hong, Sung Pil; Cheon, Jae Hee; Kim, Tae Il; Kim, Won Ho

2015-11-23

Anemia in patients with inflammatory bowel disease significantly affects the quality of life. The aim of this study was to investigate the frequency of and risk factors for anemia and to describe the management of anemia in patients with intestinal Behçet's disease (BD) in actual clinical practice. We included 64 patients with intestinal BD who visited the outpatient clinic of a tertiary referral center in June 2011 and had available laboratory data for the subsequent 6 months. Anemia was detected in 26 patients (40.6%). After 6 months, anemia was still present in 14 of these patients (53.8%). The cause of anemia was investigated in eight patients (30.8%), and oral iron supplementation was prescribed to four patients (15.4%). Of these four patients, two (50%) recovered completely within 6 months. Anemia was associated with a high Disease Activity Index for Intestinal Behçet's Disease (DAIBD, p=0.024), erythrocyte sedimentation rate (p=0.003), and C-reactive protein (p=0.049) in univariate analysis. In multivariate analysis, the factor predictive for anemia in patients with intestinal BD was a higher DAIBD (≥40; odds ratio, 4.08; 95% confidence interval, 1.21 to 13.71; p=0.023). Although anemia is common in intestinal BD patients, its clinical importance is overlooked in daily practice. Moderate to severe disease activity is predictive of anemia.

Concurrent determination of olanzapine, risperidone and 9-hydroxyrisperidone in human plasma by ultra performance liquid chromatography with diode array detection method: application to pharmacokinetic study.

PubMed

Siva Selva Kumar, M; Ramanathan, M

2016-02-01

A simple and sensitive ultra-performance liquid chromatography (UPLC) method has been developed and validated for simultaneous estimation of olanzapine (OLZ), risperidone (RIS) and 9-hydroxyrisperidone (9-OHRIS) in human plasma in vitro. The sample preparation was performed by simple liquid-liquid extraction technique. The analytes were chromatographed on a Waters Acquity H class UPLC system using isocratic mobile phase conditions at a flow rate of 0.3 mL/min and Acquity UPLC BEH shield RP18 column maintained at 40°C. Quantification was performed on a photodiode array detector set at 277 nm and clozapine was used as internal standard (IS). OLZ, RIS, 9-OHRIS and IS retention times were found to be 0.9, 1.4, .1.8 and 3.1 min, respectively, and the total run time was 4 min. The method was validated for selectivity, specificity, recovery, linearity, accuracy, precision and sample stability. The calibration curve was linear over the concentration range 1-100 ng/mL for OLZ, RIS and 9-OHRIS. Intra- and inter-day precisions for OLZ, RIS and 9-OHRIS were found to be good with the coefficient of variation <6.96%, and the accuracy ranging from 97.55 to 105.41%, in human plasma. The validated UPLC method was successfully applied to the pharmacokinetic study of RIS and 9-OHRIS in human plasma. Copyright © 2015 John Wiley & Sons, Ltd.

Fast and parallel determination of PCB 77 and PCB 180 in plasma using ultra performance liquid chromatography with diode array detection: A pharmacokinetic study in Swiss albino mouse.

PubMed

Ramanujam, N; Sivaselvakumar, M; Ramalingam, S

2017-11-01

A simple, sensitive and reproducible ultra-performance liquid chromatography (UPLC) method has been developed and validated for simultaneous estimation of polychlorinated biphenyl (PCB) 77 and PCB 180 in mouse plasma. The sample preparation was performed by simple liquid-liquid extraction technique. The analytes were chromatographed on a Waters Acquity H class UPLC system using isocratic mobile phase conditions at a flow rate of 0.3 mL/min and Acquity UPLC BEH shield RP 18 column maintained at 35°C. Quantification was performed on a photodiode array detector set at 215 nm and PCB 101 was used as internal standard (IS). PCB 77, PCB 180, and IS retention times were 2.6, 4.7 and 2.8 min, respectively, and the total run time was 6 min. The method was validated for specificity, selectivity, recovery, linearity, accuracy, precision and sample stability. The calibration curve was linear over the concentration range 10-3000 ng/mL for PCB 77 and PCB 180. Intra- and inter-day precisions for PCBs 77 and 180 were found to be good with CV <4.64%, and the accuracy ranged from 98.90 to 102.33% in mouse plasma. The validated UPLC method was successfully applied to the pharmacokinetic study of PCBs 77 and 180 in mouse plasma. Copyright © 2017 John Wiley & Sons, Ltd.

Behçet syndrome.

PubMed

Altiner, Ahmet; Mandal, Rajni

2010-11-15

We present a 34-year-old man with a two-year history of aphthous stomatitis, who later developed painful, erythematous nodules on his lower extremities. A pathergy test was positive, and the diagnosis of Behçet syndrome (BS) was made. It is important for the dermatologist to recognize the wide variety of cutaneous manifestations of this disorder. A pathergy test is a simple diagnostic tool that may assist in making a diagnosis. Case reports of other unusual skin manifestations in BS also are reviewed.

Literature mining, gene-set enrichment and pathway analysis for target identification in Behçet's disease.

PubMed

Wilson, Paul; Larminie, Christopher; Smith, Rona

2016-01-01

To use literature mining to catalogue Behçet's associated genes, and advanced computational methods to improve the understanding of the pathways and signalling mechanisms that lead to the typical clinical characteristics of Behçet's patients. To extend this technique to identify potential treatment targets for further experimental validation. Text mining methods combined with gene enrichment tools, pathway analysis and causal analysis algorithms. This approach identified 247 human genes associated with Behçet's disease and the resulting disease map, comprising 644 nodes and 19220 edges, captured important details of the relationships between these genes and their associated pathways, as described in diverse data repositories. Pathway analysis has identified how Behçet's associated genes are likely to participate in innate and adaptive immune responses. Causal analysis algorithms have identified a number of potential therapeutic strategies for further investigation. Computational methods have captured pertinent features of the prominent disease characteristics presented in Behçet's disease and have highlighted NOD2, ICOS and IL18 signalling as potential therapeutic strategies.

Use of ultra-wide-field retinal imaging in the management of active Behçet retinal vasculitis.

PubMed

Mesquida, Marina; Llorenç, Victor; Fontenla, José Ramón; Navarro, Manuel Javier; Adán, Alfredo

2014-10-01

Retinal vasculitis (RV) is an important component of Behçet disease. It may be difficult to detect either clinically or with conventional retinal imaging. The role of ultra-wide-field (UWF) retinal imaging was assessed in the diagnosis and management of RV associated with Behçet disease. A total of 38 eyes of 20 patients with active RV associated to Behçet disease underwent UWF imaging with the Optos scanning laser ophthalmoscope, fundus autofluorescence, and/or fluorescein angiography. This study determined the UWF findings and percentage of patients in whom this imaging modality assisted in diagnosing the extent of vasculitis, planning treatment, and monitoring disease activity. Optos UWF imaging assisted in diagnosing and quantifying the extent of RV in 16 patients (80%), planning medical treatment or laser photocoagulation in 13 of 20 patients (65%), and enhanced disease monitoring in 11 of 20 patients (55%). UWF fluorescein angiography revealed vasculitis not clinically evident in 28 of 33 eyes (84.8%). Predominant angiographic findings were diffuse vascular leakage (75.7%), peripheral retinal nonperfusion (66.7%), optic disk leakage (63.6%), macular leakage (30.3%), and macular edema (27.3%). Eighteen patients (34 eyes) underwent UWF fundus autofluorescence, showing multiple hyperfluorescent spots in retinal periphery in 28 eyes (82.3%). Ultra-wide-field imaging is a valuable tool in the management of patients with RV associated to Behçet disease and can be used for the diagnosis, treatment, and follow-up. Additional studies, including longitudinal evaluations, are needed to elucidate whether these findings or the subsequent management alterations may improve patients' outcomes.

Fractalkine (CX3CL1) levels in patients with Behçet's disease and neuro-Behçet's disease.

PubMed

Ceyla, Irkec; Tuba, Teksut Kuz; Adisen, Esra; Esra, Adisen; Banu, Ozturk; Isil, Fidan; Ali, Gurer M; Turgut, Imir; Banu, Bozkurt

2012-04-15

The aim of the present study was to assess the role of CX3CL1 in patients with active and inactive Behçet's Disease (BD), Neuro-Behçet's Disease (NBD) and control subjects. Fifty-six patients admitted to the BD and NBD Outpatient Clinics, and 30 healthy controls were enrolled in the study. Serum CX3CL1 levels were measured by an enzyme linked immunosorbent assay (ELISA). No significant difference was found between the serum CX3CL1 levels of control subjects, and patients with active and inactive BD or NBD, regardless of treatment. To our knowledge, this is the first study analyzing CX3CL1 levels in patients with BD and NBD. Our results demonstrated that serum CX3CL1 levels were not changed in active and inactive BD and NBD. However, further large-scale studies are needed to confirm our results. Copyright © 2011 Elsevier B.V. All rights reserved.

Transcatheter embolization of renal artery aneurysm in Behçet's disease.

PubMed

Planer, D; Verstandig, A; Chajek-Shaul, T

2001-01-01

A 20-year-old man with Behçet's disease presented with a ruptured renal artery aneurysm. This patient had previously had aneurysms of the coronary arteries and coronary vein thrombosis that were treated with immunosuppression. A selective transcatheter embolization of the renal artery branch was done successfully and treatment with corticosteroids and methotrexate was added. Presented here is a rare complication of Behçet's disease, with discussion on the pathophysiology, differential diagnosis, and the advantages and disadvantages of the angiographic treatment. This paper is supplemented with a comprehensive review of the literature.

Association of myasthenia gravis and Behçet's disease: A case report.

PubMed

Kisabay, Aysin; Sari, Ummu Serpil; Boyaci, Recep; Batum, Melike; Yilmaz, Hikmet; Selcuki, Deniz

2016-01-01

Myasthenia gravis is a disease of neuromuscular junction due to auto-immune destruction of the acetylcholine receptors. Behçet's disease, on the other hand, is a multisystemic vascular-inflammatory disease. Both conditions are not common in the general population although their association has not been reported in the literature. We wanted to present our patient who developed clinical course of myasthenia gravis following discontinuation of medications due to complications of corticosteroid for Behçet's disease. It was observed that clinical findings of myasthenia gravis recovered following restarting steroid treatment and he did not experience attacks of both conditions. Although Myasthenia gravis and Behçet's disease are distinct entities clinically as well as in terms of pathogenesis, they share common physiopathological features and their treatment is based on their common features. Copyright © 2016 Polish Neurological Society. Published by Elsevier Urban & Partner Sp. z o.o. All rights reserved.

Pseudotumeur cardiaque révélant une maladie de Behçet

PubMed Central

Nya, Fouad; Abdou, Abdessamad; Bamous, Mehdi; Moutakiallah, Younes; Atmani, Noureddine; Seghrouchni, Aniss; Houssa, Mahdi Ait; Boulahya, Abdellatif

2017-01-01

La thrombose intracardiaque est une complication rare de la maladie de Behçet (MB), qui peut se présenter comme une tumeur intracardiaque. Sa découverte précède, dans la moitié des cas, le diagnostic de MB. La mortalité élevée peut être en rapport avec des complications post-chirurgicales et/ou une atteinte associée des artères pulmonaires. Nous rapportons l’observation d’un jeune patient de 29 ans, aux antécédents d’aphtose bipolaire, qui a bénéficie d’une intervention chirurgicale après la découverte d’une tumeur de l’atrium et du ventricule droits. Il s’agissait d’un thrombus à l’examen anatomopathologique et dans les suites opératoires nous avons diagnostiqué une MB. L’évolution a été favorable sous traitement médical associant une corticothérapie, de la colchicine et des antivitamines K (AVK). La découverte d’une masse intracardiaque chez un sujet jeune doit faire évoquer le diagnostic de thrombus cardiaque et de maladie de Behçet, même en l’absence de facteur ethnique ou géographique prédisposant. PMID:28533874

Rituximab is effective in severe treatment-resistant neurological Behçet's syndrome.

PubMed

Kidd, D P

2015-12-01

The objective of this study is to describe a case of severe and treatment-resistant neurological Behçet's syndrome responsive to a novel therapy. This case report describes the patient who failed to respond to conventional therapy but the brain stem lesion resolved with the anti-CD20 biological agent rituximab. Neurological complications are uncommon in Behçet's syndrome; 80% involve a meningoencephalitis which can be severe and relapsing. This is the first report of effectiveness of rituximab in this uncommon disease.

Development of Immunopathogenesis Strategies to Treat Behçet's Disease

PubMed Central

Köse, Osman

2012-01-01

Behçet disease is a chronic relapsing vasculitis with unclear etiology and immunopathogenesis. Antigenic stimuli, antigen presenting cells, T cells, monocyte, and neutrophil and endothelial cells are major parts of the pathology of the disease. Understanding of the new pathogenic mechanisms based on molecular structure of the disease helps us in improving the novel therapeutic modalities. These drugs target specific and nonspecific inhibition of the immun system. These therapies include biologic agents, new topical and systemic immunosuppressants, tolerizing agents, and immunoablation. Novel treatment will be promising to treat the especially recalcitrant cases to conventional therapy. In this paper, new aspect of the immunopathogenesis of Behçet's diseases and novel treatment modalities will be discussed. PMID:22550612

Behçet's syndrome.

PubMed

Hatemi, Gulen; Yazici, Yusuf; Yazici, Hasan

2013-05-01

Behçet's syndrome (BS) shows a peculiar distribution, with a much higher prevalence in countries along the ancient Silk Road compared with rest of the world. BS also seems to follow a more severe course in ethnic groups with higher prevalence. Diagnosis depends on clinical findings. Criteria sets may not help in patients with less frequent types of involvement. Management strategies should be modified according to the age and sex of the patient and the organs involved. Being a serious health problem in endemic areas, BS also attracts global attention as a model to study inflammatory diseases of unknown cause. Copyright © 2013 Elsevier Inc. All rights reserved.

Behçet syndrome: from pathogenesis to novel therapies.

PubMed

Mazzoccoli, Gianluigi; Matarangolo, Angela; Rubino, Rosa; Inglese, Michele; De Cata, Angelo

2016-02-01

Behçet syndrome is a chronic disease hallmarked by inflammation of the blood vessels that is related to an autoimmune reaction caused by inherited susceptibility due to specific genes and environmental factors, probably components of infectious microorganisms, which turn on or get going the disease in genetically susceptible subjects. The more common clinical expression of the disease is represented by a triple-symptom complex of recurrent oral aphthous ulcers, genital ulcers, and uveitis, sometimes associated with inflammatory arthritis, phlebitis, iritis, as well as inflammation of the digestive tract, brain, and spinal cord. The treatment strategies used to manage the manifestations of Behçet syndrome have gradually progressed, and a number of new therapeutic resources have been implemented in recent years, allowing better control of pathogenic mechanisms, reducing symptoms and suffering, and ameliorating patient's outcome.

Dense genotyping of immune-related loci implicates host responses to microbial exposure in Behçet's disease susceptibility.

PubMed

Takeuchi, Masaki; Mizuki, Nobuhisa; Meguro, Akira; Ombrello, Michael J; Kirino, Yohei; Satorius, Colleen; Le, Julie; Blake, Mary; Erer, Burak; Kawagoe, Tatsukata; Ustek, Duran; Tugal-Tutkun, Ilknur; Seyahi, Emire; Ozyazgan, Yilmaz; Sousa, Inês; Davatchi, Fereydoun; Francisco, Vânia; Shahram, Farhad; Abdollahi, Bahar Sadeghi; Nadji, Abdolhadi; Shafiee, Niloofar Mojarad; Ghaderibarmi, Fahmida; Ohno, Shigeaki; Ueda, Atsuhisa; Ishigatsubo, Yoshiaki; Gadina, Massimo; Oliveira, Sofia A; Gül, Ahmet; Kastner, Daniel L; Remmers, Elaine F

2017-03-01

We analyzed 1,900 Turkish Behçet's disease cases and 1,779 controls genotyped with the Immunochip. The most significantly associated SNP was rs1050502, a tag SNP for HLA-B*51. In the Turkish discovery set, we identified three new risk loci, IL1A-IL1B, IRF8, and CEBPB-PTPN1, with genome-wide significance (P < 5 × 10 -8 ) by direct genotyping and ADO-EGR2 by imputation. We replicated the ADO-EGR2, IRF8, and CEBPB-PTPN1 loci by genotyping 969 Iranian cases and 826 controls. Imputed data in 608 Japanese cases and 737 controls further replicated ADO-EGR2 and IRF8, and meta-analysis additionally identified RIPK2 and LACC1. The disease-associated allele of rs4402765, the lead marker at IL1A-IL1B, was associated with both decreased IL-1α and increased IL-1β production. ABO non-secretor genotypes for two ancestry-specific FUT2 SNPs showed strong disease association (P = 5.89 × 10 -15 ). Our findings extend the list of susceptibility genes shared with Crohn's disease and leprosy and implicate mucosal factors and the innate immune response to microbial exposure in Behçet's disease susceptibility.

Endovascular aneurysm exclusion along a femorodistal venous bypass in active Behçet's disease.

PubMed

Gretener, Silvia B; Do, Dai-Do; Baumgartner, Iris; Dinkel, Hans-Peter; Schmidli, Jürg; Birrer, Manuela

2002-10-01

To report the endovascular repair of dual aneurysms along a femorodistal venous bypass graft in a patient with Behçet's disease. A 55-year-old man of middle European ancestry with Behçet's disease had dual aneurysms evolve along the proximal segment of a femorodistal venous bypass that had been implanted 2.5 years earlier for recurrent false aneurysm formation. Owing to the lack of suitable venous conduits and the active nature of the disease, the aneurysms were successfully excluded with overlapping Hemobahn and Jostent endografts; the immunosuppressive therapy was intensified. Rupture of the aneurysms was successfully prevented, but the stent-grafts thrombosed 6 weeks later owing to exacerbation of the underlying disease. Endovascular exclusion of aneurysm in venous bypass grafts in Behçet's disease is feasible. Although the stent-grafts thrombosed, they did prevent rupture of the aneurysms.

Diagnostic dilemma: Intracardiac mass in a woman with Behçet's syndrome.

PubMed

Núñez-Cabarcas, Edilberto; López-Ruiz, Nilson; Ramírez-Rincón, Alex

2014-01-01

Intracardiac thrombosis is a rare manifestation of cardiac involvement in Behçet's disease, and it may be mistaken for a heart tumor. In this letter we present the case of a patient diagnosed with Behçet's disease who was incidentally found to have a mass in the right atrium suspicious of a cardiac tumor. Nevertheless, cardiac magnetic resonance showed a cardiac thrombus. Immunosuppressive therapy and anticoagulation were effective for thrombus resolution. Copyright © 2014 Instituto Nacional de Cardiología Ignacio Chávez. Published by Masson Doyma México S.A. All rights reserved.

Behçet's disease (syndrome) with myalgia and its response to intravenous amino acids: a case series.

PubMed

Bryan, Thomas

2011-09-01

To present a case series of patients with refractory Behçet's disease who presented with myalgia and with signs such as mouth and genital ulcerations and skin lesions and were treated with intravenous amino acids. Case series of patients with Behçet's Disease who presented to a clinical practice devoted to Pain Medicine and Neurology between 2000 and 2009 for treatment of myalgia. All patients were treated with prednisone 60 mg by mouth daily for exacerbations of their disease. When this failed, eleven patients received intravenous administration of amino acids (Procalamine). Ten of eleven patients had a complete resolution of their Behçet's exacerbation, including myalgia; their painful ulcers became painless and began to heal with the infusion of amino acids for 2-5 days. Physicians treating myalgia should observe for signs of Behçet's disease, such as oral and genital ulcerations, and consider intravenous amino acids if steroids are not effective. Wiley Periodicals, Inc.

Dense genotyping of immune-related loci implicates host responses to microbial exposure in Behçet’s disease susceptibility

PubMed Central

Takeuchi, Masaki; Mizuki, Nobuhisa; Meguro, Akira; Ombrello, Michael J.; Kirino, Yohei; Satorius, Colleen; Le, Julie; Blake, Mary; Erer, Burak; Kawagoe, Tatsukata; Ustek, Duran; Tugal-Tutkun, Ilknur; Seyahi, Emire; Ozyazgan, Yilmaz; Sousa, Inês; Davatchi, Fereydoun; Francisco, Vânia; Shahram, Farhad; Abdollahi, Bahar Sadeghi; Nadji, Abdolhadi; Shafiee, Niloofar Mojarad; Ghaderibarmi, Fahmida; Ohno, Shigeaki; Ueda, Atsuhisa; Ishigatsubo, Yoshiaki; Gadina, Massimo; Oliveira, Sofia A.; Gül, Ahmet; Kastner, Daniel L.; Remmers, Elaine F.

2017-01-01

We analyzed 1,900 Turkish Behçet’s disease cases and 1,779 controls genotyped with the Immunochip. The most significantly associated single nucleotide polymorphism (SNP) was rs1050502, a tag SNP for HLA-B*51. In the Turkish discovery set, we identified three novel loci, IL1A-IL1B, IRF8, and CEBPB-PTPN1, with genome-wide significance (P<5×10−8) by direct genotyping, and ADO-EGR2 by imputation. ADO-EGR2, IRF8, and CEBPB-PTPN1 replicated by genotyping 969 Iranian cases and 826 controls. Imputed data in 608 Japanese cases and 737 controls replicated ADO-EGR2 and IRF8 and meta-analysis additionally identified RIPK2 and LACC1. The disease-associated allele of rs4402765, the lead marker of the IL1A-IL1B locus, was associated with both decreased interleukin-1α and increased interleukin-1β production. ABO non-secretor genotypes of two ancestry-specific FUT2 SNPs showed strong disease association (P=5.89×10−15). Our findings extend shared susceptibility genes with Crohn’s disease and leprosy, and implicate mucosal factors and the innate immune response to microbial exposure in Behçet’s disease susceptibility. PMID:28166214

Development and validation of a rapid and simple LC-MS/MS method for quantification of vemurafenib in human plasma: application to a human pharmacokinetic study.

PubMed

Bihan, Kevin; Sauzay, Chloé; Goldwirt, Lauriane; Charbonnier-Beaupel, Fanny; Hulot, Jean-Sebastien; Funck-Brentano, Christian; Zahr, Noël

2015-02-01

Vemurafenib (Zelboraf) is a new tyrosine kinase inhibitor that selectively targets activated BRAF V600E gene and is indicated for the treatment of advanced BRAF mutation-positive melanoma. We developed a simple method for vemurafenib quantification using liquid chromatography-tandem mass spectrometry. A stability study of vemurafenib in human plasma was also performed. (13)C(6)-vemurafenib was used as the internal standard. A single-step protein precipitation was used for plasma sample preparation. Chromatography was performed on an Acquity UPLC system (Waters) with chromatographic separation by the use of an Acquity UPLC BEH C18 column (2.1 × 50 mm, 1.7-mm particle size; Waters). Quantification was performed using the monitoring of multiple reactions of following transitions: m/z 488.2 → 381.0 for vemurafenib and m/z 494.2 → 387.0 for internal standard. This method was linear over the range from 1.0 to 100.0 mcg/mL. The lower limit of quantification was 0.1 mcg/mL for vemurafenib in plasma. Vemurafenib remained stable for 1 month at all levels tested, when stored indifferently at room temperature (20 °C), at +4 °C, or at -20 °C. This method was used successfully to perform a plasma pharmacokinetic study of vemurafenib in a patient after oral administration at a steady state. This liquid chromatography-tandem mass spectrometry method for vemurafenib quantification in human plasma is simple, rapid, specific, sensitive, accurate, precise, and reliable.

Evaluation of cochlear involvement by distortion product otoacoustic emission in Behçet's disease.

PubMed

Dagli, Muharrem; Eryilmaz, Adil; Tanrikulu, Salih; Aydin, Acar; Gonul, Muzeyyen; Gul, Ulker; Gocer, Celil

2008-09-01

The aim of this study was to investigate cochlear involvement in patients with Behçet's disease. Twenty-six Behçet's disease patients (52 ears) and 24 sex and age-matched healthy control subjects (48 ears) were included in the study. Pure-tone audiometry at frequencies 250, 500, 1000, 2000, 4000, 6000 Hz, immittance measures including tympanometry and acoustic reflex testing and DPOAE (distortion product otoacoustic emission) testing were performed in the patients and controls. A sensorineural hearing loss was found in eight patients (30.7%) as it was bilateral in five and unilateral in three patients. Although no typical audiometric configuration was found, one patient had a flat type audiogram, and the others had a high frequency hearing loss. The DPOAE responses of the patients and controls were significantly different in all frequencies (p<0.05). These results indicate that cochlea is affected by damage of outer hair cells in Behçet's disease.

Determination of multicomponent contents in Calculus bovis by ultra-performance liquid chromatography-evaporative light scattering detection and its application for quality control.

PubMed

Kong, Weijun; Jin, Cheng; Xiao, Xiaohe; Zhao, Yanling; Liu, Wei; Li, Zulun; Zhang, Ping

2010-06-01

A fast ultra-performance liquid chromatography-evaporative light scattering detection (UPLC-ELSD) method was established for simultaneous quantification of seven components in natural Calculus bovis (C. bovis) and its substitutes or spurious breeds. On a Waters Acquity UPLC BEH C(18) column, seven analytes were efficiently separated using 0.2% aqueous formic acid-acetonitrile as the mobile phase in a gradient program. The evaporator tube temperature of ELSD was set at 100 degrees C with the nebulizing gas flow-rate of 1.9 L/min. The results showed that this established UPLC-ELSD method was validated to be sensitive, precise and accurate with the LODs of seven analytes at 2-11 ng, and the overall intra-day and inter-day variations less than 3.0%. The recovery of the method was in the range of 97.8-101.6%, with RSD less than 3.0%. Further results of PCA on the contents of seven investigated analytes suggested that compounds of cholic acid, deoxycholic acid and chenodeoxycholic acid or cholesterol should be added as chemical markers to UPLC analysis of C. bovis samples for quality control and to discriminate natural C. bovis sample and its substitutes or some spurious breeds, then normalize the use of natural C. bovis and ensure its clinical efficacy.

A polysomnographic and clinical study of sleep disorders in patients with Behçet and neuro-Behçet syndrome.

PubMed

Uygunoğlu, Uğur; Benbir, Gulcin; Saip, Sabahattin; Kaynak, Hakan; Siva, Aksel

2014-01-01

Brainstem is the most common site of involvement in neuro-Behçet syndrome (NBS). On the other hand, the critical importance of this anatomical region in the regulation of sleep has been disregarded in the literature. We aimed to investigate the microstructure of sleep in patients with Behçet syndrome (BS) and NBS. Patients were allocated to 2 groups: (1) BS without any neurological involvement and (2) NBS with brainstem lesions only. A control group was also enrolled in this study. The comparison of polysomnographic parameters between all patients (BS and NBS) with the control group showed that sleep onset was longer (p = 0.006), the duration of superficial NREM sleep stage (N2) was significantly longer (p = 0.018), and the respiratory disturbance index was significantly higher (p = 0.034) in patients. Sleep apnea and restless legs syndrome are more commonly observed in BS and NBS. Our findings emphasize the importance of questioning the quality of sleep and its disorders in patients with BS in order to better handle the common somatic complaints in these patients, such as fatigue or daytime sleepiness . © 2014 S. Karger AG, Basel.

Immunopathogenesis of Ocular Behçet's Disease

PubMed Central

Park, Un Chul; Kim, Tae Wan; Yu, Hyeong Gon

2014-01-01

Behçet's disease (BD) is a chronic recurrent systemic inflammatory disorder of unknown etiology characterized by oral and genital ulcerations, skin lesions, and uveitis. The ocular involvement of BD, or Behçet's uveitis (BU), is characterized by panuveitis or posterior uveitis with occlusive retinal vasculitis and tends to be more recurrent and sight threatening than other endogenous autoimmune uveitides, despite aggressive immunosuppression. Although pathogenesis of BD is unclear, researches have revealed that immunological aberrations may be the cornerstone of BD development. General hypothesis of BD pathogenesis is that inflammatory response is initiated by infectious agents or autoantigens in patients with predisposing genetic factors and perpetuated by both innate and acquired immunity. In addition, a network of immune mediators plays a substantial role in the inflammatory cascade. Recently, we found that the immunopathogenesis of BU is distinct from other autoimmune uveitides regarding intraocular effector cell profiles, maturation markers of dendritic cells, and the cytokine/chemokine environment. In addition, accumulating evidence indicates the involvement of Th17 cells in BD and BU. Recent studies on genetics and biologics therapies in refractory BU also support the immunological association with the pathogenesis of BU. In this review, we provide an overview of novel findings regarding the immunopathogenesis of BU. PMID:25061613

Gastrointestinal Behçet's disease: A review

PubMed Central

Skef, Wasseem; Hamilton, Matthew J; Arayssi, Thurayya

2015-01-01

Behçet’s disease (BD) is an idiopathic, chronic, relapsing, multi-systemic vasculitis characterized by recurrent oral and genital aphthous ulcers, ocular disease and skin lesions. Prevalence of BD is highest in countries along the ancient silk road from the Mediterranean basin to East Asia. By comparison, the prevalence in North American and Northern European countries is low. Gastrointestinal manifestations of Behçet’s disease are of particular importance as they are associated with significant morbidity and mortality. Although ileocecal involvement is most commonly described, BD may involve any segment of the intestinal tract as well as the various organs within the gastrointestinal system. Diagnosis is based on clinical criteria - there are no pathognomonic laboratory tests. Methods for monitoring disease activity on therapy are available but imperfect. Evidence-based treatment strategies are lacking. Different classes of medications have been successfully used for the treatment of intestinal BD which include 5-aminosalicylic acid, corticosteroids, immunomodulators, and anti-tumor necrosis factor alpha monoclonal antibody therapy. Like inflammatory bowel disease, surgery is reserved for those who are resistant to medical therapy. A subset of patients have a poor disease course. Accurate methods to detect these patients and the optimal strategy for their treatment are not known at this time. PMID:25852265

Anti-Neutrophil Cytoplasmic Antibody in Behçet’s Disease

PubMed Central

Duzgun, Nursen; Sahin, Mehmet; Ayaslioglu, Ergin

2006-01-01

Anti neutrophil cytoplasmic antibody (ANCA) is strongly associated with some vasculitic disorders. Behçet’s disease (BD) is a systemic vasculitis of unknown etiology. In this study, ANCA was found to be positive in 8 out of 66 patients (10.2%) with BD by combination testing consisting of immunofluorescence and ELISA [one patient showed an atypical pattern by indirect immunofloresence techique, 6 patients were reactive to bacterial-permeability increasing protein (BPI) and one patient was reactive to Cathepsin G in ELISA]. There were no vascular manifestations such as veneous or arterial thrombosis and arterial aneurysms in ANCA-positive patients with BD. The results suggest that ANCA may be found in a minority of BD as those in previous published studies. PMID:23674967

Targeted resequencing of candidate genes reveals novel variants associated with severe Behçet's uveitis.

PubMed

Kim, Sang Jin; Lee, Seungbok; Park, Changho; Seo, Jeong-Sun; Kim, Jong-Il; Yu, Hyeong Gon

2013-10-18

Behçet's disease (BD) is a chronic systemic inflammatory disorder characterized by four major manifestations: recurrent uveitis, oral and genital ulcers and skin lesions. To identify some pathogenic variants associated with severe Behçet's uveitis, we used targeted and massively parallel sequencing methods to explore the genetic diversity of target regions. A solution-based target enrichment kit was designed to capture whole-exonic regions of 132 candidate genes. Using a multiplexing strategy, 32 samples from patients with a severe type of Behçet's uveitis were sequenced with a Genome Analyzer IIx. We compared the frequency of each variant with that of 59 normal Korean controls, and selected five rare and eight common single-nucleotide variants as the candidates for a replication study. The selected variants were genotyped in 61 cases and 320 controls and, as a result, two rare and seven common variants showed significant associations with severe Behçet's uveitis (P<0.05). Some of these, including rs199955684 in KIR3DL3, rs1801133 in MTHFR, rs1051790 in MICA and rs1051456 in KIR2DL4, were predicted to be damaging by either the PolyPhen-2 or SIFT prediction program. Variants on FCGR3A (rs396991) and ICAM1 (rs5498) have been previously reported as susceptibility loci of this disease, and those on IFNAR1, MTFHR and MICA also replicated the previous reports at the gene level. The KIR3DL3 and KIR2DL4 genes are novel susceptibility genes that have not been reported in association with BD. In conclusion, this study showed that target enrichment and next-generation sequencing technologies can provide valuable information on the genetic predisposition for Behçet's uveitis.

Ocular Behçet disease: current therapeutic approaches.

PubMed

Evereklioglu, Cem

2011-11-01

To alert physician to timely recognition and current treatment of recurrent hypopyon iridocyclitis or panuveitis in ocular Behçet disease (OBD). Interferon-α, rituximab, intravitreal triamcinolone, and biological response modifiers by tumor necrosis factor inhibitors such as infliximab and adalimumab are being used increasingly for the treatment of severe sight-threatening ocular inflammation including retinal vasculitis and cystoid macular edema (CME). Biological agents offer tremendous potential in the treatment of OBD. Given that OBD predominantly afflicts the younger adults in their most productive years, dermatologist, rheumatologist, internist, or general practitioners supervising patients with oculo-articulo-oromucocutaneous syndromes should be aware of systemic Behçet disease. Early recognition of ocular involvement is important and such patients should strongly be instructed to visit immediately an ophthalmologist, as uveitis management differs from extraocular involvements with high ocular morbidity from sight-threatening complications due to relapsing inflammatory attacks in the posterior segment of the eye. A single infliximab infusion should be considered for the control of acute panuveitis, whereas repeated long-term infliximab infusions were proved to be more effective in reducing the number of episodes in refractory uveoretinitis with faster regression and complete remission of CME.

Simultaneous determination of bisphenols and alkylphenols in water by solid phase extraction and ultra performance liquid chromatography-tandem mass spectrometry.

PubMed

Shan, Xiao Mei; Shen, Deng Hui; Wang, Bing Shuang; Lu, Bei Bei; Huang, Fa Yuan

2014-06-01

To establish an analytical method for determination of four bisphenols (BPA, BPB, BPF, and BPS) and two alkylphenols (4-n-OP, 4-n-NP) in water by ultra performance liquid chromatography- tandem mass spectrometry (UPLC/MS/MS). The water samples were extracted and condensed with solid-phase extraction (SPE) using C18 cartridges and eluted by acetonitrile. Separation was carried out with Acquity BEH C8 column and detection were performed by UPLC/MS/MS. Quantification was calculated by using the internal standard BPA-d16 and 4-n-NP-d8. The linear correlation coefficients of these compounds in the range of 1.0-100.0 μg/L were all over 0.999. The minimum detectable concentrations were 0.75-1.0 ng/L, and the recoveries ranged from 87.0% to 106.9%. Relative standard deviations (RSDs) were between 1.26% and 3.67%. Applying this method to detect the source water of Chaohu Lake and drinking water of Hefei, six target compounds were detected in different levels. This method is simple with high sensitivity and selectivity, could be suitable for the determination of these compounds in source and drinking water. Copyright © 2014 The Editorial Board of Biomedical and Environmental Sciences. Published by China CDC. All rights reserved.

Bilateral Neuroretinitis and a Unilateral Superior Hemivein Occlusion with Frosted Branch Angiitis Pattern Presenting Simultaneously in Behçet's Disease.

PubMed

Schwartz, Roy; Borok, Sara; Goldstein, Michaella; Kesler, Anat; Regev, Keren; Elkayam, Ori; Habot-Wilner, Zohar

2016-01-01

To report a unique case of Behçet's disease that presented with atypical ocular manifestations. Case report. A 23-year-old homosexual male presented with bilateral anterior uveitis, vitritis, neuroretinitis and a unilateral superior hemivein occlusion with frosted branch angiitis pattern. These were accompanied by systemic findings of recurrent oral aphthous ulcers, erythema nodosum, and neurological and gastrointestinal involvement. A positive HLA-B51 examination supported the diagnosis of Behçet's disease. Neuroretinitis and frosted branch angiitis may be the clinical manifestations of Behçet's disease and may present simultaneously.

Right ventricular thrombus with Behçet's syndrome: successful treatment with warfarin and immunosuppressive agents.

PubMed

Dogan, Sait M; Birdane, Alparslan; Korkmaz, Cengiz; Ata, Necmi; Timuralp, Bilgin

2007-01-01

Behçet's syndrome is a chronic multisystem disease that presents with recurrent oral and genital ulceration and recurrent uveitis. Cardiac involvement is an extremely rare manifestation of this disorder. A 33-year-old man with Behçet's syndrome was admitted to our department with a history of cough, fever, chest pain, hemoptysis, and weight loss. Transthoracic and transesophageal echocardiography revealed a right ventricular thrombus. After 1 month of treatment with warfarin, cyclophosphamide, and corticosteroid, the intracardiac thrombus resolved.

Treatment of severe generalized chronic periodontitis in a patient with Behçet's disease: A case report.

PubMed

Morikawa, Satoru; Ouchi, Takehito; Asoda, Seiji; Horie, Nobuyuki; Tsunoda, Kazuyuki; Kawana, Hiromasa; Nakagawa, Taneaki

2018-05-01

Behçet's disease is a systemic disorder of unknown etiology. It involves multiple organ systems and is characterized by recurring episodes of oral ulcers as well as ocular, genital, and skin lesions. Oral ulcers can affect tooth brushing and impair proper oral hygiene. As a result, a dental biofilm accumulates, and the condition of the teeth and periodontal tissue deteriorates. The aim of this case report is to highlight the efficacy of periodontal treatment for patients with Behçet's disease. A 51-year-old man with Behçet's disease presented with generalized severe periodontitis. After basic treatment of the periodontal tissues, periodontal surgery was performed at several sites with bony defects. However, the patient developed severe stomatitis in the oral mucosa and gingiva after periodontal surgery. Administration of the antimicrobial agent cefdinir had little effect on recovery; however, subsequent administration of sitafloxacin resulted in significant improvement of the stomatitis. This case demonstrates that periodontal therapy is very useful for alleviating the oral signs and symptoms of Behçet's disease. Systemic antibiotic treatment with sitafloxacin (but not cefdinir) and mechanical debridement were effective in preventing the recurrence of aphthous ulcer outbreaks after periodontal surgery.

Adalimumab for treatment of severe Behçet's uveitis: a retrospective long-term follow-up study.

PubMed

Interlandi, Emanuela; Leccese, Pietro; Olivieri, Ignazio; Latanza, Loredana

2014-01-01

Behçet's disease (BD) is a chronic multisystem inflammatory disorder associated to uveitis that may represent a serious sight-threatening condition. The purpose of the present study is to assess the effectiveness of adalimumab as new strategic therapeutic approach in patients affected by severe Behçet's uveitis. Clinical data from twelve selected patients (22 eyes) were retrospectively analysed. All patients received 40 mg of adalimumab subcutaneously, once every 2 weeks, in addition to traditional immunosuppressive on-going therapy and eight of them were switched to adalimumab after failure of infliximab therapy. Primary outcome measures included ocular inflammatory activity, frequency of uveitis attacks and steroid-sparing effect. Secondary outcomes were changes of best-corrected visual acuity (BCVA), impact on traditional immunosuppressive therapy and occurrence of adalimumab-related side effects. Mean age of patients (11 males and 1 female) at the onset of disease was 24.34 years (±8.62 SD). Ocular involvement resulted bilateral in 83% of cases and mainly consisted in panuveitis (68% of eyes). After mean follow-up of 21 months (±9.63 SD) all patients but one (92%) achieved uveitis remission with BCVA improvement at least in one eye. Average uveitis attacks decreased from 2 to 0,42 during adalimumab (p<0.001) and daily-steroid dose was tapered in all adalimumab responders up to suspension in seven of them. No patient developed related side effects during adalimumab administration. Our results demonstrate that adalimumab is a very effective and safe option for treatment of patients with severe and resistant Behçet's uveitis, providing an appropriate and long-term control of ocular inflammation.

Impact of the column hardware volume on resolution in very high pressure liquid chromatography non-invasive investigations.

PubMed

Gritti, Fabrice; McDonald, Thomas; Gilar, Martin

2015-11-13

The impact of the column hardware volume (≃ 1.7 μL) on the optimum reduced plate heights of a series of short 2.1 mm × 50 mm columns (hold-up volume ≃ 80-90 μL) packed with 1.8 μm HSS-T3, 1.7 μm BEH-C18, 1.7 μm CSH-C18, 1.6 μm CORTECS-C18+, and 1.7 μm BEH-C4 particles was investigated. A rapid and non-invasive method based on the reduction of the system dispersion (to only 0.15 μL(2)) of an I-class Acquity system and on the corrected plate heights (for system dispersion) of five weakly retained n-alkanophenones in RPLC was proposed. Evidence for sample dispersion through the column hardware volume was also revealed from the experimental plot of the peak capacities for smooth linear gradients versus the corrected efficiency of a weakly retained alkanophenone (isocratic runs). The plot is built for a constant gradient steepness irrespective of the applied flow rates (0.01-0.30 mL/min) and column lengths (2, 3, 5, and 10 cm). The volume variance caused by column endfittings and frits was estimated in between 0.1 and 0.7 μL(2) depending on the applied flow rate. After correction for system and hardware dispersion, the minimum reduced plate heights of short (5 cm) and narrow-bore (2.1mm i.d.) beds packed with sub-2 μm fully and superficially porous particles were found close to 1.5 and 0.7, respectively, instead of the classical h values of 2.0 and 1.4 for the whole column assembly. Copyright © 2015 Elsevier B.V. All rights reserved.

[Neurological manifestations of Behçet's disease].

PubMed

Noel, N; Drier, A; Wechsler, B; Piette, J-C; De Paz, R; Dormont, D; Cacoub, P; Saadoun, D

2014-02-01

Neurological manifestations of Behçet's disease (BD) occur in 5.3 to more than 50% of patients. They are divided into two major forms: "parenchymal" lesions, which include mainly meningoencephalitis as opposed to "extra-parenchymal" lesions (i.e. cerebral venous thrombosis and arterial aneurysms). Myelitis or peripheral neuropathy is exceptional. The neuro-Behçet syndrome (NBS) should be considered in the setting of neurological manifestations, particularly headache and pyramidal signs, in a young man diagnosed with BD. However, its recognition may be difficult when neurological manifestations are the presenting features of BD (one third of cases), and requires a thorough knowledge of clinical manifestations and morphological lesions. Thus, parenchymal NB lesions classically exhibit inflammatory characteristics on MRI and are located at the meso-diencephalic junction and in the brainstem, rarely with a supratentorial extension. Meningitis is not systematically associated, and may be absent in about 30% of cases. The pathogenesis of these lesions is incompletely understood, but inflammatory infiltrates include mainly neutrophils and activated T cells (mainly Th17). Differential diagnoses include infectious diseases (herpes, listeria, tuberculosis), and inflammatory diseases (i.e. multiple sclerosis and sarcoidosis). A prompt recognition of NBS should lead to initiate adequate therapies in order to limit the risk of sequelae, relapses or death. Copyright © 2013. Published by Elsevier SAS.

Fatigue is correlated with disease activity but not with the type of organ involvement in Behçet's syndrome: a comparative clinical survey.

PubMed

Buyuktas, Deram; Hatemi, Gulen; Yuksel-Findikoglu, Sukran; Ugurlu, Serdal; Yazici, Hasan; Yurdakul, Sebahattin

2015-01-01

Fatigue is an important problem in inflammatory diseases and affects the quality of life (QoL). We aimed to evaluate the severity and impact of fatigue in Behçet's syndrome (BS) and to determine its association with type of organ involvement and gender. One hundred and fifty-two BS, 51 rheumatoid arthritis (RA), 51 systemic lupus erythematosus (SLE), 51 ankylosing spondylitis (AS) patients and 65 healthy controls were evaluated by the fatigue severity scale, fatigue impact scale, fibromyalgia impact questionnaire (FIQ), RAPID3, SF-36 and Behçet's syndrome activity scale (the latter only in BS patients). We also analysed subgroups of BS patients with predominantly eye, vascular, joint and mucocutaneous involvement and did an additional gender analysis. Fatigue severity and fatigue impact scores were similar among BS, RA, SLE and AS patients and significantly higher than that in healthy controls (F4df=8.51; p<0.001 and F4df=8.67; p<0.001, respectively). The fatigue severity and fatigue impact scores were similarly high in BS subgroups with different types of organ involvement, and in both genders. Fatigue is an important problem in BS, as it is in other inflammatory conditions. It is similarly severe in subgroups of patients with eye, vascular, joint and mucocutaneous involvement and in either gender. Fatigue is a candidate outcome measure for clinical trials, to assess the life impact of Behçet's syndrome.

Bilateral Neuroretinitis and a Unilateral Superior Hemivein Occlusion with Frosted Branch Angiitis Pattern Presenting Simultaneously in Behçet's Disease

PubMed Central

Schwartz, Roy; Borok, Sara; Goldstein, Michaella; Kesler, Anat; Regev, Keren; Elkayam, Ori; Habot-Wilner, Zohar

2016-01-01

Purpose To report a unique case of Behçet's disease that presented with atypical ocular manifestations. Methods Case report. Results A 23-year-old homosexual male presented with bilateral anterior uveitis, vitritis, neuroretinitis and a unilateral superior hemivein occlusion with frosted branch angiitis pattern. These were accompanied by systemic findings of recurrent oral aphthous ulcers, erythema nodosum, and neurological and gastrointestinal involvement. A positive HLA-B51 examination supported the diagnosis of Behçet's disease. Conclusion Neuroretinitis and frosted branch angiitis may be the clinical manifestations of Behçet's disease and may present simultaneously. PMID:27065852

Tracing Behçet's disease origins along the Silk Road: an anthropological evolutionary genetics perspective.

PubMed

Sazzini, Marco; Garagnani, Paolo; Sarno, Stefania; De Fanti, Sara; Lazzano, Teresa; Yang Yao, Daniele; Boattini, Alessio; Pazzola, Giulia; Maramotti, Sally; Boiardi, Luigi; Franceschi, Claudio; Salvarani, Carlo; Luiselli, Donata

2015-01-01

Behçet's disease is a multifactorial vasculitis that shows its highest prevalence in geographical areas historically involved in the Silk Road, suggesting that it might have originated somewhere along these ancient trade routes. This study aims to provide a first clue towards genetic evidence for this hypothesis by testing it via an anthropological evolutionary genetics approach. Behçet's disease variation at ancestry informative mitochondrial DNA control region and haplogroup diagnostic sites was characterised in 185 disease subjects of Italian descent and set into the Eurasian mitochondrial landscape by comparison with nearly 9,000 sequences representative of diversity observable in Italy and along the main Silk Road routes. Dissection of the actual genetic ancestry of disease individuals by means of population structure, spatial autocorrelation and haplogroup analyses revealed their closer relationships with some Middle Eastern and Central Asian groups settled along the Silk Road than with healthy Italians. These findings support the hypothesis that the Behçet's disease genetic risk has migrated to western Eurasia in parallel with ancestry components typical of Silk Road-related groups. This provided new insights that are useful to improve the understanding of disease origins and diffusion, as well as to inform future association studies aimed at properly accounting for the actual genetic ancestry of the examined Behçet's disease samples in order to minimise the detection of spurious associations and to improve the identification of genetic variants with actual clinical relevance.

Behçet syndrome: the vascular cluster.

PubMed

Yazıcı, Hasan; Seyahi, Emire

2016-11-17

Although skin-mucosa lesions are common in almost all patients with Behçet syndrome (BS), clinical properties may differ from one patient to another. Within BS, there are subsets with different organ involvement and hence probably different pathological pathways. These subsets can be described as a) solo skin-mucosa disease with no major organ involvement, b) eye disease, c) seronegative spondyloarthropathy-like disease (arthritis, enthesopathy, and folliculitis), d) Crohn-like disease, and finally the topic of this chapter: e) vascular disease. In the vascular disease subset, not surprisingly, several types of vascular involvement may be observed in the same individual. These subsets may make up the total clinical picture all at the same time or step by step with each relapse. Significant correlations exist between cerebral vascular thrombosis and pulmonary artery involvement, intracardiac thrombi and pulmonary artery involvement, Budd-Chiari syndrome, and inferior vena cava syndrome. Lower extremity vein thrombosis is often present in these associations and even precedes them. The recognition of these clusters is not only important in diagnosis and management but also in basic science, including genetic studies.

The UHPLC-DAD fingerprinting method for analysis of extracellular metabolites of fungi of the genus Geosmithia (Acomycota: Hypocreales).

PubMed

Tylová, Tereza; Kolařík, Miroslav; Olšovská, Jana

2011-07-01

A new simple ultra-high-performance liquid chromatography method with diode array detection (UHPLC-DAD) was developed for chemical fingerprinting analysis of extracellular metabolites in fermentation broth of Geosmithia spp. The SPE method employing Oasis MCX strong cation-exchange mixed-mode polymeric sorbent was chosen for extraction of the metabolites. The analyses were performed on an Acquity UPLC BEH C18 column (100 × 2.1 mm i.d.; particle size, 1.7 μm; Waters) using a gradient elution program with an aqueous solution of trifluoroacetic acid and acetonitrile as the mobile phase. The applicability of the method was proved by analysis of 38 strains produced by different species and isolated from different sources (hosts). The results revealed the correlation of obtained UHPLC-DAD fingerprints with taxonomical identity.

Dysfunctional C8 beta chain in patients with C8 deficiency.

PubMed

Tschopp, J; Penea, F; Schifferli, J; Späth, P

1986-12-01

Two sera from unrelated individuals, each lacking C8 activity, were examined by Western blot analysis. Using antisera raised against whole C8, the two sera are shown to lack the C8 beta chain, indicating a C8 beta deficiency, which is frequently observed in cases of dysfunctional C8. In contrast, by means of a specific anti-C8-beta antiserum, a C8 beta-like polypeptide chain of apparently identical molecular weight compared to normal C8 beta was detected. Digestion of normal and dysfunctional C8 beta with Staphylococcus aureus V8 protease revealed distinct differences in the enzymatic digestion pattern. We conclude that the dysfunction in the C8 protein in these two patients resides in the dysfunctional C8 beta chain, and that this form of C8 deficiency is distinct from C8 deficiencies previously reported, in which one or both C8 subunits are lacking.

Intestinal Behçet and Crohn's disease: two sides of the same coin.

PubMed

Valenti, Simona; Gallizzi, Romina; De Vivo, Dominique; Romano, Claudio

2017-04-20

Behçet's disease (BD) and Crohn's disease (CD) are chronic immune-mediated, inflammatory disorders affecting many different systems (joints, skin, eyes, gastrointestinal and biliary tracts). Both disorders have fluctuating courses and when gastrointestinal symptoms are prevalent, differential diagnosis can be difficult. BD involves the gastrointestinal tract in 10-15% of cases with localized lesions in the ileocecal region. The clinical picture is heterogeneous with various clusters of disease expression. CD is a chronic inflammatory disorder, which can affect any part of the intestinal tract, as well as extra-intestinal tissue. Factors that contribute towards the pathogenesis of both disease include the host's genetic profile, and immune system, and environmental factors such as the gut microbiota. The aim of this manuscript is to provide a narrative review of clinical features of BD and CD, highlighting the importance of differential diagnosis and therapeutic approach, especially in the presence of gastrointestinal involvement. A comprehensive search of published literature using the Pubmed ( http://www.ncbi.nlm.nih.gov/pubmed/ ) database was carried out to identify all articles published in English from 1999 to October 2016, using 4 key terms: "Behçet Disease", "Intestinal Behçet's Disease", "Crohn's Disease" and" Inflammatory Bowel Disease".

Behçet disease and protein-losing enteropathy due to intestinal lymphangiectasia.

PubMed

Rodríguez-Muguruza, Samantha; Caballero, Noemí; Horneros, Judith; Domenech, Eugeni; Mateo, Lourdes

2015-01-01

We report an unusual case of a patient with Behçet's disease that developed protein-losing enteropathy due to intestinal lymphangiectasia. Copyright © 2014 Elsevier España, S.L.U. All rights reserved.

[Cardiovascular involvement in Behçet's disease].

PubMed

Desbois, A-C; Wechsler, B; Cluzel, P; Helft, G; Boutin, D; Piette, J-C; Cacoub, P; Saadoun, D

2014-02-01

Vascular involvement is a common complication of Behçet's disease (BD) and affects up to 40% of BD patients. These complications worsen the prognosis of BD. The concept of vasculo-Behçet has been adopted for cases in which vascular complications dominate the clinical features. Vascular manifestations affect particularly young men, during the first years following onset of the disease. Venous complications are the most frequent vascular complications, affecting 14 to 40% of BD patients. Superficial and deep lower limb thrombosis is the most frequent venous complications but one third of venous thrombosis concern large vessels (such as cerebral venous thrombosis, pulmonary embolism, and inferior or superior vena cava, etc.). Budd-Chiari syndrome is the worst prognostic factor increasing mortality by 9 times. Arterial complications (2 to 17% of BD patients) include aneurysms and occlusions/stenosis. Main locations of arterial lesions are aortic (abdominal and thoracic), femoral, pulmonary and iliac arteries. Aneurysms are the most severe arterial complications, particularly pulmonary aneurysms associated with a high risk of massive bleeding. Cardiac complications (up to 6% of BD patients) include pericarditis, endocardial lesions (aortic regurgitation and less often mitral insufficiency), myocardial lesions (myocardial infarction, myocarditis and endomyocardial fibrosis) and intracardiac thrombosis (right ventricle and atrium). Coronary lesions complicated to myocardial infarction are the most severe cardiac complications. Treatment is based on corticosteroids and immunosuppressive drugs. The use of anticoagulation in venous thrombosis is still controversial. Copyright © 2014. Published by Elsevier SAS.

Neuro-Behçet syndrome.

PubMed

Saip, Sabahattin; Akman-Demir, Gulsen; Siva, Aksel

2014-01-01

Behçet syndrome (BS) is an idiopathic chronic relapsing multisystem vascular-inflammatory disease of unknown origin. As the disease affects many organs and systems and shows a wide range of clinical manifestations and presentations, it is prefereable to call Behçet's a syndrome (BS) rather than a disease. Nervous system involvement, known as "neuro-BS" (NBS), is seen in about 5-10% of all cases. Clinical and imaging evidence suggests that primary neurologic involvement in BS may be subclassified into two major forms: the first, which is seen in the majority of patients, may be characterized as a vascular-inflammatory central nervous system disease with focal or multifocal parenchymal involvement, mostly presenting with a subacute brainstem syndrome and hemiparesis (intra-axial NBS); the other, which has few symptoms and a better neurologic prognosis, may be caused by isolated cerebral venous sinus thrombosis and intracranial hypertension (extra-axial NBS), occurring in 10-20% of the cases. These two types are rarely seen in the same individual, and their pathogenesis is likely to be different. Isolated behavioral syndromes and peripheral nervous system involvement are rare, whereas a vascular type headache is relatively common and independent from neurologic involvement. Neurologic complications secondary to systemic involvement of BS, as well as neurologic complications related to BS treatments are considered as secondary neurologic involvement of the syndrome. The core histopathologic phenomenon seems to be a vasculitic involvement in some cases, and low-grade chronic nonspecific inflammation in others. As the neurologic involvement in this syndrome is so heterogeneous, it is difficult to predict its course and prognosis, and its response to treatment. Currently, treatment options for NBS are limited to attack therapies with high-dose intravenous methylprednisolone followed by a prolonged oral taper, symptomatic management, and generally the use of azathioprine

A Clinical Picture of the Visual Outcome in Adamantiades-Behçet's Disease

PubMed Central

Figus, Michele; Albert, Timothy G.; Talarico, Rosaria; Nardi, Marco

2015-01-01

Adamantiades-Behçet's disease is a multisystemic vasculitis with multiorgan involvement. Ocular disorders occur often in this syndrome typically in the form of a relapsing-remitting panuveitis and vasculitis and can lead to blindness as one of its most disabling complications if left untreated. There are known risk factors related with the worst visual prognosis, which require early and intensive treatment in order to obtain a rapid suppression of inflammation and to prevent future relapses. The management strategy to avoid vision loss and blindness currently involves the use of local and systemic drugs including steroids and immunosuppressive and biologic agents. This review aims to demonstrate how the introduction and the use of biologic agents improves the visual outcome of patients with Adamantiades-Behçet's disease. PMID:26558256

Apremilast for Behçet's syndrome--a phase 2, placebo-controlled study.

PubMed

Hatemi, Gulen; Melikoglu, Melike; Tunc, Recep; Korkmaz, Cengiz; Turgut Ozturk, Banu; Mat, Cem; Merkel, Peter A; Calamia, Kenneth T; Liu, Ziqi; Pineda, Lilia; Stevens, Randall M; Yazici, Hasan; Yazici, Yusuf

2015-04-16

Oral ulcers, the hallmark of Behçet's syndrome, can be resistant to conventional treatment; therefore, alternative agents are needed. Apremilast is an oral phosphodiesterase-4 inhibitor that modulates several inflammatory pathways. We conducted a phase 2, multicenter, placebo-controlled study in which 111 patients with Behçet's syndrome who had two or more oral ulcers were randomly assigned to receive 30 mg of apremilast twice daily or placebo for 12 weeks. This regimen was followed by a 12-week extension phase in which the placebo group was switched to apremilast and a 28-day post-treatment observational follow-up phase. The patients and clinicians were unaware of the study assignments throughout the trial. The primary end point was the number of oral ulcers at week 12. Secondary outcomes included pain from these ulcers (measured on a 100-mm visual-analogue scale, with higher scores indicating worse pain), the number of genital ulcers, overall disease activity, and quality of life. The mean (±SD) number of oral ulcers per patient at week 12 was significantly lower in the apremilast group than in the placebo group (0.5±1.0 vs. 2.1±2.6) (P<0.001). The mean decline in pain from oral ulcers from baseline to week 12 was greater with apremilast than with placebo (-44.7±24.3 mm vs. -16.0±32.5 mm) (P<0.001). Nausea, vomiting, and diarrhea were more common in the apremilast group (with 22, 9, and 12 incidents, respectively, among 55 patients) than in the placebo group (with 10, 1, and 2 incidents, respectively, among 56 patients), findings that were similar to those in previous studies of apremilast. There were two serious adverse events in patients receiving apremilast. Apremilast was effective in treating oral ulcers, which are the cardinal manifestation of Behçet's syndrome. This preliminary study was neither large enough nor long enough to assess long-term efficacy, the effect on other manifestations of Behçet's syndrome, or the risk of uncommon serious

Behçet's disease.

PubMed

Saadoun, David; Wechsler, Bertrand

2012-04-12

DEFINITION OF THE DISEASE: Behçet disease (BD) is a chronic, relapsing, multisystemic disorder characterized by mucocutaneous, ocular, vascular and central nervous system manifestations. BD seems to cluster along the ancient Silk Road, which extends from eastern Asia to the Mediterranean basin. European cases are often described, not exclusively in the migrant population. The clinical spectrum includes oral and genital ulcerations, uveitis, vascular, neurological, articular, renal and gastrointestinal manifestations. The etiopathogenesis of the disease remains unknown, although genetic predisposition, environmental factors and immunological abnormalities have been implicated. Diagnosis is only based on clinical criteria. DIFFERRENTIAL DIAGNOSIS: It depends on the clinical presentation of BD, but sarcoidosis, multiple sclerosis, Crohn's disease, Takayasu's arteritis, polychondritis or antiphospholipid syndrome need to be considered. Treatment is symptomatic using steroids and immunomodulatory therapy. It is efficient depending on the rapidity of initiation, the compliance, and the duration of therapy. The prognosis is severe due to the ocular, neurological and arterial involvement.

PFAPA syndrome and Behçet's disease: a comparison of two medical entities based on the clinical interviews performed by three different specialists.

PubMed

Cantarini, Luca; Vitale, Antonio; Bersani, Giulia; Nieves, Laura Martin; Cattalini, Marco; Lopalco, Giuseppe; Caso, Francesco; Costa, Luisa; Iannone, Florenzo; Lapadula, Giovanni; Galeazzi, Mauro; Ceribelli, Angela; Brunetta, Enrico; Selmi, Carlo; Rigante, Donato

2016-02-01

The pediatric syndrome characterized by periodic fever, aphthous stomatitis, pharyngitis, and cervical adenitis (PFAPA) and adult Behçet's disease share some clinical manifestations and are both polygenic autoinflammatory disorders with interleukin-1β showing to play a pivotal role. However, the diagnosis is mostly clinical and we hypothesize that specific criteria may be addressed differently by different physicians. To determine the diagnostic variability, we compared the answers of 80 patients with a definite diagnosis of Behçet's disease (age 42.1 ± 13.7 years) obtained by separate telephone interviews conducted by a rheumatologist, a pediatrician, and an internist working largely in the field of autoinflammatory disorders. Questions were related to the age of symptom onset, the occurrence of recurrent fevers during childhood, and the association with oral aphthosis, cervical adenitis and/or pharyngitis, previous treatments, possible growth impairment, the time lapse between PFAPA-like symptoms and the onset of Behçet's disease, and the occurrence of Behçet-related manifestation during childhood. The rheumatologist identified 30 % of patients with Behçet's disease fulfilling PFAPA syndrome diagnostic criteria, compared to the pediatrician and the internist identifying 10 and 7.5 %, respectively. Most of the patients suffered from recurrent oral aphthosis in childhood also without fever (50, 39, and 48 % with each interviewer), yet no patient fulfilled the Behçet's disease diagnostic criteria. Our data suggest that physician awareness and expertise are central to the diagnosis of autoinflammatory disorders through an accurate collection of the medical history.

Acute Transverse Myelitis at the Conus Medullaris Level After Rabies Vaccination in a Patient With Behçet's Disease

PubMed Central

Bir, Levent Sinan; Özdemir Eşmeli, Fatma; Cenikli, Utku; Erdoğan, Çağgdaş; Değirmenci, Eylem

2007-01-01

Case report: A 25-year-old man with Behçet's disease was admitted because of weakness of the lower limbs and difficulty in urination. He had received a rabies vaccination 2 months previous because he had been bitten by a dog. Findings: Clinical and laboratory findings supported acute transverse myelitis. A hyperintense lesion and expansion at the level of conus medullaris was detected on spinal magnetic resonance imaging. Conclusion: Although neurologic involvement is one of the main causes of mortality and morbidity in Behçet's disease, the factors that aggravate the involvement of the nervous system are still unclear. Vaccination may have been the factor that had activated autoimmune mechanisms in this case. To our knowledge, involvement of the conus medullaris in Behçet's disease after rabies vaccination has not been reported. PMID:17684898

High-throughput and simultaneous analysis of eight central-acting muscle relaxants in human plasma by ultra-performance liquid chromatography-tandem mass spectrometry in the positive and negative ionization modes.

PubMed

Ogawa, Tadashi; Hattori, Hideki; Kaneko, Rina; Ito, Kenjiro; Iwai, Masae; Mizutani, Yoko; Arinobu, Tetsuya; Ishii, Akira; Seno, Hiroshi

2011-06-01

In this report, a high-throughput and sensitive method for analysis of eight central-acting muscle relaxants in human plasma by ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) in the positive and negative ionization modes using tolbutamide as internal standard is presented. After pretreatment of a plasma sample by solid-phase extraction with an Oasis HLB cartridge, muscle relaxants were analyzed by UPLC with Acquity UPLC BEH C(18) column and Acquity TQD tandem quadrupole mass spectrometer equipped with an electrospray ionization interface. The calibration curves for muscle relaxants spiked into human plasma equally showed good linearities in the nanogram per milliliter order range. The detection limits (signal-to-noise ratio = 3) was as low as 0.1-2 ng/mL. The method gave satisfactory recovery rates, accuracy, and precision for quality control samples spiked with muscle relaxants. To further validate the present method, 250 mg of chlorphenesin carbamate was orally administered to a healthy male volunteer, and the concentrations of chlorphenesin carbamate in plasma were measured 0.5, 1, 2, 4, 6, and 8 h after dosing; their concentrations in human plasma were between 0.62 and 2.44 μg/mL. To our knowledge, this is the first report describing simultaneous analysis of over more than two central-acting muscle relaxants by liquid chromatography-tandem mass spectrometry. This has been realized by the capability of our instrument for simultaneous multiple reaction monitoring of the target compounds in both positive and negative ionization modes. Therefore, the present method seems very useful in forensic and clinical toxicology and pharmacokinetic studies.

Update on the Medical Management of Gastrointestinal Behçet's Disease

PubMed Central

Venerito, Vincenzo; Franceschini, Rossella; Lapadula, Giovanni; Galeazzi, Mauro; Frediani, Bruno; Iannone, Florenzo

2017-01-01

Behçet's disease (BD) is a multisystemic disorder of unknown etiology mainly defined by recurrent oral aphthosis, genital ulcers, and chronic relapsing bilateral uveitis, all of which represent the “stigmata” of disease. However, many other organs including the vascular, neurological, musculoskeletal, and gastrointestinal systems can be affected. The gastrointestinal involvement in Behçet's disease (GIBD), along with the neurological and vascular ones, represents the most feared clinical manifestation of BD and shares many symptoms with inflammatory bowel diseases, such as Crohn's disease and ulcerative colitis. Consequently, the differential diagnosis is often a daunting task, albeit the presence of typical endoscopic and pathologic findings may be a valuable aid to the exact diagnosis. To date, there are no standardized medical treatments for GIBD; therefore therapy should be tailored to the single patient and based on the severity of the clinical features and their complications. This work provides a digest of all current experience and evidence about pharmacological agents suggested by the medical literature as having a potential role for managing the dreadful features of GIBD. PMID:28210071

Neurological manifestations of Behçet's disease: Case report and literature review.

PubMed

López Bravo, Alba; Parra Soto, Carlos; Bellosta Diago, Elena; Cecilio Irazola, Álvaro; Santos-Lasaosa, Sonia

2017-05-22

Neurological involvement in Behçet's disease is rare, especially at the onset. It can present in the form of parenchymal changes or as damage to the vascular structures in its nonparenchymal form. The coexistence of both kinds of manifestations in the same patient is exceptional. We report the case of a 32-year-old patient with a history of deep venous thrombosis, who was being treated for holocranial headache, apathy, and oral and genital ulcers. Brain magnetic resonance imaging showed hyperintense lesions in the basal ganglia and white matter, and the vascular study evidenced venous thrombosis of the left transverse sinus. After confirming the diagnosis of Behçet's disease with parenchymal and nonparenchymal cerebral involvement, immunosuppressive and corticosteroid therapy was started, resulting in the remission of the symptoms. Copyright © 2017 Elsevier España, S.L.U. and Sociedad Española de Reumatología y Colegio Mexicano de Reumatología. All rights reserved.

A new application of continuous wavelet transform to overlapping chromatograms for the quantitative analysis of amiloride hydrochloride and hydrochlorothiazide in tablets by ultra-performance liquid chromatography.

PubMed

Dinç, Erdal; Büker, Eda

2012-01-01

A new application of continuous wavelet transform (CWT) to overlapping peaks in a chromatogram was developed for the quantitative analysis of amiloride hydrochloride (AML) and hydrochlorothiazide (HCT) in tablets. Chromatographic analysis was done by using an ACQUITY ultra-performance LC (UPLC) BEH C18 column (50 x 2.1 mm id, 1.7 pm particle size) and a mobile phase consisting of methanol-0.1 M acetic acid (21 + 79, v/v) at a constant flow rate of 0.3 mL/min with diode array detection at 274 nm. The overlapping chromatographic peaks of the calibration set consisting of AML and HCT mixtures were recorded rapidly by using an ACQUITY UPLC H-Class system. The overlapping UPLC data vectors of AML and HCT drugs and their samples were processed by CWT signal processing methods. The calibration graphs for AML and HCT were computed from the relationship between concentration and areas of chromatographic CWT peaks. The applicability and validity of the improved UPLC-CWT approaches were confirmed by recovery studies and the standard addition technique. The proposed UPLC-CWT methods were applied to the determination of AML and HCT in tablets. The experimental results indicated that the suggested UPLC-CWT signal processing provides accurate and precise results for industrial QC and quantitative evaluation of AML-HCT tablets.

[Study on UPLC specific chromatogram of Lily and its specific peaks compositions analysis by QTOF-MS].

PubMed

Nie, Hui; Yan, Hui; Qian, Da-Wei; Duan, Jin-Ao; Ou, Yang-Zhen; Qian, Ye-Fei; Guan, Han-Liang

2013-07-01

To establish the UPLC specific chromatogram of Lily and analyze the specific peaks compositions by ESI-QTOF-MS. The samples were conducted by ACQUITY UPLC BEH C18 Column (2.1 mm x 100 mm, 1.7 microm) and eluted with acetonitrile and 0.1% formic acid at the flow rate of 0.4 mL/min. The detection wavelength was set at 320 nm and column temperature was 35 degrees C. Negative ion mode was chosen for qualitative analysis. The capillary voltage was set at 3.0 kV. The nebulization gas was set to 600 L/h at 350 degrees C, and the source temperature was 120 degrees C. The specific chromatogram of Lily was obtained. There were 19 common peaks. Twelve phenylpropenoid glycerides compositions were identified. Among them, 6 compositions were identified by comparison with the reference substances and others were identified by MS and MS2 data. UPLC specific chromatogram can be used for the quality evaluation of Lily, giving support to quality control comprehensively.

Frosted branch angiitis and cerebral venous sinus thrombosis as an initial onset of neuro-Behçet's disease: a case report and review of the literature.

PubMed

Ferreira, Bruno Fortaleza de Aquino; Rodriguez, Ever Ernesto Caso; Prado, Leandro Lara do; Gonçalves, Celio Roberto; Hirata, Carlos Eduardo; Yamamoto, Joyce Hisae

2017-04-15

Frosted branch angiitis is a rare, severe condition. It can be either a primary or a secondary condition and is characterized by rapid deterioration of vision and fulminant retinal vasculitis that manifests as diffuse sheathing of retinal vessels, macular edema, papillitis, vitritis and anterior uveitis. We aimed to describe a case of frosted branch angiitis and cerebral venous sinus thrombosis as an initial neuro-Behçet's disease onset. Diagnosis of Behçet's disease was based on the current 2014 International Criteria for Behçet's Disease and the International consensus recommendation criteria for neuro-Behçet's disease. In addition, a literature review using search parameters of "frosted branch angiitis", "Behçet" and "neuro-Behçet" in the PubMed database is presented. A 28-year-old Brazilian pardo woman presented to our hospital with abrupt bilateral vision loss associated with recurrent aphthous oral ulcers 6 months before visual symptom onset. A fundus examination showed bilateral widespread retinal vasculitis with venous and arterial white sheathing, optic disc swelling, macular edema, and retinal hemorrhages, leading to the diagnosis of frosted branch angiitis. An extensive systemic workup for retinal vasculitis was uneventful, except for brain magnetic resonance imaging demonstrating cerebral venous sinus thrombosis and lymphocytic aseptic meningitis. A diagnosis of neuro-Behçet's disease was made, and treatment was started with methylprednisolone therapy 1 g/day for 5 consecutive days, followed by oral mycophenolate mofetil and infliximab 5 mg/kg infusion. The patient's response was rapid, with improvement of visual acuity to hand movement and counting fingers by day 7 and final visual acuity of counting fingers and 20/130. Frosted branch angiitis may be associated with infectious, noninfectious, or idiopathic causes. An extensive workup should be done to exclude systemic vasculitis such as Behçet's disease. Treatment with systemic steroids must be

Cerebral venous thrombosis in Behçet's disease.

PubMed

Saadoun, D; Wechsler, B; Resche-Rigon, M; Trad, S; Le Thi Huong, D; Sbai, A; Dormont, D; Amoura, Z; Cacoub, P; Piette, J C

2009-04-15

To analyze the clinical findings, treatment, outcome, and prevalence of cerebral venous thrombosis (CVT) in a large cohort of patients with Behçet's disease (BD) from a single center. We reported a series of 64 consecutive patients with CVT who fulfilled the international criteria for BD. Multivariate analysis was performed to define factors that affect prognosis. Among a cohort of 820 patients with BD, CVT was present in 64 (7.8%). Compared with BD patients without CVT, those with CVT had lower parenchymal central nervous system involvement (4.7% versus 28.7%; P = 0.0001) and higher extraneurologic vascular lesions (62.5% versus 38.8%; P = 0.03). Up to 90% of patients responded to anticoagulation therapy without severe hemorrhagic complications. Neither steroid nor immunosuppressant use provided better outcome. Severe visual loss due to optic atrophy was the main complication of CVT, being found in 15% of patients. In multivariate analysis, papilledema (odds ratio [OR] 7.1, 95% confidence interval [95% CI] 1.6-31.9) and concurrent prothrombotic risk factors (OR 4.6, 95% CI 1.1-20.2) were independently associated with the occurrence of sequelae. Factors associated with relapse of thrombosis were concurrent prothrombotic risk factors (hazard ratio [HR] 4.9, 95% CI 1.5-15.4) and a peripheral venous thrombosis (HR 2.8, 95% CI 0.7-10.5). After a mean +/- SD followup of 8.2 +/- 6.9 years, 4 deaths unrelated to CVT were noted. CVT in patients with BD may result in serious neurologic outcomes. Anticoagulation represents a safe and effective therapy. Extensive investigation of prothrombotic disorders should be considered.

Simultaneous determination of neochlorogenic acid, chlorogenic acid, cryptochlorogenic acid and geniposide in rat plasma by UPLC-MS/MS and its application to a pharmacokinetic study after administration of Reduning injection.

PubMed

Wang, Yanjuan; Wen, Jing; Zheng, Weihua; Zhao, Longshan; Fu, Xiaohuan; Wang, Zhenzhong; Xiong, Zhili; Li, Famei; Xiao, Wei

2015-01-01

A simple, specific and sensitive ultra-performance liquid chromatography tandem mass spectrometry (UPLC-MS/MS) method was established and validated for simultaneous determination of neochlorogenic acid, chlorogenic acid, cryptochlorogenic acid and geniposide in rat plasma using puerarin as an internal standard (IS). Plasma samples were pretreated by a one-step direct protein precipitation procedure with acetonitrile after acidified using as little as 50 μL plasma. Chromatographic separation was performed on an Acquity BEH C18 column (100 × 2.1 mm, 1.7 µm) at a flow rate of 0.2 mL/min by a gradient elution, using 0.2% acetic acid-methanol as mobile phase. The detection was performed on a triple quadrupole tandem mass spectrometer by multiple reaction monitoring via electrospray ionization source with negative ion mode. Calibration curves showed good linearity (r > 0.995) over wide concentration ranges. The intra- and inter-day precisions were <15%, and the accuracy was within ±8.0%. The validated method was successfully applied to a pharmacokinetic study of the four bioactive components in rats after intravenous administration of Reduning injection. Copyright © 2014 John Wiley & Sons, Ltd.

Protracted fever of unknown origin as the presenting symptom of Behçet's disease. Report of a case.

PubMed

Niamane, Radouane; Karim Moudden, Mohamed; Zyani, Mahamed; Hda, Ali

2005-03-01

We report a case of Behçet's disease that presented as protracted fever of unknown origin. The diagnosis was established when a thromboembolic event and ora3l aphthous ulcers occurred simultaneously. Antibiotics had no effect on the fever, which resolved when glucocorticoid and anticoagulant therapy was given. Among causes of protracted fever of unknown origin, Behçet's disease is exceedingly rare but should be considered together with the other vasculitides. Above all, the presence of a fever should prompt a search for a thromboembolic complication.

TAP polymorphism in patients with Behçet's disease.

PubMed Central

González-Escribano, M F; Morales, J; García-Lozano, J R; Castillo, M J; Sánchez-Román, J; Núñez-Roldán, A; Sánchez, B

1995-01-01

OBJECTIVE--To determine if susceptibility to Behçet's disease (BD) is associated with polymorphism of HLA-DRB1, HLA-DQB1, DQB1, and TAP1 and TAP2 genes. METHODS--Fifty eight Spanish BD patients and 116 ethnically matched unrelated healthy subjects were typed at the HLA-DRB1 and HLA-DQB1 loci using polymerase chain reaction/sequence specific oligotyping (PCR/SSO). TAP1 and TAP2 alleles were assigned using amplification refractory mutation system-PCR. RESULTS--TAP1C was absent in BD patients, but was found in 12.1% of control subjects (pcorr < 0.05; relative risk = 0.06). Additionally, a linkage disequilibrium between HLA-DQB1*0501 and TAP2B was observed in BD patients (delta = 0.095, pcorr < 0.02), but not in the control group (delta = -0.0031, p > 0.05). CONCLUSIONS--The complete absence of TAP1C alleles in BD patients may indicate that TAP1 polymorphism is not without some significance in the development of BD. Furthermore, the existence of a linkage disequilibrium between HLA-DQB1*0501 and TAP2B in our patients suggests that the gene conferring susceptibility for BD is inherited as an extended haplotype in the population studied. PMID:7794046

[Ocular manifestations of Behçet's disease].

PubMed

Saadoun, D; Cassoux, N; Wechsler, B; Boutin, D; Terrada, C; Lehoang, P; Bodaghi, B; Cacoub, P

2010-08-01

Eye involvement in Behçet's disease (BD) is frequent and an important cause of morbidity. The mean age at onset of uveitis is between 20 and 30 years in male and 30 years in female patients. Ocular involvement includes anterior, posterior or panuveitis. Uveitis may be the presenting manifestation of the disease in 20% of cases or may appear 2 or 3 years after the disease onset. The estimated risk of blindness at 5 years ranges from 15 to 25%. The main goals in the management of patients with BD uveitis are the rapid control of intraocular inflammation, the prevention of recurrent attacks, the achievement of complete remission, and preservation of vision. The medical treatment of patients with severe uveitis relies on the use of systemically administered drugs, including corticosteroids and cytotoxic agents. Anti-TNF agents and interferon-alpha seem to be efficient and well-tolerated alternative therapeutic options. Controlled clinical trials are mandatory to define the place of these new immunomodulatory agents in the therapeutic strategy, and especially their use as first-line therapy. Copyright (c) 2010 Société nationale française de médecine interne (SNFMI). Published by Elsevier SAS. All rights reserved.

Behçet's disease

PubMed Central

2012-01-01

Definition of the disease Behçet disease (BD) is a chronic, relapsing, multisystemic disorder characterized by mucocutaneous, ocular, vascular and central nervous system manifestations. Epidemiology BD seems to cluster along the ancient Silk Road, which extends from eastern Asia to the Mediterranean basin. European cases are often described, not exclusively in the migrant population. Clinical description The clinical spectrum includes oral and genital ulcerations, uveitis, vascular, neurological, articular, renal and gastrointestinal manifestations. Etiology The etiopathogenesis of the disease remains unknown, although genetic predisposition, environmental factors and immunological abnormalities have been implicated. Diagnostic methods Diagnosis is only based on clinical criteria. Differrential diagnosis It depends on the clinical presentation of BD, but sarcoidosis, multiple sclerosis, Crohn’s disease, Takayasu’s arteritis, polychondritis or antiphospholipid syndrome need to be considered. Management Treatment is symptomatic using steroids and immunomodulatory therapy. It is efficient depending on the rapidity of initiation, the compliance, and the duration of therapy. Prognosis The prognosis is severe due to the ocular, neurological and arterial involvement. PMID:22497990

ABO blood groups, Rhesus factor, and Behçet's disease.

PubMed

Ozyurt, Kemal; Oztürk, Perihan; Gül, Mustafa; Benderli, Yasemin Cihan; Cölgeçen, Emine; Inci, Rahime

2013-09-01

Recently, numerous studies have been carried out to explain the genetics and immunopathogenesis of Behçet's disease (BD). There is still insufficient understanding of its etiopathogenesis, but substantial genetic and immune system abnormalities have been suggested. Several studies have shown remarkable associations of ABO blood groups with various diseases. This study investigated the relationship between ABO and Rhesus (D) blood groups and Behçet's disease in Turkish patients. Clinical data on gender, ABO, and Rhesus blood type of patients with BD were collected at the Kayseri Education and Research Hospital from 2005 to 2012. A total of 115 patients with BD were assessed for their association with ABO or Rhesus (D) blood groups and compared with the distribution of the blood groups of 25,701 healthy donors admitted to the Kayseri Education and Research Hospital Blood Center in 2010 and 2011. The distribution of ABO and Rhesus blood groups in patients with BD was similar to the healthy donors. No relationship was found between ABO or Rhesus blood groups and BD at our hospital. Further studies with a larger series and in different centers may be valuable for identifying the association between ABO or Rhesus (D) blood groups and BD.

Results of a questionnaire on the treatment of patients with Behçet's syndrome: a trend for more intensive treatment.

PubMed

Turkstra, F; van Vugt, R M; Dijkmans, B A C; Yazici, Y; Yazici, H

2012-01-01

To determine the preferred treatment for patients with Behçet's syndrome. A questionnaire was given to all participants of the 2010 meeting of the International Society for Behçet's Disease. Forty-one respondents from 6 different subspecialties. In the case of a patient with (severe) posterior uveitis or parenchymal central nervous system (CNS) disease no consensus was seen. A diffuse spectrum of different schedules were given. In both uveitis and CNS disease the majority of respondents preferred treatment options consisting of combination systemic therapy and systemic corticosteroids. TNF was preferred as first line drug in uveitis in 7.5% and in severe uveitis in 32.5% of respondents. In parenchymal CNS disease TNF blockage was given by 17% of the respondents. EULAR guidelines regarding uveitis were followed by 12/40 physicians. In patients with a new deep vein thrombosis, 90% of respondents would intensify immunosuppression. More than half would also anticoagulate. Although consensus about how to treat patients with Behçet syndrome in different clinical situations is far from present, treatment has become more intensive when compared to 10-20 years ago. More uniformity should be sought for in the decision process in individual patients with Behçet's syndrome, regarding their treatment, as well as adhering to evidence, as presented in the EULAR guidelines, when present.

Role of IL-22– and TNF-α–Producing Th22 Cells in Uveitis Patients with Behçet’s Disease

PubMed Central

Kawazoe, Yuko; Imai, Ayano; Kawaguchi, Tatsushi; Horie, Shintaro; Keino, Hiroshi; Takahashi, Masayo; Mochizuki, Manabu

2013-01-01

Behçet’s disease is a systemic inflammatory disorder with recurrent episodes of oral ulceration, skin lesions, genital ulceration, and intraocular inflammation (uveitis). The intraocular inflammation is strictly associated with Th effector cells. IL-22 is a member of the IL-10 cytokine family that is involved in inflammatory processes. Recently, Th22 cells were identified as a Th cell population that produces IL-22 and TNF-α and are distinct from Th1, Th2, and Th17 cells. In this study, we established Th22-type T cell clones from ocular samples taken from Behçet’s disease patients with active uveitis. These clones produced large amounts of IL-22 and TNF-α but not the Th1 cytokine IFN-γ and the Th17 cytokine IL-17. CD4+ T cells from the peripheral blood of Behçet’s disease patients differentiated into Th22 cells in the presence of IL-6 and TNF-α in vitro. The polarized Th22 cell lines produced large amounts of IL-22, and the polarized Th1 and Th17 cells also produced IL-22. In the presence of anti–TNF-α– and anti–IL-6–blocking Abs, Behçet’s disease Th22-type T cells failed to produce IL-22. In addition, infliximab-pretreated Th22 cells and Th22-type ocular T cells produced less IL-22 and TNF-α. Moreover, IL-22–producing T cells were isolated from mice with experimental autoimmune uveitis, an animal model of Behçet’s disease, and the intraocular T cells from uveitis models produced large amounts of IL-22 in the presence of retinal Ags. Our results suggest that inflammatory cytokines IL-22 and TNF-α may play a key role in the ocular immune response in Behçet’s disease. PMID:23630362

[Otorhinolaryngological manifestations in patients with Behçet disease].

PubMed

Morales-Angulo, Carmelo; Vergara Pastrana, Sandra; Obeso-Agüera, Sergio; Acle, Leticia; González-Gay, Miguel Ángel

2014-01-01

Behçet disease (BD) is a systemic immune-mediated vasculitis of unknown origin characterised by recurrent orogenital ulceration, ocular inflammation and skin lesions. The aim of our study was to identify ear, nose and throat (ENT) manifestations associated with BD. Retrospective review of the medical records of all patients diagnosed with BD who attended a tertiary public hospital in Cantabria (Spain) over a period of 22 years. Clinical manifestations, in particular those concerning ENT, were retrieved from medical records. A medical literature review of ENT manifestations was conducted. Thirty-three patients (age range: 17-64 years) were included in the study. Most of them presented oral ulcers (97%). Eight patients (24%) presented oropharyngeal ulcers and 5 patients (15%) experienced audiovestibular symptoms (high frequency sensorineural hearing loss, vertigo and bilateral vestibular hypofunction). One patient had symptoms compatible with vestibular neuronitis as the presentation manifestation of Neuro-Behçet. In 4 patients (12%) the presence of odynophagia secondary to the presence of oropharyngeal lesions, initially interpreted as acute or recurrent tonsillitis, was the first manifestation of the disease, alone or associated with cutaneous or ocular lesions. In addition to the characteristic oral ulcers present in most patients with BD, ulcers in the oropharynx, occasionally interpreted as acute pharyngitis, are also common in these patients. Audiovestibular manifestations frequently appear during the course of the disease and may be the first symptom of central nervous system involvement. Copyright © 2013 Elsevier España, S.L. All rights reserved.

Estimation of human percutaneous bioavailability for two novel brominated flame retardants, 2-ethylhexyl tetrabromobenzoate (EH-TBB) and bis(2-ethylhexyl) tetrabromophthalate (BEH-TEBP), using the parallelogram approach

EPA Science Inventory

2-ethylhexyltetrabromobenzoate (EH-TBB) and bis(2-ethylhexyl)tetrabromophthalate (BEH-TEBP) are novel brominated flame retardants (FRs). BEH-TEBP is used alone as a plasticizer or with EH-TBB in polyurethane foams; both are contaminants in the indoor and outdoor environments. In ...

Clinical Immunology Review Series: An approach to the patient with recurrent orogenital ulceration, including Behçet's syndrome

PubMed Central

Keogan, M T

2009-01-01

Patients presenting with recurrent orogenital ulcers may have complex aphthosis, Behçet's disease, secondary complex aphthosis (e.g. Reiter's syndrome, Crohn's disease, cyclical neutropenia) or non-aphthous disease (including bullous disorders, erythema multiforme, erosive lichen planus). Behçet's syndrome is a multi-system vasculitis of unknown aetiology for which there is no diagnostic test. Diagnosis is based on agreed clinical criteria that require recurrent oral ulcers and two of the following: recurrent genital ulcers, ocular inflammation, defined skin lesions and pathergy. The condition can present with a variety of symptoms, hence a high index of suspicion is necessary. The most common presentation is with recurrent mouth ulcers, often with genital ulcers; however, it may take some years before diagnostic criteria are met. All patients with idiopathic orogenital ulcers should be kept under review, with periodic focused assessment to detect evolution into Behçet's disease. There is often a delay of several years between patients fulfilling diagnostic criteria and a diagnosis being made, which may contribute to the morbidity of this condition. Despite considerable research effort, the aetiology and pathogenesis of this condition remains enigmatic. PMID:19210521

Bibliometric analysis on global Behçet disease publications during 1980-2014: is there a Silk Road in the literature?

PubMed

Şenel, E; Demir, E; Alkan, R M

2017-03-01

Behçet disease (BD) is a chronic and multisystemic vasculitis characterized with recurrent oral and genital ulcers, uveitis, arthritis and skin manifestations. The highest prevalence of the disease has been reported in regions historically involved in the Silk Road routes. We aimed to analyse Behçet literature and evaluate whether there is a concordance between ancient Silk Road regions and the distribution of publication productivity. The bibliometric analysis of the publications published during 1980-2014 using Thomson Reuters Web of Science database was performed. We generated infographics of productivity and also analysed the correlations among economical productivities, technological advancement levels and humanity index and productivity performances of 78 countries in Behçet literature. Turkey ranked first in Behçet literature with 1837 articles followed by Japan and the USA. Turkey, Tunisia and Israel occupied the first three places in productivity. Significant correlations were noted between 2014 gross economic and technological indices and publication numbers of the countries. We found that European countries had high productivity, although they had low prevalence of BD. We detected no concordance between the productivity density of the countries and the ancient Silk Road routes. Most publications were reported from developed countries although undeveloped or developing countries had higher prevalence of BD. Physicians in undeveloped and developing countries should be supported and encouraged to perform novel studies on BD. © 2016 European Academy of Dermatology and Venereology.

Botulinum toxin-induced acute anterior uveitis in a patient with Behçet's disease under infliximab treatment: a case report.

PubMed

Sasajima, Hirofumi; Yagi, Syunsuke; Osada, Hiromu; Zako, Masahiro

2017-05-04

Injections of lipopolysaccharide in animal models generate acute anterior uveitis (also known as endotoxin-induced uveitis), but the effects of lipopolysaccharide injection are unknown in humans. We describe an unusual case in which acute anterior uveitis was dramatically activated subsequent to botulinum toxin injection in a patient with Behçet's disease but the acute anterior uveitis was satisfactorily attenuated by infliximab. A 53-year-old Japanese man had normal ocular findings at his regularly scheduled appointment. He had been diagnosed as having incomplete-type Behçet's disease 11 years before. Three years after the diagnosis he was given systemic infusions of 5 mg/kg infliximab every 8 weeks and he had not experienced a uveitis attack for 8 years with no treatment other than infliximab. Two days after the eye examination, he received intracutaneous botulinum toxin injections to treat axillary hyperhidrosis on both sides. Three hours after the injections, he noted rapidly increasing floaters in his right eye. Four days after the injections, his right eye showed severe acute anterior uveitis with deteriorated aqueous flare and anterior vitreous opacity. He received his scheduled infliximab injection, and the right acute anterior uveitis immediately attenuated. Botulinum toxin may have clinical effects similar to those of lipopolysaccharide in endotoxin-induced uveitis models. To the best of our knowledge, this is the first report to suggest that botulinum toxin may trigger acute anterior uveitis, although the precise mechanism is still unclear.

Inner ear involvement in Behçet's disease.

PubMed

Süslü, Ahmet Emre; Polat, Mualla; Köybaşi, Serap; Biçer, Yusuf Ozgür; Funda, Yasemin Ongun; Parlak, Ali Haydar

2010-06-01

To assess cochlear involvement and hearing loss in patients with Behçet's disease (BD). Forty-two patients with BD and 24 sex and age matched healthy subjects were included in the study. pure-tone audiometry including high frequencies (250-16000Hz) and DPOAE were performed to all participants. Results of the audiological evaluation were compared and correlation between the audiologic status and clinical manifestations of the BD were investigated. Bilateral sensorineural hearing loss was detected in 27 (64.3%) patients. Hearing thresholds were found to be higher in patients with BD at all of the frequencies except at 500Hz when compared to control group (p<0.05). The difference in the hearing levels tend to increase in high frequencies. Compared with control group, distortion products and SNR of the BD patients were lower in all of the tested frequencies (p<0.05) which indicates weaker outer hair cell motility. There was no correlation between the clinical manifestations and the audiological parameters. Even having hearing levels within normal limits in speech frequencies, increased hearing thresholds in high frequencies and decreased signal-noise ratios (SNR) in distortion product otoacoustic emission (DPOAE) indicate a cochlear involvement in patients with BD. Copyright (c) 2009 Elsevier Ireland Ltd. All rights reserved.

Carpal Tunnel Syndrome in Behçet's Disease.

PubMed

Lee, Jungsoo; Cho, Suhyun; Kim, Do Young; Zheng, Zhenlong; Park, Hoon; Bang, Dongsik

2015-07-01

Behçet's disease (BD) is a chronic inflammatory disease characterized by orogenital ulcers, skin and ocular lesions, in addition to articular, vascular, and neurologic symptoms. Carpal tunnel syndrome (CTS), can also occur in BD patients secondary to inflammation in the connective tissues, vessels, and tendons, as well as nerve involvement in BD itself. However, reports of patients who have CTS in BD are rare. The aim of this study was to evaluate the clinical characteristics of CTS in BD patients. Retrospective analysis of the medical records of 1750 BD patients, and 14 (0.8%) BD patients who were diagnosed with CTS was performed at the BD Specialty Clinic of Severance Hospital. Patient demographics, disease activity/severity for both diseases, and the clinical characteristics of CTS in BD were recorded and analyzed. All 14 BD patients with CTS were women. Twelve patients (85.7%) were diagnosed with active BD. The CTS was mild in 8 patients (57.2%), moderate in 3 patients (21.4%), and severe in 3 patients (21.4%). Ten patients (71.4%) had BD prior to the diagnosis of CTS, and these 10 patients all had active BD. CTS can occur as a result of the inflammation associated with BD and can also be the presenting symptom of nerve involvement in BD. CTS can also develop as the initial symptom of BD. Therefore, a higher degree of suspicion should be maintained for CTS in patients with BD and vice versa; however, the exact relationship is uncertain.

Oligoclonal T cell expansions in patients with Behçet's disease

PubMed Central

DIRESKENELI, H; EKSIOGLU-DEMIRALP, E; KIBAROGLU, A; YAVUZ, S; ERGUN, T; AKOGLU, T

1999-01-01

Behçet's disease (BD) is a multisystem disorder with oral and genital ulcers, mucocutaneous, ocular, joint, vascular and central nervous system involvement. In this study, the peripheral T cell repertoire was analysed in patients with BD with MoAbs against T cell receptor (TCR) Vβ gene products in CD4+ and CD8+ T cell compartments, and these were compared with rheumatoid arthritis (RA) patients and healthy controls (HC). In the CD4+ T cell compartment, oligoclonal TCR Vβ expression was observed in 56% of BD (10/18), 71% of RA (5/7) patients and 21% (3/14) of HC. In the CD8+ T cell group 50% of BD (9/18), 57% of RA patients and 28% of HC (4/14) had an oligoclonal TCR repertoire. An increase of TCR Vβ5.1 subset was observed in five BD patients among CD8+ T cells. Other elevations of TCR Vβ subsets were heterogeneously distributed with one to three different Vβ subsets. Our results suggest an antigen-driven oligoclonal increase of T cells in BD. There was no overall increase in any Vβ group to suggest a superantigen effect. Analysis of the responsible antigens causing the increase in T cell subsets may give insights into the aetiopathogenesis of BD and immunomodulation of these T cells may lead to new treatments. PMID:10403931

In vivo and in vitro IL-18 production during uveitis associated with Behçet disease: effect of glucocorticoid therapy.

PubMed

Belguendouz, H; Messaoudene, D; Lahmar-Belguendouz, K; Djeraba, Z; Otmani, F; Terahi, M; Tiar, M; Hartani, D; Lahlou-Boukoffa, O S; Touil-Boukoffa, C

2015-03-01

Uveitis represents one of the major diagnostic criteria in Behçet's disease. It is most prevalent in the countries of the Mediterranean area, including Algeria, and along the Silk Road. Clinical features include oral and genital ulcers, ocular and skin lesions, as well as central nervous system, joint, vascular, gastrointestinal, or pulmonary manifestations. Many studies have reported that Th1 immune responses are involved in the physiopathology. We have previously studied the production of IL-12 and IFN-γ, cytokine markers in the Th1 pathway involved in Behçet's disease. In our study, we investigate in vivo and in vitro IL-18 production in Algerian patients with Behçet's disease with ocular manifestations in various stages of the disease. We examined the effect of glucocorticoids on IL-18 production during the active stage of the disease. Our results suggest that IL-18 could be a good biomarker for monitoring disease activity and its regression, demonstrating the effectiveness of treatment on the underlying immunopathologic process. Copyright © 2015 Elsevier Masson SAS. All rights reserved.

Behçet syndrome manifestations and activity in the United States versus Turkey -- a cross-sectional cohort comparison.

PubMed

Sibley, Cailin; Yazici, Yusuf; Tascilar, Koray; Khan, Nafiz; Bata, Yasmin; Yazici, Hasan; Goldbach-Mansky, Raphaela; Hatemi, Gulen

2014-07-01

To compare clinical manifestations and activity of Behçet syndrome (BS) in the United States versus Turkey using validated outcome measures. Consecutive patients with BS from the US National Institutes of Health (NIH), New York University, and the University of Istanbul were evaluated. Disease activity was measured using the Behçet's Syndrome Activity Scale (BSAS) and the Behçet's Disease Current Activity Form (BDCAF) with quality of life measured by the Behçet Disease Quality of Life (BDQOL) form. One-way ANOVA, t-tests, and multivariate regression analyses were performed. Mean age did not differ between sites; however, more women were seen in the United States versus in Turkey (p < 0.001), and disease duration was longer in the United States (p = 0.02). Organ manifestations were similar for oral and genital ulcers, skin disease, arthralgia, eye disease, and thrombosis. However, more gastrointestinal (p < 0.001) and neurologic disease (p = 0.003) was seen in the United States. BSAS and BDCAF scores were worse in the United States compared to Turkey (p = 0.013 and < 0.001, respectively). Worse mean BDQOL scores were observed at the NIH compared to Istanbul (not significant). Multivariable regression models showed worse scores in ethnically atypical patients for BSAS and BDCAF (p = 0.04 and p = 0.001), American patients for BDCAF (p = 0.01), older age for BDCAF (p = 0.005), and women for BDQOL (p = 0.01). Demographic and clinical manifestations of BS differ between sites with higher disease activity in the United States compared to Turkey. Referral patterns, age, sex, ethnicity, and country of origin may be important in these differences. These observations raise the question of whether pathogenic mechanisms differ in Turkish and American patients.

Behçet's syndrome: a critical digest of the 2014-2015 literature.

PubMed

Hatemi, Gulen; Seyahi, Emire; Fresko, Izzet; Talarico, Rosaria; Hamuryudan, Vedat

2015-01-01

Several studies were published last year which focused on the epidemiology, immunopathogenesis, genetics, clinical manifestations and management of Behçet's syndrome. Recent epidemiologic studies support the earlier contention that the frequency of BS increases from North to South in Europe, BS is rare in Sub-Saharan Africa, it follows a more severe course among young men, especially if the disease onset is at a young age and that in European countries, the frequency is higher among immigrants from BS prevalent countries compared to locals living in the same environment. The relationship between HLA-B51 and Behçet's was re-emphasised and a functional role affecting cellular cytotoxicity was proposed. Innate immunity was explored and TLR7 copy number variations and nucleic acid sensors of varying inflammasome pathways were studied. Vascular relapse risk is decreased when BS patients are treated with immunosuppressives with or without anti-coagulation rather than anti-coagulation alone. Although rare in the Far East, the clinical picture of the vascular involvement was quite similar to the previously published reports. Interestingly a female predominance among those with cerebral vein thrombosis was noted. Venous claudication is a frequent and severe symptom among BS patients with lower extremity DVT. Budd-Chiari syndrome associated with BS is usually associated with IVC thrombosis. Silent cases exist and have a better prognosis. The mortality rate among the patients symptomatic for liver disease remains high. Methotrexate seems to be effective in the treatment of chronic progressive neuro-Behçet's disease. Renal involvement is an uncommon disorder in BS. Suicidal thoughts are increased among BS patients with severe organ involvement. Work-related disability in BS is high and under-appreciated. Apremilast, an inhibitor of phosphodiesterase-4, was effective in a phase 2, double blind, placebo-controlled study. Adalimumab seems to be effective in severe uveitis of

[Aortic inflammatory lesions in Behçet's disease].

PubMed

Desbois, A-C; Wechsler, B; Cacoub, P; Saadoun, D

2016-04-01

The arterial lesions affect about 10% of patients with Behçet's disease (BD). Aortic inflammatory involvement includes predominantly aortic aneurysmal lesions affecting most often the abdominal aorta. They account for the severity of the disease and are a leading cause of death when they hit the aorta or pulmonary arteries. Within the arterial lesions of BD, aortic involvement is, with femoral lesions, the most common site involved (18-28% of patients with vascular disease). Unlike other large vessels vasculitis (i.e. giant cell arteritis and Takayasu's arteritis) diffuse aortitis is observed in less than 5% of patients with BD. Aortic lesions of BD may be asymptomatic (systematic imaging or occasionally associated with other vascular event) or be revealed by the occurrence of abdominal, thoracic or lumbar pain, or an aortic valve insufficiency. Fever is frequently associated. Increase in acute phase reactants is common in these patients. Histological analysis may show infiltration by lymphocytes, neutrophils and plasma cells in the media and adventitia and a proliferation of the vasa vasorum in the media as well as a fibroblastic proliferation. In the later phase, a fibrous thickening of the media and adventitia is observed as well as a proliferation and thickening of the vasa vasorum. The therapeutic management should always include a medical treatment for the control of inflammation (corticosteroids, immunosuppressive drugs and/or biotherapy) and often an endovascular or surgical treatment if the aneurysm is threatening. The choice between endovascular or surgical treatment is considered case by case, depending on the experience of the team, anatomical conditions and of the clinical presentation. In this review, we provide a detailed and updated review of the literature to describe the aortic inflammatory damage associated with Behçet's disease. Copyright © 2015 Société nationale française de médecine interne (SNFMI). Published by Elsevier SAS. All rights

Fatal pulmonary artery thrombosis in a patient with Behçet's disease, activated protein C resistance and hyperhomocystinemia.

PubMed

Misgav, M; Goldberg, Y; Zeltser, D; Eldor, A; Berliner, A S

2000-07-01

Behçet's disease (BD) is known for its tendency for thromboembolism, which is thought to be due to vascular injury. The important role of inherited thrombophilias is now becoming increasingly clear. However, conflicting data exist in terms of the contribution of these factors to the thrombotic risk in BD. In this case report, we describe a patient with BD who presented with severe cor pulmonale due to recurrent chronic venous thromboembolism and pulmonary artery thrombosis. The biochemical evaluation revealed that the patient was homozygotic for the factor V Leiden (R506Q) mutation and had increased levels of homocysteine. His condition deteriorated despite adequate anticoagulation treatment, and he died suddenly after 7 months of follow-up. We assume that the presence of thrombophilic risk factors augments and synergizes with the hypercoagulable state already existing in BD, leading to fatal thrombosis in this patient.

[Determination of terpene lactones in Ginkgo biloba leaves in different ages by UPLC-TQ-MS].

PubMed

Yao, Xin; Zhou, Gui-Sheng; Tang, Yu-Ping; Qian, Ye-Fei; Shang, Er-Xin; Su, Shu-Lan; Qian, Da-Wei; Duan, Jin-Ao

2013-02-01

To establish an ultra-high performance liquid chromatography coupled with triple quadrupole mass (UPLC-TQ-MS) for determination of four terpene lactones. Chromatographic separation was carried out on a ACQUITY UPLC BEH C18 column (2.1 mm x 100 mm, 1.7 microm) with isocratic elution of 70% methanol at a flow rate of 0.4 mL x min(-1), the column temperature was set at 30 degrees C; Waters Xevo TQ worked in multiple reaction monitoring mode. All calibration curves were linear (r > 0.990 3) over the tested ranges. The average recoveries ranged from 98.83% to 103.9% with RSD value below 3.0%. The contents of total terpene lactones in Ginkgo biloba leaves were significantly different in different ages. The contents in the leaves of young ginkgo tree were higher than that in old tree. The method was simple and fast with high precision, sensitivity and repeatability, which can be used for qualitative and quantitative analysis of terpene lactones in G. biloba leaves.

A UPLC-MS/MS method for qualification of quercetin-3-O-β-D-glucopyranoside-(4→1)-α-L-rhamnoside in rat plasma and application to pharmacokinetic studies.

PubMed

Yao, Xin; Zhou, Guisheng; Tang, Yuping; Li, Zhenhao; Su, Shulan; Qian, Dawei; Duan, Jin-Ao

2013-03-07

A sensitive and accurate ultra-performance liquid chromatography coupled with triple quadrupole mass (UPLC-MS/MS) method was developed for the determination of quercetin-3-O-β-D-glucopyranoside-(4→1)-α-L-rhamnoside (QGR) in rat plasma using rutin as internal standard. Chromatographic separation was achieved on a Acquity BEH C18 column (100 mm × 2.1 mm, 1.7 μm) with a gradient elution of acetonitrile and 0.10% formic acid (v/v) at a flow rate of 0.4 mL/min. QGR and rutin were detected using electrospray negative ionization mass spectrometry in the multiple reaction monitoring (MRM) mode. The method demonstrated good linearity and did not show any endogenous interference with the QGR and rutin peaks. This method was successfully applied to a pharmacokinetic study of QGR in rats after intravenous (20 mg/kg) and oral (40 mg/kg) administration, and the results showed that the compound was poorly absorbed, with an absolute bioavailability of approximately 3.41%.

Chromatographic fingerprint analysis of yohimbe bark and related dietary supplements using UHPLC/UV/MS.

PubMed

Sun, Jianghao; Chen, Pei

2012-03-05

A practical ultra high-performance liquid chromatography (UHPLC) method was developed for fingerprint analysis of and determination of yohimbine in yohimbe barks and related dietary supplements. Good separation was achieved using a Waters Acquity BEH C(18) column with gradient elution using 0.1% (v/v) aqueous ammonium hydroxide and 0.1% ammonium hydroxide in methanol as the mobile phases. The study is the first reported chromatographic method that separates corynanthine from yohimbine in yohimbe bark extract. The chromatographic fingerprint analysis was applied to the analysis of 18 yohimbe commercial dietary supplement samples. Quantitation of yohimbine, the traditional method for analysis of yohimbe barks, were also performed to evaluate the results of the fingerprint analysis. Wide variability was observed in fingerprints and yohimbine content among yohimbe dietary supplement samples. For most of the dietary supplements, the yohimbine content was not consistent with the label claims. Copyright © 2011. Published by Elsevier B.V.

Simultaneous determination of mangiferin and neomangiferin in rat plasma by UPLC-MS/MS and its application for pharmacokinetic study.

PubMed

Qiu, Xiangjun; Zhao, Jian-Long; Hao, Cong; Yuan, Canli; Tian, Nuan; Xu, Zhi-Sheng; Zou, Ruan-Min

2016-05-30

In this study, a sensitive and rapid ultra performance liquid chromatography tandem mass spectrometry (UPLC-MS/MS) method was developed to determine mangiferin and neomangiferin in rat plasma simultaneously. Chromatographic separation was carried out on an Acquity UPLC BEH C18 column and mass spectrometric analysis was performed using a Xevo TQD triple quadruple mass spectrometer coupled with an electrospray ionization (ESI) source. The MRM transitions of m/z 423.2 → 303.1 and m/z 585.0 → 273.1 were used to quantify for mangiferin and neomangiferin, respectively. The linearity of this method was found to be within the concentration range of 5-2000 ng/mL for mangiferin, and 2-1000 ng/mL for neomangiferin in rat plasma, respectively. Only 3.0 min was needed for an analytical run. This assay was used to support a preclinical study to investigate the pharmacokinetics of mangiferin and neomangiferin in rats. Copyright © 2016 Elsevier B.V. All rights reserved.

Lymphocyte ceruloplasmin and Behçet's disease.

PubMed

Oliveira, Rita; Banha, João; Martins, Fátima; Paixão, Eleonora; Pereira, Dina; Barcelos, Filipe; Teixeira, Ana; Patto, José Vaz; Costa, Luciana

2006-01-01

Behçet's disease (BD) is a rare chronic inflammatory disorder of unknown aetiology. However, it has been postulated that a dysregulation of the prooxidant/antioxidant balance may be important to its pathogenesis. Ceruloplasmin (CP) is an acute phase protein expressed at the surface of peripheral blood lymphocytes (PBL) with antioxidant properties and with a relevant role in iron (Fe) metabolism. To study CP expression at the surface of PBL (PBLCP) in patients with BD. We measured serum CP and PBLCP obtained from BD patients (n=10) and respective controls (n=10) using nephelometry and flow cytometry techniques, respectively. Additionally, haematological parameters, biochemical Fe metabolism markers [serum Fe, serum ferritin, serum transferrin, total Fe binding capacity (TIBC), transferrin saturation] and non-specific markers of inflammation [serum C reactive protein (CRP), beta2-microglobulin] were measured in all individuals. Despite the absence of significant differences between the two study groups when comparing serum CP, a significant difference in PBLCP was found in BD patients mainly due to a significant decrease of CP expression at the surface of CD3-CD56+ lymphocytes. Also, a significant decrease of PBLCP was observed in patients treated with azathioprine compared to patients that were not being treated with this drug. According to this study, we suggest that the significant decrease of PBLCP observed in BD patients might be due to azathioprine treatment and not directly related to the pathophysiology of BD.

Biotherapies in Behçet's disease.

PubMed

Comarmond, Cloé; Wechsler, Bertrand; Bodaghi, Bahram; Cacoub, Patrice; Saadoun, David

2014-07-01

Behçet's disease (BD) is a systemic large-vessel vasculitis characterized by a wide clinical spectrum including recurrent oral and genital ulcerations, uveitis, vascular, neurological, articular, renal and gastrointestinal manifestations. Therapeutic management of BD depends on the clinical presentation and organ involved. Although colchicine, nonsteroidal antiinflammatory agents and topical treatments with corticosteroids are often sufficient for mucocutaneous and joint involvements, more aggressive approach with immunosuppressive agents is warranted for severe manifestations such as posterior uveitis, retinal vasculitis, vascular, and neurological and gastrointestinal involvements. However, some patients still have refractory disease, relapse, sight threatening eye disease, or irreversible organ damage. Recent improvements in the understanding of the pathogenic mechanisms have led to the identification of potential targets and future biological therapies for BD. In contrast to current non-specific immunosuppressive agents, the emergence of biotherapies provides the possibility of interfering with specific pathogenic pathways. Novel targeted biotherapies might be used in the future for BD. Copyright © 2014 Elsevier B.V. All rights reserved.

Chemiluminescence of neutrophils from patients with Behçet's disease and its correlation with an increased proportion of uncommon serotypes of Streptococcus sanguis in the oral flora.

PubMed

Isogai, E; Ohno, S; Kotake, S; Isogai, H; Tsurumizu, T; Fujii, N; Yokota, K; Syuto, B; Yamaguchi, M; Matsuda, H

1990-01-01

Zymosan-induced chemiluminescence was investigated in whole blood and in neutrophils: in both, the peak count was frequently elevated in Behçet's disease, and was significantly higher than in healthy controls; similarly the peak time was shorter. There were more uncommon serotypes of Streptococcus sanguis in the oral flora of patients with Behçet's disease. Common serotypes were present in the flora of healthy controls, but not in patients with the disease. The percentage of Strep. sanguis in the oral flora was significantly correlated with the level of chemiluminescence response. Thus infection with uncommon serotypes of Strep. sanguis may play a role in the aetiology of Behçet's disease.

Behçet Syndrome Manifestations and Activity in the United States versus Turkey — A Cross-sectional Cohort Comparison

PubMed Central

Sibley, Cailin; Yazici, Yusuf; Tascilar, Koray; Khan, Nafiz; Bata, Yasmin; Yazici, Hasan; Goldbach-Mansky, Raphaela; Hatemi, Gulen

2015-01-01

Objective To compare clinical manifestations and activity of Behçet syndrome (BS) in the United States versus Turkey using validated outcome measures. Methods Consecutive patients with BS from the US National Institutes of Health (NIH), New York University, and the University of Istanbul were evaluated. Disease activity was measured using the Behçet’s Syndrome Activity Scale (BSAS) and the Behçet’s Disease Current Activity Form (BDCAF) with quality of life measured by the Behçet Disease Quality of Life (BDQOL) form. One-way ANOVA, t-tests, and multivariate regression analyses were performed. Results Mean age did not differ between sites; however, more women were seen in the United States versus in Turkey (p < 0.001), and disease duration was longer in the United States (p = 0.02). Organ manifestations were similar for oral and genital ulcers, skin disease, arthralgia, eye disease, and thrombosis. However, more gastrointestinal (p < 0.001) and neurologic disease (p = 0.003) was seen in the United States. BSAS and BDCAF scores were worse in the United States compared to Turkey (p = 0.013 and < 0.001, respectively). Worse mean BDQOL scores were observed at the NIH compared to Istanbul (not significant). Multivariable regression models showed worse scores in ethnically atypical patients for BSAS and BDCAF (p = 0.04 and p = 0.001), American patients for BDCAF (p = 0.01), older age for BDCAF (p = 0.005), and women for BDQOL (p = 0.01). Conclusion Demographic and clinical manifestations of BS differ between sites with higher disease activity in the United States compared to Turkey. Referral patterns, age, sex, ethnicity, and country of origin may be important in these differences. These observations raise the question of whether pathogenic mechanisms differ in Turkish and American patients. PMID:24931953

Clinical Experience of Interferon Alfa-2a Treatment for Refractory Uveitis in Behçet's Disease.

PubMed

Park, Ji-Youn; Chung, Yoo-Ri; Lee, Kihwang; Song, Ji Hun; Lee, Eun-So

2015-07-01

Behçet's disease (BD) involves multisystem vasculitis of unknown origin. Ocular manifestations of BD mostly include bilateral panuveitis and retinal vasculitis, which are very challenging to treat. Interferon alfa-2a (IFN) has been recently introduced for treating refractory Behçet uveitis, mainly in Germany and Turkey. Nonetheless, there is so far no consensus about the ideal treatment regimen of IFN for Behçet uveitis. We report our experience of IFN treatment in five Korean BD patients with refractory uveitis. All patients complained of oral ulcers; one patient had a positive pathergy test and 2 showed the presence of HLA-B51. Immunosuppressive agents used prior to IFN treatment included cyclosporine and methotrexate. The IFN treatment was commenced with a dose of 6-9 MIU/day for 7 days, adjusted according to individual ocular manifestations, tapered down to 3 MIU three times in a week, and then discontinued. All patients showed positive response to IFN treatment; 50% of them showed complete response without additional major ocular inflammation during the follow-up period. Other BD symptoms also improved after IFN treatment in most cases. After treatment, the relapse rate and the required dose of oral corticosteroid were decreased in most cases, showing a significant steroid-sparing effect. However, the visual acuity was not improved in most cases due to irreversible macular sequelae. Despite the small sample size of this study, we suggest that, in Korean patients, IFN is an effective treatment modality for BD uveitis as was observed in German and Turkish patients.

TNF-alpha antagonists and thalidomide for the management of gastrointestinal Behçet's syndrome refractory to the conventional treatment modalities: a case series and review of the literature.

PubMed

Hatemi, Ibrahim; Hatemi, Gulen; Pamuk, Omer Nuri; Erzin, Yusuf; Celik, Aykut Ferhat

2015-01-01

Gastrointestinal involvement of Behçet's syndrome is usually treated with glucocorticoids, 5-aminosalicylic acid compounds and azathioprine. However, some patients are refractory to these conventional therapy modalities. In this paper we report our experience on 13 patients with gastrointestinal involvement of Behçet's syndrome who were refractory to the conventional therapy and who were treated with TNF-alpha antagonists and/or thalidomide. We reviewed the charts of our Behçet's syndrome patients with gastrointestinal involvement and identified those who were treated with TNF-alpha antagonists and/or thalidomide. Demographic features, previous and concomitant drugs, previous surgery, time to remission and duration of remission were tabulated. We also performed a systematic review of publications on gastrointestinal involvement of Behçet's syndrome patients treated with TNF-alpha antagonists and/or thalidomide. Among our 64 patients with gastrointestinal involvement of Behçet's syndrome, we identified 13 (20%) (7 women, 6 men, mean age 27.4±9.4) who had been treated with TNF-alpha antagonists and/or thalidomide. Their previous medications were glucocorticoids (13/13), azathioprine (13/13), 5-aminosalicylic acid derivatives (3/13) and budesonide (1/13). Clinical and endoscopic remission was obtained in 10 patients. One patient died with sepsis. The systematic literature search revealed 91 cases who had used TNF-alpha antagonists and 15 who had used thalidomide. Among the patients who had received TNF-alpha antagonists, clinical remission was obtained in 47/91 patients (51%), while endoscopic remission was observed in 21/46 (45%) who had a control colonoscopy. One fifth of our Behçet's syndrome patients with gastrointestinal involvement were refractory to conventional treatment modalities. Remission was obtained with TNF-alpha antagonists and/or thalidomide in about 75% of the cases.

40 CFR 180.1284 - Ammonium salts of higher fatty acids (C8-C18 saturated; C8-C12 unsaturated); exemption from the...

Code of Federal Regulations, 2010 CFR

2010-07-01

... 40 Protection of Environment 23 2010-07-01 2010-07-01 false Ammonium salts of higher fatty acids... Ammonium salts of higher fatty acids (C8-C18 saturated; C8-C12 unsaturated); exemption from the requirement of a tolerance. Ammonium salts of C8-C18 saturated and C8-C12 unsaturated higher fatty acids are...

40 CFR 180.1284 - Ammonium salts of higher fatty acids (C8-C18 saturated; C8-C12 unsaturated); exemption from the...

Code of Federal Regulations, 2011 CFR

2011-07-01

... 40 Protection of Environment 24 2011-07-01 2011-07-01 false Ammonium salts of higher fatty acids... Ammonium salts of higher fatty acids (C8-C18 saturated; C8-C12 unsaturated); exemption from the requirement of a tolerance. Ammonium salts of C8-C18 saturated and C8-C12 unsaturated higher fatty acids are...

Determination of pyrethrin and pyrethroid residues in animal fat using liquid chromatography coupled to tandem mass spectrometry.

PubMed

Moloney, M; Tuck, S; Ramkumar, A; Furey, A; Danaher, M

2018-03-01

A method was developed for the confirmatory and quantitative analysis of one pyrethrin and 18 pyrethroid residues in animal fat. Fat was extracted was collected from adipose tissue melted in an oven at 65 °C for 2 h. Fat samples (1 g) were dispersed with deactivated Florisil ® sorbent and extracted with MeCN. Sample extracts were purified by cold temperature precipitation at -30 °C for 4 h and further purified using dispersive solid-phase extraction (d-SPE) clean-up in tubes containing 500 mg of Z-SEP+ and 125 mg of PSA bonded silica. Purified samples were analysed by ultra-high performance liquid chromatography coupled to tandem mass spectrometry (UHPLC-MS/MS) detection. Chromatographic separation was carried out on a Acquity C 8 BEH column, using a binary gradient separation comprising of mobile phase A, 5 mM ammonium formate in water:MeOH (80:20, v/v,) and mobile phase B, 5 mM ammonium formate in MeOH. The mass spectrometer was operated in the positive electrospray ionisation mode (ESI(+)). Validation was performed following the 2002/657/EC guidelines. Trueness ranged between 84% and 143% and precision ranged between 3.9% and 29%. The developed method is particularly advantageous because the sample preparation procedure does not require complex sample extraction equipment and uses less solvent compared to other sample preparation protocols. Copyright © 2017 Elsevier B.V. All rights reserved.

Determination of a selection of synthetic cannabinoids and metabolites in urine by UHPSFC-MS/MS and by UHPLC-MS/MS.

PubMed

Berg, Thomas; Kaur, Lakhwinder; Risnes, Anna; Havig, Stine Marie; Karinen, Ritva

2016-07-01

Two different analytical techniques, ultra-high performance supercritical fluid chromatography-tandem mass spectrometry (UHPSFC-MS/MS) and reversed phase ultra-high performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS), were used for the determination of two synthetic cannabinoids and eleven metabolites in urine; AM-2201 N-4-OH-pentyl, AM-2233, JWH-018 N-5-OH-pentyl, JWH-018 N-pentanoic acid, JWH-073 N-4-OH-butyl, JWH-073 N-butanoic acid, JWH-122 N-5-OH-pentyl, MAM-2201, MAM-2201 N-4-OH-pentyl, RCS-4 N-5-OH-pentyl, UR-144 degradant N-pentanoic acid, UR-144 N-4-OH-pentyl, and UR-144 N-pentanoic acid. Sample preparation included a liquid-liquid extraction after deconjugation with ß-glucuronidase. The UHPSFC-MS/MS method used an Acquity UPC(2 TM) BEH column with a mobile phase consisting of CO2 and 0.3% ammonia in methanol, while the UHPLC-MS/MS method used an Acquity UPLC® BEH C18 column with a mobile phase consisting of 5 mM ammonium formate (pH 10.2) and methanol. MS/MS detection was performed with positive electrospray ionization and two multiple reaction monitoring transitions. Deuterated internal standards were used for six of the compounds. Limits of quantification (LOQs) were between 0.04 and 0.4 µg/L. Between-day relative standard deviations at concentrations ≥ LOQ were ≤20%, with biases within ±19%. Recoveries ranged from 40 to 90%. Corrected matrix effects were within 100 ± 10%, except for MAM-2201 with UHPSFC-MS/MS, and for UR-144 N-pentanoic acid and MAM-2201 N-4-OH-pentyl with UHPLC-MS/MS. Elution order obtained by UHPSFC-MS/MS was almost opposite to that obtained by UHPLC-MS/MS, making this instrument setup an interesting combination for screening and confirmation analyses in forensic cases. The UHPLC-MS/MS method has, since August 2014, been successfully used for confirmation of synthetic cannabinoids in urine samples revealing a positive immunoassay screening result. Copyright © 2015

The natural outcome of melamine-induced bladder stones with bladder epithelial hyperplasia after the withdrawal of melamine in mice.

PubMed

Ren, Shu-Ting; Xu, Chang-Fu; Du, Yun-Xia; Gao, Xiao-Li; Sun, Ying; Jiang, Yi-Na

2012-07-01

The natural outcome of melamine-induced bladder stones (cystoliths) with bladder epithelial hyperplasia (BEH) after melamine withdrawn is unclear. Using an ideal dual-model system, three experiments were conducted in BALB/c mice. Each experiment included a control, model 1 and model 2 groups. The mice were fed a regular diet in controls or a 9373 ppm melamine diet in models, and the first day was designated as dosing day 1. The melamine diet was then replaced by the regular diet in the model 2 groups, and the first day was designated as post-dosing day 1. On dosing days 12, 35 and 49, the incidence of cystoliths and diffusely active BEH was 8/8 in the mice of three model 1 groups. On post-dosing days 1, 4 and 8, in the mice of three model 2 groups, the incidence of cystoliths was 2/8, 0/8 and 1/8, respectively, and the progressive regression of BEH was observed. In conclusion, both the stones and BEH have the natural property of rapid development and rapid regression, and melamine withdrawn plays a key role in the stone dissolution-discharge necessary for BEH regression. BEH may be reversible after the discharge of the stones. The conventionally conservative therapy is thus reasonable. Copyright © 2012 Elsevier Ltd. All rights reserved.

Supercritical Fluid Chromatography with Photodiode Array Detection in the Determination of Fat-Soluble Vitamins in Hemp Seed Oil and Waste Fish Oil.

PubMed

Tyśkiewicz, Katarzyna; Gieysztor, Roman; Maziarczyk, Izabela; Hodurek, Paweł; Rój, Edward; Skalicka-Woźniak, Krystyna

2018-05-10

In the presented study for the first time a new, optimized, fast SFC (supercritical fluid chromatography) method was applied to separate in one run fat-soluble vitamins from waste fish oil, including cis -and tran s-retinyl palmitate, cis - and trans -retinyl acetate, retinol, α-tocopherol, β-tocopherol, γ‑tocopherol, δ-tocopherol, ergocalciferol (D₂), cholecalciferol (D₃), cis - and trans -phylloquinone (K₁) and menaquinone-4 (K₂-MK4). Vitamins were baseline separated on an Acquity UPC² (ultra performance convergence chromatography) HSS C18 SB (highly strength chemically modified silica) column within 13 min. The influence of the stationary phase, such as Torus 1-AA (1-aminoanthracene), Torus Diol (high density diol), Torus DEA (diethylamine), BEH (silica with no bonding), BEH-2EP (2-ethylpirydine), CSH Fluoro-Phenyl (silica with fluoro-phenyl groups), column temperature, flow rate and back pressure on the separation of the compounds was described. The application of the modified saponification procedure allowed us to increase concentration in the sample prepared for the analysis of γ‑tocopherol from less than 1% (wt %) to 14% for the first time. In addition, α‑tocopherol, γ‑tocopherol, δ‑tocopherol and retinol were identified in waste fish oil. Vitamin purification and analysis in waste fish oil are reported for the first time here. Due to the short time and effectiveness of the proposed method, it can be easily applied in industrial processes.

Histopathological and electron microscopic studies of lymphangiectasia of the small intestine in Behçet's disease

PubMed Central

Asakura, Hitoshi; Morita, Akira; Morishita, Tetsuo; Tsuchiya, Masaharu; Watanabe, Yoonosuke; Enomoto, Yasuhiro

1973-01-01

The gastrointestinal involvement and immunological findings in 16 patients with Behçet's disease are described. Four of 15 biopsy specimens of jejunal mucosa showed marked lymphangiectasia in the lamina propria similar to the appearance which was thought to be a characteristic finding in protein-losing enteropathy. None of the patients had hypoproteinaemia. Increases in serum immunoglobulin IgA were proved in six of 15 cases; in IgM, five of 15; and in IgG, one of 15. Electron microscopic studies showed that there were thousands of precipitated lymph protein bodies in the extracellular spaces of the lamina propria. Ulcers and healed ulcers of the large intestine were studied by light microscopy. ImagesFig. 1Fig. 2Fig. 3Fig. 4Fig. 7Fig. 8Fig. 9 PMID:4700433

The association between the parenchymal neurological involvement and posterior uveitis in Behçet's syndrome.

PubMed

Bitik, Berivan; Tufan, Abdurrahman; Sahin, Kubilay; Sucullu Karadag, Yesim; Can Sandikci, Sevinc; Mercan, Ridvan; Ak, Fikri; Karaaslan, Yasar; Ozturk, Mehmet Akif; Goker, Berna; Haznedaroglu, Seminur

2016-01-01

Behçet's syndrome (BS) is a systemic vasculitis, which may involve multiple organ systems simultaneously. Clinical findings in BS often fit into well-recognized patterns, such as the association between papulo-pustular skin lesions and arthritis. We have recently observed a distinct pattern, in which a subtype of neuro-Behçet's syndrome (NBS) is often preceded by specific ophthalmic manifestations of the disease process. The purpose of this study is to evaluate the association between the parenchymal subtype of NBS and posterior uveitis (PU). We have retrospectively reviewed the clinical records of 295 patients with BS, who met the international classification criteria for BS, diagnosed at two major rheumatology clinics from 2010 to 2014. Patient demographics, ophthalmic examinations, clinical and radiologic patterns of neurological involvement were recorded. Manifestations of BS were classified as PU, NBS, vascular involvement, and arthritis. The association between clinical findings was analysed for statistical significance. Of the 295 patients, 100 had PU and 44 had NBS. 30 patients had parenchymal NBS and 14 had vascular NBS. Patients with PU were significantly more likely to have neurological involvement compared to those without PU (p<0.001; Odds Ratio: 3.924; 95% CI: 1.786-8.621). Rate of posterior uveitis was higher in patients with parenchymal NBS when compared to patients with vascular NBS, vascular BS or arthritis (63.3%, 21.4%, 22% and 4.2% respectively, p<0.001). Our findings suggest a clinically and statistically significant association between posterior uveitis and parenchymal type of neurologic involvement in BS. The development of posterior uveitis in a patient with previously diagnosed BS should be recognized as a "warning sign" for predisposition to neurologic involvement. These patients should be informed about the possible signs and symptoms of neurological involvement, which can cause very rapid and irreversible damage unless recognized and

Mortality in Behçet's disease.

PubMed

Saadoun, D; Wechsler, B; Desseaux, K; Le Thi Huong, D; Amoura, Z; Resche-Rigon, M; Cacoub, P

2010-09-01

To report the long-term mortality in patients with Behçet's disease (BD). A cohort of 817 patients fulfilling the international criteria for BD from a single center in France were analyzed for causes of death, the standardized mortality ratio (SMR), and the factors associated with mortality. Among the 817 patients with BD, 41 (5%) died after a median followup of 7.7 years, of whom 95.1% were male. The mean ± SD age at death was 34.8 ± 11.9 years. Main causes of death included major vessel disease (mainly, arterial aneurysm and Budd-Chiari syndrome) (43.9%), cancer and malignant hemopathy (14.6%), central nervous system involvement (12.2%), and sepsis (12.2%). The mortality rate at 1 year and 5 years was 1.2% and 3.3%, respectively. There was an increased mortality among patients ages 15-24 years (SMR 2.99, 95% confidence interval [95% CI] 1.54-5.39) and those ages 25-34 years (SMR 2.90, 95% CI 1.80-4.49) as compared with age-and sex-matched healthy controls. The mortality decreased in patients older than age 35 years (SMR 1.23, 95% CI 0.75-1.92). In multivariate analyses, male sex (hazard ratio [HR] 4.94, 95% CI 1.53-16.43), arterial involvement (HR 2.51, 95% CI 1.07-5.90), and a high number of BD flares (HR 2.37, 95% CI 1.09-5.14) were independently associated with the risk of mortality. The overall mortality in our BD cohort was 5% after a median followup of 7.7 years. Male sex, arterial involvement, and the number of flares were associated with mortality in BD.

Recurrent aortic aneurysms in Behçet disease.

PubMed

Adams, Corey; Zhen-Yu Tong, Michael; Lawlor, D Kirk; DeRose, Guy; Forbes, Thomas L

2010-01-01

The following is a case of a 22-year-old male with recurrent thoracic aneurysms with several constitutional symptoms, including gastrointestinal discomfort, irritable bowel syndrome, lactose intolerance, and a 2-week history of severe lower back pain. The patient underwent an initial thoracoabdominal repair of a visceral aneurysm followed by endovascular repair of a recurrent thoracic pseudoaneurysm. The etiology of the visceral aneurysm was initially hypothesized to be mycotic; however, further information revealed signs and symptoms consistent with the diagnostic criteria for Behçet disease (BD). We suggest that BD be considered in younger patients who present with an aortic aneurysm. Although open repair is the traditional approach for arterial lesions in BD, the role for endovascular intervention should be considered as it represents a surgical repair with a significant reduction in morbidity.

[Treatment of Behçet's disease].

PubMed

Comarmond, C; Wechsler, B; Cacoub, P; Saadoun, D

2014-02-01

Behçet's disease (BD) is a systemic large-vessel vasculitis characterized by a wide clinical spectrum including recurrent oral and genital ulcerations, uveitis, vascular, neurological, articular, and gastrointestinal manifestations. Therapeutic management of BD depends on the clinical presentation and organ involved. Although colchicine, non-steroidal anti-inflammatory agents and topical treatments with corticosteroids are often sufficient for mucocutaneous and joint involvement, a more aggressive approach with immunosuppressive agents is warranted for severe manifestations such as posterior uveitis, retinal vasculitis, vascular, neurological and gastrointestinal involvement. However, some patients still have refractory disease, relapses, sight threatening eye disease, or irreversible organ damage. Recent improvements in the understanding of the pathogenic mechanisms have led to the identification of potential targets and future therapies for BD. In contrast to current non-specific immunosuppressive agents, the emergence of immunomodulatory drugs provides the possibility of interfering with specific pathogenic pathways. Novel targeted immunosuppressive therapies might be used in the future for BD. Copyright © 2013 Société nationale française de médecine interne (SNFMI). Published by Elsevier SAS. All rights reserved.

Comparison of Ion Chemistries in Octafluoro-2-butene (2-C4F8) and in Octfluorocyclobutane (c-C4F8)

NASA Astrophysics Data System (ADS)

Jiao, Charles; Dejoseph, Charles; Garscadden, Alan

2007-10-01

2-C4F8 is one of the promising candidates to replace c-C4F8 that has been widely used for dielectric etching but is not environmentally friendly. In this study we have investigated electron impact ionization and ion-molecule reactions of 2-C4F8 using Fourier transform mass spectrometry (FTMS), and compared the results with those of c-C4F8 we have studied previously. Electron impact ionization of 2-C4F8 produces 15 ionic species including C4F7,8^+, C3F3,5,6^+, C2F4^+ and CF1-3^+ as the major ions. The total ionization cross section of 2-C4F8 reaches a maximum of 1.8x10-15 cm^2 at 90 eV. The ionization is dominated by the channel forming the parent ion C4F8^+ from 12 to 18 eV, and by the channel forming C3F5^+ from 18 to 70 eV. After 70 eV, CF3^+ becomes the dominant product ion. Among the major ions generated from the electron impact ionization of 2-C4F8, only CF^+, CF2^+ and CF3^+ are found to react with 2-C4F8, via F^- abstraction or charge transfer mechanism. The charge transfer reaction of Ar^++2-C4F8 produces primarily C4F7^+.

Hyperhomocysteinemia in patients with Behçet's disease: is it due to inflammation or therapy?

PubMed

Yesilova, Zeki; Pay, Salih; Oktenli, Cagatay; Musabak, Ugur; Saglam, Kenan; Sanisoglu, S Yavuz; Dagalp, Kemal; Erbil, M Kemal; Kocar, Ismail H

2005-08-01

Considerable discrepancies exist in the literature with respect to plasma total homocysteine (tHcy) levels in Behçet's disease (BD). The aim of this study was to evaluate tHcy concentrations in these patients. Thirty-two patients with BD and 20 age- and body mass index-matched healthy volunteers were enrolled. Plasma tHcy concentrations were significantly higher, while vitamin B12 and folate levels were significantly lower in patients with thrombosis and eye involvement than those without. C-reactive protein levels also correlated significantly in a negative manner with vitamin B12 and folate but positively with tHcy. In conclusion, increased use or accelerated catabolism of folate and vitamin B12 due to chronic inflammation and moderately increased tHcy concentrations related with deficiency of these cofactors, and immunosuppressive drug administration might be potential threats of vascular disease in BD.

7Li(15N, 14C)8Be reaction at 81 MeV and 14C + 8Be interaction versus that of 13C + 8Be

NASA Astrophysics Data System (ADS)

Rudchik, A. T.; Rudchik, A. A.; Muravynets, L. M.; Kemper, K. W.; Rusek, K.; Koshchy, E. I.; Piasecki, E.; Trzcinska, A.; Pirnak, Val. M.; Ponkratenko, O. A.; Strojek, I.; Stolarz, A.; Plujko, V. A.; Sakuta, S. B.; Siudak, R.; Ilyin, A. P.; Stepanenko, Yu. M.; Shyrma, Yu. O.; Uleshchenko, V. V.

2018-03-01

Angular distributions of the 7Li(15N, 14C)8Be reaction were measured at the energy Elab(15N) = 81 MeV. Data for transfer to the ground and first two excited states in 8Be were acquired as well as to the 14C ground and excited states. The reaction data were analyzed within the coupled-reaction-channels (CRC) method. The required 15N + 7Li entrance channel potential was taken from the 15N + 7Li elastic scattering. The 14C + 8Be potential was found by fitting Woods-Saxon form potentials to those generated by double folded real and imaginary potentials in the region of interaction. These generated potentials were then used in the CRC calculations. Proton transfer dominants this reaction, including to the excited states of 8Be. The reaction dependence on the exit channel potential was examined by using the 13C + 8Be potential previously deduced from the 9Be(12C, 13C)8Be reaction and 14C + 8Be from the 13C(9Be, 8Be)14C reaction.

Oligoclonal banding of IgG in CSF, blood-brain barrier function, and MRI findings in patients with sarcoidosis, systemic lupus erythematosus, and Behçet's disease involving the nervous system.

PubMed Central

McLean, B N; Miller, D; Thompson, E J

1995-01-01

A retrospective study of CSF and serum analysis from a total of 43 patients with sarcoidosis, 20 with systemic lupus erythematosus, and 12 with Behçet's disease with neurological involvement found local synthesis of oligoclonal IgG using isoelectric focusing and immunoblotting in 51%, 25%, and 8% respectively at some stage in their disease. Blood-brain barrier breakdown, when assessed with an albumin ratio found 47% of patients with sarcoidosis, 30% of those with systemic lupus erythematosus, and 42% of patients with Behçet's disease exhibiting abnormal barrier function at some time. Serial CSF analysis showed that clinical relapses were associated with worsening barrier function and in some patients the development of local oligoclonal IgG synthesis; conversely steroid treatment led to a statistically significant improvement in barrier function, and in two patients a loss of oligoclonal IgG bands. A higher proportion of patients had MRI abnormalities than oligoclonal IgG or blood-brain barrier breakdown, MRI being abnormal in 16 of 19 patients with sarcoidosis, three of four patients with systemic lupus erythematosus, and seven of nine patients with Behçet's disease, although this may have been due to temporal factors. In the differential diagnosis of chronic neurological disorders, locally synthesised oligoclonal IgG cannot distinguish between diseases, but the loss of bands seen in two patients contrasts with what is seen in multiple sclerosis, and thus may be a useful diagnostic clue. PMID:7745401

Mean platelet volume in ocular Behçet's disease.

PubMed

Türkcü, Fatih Mehmet; Cingü, Abdullah Kürşat; Yüksel, Harun; Cınar, Yasin; Akkurt, Meltem; Sahin, Muhammed; Ozkurt, Zeynep; Sahin, Alparslan; Caça, Ihsan

2013-01-01

To determine whether mean platelet volume (MPV) is an indicator of disease severity in ocular Behçet's Disease (BD). The study population was 30 newly diagnosed ocular BD patients who presented with active uveitis. These patients had no past history of smoking, drug use, or systemic diseases including diabetes mellitus, hypertension, cardiovascular disease, and renal disease. A control group consisting of 34 healthy individuals was included for comparison. MPV measurements were performed serially upon presentation with active uveitis and at one and three month thereafter in BD group whereas only at presentation in the controls. Upon presentation with active uveitis, the mean MPV levels were 7.88 ± 1.14 femtoliters (fL) for BD group. During the posttreatment follow-up period at first and third months, BD patients demonstrated a mean MPV level of 7.71 ± 1.12 fL and 7.65 ± 1.04 fL, respectively. The mean MPV value of control group, was 8.39 ± 0.66 fL at presentation. Fluctuations in MPV values were not significant in the BD group, while there was a significant difference between the initial measurements of the BD and control groups. MPV measurement in ocular BD is not a predictive laboratory test to determine the clinical improvement in early stages following classical immunosuppressive treatment.

Mean Platelet Volume in Ocular Behçet's Disease

PubMed Central

Türkcü, Fatih Mehmet; Cingü, Abdullah Kürşat; Yüksel, Harun; Çınar, Yasin; Akkurt, Meltem; Şahin, Muhammed; Özkurt, Zeynep; Şahin, Alparslan; Çaça, İhsan

2013-01-01

Objective. To determine whether mean platelet volume (MPV) is an indicator of disease severity in ocular Behçet's Disease (BD). Materials and Methods. The study population was 30 newly diagnosed ocular BD patients who presented with active uveitis. These patients had no past history of smoking, drug use, or systemic diseases including diabetes mellitus, hypertension, cardiovascular disease, and renal disease. A control group consisting of 34 healthy individuals was included for comparison. MPV measurements were performed serially upon presentation with active uveitis and at one and three month thereafter in BD group whereas only at presentation in the controls. Results. Upon presentation with active uveitis, the mean MPV levels were 7.88 ± 1.14 femtoliters (fL) for BD group. During the posttreatment follow-up period at first and third months, BD patients demonstrated a mean MPV level of 7.71 ± 1.12 fL and 7.65 ± 1.04 fL, respectively. The mean MPV value of control group, was 8.39 ± 0.66 fL at presentation. Fluctuations in MPV values were not significant in the BD group, while there was a significant difference between the initial measurements of the BD and control groups. Conclusion. MPV measurement in ocular BD is not a predictive laboratory test to determine the clinical improvement in early stages following classical immunosuppressive treatment. PMID:24250258

High prevalence of Behçet's disease in southern Italy.

PubMed

Olivieri, Ignazio; Leccese, Pietro; Padula, Angela; Nigro, Angelo; Palazzi, Carlo; Gilio, Michele; D'Angelo, Salvatore

2013-01-01

This paper aims to estimate the prevalence of Behçet's disease (BD) in the city of Potenza, the regional capital of Basilicata (or Lucania) Region, in southern Italy. Patients with BD living in Potenza for at least 12 months prior to diagnosis were identified through the following sources: general practitioners, community-based specialists, San Carlo Hospital specialists, the Basilicata centralised index and the Basilicata database for rare diseases. All identified patients were contacted by phone and were recalled to our outpatient clinic for re-evaluation. Patients were classified as having complete BD if they met the International Study Group (ISG) criteria for BD. By surveying a population of 69.060 subjects, 13 patients with a diagnosis of BD were identified. All were white and Italian by descendent. Eleven out of these satisfied the ISG criteria and allowed us to obtain a prevalence rate of 15.9 per 100.000 (95%CI 8.9-28.5), which is the highest ever found value in Europe. This cross-sectional population-based study suggests that BD is more frequent in the southern part than in the northern part of Italy and confirms that the prevalence of the disease increases in a north-to-south manner within the European continent.

Early treatment with infliximab in bilateral occlusive vasculitis as a presenting manifestation of Behçet' disease.

PubMed

Bañeros-Rojas, P; Berrozpe-Villabona, C; Peraza-Nieves, J E; Díaz-Valle, D

2015-06-01

A 24 year old woman who complained of maculo-papulo rash, genital and bucal aphthous ulcers, abdominal pain, minor dyspnea and visual loss in both eyes. Funduscopy revealed a bilateral occlusive vasculitis including central vessels. Treatment was initiated with a methylprednisolone bolus (1 g/24h) and infliximab 5mg/kg/day (0-2-6 weeks and every 8 weeks). The treatment prescribed induced a fast remission. Visual acuity improved. The patient did not suffer any other relapse after one year of follow-up. An initial treatment with Infliximab should be considered in Behçet disease for serious outbreaks, such as macular occlusive vasculitis with ischemia. Copyright © 2013 Sociedad Española de Oftalmología. Published by Elsevier España, S.L.U. All rights reserved.

Anti-interleukin 6 receptor tocilizumab in refractory uveitis associated with Behçet's disease: multicentre retrospective study.

PubMed

Atienza-Mateo, Belén; Calvo-Río, Vanesa; Beltrán, Emma; Martínez-Costa, Lucía; Valls-Pascual, Elia; Hernández-Garfella, Marisa; Atanes, Antonio; Cordero-Coma, Miguel; Miquel Nolla, Joan; Carrasco-Cubero, Carmen; Loricera, Javier; González-Vela, María C; Vegas-Revenga, Nuria; Fernández-Díaz, Carlos; Demetrio-Pablo, Rosalía; Domínguez-Casas, Lucía C; Luis Martín-Varillas, José; Palmou-Fontana, Natalia; Hernández, José L; González-Gay, Miguel Á; Blanco, Ricardo

2018-05-01

To assess the efficacy of tocilizumab (TCZ) in refractory uveitis of Behçet's disease (BD). Multicentre study of patients with BD-associated uveitis. Patients were refractory to conventional and biologic immunosuppressive drugs. The main outcome measures were intraocular inflammation, macular thickness, visual acuity and corticosteroid-sparing effects. We studied 11 patients (7 men) (20 affected eyes); median age 35 years. Uveitis was bilateral in nine patients. The patterns of ocular involvement were panuveitis (n = 8, with retinal vasculitis in 4), anterior uveitis (n = 2) and posterior uveitis (n = 1). Cystoid macular oedema was present in seven patients. The clinical course was recurrent (n = 7) or chronic (n = 4). Before TCZ, patients had received systemic corticosteroids, conventional immunosuppressants and the following biologic agents: adalimumab (n = 8), infliximab (n = 4), canakimumab (n = 1), golimumab (n = 3), etanercept (n = 1). TCZ was used as monotherapy or combined with conventional immunosuppressants at 8 mg/kg/i.v./4 weeks (n = 10) or 162 mg/s.c./week (n = 1). At TCZ onset the following extraocular manifestations were present: oral and/or genital ulcers (n = 7), arthritis (n = 4), folliculitis/pseudofolliculitis (n = 4), erythema nodosum (n = 2), livedo reticularis (n = 1) and neurological involvement (n = 2). TCZ yielded rapid and maintained improvement in all ocular parameters of the patients, with complete remission in eight of them. However, this was not the case for the extraocular manifestations, since TCZ was only effective in three of them. After a mean (s.d.) follow-up of 9.5 (8.05) months, TCZ was withdrawn in two cases, due to a severe infusion reaction and arthritis impairment, respectively. TCZ could be a therapeutic option in patients with BD and refractory uveitis.

Bell's palsy during interferon alpha 2a treatment in a case with Behçet uveitis.

PubMed

Yalçindağ, Fatime Nilüfer; Alay, Cem

2013-01-01

To present a case who developed Bell's palsy while using interferon alpha 2a for Behçet uveitis. A patient with Behçet disease presented with decreased vision in his right eye. Ophthalmic examination, fundus fluorescein angiography and optical coherence tomography were performed. After developing facial paralysis while on interferon therapy, the patient was referred to our neurology service for differential diagnosis and treatment. Examination of right eye revealed panuveitis with branch retinal vein occlusion, so high dose steroids were prescribed. In three days there was no improvement in terms of vitreous inflammation and so steroids were replaced with interferon. At the seventh month, patient experienced a facial paralysis. After eliminating other causes, including viral infections, trauma, cold exposure and neurological evaluation with cranial MRI, the patient was diagnosed to have Bell's palsy by a neurologist. Interferon was replaced with mycophenolate mofetil and the Bell's palsy was treated with oral steroids. It is important to be alert to both common and rare complications while treating with interferon.

Ulcerative colitis followed by the development of typical intestinal Behçet disease: A case report.

PubMed

Zhu, Zhenhua; Shu, Xu; Long, Shunhua; Jiang, Xiaozhen; Lu, Nonghua; Zhu, Xuan; Liao, Wangdi

2018-02-01

Intestinal Behçet disease (intestinal BD) and inflammatory bowel disease (IBD) share a lot of characteristics, including genetic background, clinical manifestations, and therapeutic strategies, especially the extraintestinal manifestations, such as oral ulcers, arthralgia, eye lesions, skin lesions, etc, but the coexistence of these 2 diseases are uncommon. Behçet disease with gastrointestinal involvement in ulcerative colitis (UC) patient has been reported in just 1 previous case report, but, which can not be diagnosed as definite intestinal BD based on Korean novel diagnositic criteria due to lacking the typical ileocecal ulcer. We present a 23-year-old woman with ulcerative disease who developed typical intestinal BD, which is the first case report of patient with coexisting UC and typical intestinal BD. This patient was diagnosed as coexistence of intestinal BD and UC base on the clinical manifestations, extra intestinal manifestations and typical colonoscopic findings. Steroid and methotrexate were administered. This patient achieved clinical remission and mucosal healing. Coexistence of intestinal BD and UC is uncommon, and the combination with steroid, methotrexate, and 5-aminosalicylic acids is an effective therapy.

[Determination of 49 drugs and 5 metabolites in drinking water samples using ultra-high performance liquid chromatography-electrospray ionization tandem mass spectrometry].

PubMed

Wang, Shuo; Zhang, Xiangming; Zhang, Jing; Shao, Bing; Li, Shuming

2015-07-01

A method for the determination of 54 drugs in drinking water samples was developed by using ultra-high performance liquid chromatography-electrospray ionization tandem mass spectrometry (UPLC-ESI MS/MS). The target drugs in drinking water samples were enriched and cleaned-up by HLB solid-phase extraction (SPE) cartridges and then eluted with 5 mL methanol. The elute was collected, concentrated under a gentle stream of nitrogen gas, diluted with 0.4 mL 0.1% formic acid solution, and analyzed by UPLC-ESI MS/MS. The separation of the 54 drugs was performed on an ACQUITY UPLC™ BEH C18 column using mobile phases of 0.1% formic acid and methanol by gradient elution. The multiple reaction monitoring (MRM) mode was employed in mass spectrometry acquisition. The matrix-matched external standard calibration was used for quantitation. The results showed that the average recoveries of the drugs in ground water, tap water and surface water were 58.7%-104.4%, 53.1%-109.5%, and 50.7%-118.8%, respectively, and the corresponding relative standard deviations (RSD, n=6) were 0.3%-12.8%, 1.0%-15.5%, and 0.4%-19.3%, respectively. The method quantification limits (MQL) for target compounds were in the range of 0.002-5.000 ng/L. The developed method was applied to analyze the water samples from Beijing. The results showed that 26 drugs were detected in ground water samples.

Behçet's syndrome and health-related quality of life: influence of symptoms, lifestyle and employment status.

PubMed

Senusi, Amal A; Ola, Dennis; Mather, Jan; Mather, John; Fortune, Farida

2017-01-01

Behçet's syndrome (BS) is a chronic multisystemic disorder. The complex pattern of BS symptoms can effect negatively on patients' quality of life. The aim of this study is to evaluate the influence of BS symptoms, oral health related lifestyles and employment status on Health Related Quality of Life (HRQoL). A questionnaire was mailed to a cohort of 641 adult members of the Behçet's Syndrome Society (BSS) and patients attending a Behçet's syndrome centre in the UK. Respondents gave information on socio-demographic characteristics, disease duration, current symptoms, symptom control, health related lifestyle, diet, smoking and alcohol, employment status and quality of life (the EQ-5D index). 315 out of 426 BS participants (Males: Females=136:179) were recruited. BS symptoms and EQ-5D score model (R=0.67 and R2=0.45) and standardised coefficients for symptoms were; arthropathy (-0.336), headache (-0.227), neurological problems (-0.135), pathergy reaction (-0.119) and skin lesions (-0.107) in decreasing order. This finding was similar to a 2009 study of the same cohort. Regression analysis of tobacco consumption revealed that tobacco use was a risk factor for decreasing the EQ-5D score (beta value = - 0.72, p=0.001). Using an effective mouthwash has a positive impact on HRQoL (beta value= 0.149 and p=0.012). The mean EQ-5D in patients who continued in employment and who were not receiving benefits was better compared to other sub groups. BS symptoms, employment status, a healthy lifestyle combined with a good oral health have a significant impact on the HRQoL of BS patients.

Subzero-Temperature Liquid-Liquid Extraction Coupled with UPLC-MS-MS for the Simultaneous Determination of 12 Bioactive Components in Traditional Chinese Medicine Gegen-Qinlian Decoction.

PubMed

Shi, Zhihong; Li, Zhimin; Zhang, Shulan; Fu, Hongna; Zhang, Hongyi

2015-09-01

Based on the phase separation phenomenon of acetonitrile-water system at subzero temperature, a subzero-temperature liquid-liquid extraction coupled with ultra-performance liquid chromatography tandem quadrupole mass spectrometry : UPLC-MS-MS) method was developed for the simultaneous determination of 12 bioactive components in Gegen-Qinlian decoction. After optimization, the extraction conditions were set as follows: 3.0 mL of aqueous sample solution (pH 5.86) was extracted with 2 mL of acetonitrile at -35°C for 35 min. The separated acetonitrile phase was diluted 10-fold with water before UPLC-MS-MS analysis. Separation was performed on a Waters ACQUITY UPLC(®)BEH C18 column (2.1 × 100 mm i.d., 1.7 µm) with ammonium formate buffer solution (20 mmol L(-1), pH 3.2, adjusted by formic acid) and acetonitrile as mobile phase with gradient elution. Twelve target components could be separated within 10 min and quantified in multiple reaction monitoring mode, both positive and negative ionization modes were employed. Limits of detection were in the range of 0.0003-0.0451 μg mL(-1). Relative standard deviation values for intra- and interday precision were <2.71 and 8.94%, respectively. The established method provides a simple and effective framework for the quality control of Gegen-Qinlian decoction and related traditional Chinese medicinal preparations. © The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

A Validated Stability-Indicating RP-UPLC Method for Simultaneous Determination of Desloratadine and Sodium Benzoate in Oral Liquid Pharmaceutical Formulations.

PubMed

Kumar, Navneet; Sangeetha, Dhanaraj; Reddy, Pingili Sunil; Prakash, Lakkireddy

2012-01-01

A novel, sensitive and selective stability-indicating gradient reverse phase ultra performance liquid chromatographic method was developed and validated for the quantitative determination of desloratadine and sodium benzoate in pharmaceutical oral liquid formulation. The chromatographic separation was achieved on Acquity BEH C8 (100 mm × 2.1 mm) 1.7 μm column by using mobile phase containing a gradient mixture of solvent A (0.05 M KH(2)PO(4) and 0.07 M triethylamine, pH 3.0) and B (50:25:25 v/v/v mixture of acetonitrile, methanol and water) at flow rate of 0.4 mL/min. Column temperature was maintained at 40°C and detection was carried out at a wavelength of 272 nm. The described method shows excellent linearity over a range of 0.254 μg/mL to 76.194 μg/mL for desloratadine and 1.006 μg/mL to 301.67 μg/mL for sodium benzoate. The correlation coefficient for desloratadine and sodium benzoate was more than 0.999. To establish stability-indicating capability of the method, drug product was subjected to the stress conditions of acid, base, oxidative, hydrolytic, thermal and photolytic degradation. The degradation products were well resolved from desloratadine and sodium benzoate. The developed method was validated as per international ICH guidelines with respect to specificity, linearity, LOD, LOQ, accuracy, precision and robustness.

A New Rapid and Sensitive Stability-Indicating UPLC Assay Method for Tolterodine Tartrate: Application in Pharmaceuticals, Human Plasma and Urine Samples.

PubMed

Yanamandra, Ramesh; Vadla, Chandra Sekhar; Puppala, Umamaheshwar; Patro, Balaram; Murthy, Yellajyosula L N; Ramaiah, Parimi Atchuta

2012-01-01

A new rapid, simple, sensitive, selective and accurate reversed-phase stability-indicating Ultra Performance Liquid Chromatography (RP-UPLC) technique was developed for the assay of Tolterodine Tartrate in pharmaceutical dosage form, human plasma and urine samples. The developed UPLC method is superior in technology to conventional HPLC with respect to speed, solvent consumption, resolution and cost of analysis. Chromatographic run time was 6 min in reversed-phase mode and ultraviolet detection was carried out at 220 nm for quantification. Efficient separation was achieved for all the degradants of Tolterodine Tartrate on BEH C18 sub-2-μm Acquity UPLC column using Trifluoroacetic acid and acetonitrile as organic solvent in a linear gradient program. The active pharmaceutical ingredient was extracted from tablet dosage form using a mixture of acetonitrile and water as diluent. The calibration graphs were linear and the method showed excellent recoveries for bulk and tablet dosage form. The test solution was found to be stable for 40 days when stored in the refrigerator between 2 and 8 °C. The developed UPLC method was validated and meets the requirements delineated by the International Conference on Harmonization (ICH) guidelines with respect to linearity, accuracy, precision, specificity and robustness. The intra-day and inter-day variation was found be less than 1%. The method was reproducible and selective for the estimation of Tolterodine Tartrate. Because the method could effectively separate the drug from its degradation products, it can be employed as a stability-indicating one.

Recurrent longitudinal extensive transverse myelitis in a neuro-Behçet syndrome treated with infliximab.

PubMed

Uygunoğlu, Uğur; Pasha, Maarya; Saip, Sabahattin; Siva, Aksel

2015-01-01

Spinal cord involvement is not common, but can be seen in neuro-Behçet's syndrome (NBS). The major site of involvement is the cervical spinal cord with the myelitis-like inflammatory lesions continuing more than two segments, and extending to the brainstem. A 30-year-old male patient who has been followed with a diagnosis of Behçet's syndrome admitted to our neurology department clinically and radiologically suggestive of recurrent and extensive longitudinal myelitis. His anti-aquaporine antibody was negative. Because of insufficient effect of azathioprine, cyclophosphamide, and corticosteroids, infliximab was started. His clinical and radiological status is stationary for 3 years under infliximab treatment. Myelitis such as that occurring in our patient may have a similar presentation like neuromyelitis optica (NMO), which should therefore be included in differential diagnosis. Myelitis observed in both NMO and NBS shows spinal cord lesions longer than three or more vertebrae. Anti-aquaporine antibody must be evaluated in all patients presenting with longitudinal myelitis. Anti-tumor necrosis factor agent infliximab might be an alternative treatment in severe form of NBS such as myelitis. In our case, successful treatment of recurrent and extensive longitudinal transverse myelitis in NBS with infliximab was demonstrated.

Accurate ab initio quartic force fields for borane and BeH2

NASA Technical Reports Server (NTRS)

Martin, J. M. L.; Lee, Timothy J.

1992-01-01

The quartic force fields of BH3 and BeH2 have been computed ab initio using an augmented coupled cluster (CCSD(T)) method and basis sets of spdf and spdfg quality. For BH3, the computed spectroscopic constants are in very good agreement with recent experimental data, and definitively confirm misassignments in some older work, in agreement with recent ab initio studies. Using the computed spectroscopic constants, the rovibrational partition function for both molecules has been constructed using a modified direct numerical summation algorithm, and JANAF-style thermochemical tables are presented.

Ocular Blood Flow Changes in Behçet Disease Patients with/without Thrombotic Disease

PubMed Central

Yüksel, Harun; Türkcü, Fatih M.; Hamidi, Cihat; Cingü, Abdullah K.; Çinar, Yasin; Şahin, Muhammed; Özkurt, Zeynep; Çaça, İhsan

2014-01-01

ABSTRACT In this study, the authors aimed to evaluate ocular blood flow changes in Behçet disease (BD) with and without thrombotic disease. Ninety eyes of 90 patients with a diagnosis of BD (30 eyes with active uveitis, 23 eyes with inactive uveitis, 25 eyes without ocular involvement, and 12 eyes without ocular involvement and with a history of thrombosis) and 30 eyes of 30 age- and sex-matched control patients without any systemic disease with a total of 120 eyes were evaluated. In all cases, ophthalmic, central retinal, and ciliary artery flow parameters were measured with colour Doppler ultrasonography (CDU). The ocular blood flow parameters of all vessels in patients with active uveitis were found to be affected. All the flow parameters in the CRAs of the study groups were significantly different from the control group (p < 0.001). Additionally, in non-ocular BD patients with thrombosis, blood flow parameters were affected more than the parameters in non-ocular BD patients without thrombosis and control patients. In conclusion, major haemodynamic changes were observed using CDU in the ophthalmic vessels of ocular Behçet patients. Also, CDU may detect ocular blood flow alterations before initial ocular clinical manifestations appear in BD patients PMID:27928286

Ocular Blood Flow Changes in Behçet Disease Patients with/without Thrombotic Disease.

PubMed

Yüksel, Harun; Türkcü, Fatih M; Hamidi, Cihat; Cingü, Abdullah K; Çinar, Yasin; Şahin, Muhammed; Özkurt, Zeynep; Çaça, İhsan

2014-01-01

In this study, the authors aimed to evaluate ocular blood flow changes in Behçet disease (BD) with and without thrombotic disease. Ninety eyes of 90 patients with a diagnosis of BD (30 eyes with active uveitis, 23 eyes with inactive uveitis, 25 eyes without ocular involvement, and 12 eyes without ocular involvement and with a history of thrombosis) and 30 eyes of 30 age- and sex-matched control patients without any systemic disease with a total of 120 eyes were evaluated. In all cases, ophthalmic, central retinal, and ciliary artery flow parameters were measured with colour Doppler ultrasonography (CDU). The ocular blood flow parameters of all vessels in patients with active uveitis were found to be affected. All the flow parameters in the CRAs of the study groups were significantly different from the control group ( p  < 0.001). Additionally, in non-ocular BD patients with thrombosis, blood flow parameters were affected more than the parameters in non-ocular BD patients without thrombosis and control patients. In conclusion, major haemodynamic changes were observed using CDU in the ophthalmic vessels of ocular Behçet patients. Also, CDU may detect ocular blood flow alterations before initial ocular clinical manifestations appear in BD patients.

Cardiac thrombosis as a manifestation of Behçet syndrome.

PubMed

Louali, Fedoua El; Tamdy, Asmae; Soufiani, Aida; Oukerraj, Latifa; Omari, Driss; Bounjoum, Fadwa; Mekouar, Fadwa; Tazi-Mezalek, Zoubida; Bouhouch, Rachida; Zarzur, Jamila; Cherti, Mohamed

2010-01-01

Herein, we report 3 cases of Behçet syndrome that were accompanied by intracardiac thrombus. The 1st patient was a 30-year-old man who presented with dyspnea; a right atrial thrombus was identified upon transthoracic echocardiography. The 2nd patient was a 52-year-old man who was admitted for dyspnea; transthoracic echocardiography revealed an echogenic mass in the right ventricle. The 3rd patient was a 23-year-old man who was hospitalized for hemoptysis; the diagnosis of pulmonary embolism was made, and right ventricular thrombosis was found.Because these patients had no hemodynamic compromise, medical management consisting of immunosuppressive and anticoagulative therapy was adopted. This treatment resulted in complete dissolution of the thrombi.

Rapid determination of parabens in seafood sauces by high-performance liquid chromatography: A practical comparison of core-shell particles and sub-2 μm fully porous particles.

PubMed

Ye, Jing; Cao, Xiaoji; Cheng, Zhuo; Qin, Ye; Lu, Yanbin

2015-12-01

In this work, the chromatographic performance of superficially porous particles (Halo core-shell C18 column, 50 mm × 2.1 mm, 2.7 μm) was compared with that of sub-2 μm fully porous particles (Acquity BEH C18 , 50 mm × 2.1 mm, 1.7 μm). Four parabens, methylparaben, ethylparaben, propylparaben, and butylparaben, were used as representative compounds for calculating the plate heights in a wide flow rate range and analyzed on the basis of the Van Deemter and Knox equations. Theoretical Poppe plots were constructed for each column to compare their kinetic performance. Both phases gave similar minimum plate heights when using nonreduced coordinates. Meanwhile, the flat C-term of the core-shell column provided the possibilities for applying high flow rates without significant loss in efficiency. The low backpressure of core-shell particles allowed this kind of column, especially compatible with conventional high-performance liquid chromatography systems. Based on these factors, a simple high-performance liquid chromatography method was established and validated for the determination of parabens in various seafood sauces using the Halo core-shell C18 column for separation. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

A rapid method for the simultaneous determination of L-ascorbic acid and acetylsalicylic acid in aspirin C effervescent tablet by ultra performance liquid chromatography-tandem mass spectrometry

NASA Astrophysics Data System (ADS)

Wabaidur, Saikh Mohammad; Alothman, Zeid Abdullah; Khan, Mohammad Rizwan

2013-05-01

In present study, a rapid and sensitive method using ultra performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) was developed for the simultaneous determination of L-ascorbic acid and acetylsalicylic acid in aspirin C effervescent tablet. The optimum chromatographic separation was carried out on a reversed phase Waters® Acquity UPLC BEH C18 column (1.7 μm particle size, 100 mm × 2.1 mm ID) with an isocratic elution profile and mobile phase consisting of 0.1% formic acid in water and acetonitrile (75:25, v/v, pH 3.5) at flow rate of 0.5 mL min-1. The influences of mobile phase composition, flow rate and pH on chromatographic resolution were investigated. The total chromatographic analysis time was as short as 2 min with excellent resolution. Detection and quantification of the target compounds were carried out with a triple quadrupole mass spectrometer using negative electrospray ionization (ESI) and multiple reaction monitoring (MRM) modes. The performance of the method was evaluated and very low limits of detection less than 0.09 μg g-1, excellent coefficient correlation (r2 > 0.999) with liner range over a concentration range of 0.1-1.0 μg g-1 for both L-ascorbic acid and acetylsalicylic acid, and good intraday and interday precisions (relative standard deviations (R.S.D.) <3%), were obtained. Comparison of system performance with traditional liquid chromatography-photo diode array detector (HPLC-PDA) was made with respect to analysis time, sensitivity, linearity and precisions. The proposed UPLC-MS/MS method was found to be reproducible and appropriate for quantitative analysis of L-ascorbic acid and acetylsalicylic acid in aspirin C effervescent tablet.

Crosstalk between inflammation, iron metabolism and endothelial function in Behçet's disease.

PubMed

Oliveira, Rita; Napoleão, Patricia; Banha, João; Paixão, Eleonora; Bettencourt, Andreia; da Silva, Berta Martins; Pereira, Dina; Barcelos, Filipe; Teixeira, Ana; Patto, José Vaz; Viegas-Crespo, Ana Maria; Costa, Luciana

2014-01-01

Behçet's disease (BD) is a rare chronic vasculitis of unclear etiology. It has been suggested that inflammatory response has an important role in BD pathophysiology. Herein, we aimed to study the interplay between inflammation, iron metabolism and endothelial function in BD and search for its putative association with disease activity. Twenty five patients clinically diagnosed with BD were selected and twenty four healthy age-sex matched individuals participated as controls. Results showed an increase of total number of circulating white blood cells and neutrophils, serum transferrin, total iron binding capacity, mieloperoxidase (MPO), ceruloplasmin (Cp), C reactive protein, β2 microglobulin and Cp surface expression in peripheral blood monocytes in BD patients comparatively to healthy individuals (p < 0,05). Of notice, the alterations observed were associated to disease activity status. No significant differences between the two groups were found in serum nitric oxide concentration. The results obtained suggest an important contribution from innate immunity in the pathogenesis of this disease. In particular, surface expression of leukocyte-derived Cp may constitute a new and relevant biomarker to understand BD etiology.

Ultra-performance liquid chromatography-tandem mass spectrometry for the determination of atypical antipsychotics and some metabolites in in vitro samples.

PubMed

Li, Kun-Yan; Zhou, Yan-Gang; Ren, Hua-Yi; Wang, Feng; Zhang, Bi-Kui; Li, Huan-De

2007-05-01

The ultra-performance liquid chromatography-electrospray tandem mass spectrometry (UPLC-ESI-MS/MS) method has been developed to perform the determination of quetiapine, perospirone, aripiprazole and quetiapine sulfoxide in in vitro samples in less than 3 min. The UPLC separation was carried out using an Acquity UPLC BEH C18 column (100 mm x 2.1mm i.d., 1.7 microm particle size) that provided high efficiency and resolution in combination with high linear velocities. The UPLC system was coupled to a Waters Micromass Quattro Premier XE tandem quadrupole mass spectrometer. This system permits high-speed data acquisition without peak intensity degradation, and produces sharp and narrow chromatographic peaks (w(h) about 2.5s) of compounds. The determination was performed in multiple reaction monitoring (MRM) mode. The quantification parameters of the developed method were established, obtaining instrumental LODs lower than 0.005 microg/l and a repeatability at a low concentration level lower than 10% CV (n=10). Finally, the method was successfully applied to the analysis of atypical antipsychotics and some metabolites in in vitro samples.

[Characteristic fingerprint analysis and determination of main components on Andrographis paniculata extract by UPLC].

PubMed

Zhang, Hui-ye; Xu, Xiao-fei; Huang, Yong; Wamg, De-qin; Deng, Qiao-hua

2014-06-01

To establish an analytical method for characteristic fingerprint and determination of main components of Andrographis paniculata Extract by UPLC. The chromatographic conditions were Waters ACQUITY UPLC BEH-C18 (2. 1 mm x 0 mm,1.7 μm)by gradient elute using acetonitrile-water as mobile phase(0 -2 min,20% ~ 25% A;2 ~ 5 min,25% ~ 35% A;5 ~ 7 min,35% A;7 ~10 min,35%~ 55% A) at a flow rate of 0. 5 min/mL,detecting wavelength at 220 nm. Results:Contents of the andrographolide, neoandrographolide, 14-deoxyandrographolide and 14-deoxy-l11,12-didehydroandrographolide had good resolution with the correlation coefficients exceed 0. 9999 and the average percent recovery lied in 97. 2% to 103.9%, RSD was less than 3.0% (n = 6). The chromatograms of Andrographis paniculata Extract shared seven common peaks in which four of them were recognized by reference standard with the similarities over 0. 9. It is a fast,accurate and validated method,and can be useful in quality evaluations of Andrographis paniculata Extract.

Quantification of seven β-lactam antibiotics and two β-lactamase inhibitors in human plasma using a validated UPLC-MS/MS method.

PubMed

Carlier, Mieke; Stove, Veronique; Roberts, Jason A; Van de Velde, Eric; De Waele, Jan J; Verstraete, Alain G

2012-11-01

There is an increasing interest in monitoring plasma concentrations of β-lactam antibiotics. The objective of this work was to develop and validate a rapid ultra-performance liquid chromatographic method with tandem mass spectrometric detection (UPLC-MS/MS) for simultaneous quantification of amoxicillin, ampicillin, cefuroxime, cefazolin, ceftazidime, meropenem, piperacillin, clavulanic acid and tazobactam. Sample clean-up included protein precipitation with acetonitrile and back-extraction of acetonitrile with dichloromethane. Six deuterated β-lactam antibiotics were used as internal standards. Chromatographic separation was performed on a Waters ACQUITY UPLC system using a BEH C(18) column (1.7 μm, 100 mm×2.1 mm) applying a binary gradient elution of water and acetonitrile both containing 0.1% formic acid. The total run time was 5.5 min. The developed method was validated in terms of precision, accuracy, linearity, matrix effect and recovery. The assay has now been successfully used to determine concentrations of amoxicillin/clavulanic acid, cefuroxime and meropenem in plasma samples from intensive care patients. Copyright © 2012 Elsevier B.V. and the International Society of Chemotherapy. All rights reserved.

Ultra-high-pressure liquid chromatography-tandem mass spectrometry for the analysis of six resorcylic acid lactones in bovine milk.

PubMed

Xia, Xi; Li, Xiaowei; Ding, Shuangyang; Zhang, Suxia; Jiang, Haiyang; Li, Jiancheng; Shen, Jianzhong

2009-03-20

This work reports a rapid, reliable and sensitive multi-residue method for the simultaneous determination of six resorcylic acid lactones in bovine milk by ultra-high-pressure liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS). The resorcylic acid lactones were extracted, purified, and concentrated from milk samples in one step using a solid-phase extraction (SPE) cartridge that contained a polymeric mixed-mode anion-exchange sorbent. The analysis was performed on a Waters Acquity BEH C(18) column utilizing a gradient elution profile. Each LC run was completed in 3.5 min. The analytes were detected by multiple reaction monitoring (MRM) using electrospray ionization (ESI) negative mode. Mean recoveries from fortified samples ranged from 92.6% to 112.5%, with relative standard deviations lower than 11.4%. Using 5 mL bovine milk, the limits of detection and quantification for resorcylic acid lactones were in the ranges of 0.01-0.05 and 0.05-0.2 microg/L, respectively. The application of this newly developed method was demonstrated by analyzing bovine milk samples from markets.

An ultra-pressure liquid chromatography-tandem mass spectrometry method for the simultaneous determination of three physalins in rat plasma and its application to pharmacokinetic study of Physalis alkekengi var. franchetii (Chinese lantern) in rats.

PubMed

Zheng, Yunliang; Chen, Yong; Ren, Yiping; Luan, Lianjun; Wu, Yongjiang

2012-01-25

An ultra-high pressure liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) method was developed for the quantification of three major ingredients in Chinese lantern preparations (CLP) in rat plasma. Following extraction by ethyl acetate, the analytes were separated on an Acquity UPLC BEH Shield RP C(18) column using a gradient mobile phase system of acetonitrile-water. Electrospray ionization (ESI) tandem interface was employed prior to mass spectrometric detection. The calibration curves were linear over the range of 5.0-500.0 ng/ml for physalin D, 2.3-230.0 ng/ml for physalin G and 0.71-71.0 ng/ml for 4,7-didehydroneophysalin B. The average extraction recoveries, examined at four concentration levels, carried from 57.1% to 76.9%, and the accuracies ranged from 94.0% to 113.3% with precision (RSD) <15%. The validated method was successfully applied to the determination of the three physalins in rat plasma after intragastric administration of CLP suspension. Copyright © 2011 Elsevier B.V. All rights reserved.

[Direct determination of ethyl carbamate in Chinese rice wine and grape wine by ultra performance liquid chromatography-electrospray ionization tandem mass spectrometry].

PubMed

Wang, Lijuan; Ke, Runhui; Wang, Bing; Yin, Jianjun; Song, Quanhou

2012-09-01

An ultra performance liquid chromatography-electrospray ionization tandem mass spectrometric (UPLC-ESI-MS/MS) method was established for the direct determination of ethyl carbamate in Chinese rice wine and grape wine. The Chinese rice wine and grape wine samples were diluted with distilled water, filtered through 0. 22 microm microporous membrane. The LC separation was performed on a Waters Acquity UPLC system with a BEH C18 column, acetonitrile and 0. 1% (v/v) acetic acid aqueous solution as the mobile phase. The ethyl carbamate was determined in the mode of electrospray positive ionization (ESI+) and multiple reaction monitoring (MRM). The butyl carbamate (BC) was used as the internal standard for the quantitative determination. The calibration curve showed good linearity in the range of 2 - 500 microg/L with the correlation coefficient greater than 0.995. The limit of detection (LOD) was 1.7 microg/L and the limit of quantification (LOQ) was 5.0 microg/L. The recoveries of the ethyl carbamate in Chinese rice wine and grape wine was in the range of 90% - 102%. The relative standard deviations (RSDs) of intra-day and inter-day determinations were 0. 8% - 4.5% and 1.4% - 5.6% (n = 6). The results indicated that the proposed method is easy, fast, sensitive, and suitable for the determination of ethyl carbamate in Chinese rice wine and grape wine.

Coexistence of Guillain-Barré syndrome and Behçet's disease.

PubMed

Shugaiv, Erkingul; Kiyat-Atamer, Asli; Tüzün, Erdem; Deymeer, Feza; Oflazer, Piraye; Parman, Yesim; Akman-Demir, Gulsen

2013-01-01

Behçet's disease (BD) is a multisystemic, recurrent and inflammatory disorder. Neurological involvement is rare and affects mainly the central nervous system (CNS) in the form of brainstem meningoencephalitis or dural sinus thrombosis. Peripheral neuropathy is usually not observed during the course of BD but some reports have shown electrophysiologic evidence of subclinical neuropathy, mononeuritis multiplex and cranial neuropathy in BD patients. The co-occurrence of Guillain-Barré syndrome (GBS), an acute inflammatory demyelinating neuropathy, with other autoimmune or systemic diseases is rare. We present a case of BD with clinical and electrophysiological diagnosis of GBS. The findings of the patient were discussed with reference to literature.

Neuro-Behçet’s disease in childhood: A focus on the neuro-ophthalmological features

PubMed Central

2013-01-01

Neuro-Behçet’s disease (NBD) involves the central nervous system; peripheral nervous system involvement is not often reported. NBD is quite common in adult patients and occurs rarely during childhood and adolescence. Young patients may share symptoms and signs of NBD with other neuro-ophthalmological disorders (e.g. idiopathic intracranial hypertension); thus, making the differential diagnosis difficult. Neuroimaging is mandatory and necessary for a correct NBD diagnosis but in children radiological examinations are often difficult to perform without sedation. From 1971 to 2011, 130 patients aged ≤16 years have been reported with NBD, according to retrospective surveys, case series, and case reports. The origin of the reported cases met the well-known geographical distribution of Behçet’s disease (BD); the mean age at presentation of neurological findings was 11.8 years, with male gender prevalence (ratio, 2.9:1). We considered in detail the neuro-ophthalmological features of the 53 cases whose neuroimaging alterations were described with an assigned radiological pattern of the disease (parenchymal: 14 cases, non-parechymal: 35 cases, and mixed: 4 cases). In 19/53 patients (36%), neuro-ophthalmological symptoms anticipated any pathognomonic sign for a BD diagnosis, or only occasional aphtae were recalled by the patients. Family history was positive in 17% of subjects. Headache was reported in 75% of the patients; in those presenting with cerebral vascular involvement, headache was combined to other symptoms of intracranial hypertension. Papilledema was the most frequently reported ophthalmological finding, followed by posterior uveitis. Treatment consisted of systemic steroids in 93% of patients, often combined with other immunosuppressive drugs (especially colchicine and azathioprine). Clinical recovery or improvement was documented in the large majority of patients. Nine subjects had definitive alterations, and one died. Based on our review and personal

Cardiac Thrombosis as a Manifestation of Behçet Syndrome

PubMed Central

louali, Fedoua El; Tamdy, Asmae; Soufiani, Aida; Oukerraj, Latifa; Omari, Driss; Bounjoum, Fadwa; Mekouar, Fadwa; Tazi-Mezalek, Zoubida; Bouhouch, Rachida; Zarzur, Jamila; Cherti, Mohamed

2010-01-01

Herein, we report 3 cases of Behçet syndrome that were accompanied by intracardiac thrombus. The 1st patient was a 30-year-old man who presented with dyspnea; a right atrial thrombus was identified upon transthoracic echocardiography. The 2nd patient was a 52-year-old man who was admitted for dyspnea; transthoracic echocardiography revealed an echogenic mass in the right ventricle. The 3rd patient was a 23-year-old man who was hospitalized for hemoptysis; the diagnosis of pulmonary embolism was made, and right ventricular thrombosis was found. Because these patients had no hemodynamic compromise, medical management consisting of immunosuppressive and anticoagulative therapy was adopted. This treatment resulted in complete dissolution of the thrombi. PMID:20978571

Behçet’s syndrome: providing integrated care

PubMed Central

Esatoglu, Sinem Nihal; Kutlubay, Zekayi; Ucar, Didar; Hatemi, Ibrahim; Uygunoglu, Ugur; Siva, Aksel; Hatemi, Gulen

2017-01-01

Behçet’s syndrome (BS) is a multisystem vasculitis that presents with a variety of mucocutaneous manifestations such as oral and genital ulcers, papulopustular lesions and erythema nodosum as well as ocular, vascular, gastrointestinal and nervous system involvement. Although it occurs worldwide, it is especially prevalent in the Far East and around the Mediterranean Sea. Male gender and younger age at disease onset are associated with a more severe disease course. The management of BS depends on the severity of symptoms. If untreated, morbidity and mortality are considerably high in patients with major organ involvement. Multidisciplinary patient care is essential for the management of BS, as it is for other multisystem diseases. Rheumatologists, dermatologists, ophthalmologists, neurologists, cardiovascular surgeons and gastroenterologists are members of the multidisciplinary team. In this study, we reviewed the epidemiology, etiology, diagnostic criteria sets, clinical findings and treatment of BS and highlighted the importance of the multidisciplinary team in the management of BS. PMID:28860798

Recurrent longitudinal extensive transverse myelitis in a neuro-Behçet syndrome treated with infliximab

PubMed Central

Uygunoğlu, Uğur; Pasha, Maarya; Saip, Sabahattin; Siva, Aksel

2015-01-01

Background Spinal cord involvement is not common, but can be seen in neuro-Behçet's syndrome (NBS). The major site of involvement is the cervical spinal cord with the myelitis-like inflammatory lesions continuing more than two segments, and extending to the brainstem. Case A 30-year-old male patient who has been followed with a diagnosis of Behçet's syndrome admitted to our neurology department clinically and radiologically suggestive of recurrent and extensive longitudinal myelitis. His anti-aquaporine antibody was negative. Because of insufficient effect of azathioprine, cyclophosphamide, and corticosteroids, infliximab was started. His clinical and radiological status is stationary for 3 years under infliximab treatment. Discussion Myelitis such as that occurring in our patient may have a similar presentation like neuromyelitis optica (NMO), which should therefore be included in differential diagnosis. Myelitis observed in both NMO and NBS shows spinal cord lesions longer than three or more vertebrae. Anti-aquaporine antibody must be evaluated in all patients presenting with longitudinal myelitis. Anti-tumor necrosis factor agent infliximab might be an alternative treatment in severe form of NBS such as myelitis. Conclusion In our case, successful treatment of recurrent and extensive longitudinal transverse myelitis in NBS with infliximab was demonstrated. PMID:24673549

C6, C7, and C8 perfluoroalkyl-substituted phosphinic acids.

PubMed

Singh, R P; Shreeve, J M

2000-04-17

Reaction of red phosphorus with RfI in a 1:2 molar ratio at 230 degrees C led to the formation of a mixture of (Rf)2PI and (Rf)PI2 (Rf = C6F13, C7F15, C8F17) in about a 70:30 ratio, respectively. These mixtures were separated by vacuum distillation. (Rf)2PI (Rf = C6F13, C7F15) are yellow liquids whereas (C8F17)2PI is a yellow solid. Oxidation of (Rf)2PI with excess NO2 led to (Rf)2P(O)OH (Rf = C6F13, C7F15, C8F17) in > 90% isolated yields after aqueous hydrolysis of the anhydride intermediates. These highly fluorinated phosphinic acids are white solids with sharp melting points and are highly soluble in methyl sulfoxide (DMSO) and 1,1,2-trichlorotrifluoroethane. However, solubility in chloroform and methylene dichloride is low. These perfluoroalkylphosphinic acids were characterized by IR, NMR (1H, 19F, and 31P), and mass spectra and elemental analysis.

Investigations of electron attachment to the perfluorocarbon molecules c-C4F8, 2-C4F8, 1,3 C4F6, and c-C5F8

NASA Astrophysics Data System (ADS)

Feil, Stefan; Märk, Tilmann D.; Mauracher, Andreas; Scheier, Paul; Mayhew, Chris A.

2008-11-01

Non-dissociative and dissociative electron attachment to a series of gas-phase perfluorocarbons (PFCs), namely octafluorocyclobutane, c-C4F8, octafluorobut-2-ene (perfluoro-2-butene), 2-C4F8, hexafluorobuta-1,3-diene (1,3 perfluorobutadiene), 1,3 C4F6, and octafluorocyclopentene (perfluorocyclopentene), c-C5F8, of importance to technological plasmas, have been investigated using two different, but complimentary, instruments available in Innsbruck over the electron energy range 0-20 eV. Anion yields as a function of electron energy have been recorded, with the positions and intensities of the electron attachment resonances being determined. One of these instruments is a double focusing sector field mass spectrometer (VG-ZAB-2SEQ), which has been used for measurements requiring high sensitivity and for obtaining accurate relative anion yields. It has also been used to determine the electron detachment lifetimes of the parent anions under various accelerating voltages, and these results are also presented. The second instrument (CELIA) is a trochoidal electron monochromator coupled to a quadrupole mass filter with a pulse counting system for detecting product anionic species. This provides a much higher energy resolution than the VG-ZAB, which makes it a better instrument to investigate narrow energy resonances close to 0 eV. The results of anion yields, peak positions and the relative intensities presented in this paper are compared with previous data of electron attachment to the above PFCs, including investigations by Professor Eugen Illenberger.

15 CFR 8c.60 - Communications.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 15 Commerce and Foreign Trade 1 2010-01-01 2010-01-01 false Communications. 8c.60 Section 8c.60 Commerce and Foreign Trade Office of the Secretary of Commerce ENFORCEMENT OF NONDISCRIMINATION ON THE BASIS OF HANDICAP IN PROGRAMS OR ACTIVITIES CONDUCTED BY THE DEPARTMENT OF COMMERCE § 8c.60...

15 CFR 8c.40 - Employment.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 15 Commerce and Foreign Trade 1 2010-01-01 2010-01-01 false Employment. 8c.40 Section 8c.40... BASIS OF HANDICAP IN PROGRAMS OR ACTIVITIES CONDUCTED BY THE DEPARTMENT OF COMMERCE § 8c.40 Employment... discrimination in employment under any program or activity conducted by the agency. The definitions, requirements...

Simultaneous determination of four water-soluble vitamins in fortified infant foods by ultra-performance liquid chromatography coupled with triple quadrupole mass spectrometry.

PubMed

Lu, Baiyi; Ren, Yiping; Huang, Baifen; Liao, Wenqun; Cai, Zengxuan; Tie, Xiaowei

2008-03-01

A novel ultra-performance liquid chromatography electrospray ionization tandem triple quadrupole mass spectrometry method for the simultaneous determination of four water-soluble vitamins, including vitamin B5 (VB5), vitamin B8 (VB8), vitamin B9 (VB9), and vitamin B12 (VB12) in fortified infant foods is developed and validated. A reverse phase UPLC separation system consisting of a Waters ACQUITY UPLC BEH C-18 column (2.1 mm x 100 mm i.d., 1.7 microm) and a binary gradient acetonitrile-water mobile phase is applied for the separation of the four water-soluble vitamins. Formic acid is spiked into the mobile phase to enhance the ionization efficiency. Tandem MS-MS analysis is performed in multi-reaction monitoring mode (MRM). Product-ion traces at m/z 220.1 --> 89.9 for VB5, 245.1 --> 227.1 for VB8, 442.3 --> 295.2 for VB9, and 678.9 --> 147.0 for VB12 are used for quantitation of the corresponding vitamins, and traces at m/z 455.5 --> 308.0 are used for methotrexate (internal standard). Limits of quantitation (LOQs) are 0.016, 0.090, 0.020, and 0.019 microg/L for VB5, VB8, VB9, and VB12, respectively. Intra- and inter-day precisions for the determination of the four vitamins are better than 6.84% and 12.26% in relative standard deviations, and recoveries for the four vitamins are in the range of 86.0~101.5%. The developed approach is applied for the determination of the trace amounts of the vitamins in fortified milk powers and fortified rice powers.

Behçet's disease-like syndrome secondary to microbial infection: a case report and review of the literature.

PubMed

Zhang, Lingshu; Xu, Yuan; Peng, Yun; Yan, Bing; Liu, Yi

2015-01-01

Behçet's disease (BD)-like syndrome is an extremely rare situation occurred after Mycobacterium tuberculosis infection and virus infection. We reported a 45-year-old woman who visited our hospital complaining of swollen left ankle, painful genital ulcer, redness in the left eye and skin rash on lower limbs. The patient had a history of pleural tuberculosis and had received anti-tuberculous therapy for one year. Her left cervical lymph node sample demonstrated tubercle bacilli DNA fragmentation. The diagnosis of tuberculous lymphadenitis and Behçet's disease (BD)-like syndrome were made. This patient's symptoms remitted following treatment with anti-tuberculous therapy. This case indicates that some microbial infection can trigger the onset of BD-like syndrome in genetically susceptible subjects. However, treatment strategy of BD-like syndrome secondary to infection is totally different from primary BD. The aim of this case report is to present our experience of the different clinical signs and treatment of BD-like syndrome to expedite its early diagnosis in future. Combination of clinical, radiological, immunophenotypic, pathological, and genetic data contribute to improving the rate of diagnosis.

Long-term outcome of arterial lesions in Behçet disease: a series of 101 patients.

PubMed

Saadoun, David; Asli, Bouchra; Wechsler, Bertrand; Houman, Habib; Geri, Guillaume; Desseaux, Kristel; Piette, Jean-Charles; Huong, Du Le Thi; Amoura, Zahir; Salem, Tara Ben; Cluzel, Philippe; Koskas, Fabien; Resche-Rigon, Mathieu; Cacoub, Patrice

2012-01-01

The vasculitis of Behçet disease (BD) is distinctive because of involvement of both arteries and veins of all sizes. The concept of vasculo-Behçet disease has been adopted for cases in which vascular manifestations are present and often dominate the clinical features. While venous manifestations are frequent and have been reported in many publications, data regarding arterial lesions in patients with BD are rare and often isolated. In this study, we report the main characteristics, treatment, and long-term outcome of 101 patients with arterial lesions among a cohort of 820 (12.3%) BD patients. Factors that affect prognosis were assessed by multivariate analysis. There were 93 (91.2%) male patients; the median (Q1-Q3) age at diagnosis of BD was 33 (27-41) years. Arterial lesions included aneurysms (47.3%), occlusions (36.5%), stenosis (13.5%), and aortitis (2.7%). Lesions mainly involved the aorta (n = 25) and femoral (n = 23) and pulmonary (n = 21) arteries. Patients with arterial lesions were more frequently male (91.2% vs. 62.4%, respectively; p = 0.017) and had higher rates of venous involvement (80.4% vs. 29.8%, respectively; p < 0.001) compared to patients without arterial manifestations. Thirty-nine (38.6%) patients achieved complete remission. In multivariate analysis, the presence of venous involvement (odds ratio [OR], 0.29; 95% confidence interval [CI], 0.08-1.11) and arterial occlusive lesions (OR, 0.13; 95% CI, 0.01-1.25) were negatively associated with complete remission. The use of immunosuppressants (OR, 3.38; 95% CI, 0.87-13.23) was associated with the occurrence of complete remission. The 20-year survival rate was significantly lower in BD patients with arterial involvement than in those without arterial lesions (73% vs. 89%, respectively; p < 0.0001). In conclusion, the long-term outcome of arterial lesions in BD is poor, especially in the case of occlusive lesions and associated venous involvement. The use of immunosuppressants improved the

Crystal Structure of the MACPF Domain of Human Complement Protein C8[alpha] in Complex with the C8[gamma] Subunit

DOE Office of Scientific and Technical Information (OSTI.GOV)

Slade, Daniel J.; Lovelace, Leslie L.; Chruszcz, Maksymilian

2010-03-04

Human C8 is one of five complement components (C5b, C6, C7, C8, and C9) that assemble on bacterial membranes to form a porelike structure referred to as the 'membrane attack complex' (MAC). C8 contains three genetically distinct subunits (C8{alpha}, C8{beta}, C8{gamma}) arranged as a disulfide-linked C8{alpha}-{gamma} dimer that is noncovalently associated with C8{beta}. C6, C7 C8{alpha}, C8{beta}, and C9 are homologous. All contain N- and C-terminal modules and an intervening 40-kDa segment referred to as the membrane attack complex/perforin (MACPF) domain. The C8{gamma} subunit is unrelated and belongs to the lipocalin family of proteins that display a {beta}-barrel fold andmore » generally bind small, hydrophobic ligands. Several hundred proteins with MACPF domains have been identified based on sequence similarity; however, the structure and function of most are unknown. Crystal structures of the secreted bacterial protein Plu-MACPF and the human C8{alpha} MACPF domain were recently reported and both display a fold similar to those of the bacterial pore-forming cholesterol-dependent cytolysins (CDCs). In the present study, we determined the crystal structure of the human C8{alpha} MACPF domain disulfide-linked to C8{gamma} ({alpha}MACPF-{gamma}) at 2.15 {angstrom} resolution. The {alpha}MACPF portion has the predicted CDC-like fold and shows two regions of interaction with C8{gamma}. One is in a previously characterized 19-residue insertion (indel) in C8{alpha} and fills the entrance to the putative C8{gamma} ligand-binding site. The second is a hydrophobic pocket that makes contact with residues on the side of the C8{gamma} {beta}-barrel. The latter interaction induces conformational changes in {alpha}MACPF that are likely important for C8 function. Also observed is structural conservation of the MACPF signature motif Y/W-G-T/S-H-F/Y-X{sub 6}-G-G in {alpha}MACPF and Plu-MACPF, and conservation of several key glycine residues known to be important for

Intrathecal oligoclonal IgG bands are infrequently found in neuro-Behçet's disease.

PubMed

Saruhan-Direskeneli, Guher; Yentür, S P; Mutlu, Melike; Shugaiv, E; Yesilot, Nilufer; Kürtüncü, M; Akman-Demir, Gulsen

2013-01-01

Oligoclonal bands (OCB) of immunoglobulins (IgG) in the cerebrospinal fluid (CSF) provides an evidence for the humoral response and have been screened in the CSF and serum of patients revealing 5 different patterns. In this study, patients with Behçet's disease (BD) are screened in a larger sample to potentially provide information about the possible role of CSF oligoclonal immunoglobulins in the diagnosis of this disease. Paired CSF and serum samples from 121 consecutive BD patients with neurological complaints (43 women and 78 men) were included in this study. Parenchymal NBD was diagnosed in 74 patients, and 22 patients had cerebral venous sinus thrombosis (CVST); of the remaining patients, 18 had primary headache disorders not directly associated with BD, and 7 had a cerebrovascular event. OCB of IgG were detected by isoelectric focusing on agarose and immunoblotting of matched serum and CSF sample pairs. Intrathecal production of IgG only is considered positive (Pattern 2 or 3). In the whole group, only 8 patients had OCB in the CSF showing pattern 2. All these positive cases had parenchymal neuro-BD (10.8% positive and 78.4% negative in parenchymal neuro-BD group). All other groups were negative. The rare presence of oligoclonal IgG bands in CSF can be utilized as another laboratory finding in the diagnosis of NBD.

Validation of the classification criteria commonly used in Korea and a modified set of preliminary criteria for Behçet's disease: a multi-center study.

PubMed

Chang, H K; Lee, S S; Bai, H J; Lee, Y W; Yoon, B Y; Lee, C H; Lee, Y H; Song, G G; Chung, W T; Lee, S W; Choe, J Y; Kim, C G; Chang, D K

2004-01-01

Recently we have proposed a modified set of criteria to settle the questions raised regarding the International Study Group (ISG) criteria for Behçet's disease (BD). The aim of the present study was to validate the two pre-existing criteria sets commonly used in Korea, the ISG criteria and the criteria of the Behçet's Disease Research Committee of Japan (Japanese criteria), as well as the proposed modified criteria. The study population included 155 consecutive patients with BD and 170 controls with non-Behçet's rheumatic diseases. Detailed data for all of the subjects were recorded prospectively by the participating physicians on a standard form that listed the clinical features of BD. The sensitivity, specificity, and accuracy of each set of the criteria were measured. Of the three criteria sets employed, the modified criteria were the most accurate, with an accuracy of 96.3%. The ISG criteria often failed to classify the following patients with BD: patients with only oral and genital ulcerations, certain patients with intestinal ulcerations, patients who did not manifest oral ulcerations, and patients with acute disease but fewer than three recurrent oral ulceration relapses in a 1-year period. The Japanese criteria also failed to categorize the following patients with BD: patients with oral and genital ulcerations, and patients with oral ulcerations, skin lesions, and a positive pathergy reaction. In addition, the Japanese criteria misclassified some of the control subjects with non-Behçet's uveitis as having BD. The results of this study suggest that there are some points that need to be reconsidered in the clinical application of the two pre-existing sets of criteria. Although the modified criteria were the most accurate, further validation studies will be required in other ethnic populations.

No Definite Association between Human Parvovirus B19 Infection and Behçet Disease

PubMed Central

Habibagahi, Mojtaba; Habibagahi, Zahra; Saidmardani, Said-Mostafa; Sadeghian, Faezeh

2015-01-01

Background: The etiology of the Behçet disease (BD) has remained obscured. There have been studies to show the association of BD to infections like herpes simplex, hepatitis, and parvovirus B19 however, the findings are rather controversial. Materials and Methods: We selected 55 patients with the best matched symptoms of BD and measured the loads of B19 DNA in their plasma by quantitative real time PCR and verified their seropositivity by ELISA. All findings were compared to the results from 42 healthy persons. Results: Patients showed a wide spectrum of BD symptoms. Serologic studies showed high prevalence of B19 IgG among the tested patients which was not statistically different with the healthy population (72.7% vs. 85.7%, respectively). Similarly, the prevalence of B19 IgM between patients and controls was not different (18% vs. 11.9%, respectively). No correlation was found between the presence of anti-B19 antibodies and the clinical observations. Only one person from the patient and control groups had detectable levels of B19 DNA without any difference or correlation with the disease symptoms. Conclusion: Our data could not establish an association between B19 parvovirus infection and Behçet disease, although there have been reports of such correlation. Nevertheless, there might be indirect relation in genetically susceptible individuals after viral infections. More studies on designed animal models and surveys on patients should be done to resolve this controversy. PMID:26538777

No Definite Association between Human Parvovirus B19 Infection and Behçet Disease.

PubMed

Habibagahi, Mojtaba; Habibagahi, Zahra; Saidmardani, Said-Mostafa; Sadeghian, Faezeh

2015-11-01

The etiology of the Behçet disease (BD) has remained obscured. There have been studies to show the association of BD to infections like herpes simplex, hepatitis, and parvovirus B19 however, the findings are rather controversial. We selected 55 patients with the best matched symptoms of BD and measured the loads of B19 DNA in their plasma by quantitative real time PCR and verified their seropositivity by ELISA. All findings were compared to the results from 42 healthy persons. Patients showed a wide spectrum of BD symptoms. Serologic studies showed high prevalence of B19 IgG among the tested patients which was not statistically different with the healthy population (72.7% vs. 85.7%, respectively). Similarly, the prevalence of B19 IgM between patients and controls was not different (18% vs. 11.9%, respectively). No correlation was found between the presence of anti-B19 antibodies and the clinical observations. Only one person from the patient and control groups had detectable levels of B19 DNA without any difference or correlation with the disease symptoms. Our data could not establish an association between B19 parvovirus infection and Behçet disease, although there have been reports of such correlation. Nevertheless, there might be indirect relation in genetically susceptible individuals after viral infections. More studies on designed animal models and surveys on patients should be done to resolve this controversy.

Reactive collisions of electrons with H2+ , HD+, BeH+, BeD+ and SH+

NASA Astrophysics Data System (ADS)

Pop, Nicolina; Iacob, Felix; Mezei, János Zsolt; Motapon, Ousmanou; Niyonzima, Sebastien; Kashinski, David O.; Talbi, Dahbia; Hickman, Albert Peet; Schneider, Ioan F.

2017-12-01

In numerous cold ionized gases the dissociative recombination (DR), the elastic collisions (EC), the vibrational excitation (VE) (inelastic collisions) and the vibrational de-excitation (VdE) (super-elastic collisions) of molecular cations with electrons are major elementary processes. Using a stepwise method based on the Multichannel Quantum Defect Theory (MQDT), cross sections and rate coefficients have been obtained for reactions induced on HD+, H2+, BeH+, BeD+ and SH+. Moreover, the relative importance of the different reaction mechanisms, direct vs. indirect and rotational vs. non-rotational, have been studied for these molecular systems.

UPLC and LC-MS studies on degradation behavior of irinotecan hydrochloride and development of a validated stability-indicating ultra-performance liquid chromatographic method for determination of irinotecan hydrochloride and its impurities in pharmaceutical dosage forms.

PubMed

Kumar, Navneet; Sangeetha, Dhanaraj; Reddy, Sunil P

2012-10-01

The objective of the current investigation was to study the degradation behavior of irinotecan hydrochloride under different International Conference on Harmonization (ICH) recommended stress conditions using ultra-performance liquid chromatography and liquid chromatography-mass spectrometry and to establish a validated stability-indicating reverse-phase ultra-performance liquid chromatographic method for the quantitative determination of irinotecan hydrochloride and its seven impurities and degradation products in pharmaceutical dosage forms. Irinotecan hydrochloride was subjected to the stress conditions of oxidative, acid, base, hydrolytic, thermal and photolytic degradation. Irinotecan hydrochloride was found to degrade significantly in oxidative and base hydrolysis and photolytic degradation conditions. The degradation products were well resolved from the main peak and its impurities, thus proving the stability-indicating power of the method. Chromatographic separation was achieved on a Waters Acquity BEH C8 (100 × 2.1 mm) 1.7-µm column with a mobile phase containing a gradient mixture of solvent A (0.02M KH(2)PO(4) buffer, pH 3.4) and solvent B (a mixture of acetonitrile and methanol in the ratio of 62:38 v/v). The mobile phase was delivered at a flow rate of 0.3 mL/min with ultraviolet detection at 220 nm. The run time was 8 min, within which irinotecan and its seven impurities and degradation products were satisfactorily separated. The developed method was validated as per ICH guidelines with respect to specificity, linearity, limit of detection, limit of quantification, accuracy, precision and robustness. This method was also suitable for the assay determination of irinotecan hydrochloride in pharmaceutical dosage forms.

Development and validation of a UPLC-MS method for the determination of galantamine in guinea pig plasma and its application to a pre-clinical bioavailability study of novel galantamine formulations.

PubMed

Wang, Jiang; Pavurala, Naresh; Xu, Xiaoming; Krishnaiah, Yellela S R; Faustino, Patrick J

2018-05-04

To evaluate the bioavailability and pharmacokinetic profiles of two novel galantamine formulations as medical countermeasure products, an ultra-performance liquid chromatography-single quadrupole mass spectrometry (UPLC-MS) method was developed and validated for quantifying galantamine in guinea pig plasma using solid-phase extraction with a mixed mode strong cation exchange reversed-phase cartridge. Chromatographic separation was achieved on a Waters Acquity UPLC BEH C 18 column maintained at 40°C. The mobile phases were solution A, acetonitrile-water, 5:95 (v/v) and solution B, acetonitrile-water 90:10 (v/v), both containing 2 mM ammonium formate and 0.2% formic acid. The mobile phase was delivered utilizing a 3 min gradient program start with 95%A-5%B at a flow rate of 0.6 mL/min. The analyte and internal standard, galantamine-d3, were detected by selected ion monitoring mode on a Waters 3100 single quadrupole mass spectrometer with positive electrospray ionization. The method was validated according to the US Food and Drug Administration bioanalytical guidance. The method was selective and was linear over the analytical range of 2-2000 ng/mL. Accuracy and precision were acceptable with intra- and inter-day accuracies between 96.8 and 101% and precisions (RSD) <4.88%. The method was successfully implemented to measure galantamine plasma levels in a series of pre-clinical bioavailability studies for the evaluation of novel galantamine formulations. Published 2018. This article is a U.S. Government work and is in the public domain in the USA.

A New Rapid and Sensitive Stability-Indicating UPLC Assay Method for Tolterodine Tartrate: Application in Pharmaceuticals, Human Plasma and Urine Samples

PubMed Central

Yanamandra, Ramesh; Vadla, Chandra Sekhar; Puppala, Umamaheshwar; Patro, Balaram; Murthy, Yellajyosula. L. N.; Ramaiah, Parimi Atchuta

2012-01-01

A new rapid, simple, sensitive, selective and accurate reversed-phase stability-indicating Ultra Performance Liquid Chromatography (RP-UPLC) technique was developed for the assay of Tolterodine Tartrate in pharmaceutical dosage form, human plasma and urine samples. The developed UPLC method is superior in technology to conventional HPLC with respect to speed, solvent consumption, resolution and cost of analysis. Chromatographic run time was 6 min in reversed-phase mode and ultraviolet detection was carried out at 220 nm for quantification. Efficient separation was achieved for all the degradants of Tolterodine Tartrate on BEH C18 sub-2-μm Acquity UPLC column using Trifluoroacetic acid and acetonitrile as organic solvent in a linear gradient program. The active pharmaceutical ingredient was extracted from tablet dosage form using a mixture of acetonitrile and water as diluent. The calibration graphs were linear and the method showed excellent recoveries for bulk and tablet dosage form. The test solution was found to be stable for 40 days when stored in the refrigerator between 2 and 8 °C. The developed UPLC method was validated and meets the requirements delineated by the International Conference on Harmonization (ICH) guidelines with respect to linearity, accuracy, precision, specificity and robustness. The intra-day and inter-day variation was found be less than 1%. The method was reproducible and selective for the estimation of Tolterodine Tartrate. Because the method could effectively separate the drug from its degradation products, it can be employed as a stability-indicating one. PMID:22396907

Molecular cloning of the alpha subunit of complement component C8 (CpC8α) of whitespotted bamboo shark (Chiloscyllium plagiosum).

PubMed

Wang, Ying; Zhang, Mengmeng; Wang, Conghui; Ye, Boping; Hua, Zichun

2013-12-01

Complement-mediated cytolysis is the important effect of immune response, which results from the assembly of terminal complement components (C5b-9). Among them, α subunit of C8 (C8α) is the first protein that traverses the lipid bilayer, and then initiates the recruitment of C9 molecules to form pore on target membranes. In this article, a full-length cDNA of C8α (CpC8α) is identified from the whitespotted bamboo shark (Chiloscyllium plagiosum) by RACE. The CpC8α cDNA is 2183 bp in length, encoding a protein of 591 amino acids. The deduced CpC8α exhibits 89%, 49% and 44% identity with nurse shark, frog and human orthologs, respectively. Sequence alignment indicates that the C8α is well conserved during the evolution process from sharks to mammals, with the same modular architecture as well as the identical cysteine composition in the mature protein. Phylogenetic analysis places CpC8α and nurse shark C8α in cartilaginous fish clade, in parallel with the teleost taxa, to form the C8α cluster with higher vertebrates. Hydrophobicity analysis also indicates a similar hydrophobicity of CpC8α to mammals. Finally, expression analysis revealed CpC8α transcripts were constitutively highly expressed in shark liver, with much less expression in other tissues. The well conserved structure and properties suggests an analogous function of CpC8α to mammalian C8α, though it remains to be confirmed by further study. Copyright © 2013 Elsevier Ltd. All rights reserved.

Ultra-high performance supercritical fluid chromatography-mass spectrometry procedure for analysis of monosaccharides from plant gum binders.

PubMed

Pauk, Volodymyr; Pluháček, Tomáš; Havlíček, Vladimír; Lemr, Karel

2017-10-09

The ultra-high performance supercritical fluid chromatography-mass spectrometry (UHPSFC/MS) procedure for analysis of native monosaccharides was developed. Chromatographic conditions were investigated to separate a mixture of four hexoses, three pentoses, two deoxyhexoses and two uronic acids. Increasing water content in methanol modifier to 5% and formic acid to 4% improved peak shapes of neutral monosaccharides and allowed complete elution of highly polar uronic acids in a single run. An Acquity HSS C18SB column outperformed other three tested stationary phases (BEH (silica), BEH 2-ethylpyridine, CSH Fluoro-Phenyl) in terms of separation of isomers and analysis time (4.5 min). Limits of detection were in the range 0.01-0.12 ng μL -1 . Owing to separation of anomers, identification of critical pairs (arabinose-xylose and glucose-galactose) was possible. Feasibility of the new method was demonstrated on plant-derived polysaccharide binders. Samples of watercolor paints, painted paper and three plant gums widely encountered in painting media (Arabic, cherry and tragacanth) were decomposed prior the analysis by microwave-assisted hydrolysis at 40 bar initial pressure using 2 mol L -1 trifluoroacetic acid. Among tested temperatures, 120 °C ensured appropriate hydrolysis efficiency for different types of gum and avoided excessive degradation of labile monosaccharides. Procedure recovery tested on gum Arabic was 101% with an RSD below 8%. Aqueous hydrolysates containing monosaccharides in different ratios specific to each type of plant gum were diluted or analyzed directly. Filtration of samples before hydrolysis reduced interferences from a paper support and identification of gum Arabic in watercolor-painted paper samples was demonstrated. Successful identification of pure gum Arabic was confirmed for sample quantities as little as 1 μg. Two classification approaches were compared and principal component analysis was superior to analysis based on peak area

Trapping-mediated dissociative chemisorption of C3H8 and C3D8 on Ir(110)

NASA Astrophysics Data System (ADS)

Kelly, D.; Weinberg, W. H.

1996-07-01

We have employed molecular beam techniques to investigate the molecular trapping and trapping-mediated dissociative chemisorption of C3H8 and C3D8 on Ir(110) at low beam translational energies, Ei≤5 kcal/mol, and surface temperatures, Ts, from 85 to 1200 K. For Ts=85 K, C3H8 is molecularly adsorbed on Ir(110) with a trapping probability, ξ, equal to 0.94 at Ei=1.6 kcal/mol and ξ=0.86 at Ei=5 kcal/mol. At Ei=1.9 kcal/mol and Ts=85 K, ξ of C3D8 is equal to 0.93. From 150 K to approximately 700 K, the initial probabilities of dissociative chemisorption of propane decrease with increasing Ts. For Ts from 700 to 1200 K, however, the initial probability of dissociative chemisorption maintains the essentially constant value of 0.16. These observations are explained within the context of a kinetic model which includes both C-H (C-D) and C-C bond cleavage. Below 450 K propane chemisorption on Ir(110) arises essentially solely from C-H (C-D) bond cleavage, an unactivated mechanism (with respect to a gas-phase energy zero) for this system, which accounts for the decrease in initial probabilities of chemisorption with increasing Ts. With increasing Ts, however, C-C bond cleavage, the activation energy of which is greater than the desorption energy of physically adsorbed propane, increasingly contributes to the measured probability of dissociative chemisorption. The activation energies, referenced to the bottom of the physically adsorbed molecular well, for C-H and C-C bond cleavage for C3H8 on Ir(110) are found to be Er,CH=5.3±0.3 kcal/mol and Er,CC=9.9±0.6 kcal/mol, respectively. The activation energies for C-D and C-C bond cleavage for C3D8 on Ir(110) are 6.3±0.3 kcal/mol and 10.5±0.6 kcal/mol, respectively. The desorption activation energy of propane from Ir(110) is approximately 9.5 kcal/mol. These activation energies are compared to activation energies determined recently for ethane and propane adsorption on Ir(111), Ru(001), and Pt(110)-(1×2), and ethane

Multisystemic diseases and ethnicity: a focus on lupus erythematosus, systemic sclerosis, sarcoidosis and Behçet disease.

PubMed

Petit, A; Dadzie, O E

2013-10-01

We present an overview of the association between ethnicity and the clinical and epidemiological aspects of four multisystemic diseases: lupus erythematosus, systemic sclerosis, sarcoidosis and Behçet disease. In particular, we highlight observed ethnic differences in cutaneous manifestations of these diseases. This article should help guide clinical management, as well as serve to highlight future areas for research. © 2013 The Authors BJD © 2013 British Association of Dermatologists.

Brain stem and cerebellar atrophy in chronic progressive neuro-Behçet's disease.

PubMed

Kanoto, Masafumi; Hosoya, Takaaki; Toyoguchi, Yuuki; Oda, Atsuko

2013-01-01

Chronic progressive neuro-Behçet's disease (CPNBD) resembles multiple sclerosis (MS) on patient background and image findings, and therefore is difficult to diagnose. The purpose is to identify the characteristic magnetic resonance imaging (MRI) findings of CPNBD and to clarify the differences between the MRI findings of CPNBD and those of MS. The subjects consist of a CPNBD group (n=4; 1 male and 3 females; mean age, 51 y.o.), a MS group (n=19; 3 males and 16 females; mean age, 45 y.o.) and a normal control group (n=23; 10 males and 13 females; mean age, 45 y.o.). Brain stem atrophy, cerebellar atrophy, and leukoencephalopathy were retrospectively evaluated in each subjects. In middle sagittal brain MR images, the prepontine distance was measured as an indirect index of brain stem and cerebellar atrophy and the pontine and mesencephalic distance was measured as a direct index of brain stem atrophy. These indexes were statistically analyzed. Brain stem atrophy, cerebellar atrophy, and leukoencephalopathy were seen in all CPNBD cases. Prepontine distance was significantly different between the CPNBD group and the MS group (p<0.05), and between the CPNBD group and the normal control group (p<0.001). Pontine and mesencephalic distance were significantly different between the CPNBD group and the MS group (p<0.001, p<0.01 respectively), and between the CPNBD group and the normal control group (p<0.001). Chronic progressive neuro-Behçet's disease should be considered in patients with brain stem and cerebellar atrophy in addition to leukoencephalopathy similar to that seen in multiple sclerosis. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

Practical comparison of LC columns packed with different superficially porous particles for the separation of small molecules and medium size natural products.

PubMed

Yang, Peilin; McCabe, Terry; Pursch, Matthias

2011-11-01

Commercial C(18) columns packed with superficially porous particles of different sizes and shell thicknesses (Ascentis Express, Kinetex, and Poroshell 120) or sub-2-μm totally porous particles (Acquity BEH) were systematically compared using a small molecule mixture and a complex natural product mixture as text probes. Significant efficiency loss was observed on 2.1-mm id columns even with a low dispersion ultra-high pressure liquid chromatography system. The Kinetex 4.6-mm id column packed with 2.6-μm particles exhibited the best overall efficiency for small molecule separations and the Poroshell 120 column showed better performance for mid-size natural product analytes. The Kinetex 2.1-mm id column packed with 1.7-μm particles did not deliver the expected performance and the possible reasons besides extra column effect have been proved to be frictional heating effect and poor column packing quality. Different column retentivities and selectivities have been observed on the four C(18) columns of different brands for the natural product separation. Column batch-to-batch variability that has been previously observed on the Ascentis Express column was also observed on the Kinetex and Poroshell 120 column. Copyright © 2011 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

[Difference evaluation of three kinds of root of Aconitum carmichaelii in Sichuan based on UPLC analysis of six alkaloids and chemometrics].

PubMed

Qian, Chang-Min; Song, Zhao-Hui; Zhang, Lan-Lan; Zhou, Shui-Ping; Feng, Feng

2013-09-01

An ultra performance liquid chromatography (UPLC) method was established and validated to simultaneously determine the contents of six aconitum alkaloids in mother, daughter and fibrous roots of 19 batches of Aconitum carmichaelii from Sichuan province. The separation of the six alkaloids was achieved on a ACQUITY UPLC BEH C18 (2.1 mm x 100 mm, 1.7 microm) column at 40 degrees C with a mobile phase consisting of acetonitrile in 30 mmol x L(-1) ammonium acetate buffer solution (adjusted to pH 10.0 with aqueous ammonia) in gradient mode. The data and plots showed that the six aconitum alkaloids have different distributions. Four aconitum alkaloids were almost same in mother and daughter root except benzoylmesaconine and mesaconitine, while the fibrous root differed from the other two roots. The comparisons of significant differences of six aconitum alkaloids between the mother and daughter roots definitely demonstrated that benzoylmesaconine and mesaconitine were the representative components. The 38 detecting samples were classified as two clusters by hierarchical clustering analysis (HCA) and principle component analysis (PCA), the results indicated that the mother root was different from the daughter root on chemical material basis. The study might contribute to the reasonable clinical application of A. carmichaelii.

Ultra-performance liquid chromatography fingerprinting for quality control of Phragmitis rhizoma (Lugen) produced in Baiyangdian

PubMed Central

Li, Hong; Gao, Yu-Mei; Zhang, Jing; Wang, Lin; Wang, Xiao-Xin

2013-01-01

Objective: To establish an ultra-performance liquid chromatography (UPLC) fingerprinting method for quality control of Phragmitis rhizoma from Baiyangdian. Materials and Methods: Ultrasonic extraction with 70% methanol was performed on 10 samples of P. rhizoma collected from 10 different villages in Baiyangdian. The sample solutions were analyzed by Waters UPLC equipped with the ACQUITY UPLC BEH C18 column and photodiode array (PDA) detector, and gradient eluted with acetonitrile/water as the mobile phase. The flow rate was set to 0.1 mL/min; the column temperature was set to 25°C; and the detection wavelength was set to 285 nm. Results: The chromatograms of the 10 samples showed 27 common peaks, of which one was identified as the ferulic acid standard. The similarity indexes were all above 0.82. Hierarchical cluster analysis showed that the constituents and their quantities differed according to the diameter of the original plant, which is related to its age. Conclusion: The UPLC fingerprinting method had the advantages of being fast, accurate, and highly efficient; this indicated that it can be used for quality control of P. rhizoma produced in Baiyangdian. Also, the relation between the quality and diameter/age of the plant needs to be further investigated. PMID:24124278

Behçet’s Syndrome and Thrombosis

PubMed Central

Seyahi, Emire; Yurdakul, Sebahattin

2011-01-01

Behçet syndrome (BS) is a multisystem vasculitis with unknown etiology and a unique geographic distribution. The disease course is characterized by exacerbations and remissions while abating as the years pass. The usual onset is in the third decade. Recurrent skin mucosa lesions and sight threatening panuveitis are the hallmark of the disease. Males are more severely affected than females. Vascular involvement can occur in up to 40% of cases. BS is unique among the vasculitides in that it may involve all sizes and types of vessels. It affects the veins more than the arteries. Lower extremity vein thrombosis is the most frequent manifestation of vascular involvement, followed by vena cava thrombosis, pulmonary artery aneurysms, Budd-Chiari syndrome, peripheral artery aneurysms, dural sinus thrombosis and abdominal aorta aneurysms. Vascular involvement is frequently associated with constitut onal symptoms and increased acute phase response and is the major cause of increased mortality. A predominantly neutrophilic vasculitis around the vaso vasorum is typical of BS. The thrombus is tightly adherent to the vessel wall which probably explains why thromboembolism is so rare despite the high frequency of venous disease. Thrombophilic factors do not seem to explain thrombotic tendency in BS. Immunosuppressive treatment is essential in suppression and preventing the attacks. PMID:21869912

42 CFR 52c.8 - Additional conditions.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 42 Public Health 1 2010-10-01 2010-10-01 false Additional conditions. 52c.8 Section 52c.8 Public Health PUBLIC HEALTH SERVICE, DEPARTMENT OF HEALTH AND HUMAN SERVICES GRANTS MINORITY BIOMEDICAL RESEARCH SUPPORT PROGRAM § 52c.8 Additional conditions. The Secretary may with respect to any grant award impose...

42 CFR 52c.8 - Additional conditions.

Code of Federal Regulations, 2012 CFR

2012-10-01

... 42 Public Health 1 2012-10-01 2012-10-01 false Additional conditions. 52c.8 Section 52c.8 Public Health PUBLIC HEALTH SERVICE, DEPARTMENT OF HEALTH AND HUMAN SERVICES GRANTS MINORITY BIOMEDICAL RESEARCH SUPPORT PROGRAM § 52c.8 Additional conditions. The Secretary may with respect to any grant award impose...

42 CFR 52c.8 - Additional conditions.

Code of Federal Regulations, 2013 CFR

2013-10-01

... 42 Public Health 1 2013-10-01 2013-10-01 false Additional conditions. 52c.8 Section 52c.8 Public Health PUBLIC HEALTH SERVICE, DEPARTMENT OF HEALTH AND HUMAN SERVICES GRANTS MINORITY BIOMEDICAL RESEARCH SUPPORT PROGRAM § 52c.8 Additional conditions. The Secretary may with respect to any grant award impose...

42 CFR 52c.8 - Additional conditions.

Code of Federal Regulations, 2014 CFR

2014-10-01

... 42 Public Health 1 2014-10-01 2014-10-01 false Additional conditions. 52c.8 Section 52c.8 Public Health PUBLIC HEALTH SERVICE, DEPARTMENT OF HEALTH AND HUMAN SERVICES GRANTS MINORITY BIOMEDICAL RESEARCH SUPPORT PROGRAM § 52c.8 Additional conditions. The Secretary may with respect to any grant award impose...

42 CFR 52c.8 - Additional conditions.

Code of Federal Regulations, 2011 CFR

2011-10-01

... 42 Public Health 1 2011-10-01 2011-10-01 false Additional conditions. 52c.8 Section 52c.8 Public Health PUBLIC HEALTH SERVICE, DEPARTMENT OF HEALTH AND HUMAN SERVICES GRANTS MINORITY BIOMEDICAL RESEARCH SUPPORT PROGRAM § 52c.8 Additional conditions. The Secretary may with respect to any grant award impose...

15 CFR 8c.10 - Self-evaluation.

Code of Federal Regulations, 2014 CFR

2014-01-01

... handicaps or organizations representing individuals with handicaps, to participate in the self-evaluation... 15 Commerce and Foreign Trade 1 2014-01-01 2014-01-01 false Self-evaluation. 8c.10 Section 8c.10... BASIS OF HANDICAP IN PROGRAMS OR ACTIVITIES CONDUCTED BY THE DEPARTMENT OF COMMERCE § 8c.10 Self...

Histopathologic and direct immunofluorescence findings of the papulopustular lesions in Behçet's disease.

PubMed

Ilknur, Turna; Pabuççuoglu, Uğur; Akin, Ciler; Lebe, Banu; Gunes, Ali Tahsin

2006-01-01

Although papulopustular lesions are common in patients with Behçet's disease (BD), clinically they may not be differentiated from other diseases with papulopustular presentation such as acne vulgaris or folliculitis. Therefore, there is disagreement as to whether they should be used as a diagnostic criterion in BD. The aim of this study was to determine whether the histopathologic evaluation of the papulopustular lesions may assist in the diagnosis of BD. Eighteen patients with BD and 16 control patients consisting of eleven patients with bacterial folliculitis and five patients with acne vulgaris were included in the study. After the detailed histopathologic evaluation by two pathologists who were blinded to the clinical diagnoses, the histopathologic findings were classified into three patterns as follows; pattern I: vasculitis (lymphocytic or leucocytoclastic); pattern II: folliculitis and/or perifolliculitis; pattern III: superficial and/or deep perivascular, and/or interstitial dermatitis. In addition, direct immunofluorescence studies were performed in order to evaluate the deposition of IgM, IgG, IgA, C3, or fibrinogen in dermal blood vessels. 27.8% of the patients with BD (5 patients) revealed lymphocytic vasculitis, while none of the control group did; and the difference was found statistically significant (P=0.046). The rate of pattern II which included folliculitis and/or perifolliculitis was 50.0% in control patients and 16.7% in the patients with BD; and the difference was found statistically significant (P=0.038). No difference was found between the two groups with regard to pattern III or direct immunofluorescence findings (P>0.05). Our results indicate that only vasculitic changes can be useful when histopathological features of papulopustular lesions are to be employed as a diagnostic criterion in patients with suspected BD.

The prevalence of Behçet's disease in a city in Central Anatolia in Turkey.

PubMed

Çölgeçen, Emine; Özyurt, Kemal; Ferahbaş, Ayten; Borlu, Murat; Kulluk, Pınar; Öztürk, Ahmet; Öner, Ayşe Öztürk; Gün, İskender; Aşçıoğlu, Özcan

2015-03-01

The prevalence of Behçet's disease (BD) is much higher in countries along the ancient Silk Route, extending from Japan to Mediterranean countries including Turkey, than in northern Europe and the USA. The present study aimed to investigate the prevalence of BD in Kayseri, a city in Central Anatolia in Turkey. This study investigated cross-sectional prevalences of BD in individuals aged >10 years in Kayseri, Turkey, in two stages. The first stage aimed to identify individuals with recurrent oral ulcers (ROUs) through home visits, and the second stage aimed to further examine those with ROUs for the presence of other BD-related manifestations under hospital conditions. The study was conducted using the criteria defined by the International Study Group for Behçet's Disease. The sample size was determined to be 4697 with an expected sampling error of 5.5 per 10,000, with a 95% confidence interval. A standard questionnaire was administered to a total of 5218 individuals. A history of ROU was recorded in 470 (9.0%) of the 5218 residents, and a previous diagnosis of BD was recorded in nine individuals. The prevalence rate of BD was estimated as 17 cases per 10,000 population in Kayseri, Turkey. The present study contributes towards estimations of prevalences of BD in Turkey and towards raising public awareness about the disease. It also supports previous studies that have reported the world's highest prevalences of BD in Turkey. © 2014 The International Society of Dermatology.

Quantitative analysis of flavonoids, alkaloids and saponins of Banxia Xiexin decoction using ultra-high performance liquid chromatography coupled with electrospray ionization tandem mass spectrometry.

PubMed

Wang, Ying; Xu, Ranchi; Xiao, Juan; Zhang, Jian; Wang, Xinhong; An, Rui; Ma, Yueming

2014-01-01

Banxia Xiexin decoction (BXD) is an effective Chinese Medicinal Prescription in treating gastroenteritis diseases. In this study an ultra-high performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) method was developed to separate and determine 18 major active ingredients of BXD in order to guarantee quality. The separation of ten flavonoids, four alkaloids and four saponins was accomplished on an Acquity BEH C18 (2.1mm×100mm, 1.7μm) column using gradient elution with 0.1% (v/v) formic acid water (A) and 0.1% (v/v) formic acid in methanol (B). All the analytes were detected in positive electrospray ionization tandem mass spectrometry by selective reaction monitoring (SRM) mode. A good linear regression relationship for each analyte was obtained over the range from 2.41-438ng/ml to 20.75-4150ng/ml. The precision was evaluated by intra- and inter-day assays with relative standard deviation (RSD) less than 7.7%. The recovery measured at three concentration levels varied from 92.4% to 107.8%. The method sensitivity expressed as LOQ was typically 0.97-4.15ng/ml. The assay was successfully applied for determination of the 18 bioactive compounds in BXD. The results indicated that the new UPLC-MS/MS method was rapid and accurate, and could be reliably utilized as a quality control method for BXD. Copyright © 2013 Elsevier B.V. All rights reserved.

[Analysis of sialic acid in infant formulas using ultra performance liquid chromatography-triple quadrupole mass spectrometry].

PubMed

Xie, Honglei; Li, Chun; Liu, Ning

2013-08-01

The method for analysing sialic acid in infant formulas by ultra performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) has been established. Sialic acid in milk was released via acid hydrolysis, and purified by an HLB solid phase extraction cartridge. The UPLC separation was performed on an ACQUITY UPLC BEH HILIC column (50 mm x 2.1 mm, 1.7 microm) utilizing a gradient elution program of acetonitrile and water (containing 0.1% formic acid) as the mobile phases at a flow rate of 0.25 mL/min. Injection volume and column temperature were set at 5 microL and 30 degrees C, respectively. The identification and quantification were achieved by using electrospray ionisation (ESI)-MS/MS in positive ion mode and multiple reaction monitoring (MRM) mode. The linear range was from 0.05 to 5.0 mg/L for sialic acid and the correlation coefficient (R(2)) was greater than 0.99. The average recoveries spiked at the four concentration levels of 0.1, 0.5, 2.5 and 5.0 mg/L ranged between 84.3% and 98.9% with the relative standard deviations from 4.9% to 8.2%. The limit of detection was 0.01 mg/L. Therefore, this method has the characteristics of simple operation, high reproducibility and sensitivity. It can be widely applied to determine the total contents of sialic acid in infant formula, cow milk and human milk.

Determination of parthenolide in rat plasma by UPLC-MS/MS and its application to a pharmacokinetic study.

PubMed

Zhao, Ai-qin; Zhao, Ji-hong; Zhang, Shu-qing; Pan, Yong-yang; Huo, Xu-lei

2016-02-05

A rapid, sensitive and selective ultra-performance liquid chromatography tandem mass spectrometry (UPLC-MS/MS) method was developed and validated for the determination and pharmacokinetic investigation of parthenolide in rat plasma. Sample preparation was accomplished through a simple one-step deproteinization procedure with 0.2mL of acetonitrile containing 30ng/mL of pirfenidone (IS), and to a 0.1mL plasma sample. Plasma samples were separated by UPLC on an Acquity UPLC BEH C18 column using a mobile phase consisting of acetonitrile-0.1% formic acid in water with gradient elution. The total run time was 3.0min and the elution of parthenolide was at 1.33min. The detection was performed on a triple quadrupole tandem mass spectrometer in the multiple reaction-monitoring (MRM) mode using the respective transitions m/z 249.2→231.1 for parthenolide and m/z 186.2→92.1 for pirfenidone (IS), respectively. The calibration curve was linear over the range of 2.0-500ng/mL with a lower limit of quantitation (LLOQ) of 2.0ng/mL. Mean recovery of parthenolide in plasma was in the range of 78.2-86.6%. Intra-day and inter-day precision were both <8.3%. This method was successfully applied in pharmacokinetic study after oral and intravenous administration of parthenolide in rats. Copyright © 2015 Elsevier B.V. All rights reserved.

Lipid Storage Myopathy in Behçet's Disease: A Rare Cause of Elevated Serum Creatine Kinases Levels

PubMed Central

Yilmaz, Sedat; Cinar, Muhammet; Karslioglu, Yıldırım; Simsek, Ismail; Erdem, Hakan; Pay, Salih; Dinc, Ayhan

2012-01-01

Muscular involvement in Behçet's disease is rare and there are only a few case reports in the literature. The causes of elevated muscle enzymes in a patient with Behcet's disease are many, including myositis, drug-induced myopathy, metabolic myopathy, and the disease itself. We herein have defined an algorithmic approach to a patient with Behcet's disease and elevated muscle enzymes and report a case of coexisting of lipid storage myopathy. PMID:22937450

Salivary Distinctiveness and Modifications in Males with Diabetes and Behçet's Disease

PubMed Central

Alhaffar, Iyad

2017-01-01

Oral diseases associated with systematic diseases as metabolic and vasculitic have been included in this paper. This will enhance our understanding of the salivary function in promoting healthy oral condition. The study investigates the effects of type I and type II diabetes mellitus in well-controlled diabetic patients, in addition to Behçet disease (BD) on saliva flow rate (SFR), pH, the decay, missing, and filled tooth (DMFT) index, glucose, and major earth-alkaline ions (Ca2+ and Mg2+) compared to healthy males and age-matched controls. Saliva samples were collected from 1403 male human subjects, distributed on 7 levels including 3 control groups, and analyzed. The symptoms and clinical observations were enrolled. A preprandial salivary glucose has illustrated statistically strong significant and positive correlations with HbA1c and blood glucose levels. TIDM saliva showed lower pH, SFR, and Ca2+ but higher Mg2+, caries risk, and poor metabolic control. These led to dysfunction of secretory capacity of salivary glands. TIIDM proved higher SFR, DMFT, and glucose than TIDM patients. DM oral calcium has decreased by age while magnesium sharply slopes at seniority. BD oral fluid is associated with lower glucose and minerals but noticeably with both higher pH and DMFT. PMID:28321337

Salivary Distinctiveness and Modifications in Males with Diabetes and Behçet's Disease.

PubMed

Aljerf, Loai; Alhaffar, Iyad

2017-01-01

Oral diseases associated with systematic diseases as metabolic and vasculitic have been included in this paper. This will enhance our understanding of the salivary function in promoting healthy oral condition. The study investigates the effects of type I and type II diabetes mellitus in well-controlled diabetic patients, in addition to Behçet disease (BD) on saliva flow rate (SFR), pH, the decay, missing, and filled tooth (DMFT) index, glucose, and major earth-alkaline ions (Ca 2+ and Mg 2+ ) compared to healthy males and age-matched controls. Saliva samples were collected from 1403 male human subjects, distributed on 7 levels including 3 control groups, and analyzed. The symptoms and clinical observations were enrolled. A preprandial salivary glucose has illustrated statistically strong significant and positive correlations with HbA 1c and blood glucose levels. TIDM saliva showed lower pH, SFR, and Ca 2+ but higher Mg 2+ , caries risk, and poor metabolic control. These led to dysfunction of secretory capacity of salivary glands. TIIDM proved higher SFR, DMFT, and glucose than TIDM patients. DM oral calcium has decreased by age while magnesium sharply slopes at seniority. BD oral fluid is associated with lower glucose and minerals but noticeably with both higher pH and DMFT.

Molecular characterization of the alpha subunit of complement component C8 (GcC8alpha) in the nurse shark (Ginglymostoma cirratum).

PubMed

Aybar, Lydia; Shin, Dong-Ho; Smith, Sylvia L

2009-09-01

Target cell lysis by complement is achieved by the assembly and insertion of the membrane attack complex (MAC) composed of glycoproteins C5b through C9. The lytic activity of shark complement involves functional analogues of mammalian C8 and C9. Mammalian C8 is composed of alpha, beta, and gamma subunits. The subunit structure of shark C8 is not known. This report describes a 2341 nucleotide sequence that translates into a polypeptide of 589 amino acid residues, orthologue to mammalian C8alpha and has the same modular architecture with conserved cysteines forming the peptide bond backbone. The C8gamma-binding cysteine is conserved in the perforin-like domain. Hydrophobicity profile indicates the presence of hydrophobic residues essential for membrane insertion. It shares 41.1% and 47.4% identity with human and Xenopus C8alpha respectively. Southern blot analysis showed GcC8alpha exists as a single copy gene expressed in most tissues except the spleen with the liver being the main site of synthesis. Phylogenetic analysis places it in a clade with C8alpha orthologs and as a sister taxa to the Xenopus. 2009 Elsevier Ltd.

Molecular characterization of the alpha subunit of complement component C8 (GcC8α) in the nurse shark (Ginglymostoma cirratum)

PubMed Central

Aybar, Lydia; Shin, Dong-Ho; Smith, Sylvia L.

2009-01-01

Target cell lysis by complement is achieved by the assembly and insertion of the membrane attack complex (MAC) composed of glycoproteins C5b through C9. The lytic activity of shark complement involves functional analogues of mammalian C8 and C9. Mammalian C8 is composed of α, β, and γ subunits. The subunit structure of shark C8 is not known. This report describes a 2341 nucleotide sequence that translates into a polypeptide of 589 amino acid residues, orthologue to mammalian C8α and has the same modular architecture with conserved cysteines forming the peptide bond backbone. The C8γ-binding cysteine is conserved in the perforin-like domain. Hydrophobicity profile indicates the presence of hydrophobic residues essential for membrane insertion. It shares 41.1% and 47.4 % identity with human and Xenopus C8α respectively. Southern blot analysis showed GcC8α exists as a single copy gene expressed in most tissues except the spleen with the liver being the main site of synthesis. Phylogenetic analysis places it in a clade with C8α orthologs and as a sister taxa to the Xenopus. PMID:19524681

Manometric evaluation of the esophagus in patients with Behçet's disease.

PubMed

Bektas, Mehmet; Altan, Mehmet; Alkan, Murat; Ormeci, Necati; Soykan, Irfan

2007-01-01

Gastrointestinal (GI) involvement in Behçet's disease (BD) mainly appears in mucosa and affects 5-40% of patients, however the effects of the disease on lower esophageal sphincter (LES) pressure and esophageal contractions are not well known. The aims of this study were to evaluate esophageal motor function and to identify whether there was any specific motility pattern for patients with BD who had upper GI symptoms without endoscopic abnormality. 25 patients with BD, with a mean age of 43.1 (range 20-66) years, were admitted to our clinic whose main complaints were dyspeptic such as reflux, epigastric pain, vomiting and bloating. 25 healthy and age-matched individuals were also included in the study as controls. After one night fasting, LES pressure and esophageal contractions were measured. Esophageal motor abnormalities were detected in 16% (4/25) of these patients with manometric studies (non-specific esophageal motor disorder in 1, esophageal hypomotility in 2, and LES hypotension in 1 patient); 16% (4/25) of these patients had endoscopic findings and overall 32% (8/25) of the cases showed esophageal pathology. All cases with esophageal motor abnormalities were suffering from reflux and endoscopy showed grade B esophagitis in 2 of these cases. Median LES pressure and LES relaxation were significantly lower in patients with BD compared to the control group (16.8 +/- 10.5 vs. 20.4 +/- 6.1, p = 0.02, and 92.1 +/- 10.1 vs. 96.4 +/- 4.5, p = 0.03 respectively). Esophageal involvement in BD is significantly high. We propose manometric studies are necessary to evaluate esophageal manifestations in BD patients with esophageal symptoms even without endoscopic findings.

[Determination of aconitine, hypaconitine and mesaconitine in Shenfu injection].

PubMed

Zhang, Pan-Pan; Zhang, Jun-Zhen; Wang, Zhao-Hong; Lu, Yong-Jiang; Jiang, Ye

2013-05-01

To establish a method for the content determination of indexes for measuring aconitic compounds contained in Shenfu injection, in order to provide basis for the evaluation of the curative effect of monkshood in Shenfu injection. The sample were purified and enriched with HF-LPME. ACQUITY UPLC BEH C18 column (2.1 mm x 50 mm, 1.7 microm) was adopted and eluted with a gradient program, with acetonitrile-10 mmol x L(-1) NH4HCO3 (pH 10) as the mobile phases. The flow rate was 0.45 mL x min(-1). The content was determined with ESI and MRM. The results showed that aconitine, hypaconitine and mesaconitine showed a good linear relationship, with r > 0.999, within the range of 0.1-100 ng x L(-1). The recoveries were detected to be 100.1%, 97.4%, 97.5%, with RSD being 1.2%, 1.1%, 1.5%, respectively. This method was used to prove the safety of Shenfu injection, and provide scientific basis for correct evaluation of curative effect of monkshood, as well as a reliable, simple and practical means for quality control of monkshood-containing Chinese materia medica preparations.

[UPLC-MS/MS determination of content of three iridoids of xingnaojing oral preparation in rat brains and study on their brain pharmacokinetics].

PubMed

Xu, Pan; Du, Shou-Ying; Lu, Yang; Bai, Jie; Liu, Hui-Min; Du, Qiu; Chen, Zhen-Zhen; Wang, Zhen

2014-06-01

To establish a UPLC-MS/MS method for the simultaneous determination of geniposide, genipin 1-O-beta-D-gentiobioside and geniposidic acid in rat brains and study the brain pharmacokinetics of the three iridoid glycosides in stroke rat after the oral administration of Xingnaojing. In this experiment, brain samples were precipitated with protein for twice. Acquity BEH C18 column was adopted, with acetonitrile-0.1% formic acid-water as the mobile phase for gradient elution. ESI source was adopted for mass spectra; multiple reaction monitoring (MRM) was conducted to detect negative ions. The time for sample analysis was 3.5 min. the results showed good linear relations among the three iridoid glycosides, with the extraction recovery between 99.6% and 114.3%, good intra- and inter-day precisions and accuracies and stability in line with the requirements. The t1/2 and MRT in the three components were similar in brains of stroke rats. Geniposide and genipin 1-O-beta-D-gentiobioside showed double peaks; where as geniposidic acid showed a single peak. In conclusion, the method is so specific, sensitive, accurate and reliable that it can be used to study the brain pharmacokinetics of Xingnaojing oral preparation.

Ultrafast UPLC-ESI-MS and HPLC with monolithic column for determination of principal flavor compounds in vanilla pods.

PubMed

Sharma, Upendra K; Sharma, Nandini; Sinha, Arun K; Kumar, Neeraj; Gupta, Ajai P

2009-10-01

In this study, two novel chromatographic methods based on monolithic column high-performance liquid chromatography (HPLC) and ultra-performance liquid chromatography (UPLC) were developed for the ultrafast determination of principal flavor compounds namely vanillin, vanillic acid, p-hydroxybenzoic acid, and p-hydroxybenzaldehyde in ethanolic extracts of Vanilla planifolia pods. Good separation was achieved within 2.5 min using Chromolith RP18e column (100 mm x 4.6 mm) for HPLC and Acquity BEH C-18 (100 mm x 2.1 mm, 1.7 microm) column for UPLC. Both methods were compared in terms of total analysis time, mobile phase consumption, sensitivity, and validation parameters like precision, accuracy, LOD, and LOQ. Further, system suitability test data including resolution, capacity factor, theoretical plates, and tailing factor was determined for both the methods by ten replicate injections. Monolithic column based HPLC gave better results for most of the selected parameters while UPLC was found to be more eco-friendly with low mobile phase consumption and better sensitivity. Both methods may be used conveniently for the high throughput analysis of large number of samples in comparison to traditional particulate column.

Determination of degradation products and process related impurities of asenapine maleate in asenapine sublingual tablets by UPLC

NASA Astrophysics Data System (ADS)

Kumar, Nitin; Sangeetha, D.; Kalyanraman, L.

2017-11-01

For determination of process related impurities and degradation products of asenapine maleate in asenapine sublingual Tablets, a reversed phase, stability indicating UPLC method was developed. Acetonitrile, methanol and potassium dihydrogen phosphate buffer with tetra-n- butyl ammonium hydrogen sulphate as ion pair (pH 2.2; 0.01 M) at flow rate of 0.2 ml/min were used in gradient elution mode. Separation was achieved by using acquity BEH Shield RP18 column (1.7 μm, 2.1 mm×100 mm) at 35 ºC. UV detection was performed at 228 nm. Subsequently the liquid chromatography method was validated as per ICH. The drug product was exposed to the stress conditions of acid hydrolysis, base hydrolysis, water hydrolysis, oxidative, thermal, and photolytic. In oxidative stress and thermal stress significant degradation was observed. All the degradation products were well separated from analyte peak and its impurities. Stability indicating nature of the method was proved by demonstrating the peak purity of Asenapine peak in all the stressed samples. The mass balance was found >95% for all the stress conditions. Based on method validation, the method was found specific, linear, accurate, precise, rugged and robust.

Quantitative determination of multi markers in five varieties of Withania somnifera using ultra-high performance liquid chromatography with hybrid triple quadrupole linear ion trap mass spectrometer combined with multivariate analysis: Application to pharmaceutical dosage forms.

PubMed

Chandra, Preeti; Kannujia, Rekha; Saxena, Ankita; Srivastava, Mukesh; Bahadur, Lal; Pal, Mahesh; Singh, Bhim Pratap; Kumar Ojha, Sanjeev; Kumar, Brijesh

2016-09-10

An ultra-high performance liquid chromatography electrospray ionization tandem mass spectrometry method has been developed and validated for simultaneous quantification of six major bioactive compounds in five varieties of Withania somnifera in various plant parts (leaf, stem and root). The analysis was accomplished on Waters ACQUITY UPLC BEH C18 column with linear gradient elution of water/formic acid (0.1%) and acetonitrile at a flow rate of 0.3mLmin(-1). The proposed method was validated with acceptable linearity (r(2), 0.9989-0.9998), precision (RSD, 0.16-2.01%), stability (RSD, 1.04-1.62%) and recovery (RSD ≤2.45%), under optimum conditions. The method was also successfully applied for the simultaneous determination of six marker compounds in twenty-six marketed formulations. Hierarchical cluster analysis and principal component analysis were applied to discriminate these twenty-six batches based on characteristics of the bioactive compounds. The results indicated that this method is advance, rapid, sensitive and suitable to reveal the quality of Withania somnifera and also capable of performing quality evaluation of polyherbal formulations having similar markers/raw herbs. Copyright © 2016 Elsevier B.V. All rights reserved.

Novel rapid liquid chromatography tandem masspectrometry method for vemurafenib and metabolites in human plasma, including metabolite concentrations at steady state.

PubMed

Vikingsson, Svante; Strömqvist, Malin; Svedberg, Anna; Hansson, Johan; Höiom, Veronica; Gréen, Henrik

2016-08-01

A novel, rapid and sensitive liquid chromatography tandem-mass spectrometry method for quantification of vemurafenib in human plasma, that also for the first time allows for metabolite semi-quantification, was developed and validated to support clinical trials and therapeutic drug monitoring. Vemurafenib was analysed by precipitation with methanol followed by a 1.9 min isocratic liquid chromatography tandem masspectrometry analysis using an Acquity BEH C18 column with methanol and formic acid using isotope labelled internal standards. Analytes were detected in multireaction monitoring mode on a Xevo TQ. Semi-quantification of vemurafenib metabolites was performed using the same analytical system and sample preparation with gradient elution. The vemurafenib method was successfully validated in the range 0.5-100 μg/mL according to international guidelines. The metabolite method was partially validated owing to the lack of commercially available reference materials. For the first time concentration levels at steady state for melanoma patients treated with vemurafenib is presented. The low abundance of vemurafenib metabolites suggests that they lack clinical significance. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

15 CFR 8c.60 - Communications.

Code of Federal Regulations, 2011 CFR

2011-01-01

... 15 Commerce and Foreign Trade 1 2011-01-01 2011-01-01 false Communications. 8c.60 Section 8c.60 Commerce and Foreign Trade Office of the Secretary of Commerce ENFORCEMENT OF NONDISCRIMINATION ON THE... Communications. (a) The agency shall take appropriate steps to ensure effective communication with applicants...

15 CFR 8c.60 - Communications.

Code of Federal Regulations, 2013 CFR

2013-01-01

... 15 Commerce and Foreign Trade 1 2013-01-01 2013-01-01 false Communications. 8c.60 Section 8c.60 Commerce and Foreign Trade Office of the Secretary of Commerce ENFORCEMENT OF NONDISCRIMINATION ON THE... Communications. (a) The agency shall take appropriate steps to ensure effective communication with applicants...

Inert Reassessment Document for Alkyl (C8-C24)

EPA Pesticide Factsheets

Inert Ingredient Tolerance Reassessments: Two Exemptions from theRequirement of a Tolerance for Alkyl (C8-C24) Benzenesulfonic Acid and its Ammonium, Calcium, Magnesium, Potassium, Sodium, and Zinc Salts

Morbus Behçet - a rare disease in Central Europe.

PubMed

Woźniacka, Anna; Sysa-Jędrzejowska, Anna; Jurowski, Piotr; Jabłkowski, Maciej; Kot, Marek

2015-12-10

Behçet's disease (BD) is a multiorgan inflammatory disease of complex and not entirely elucidated etiology, which was originally diagnosed in patients with aphthous stomatitis, genital ulcerations and ocular manifestations. The entity is endemic in countries of Eastern and Central Asia, especially Turkey and Iran, but rarely seen in Central Europe. As there are no specific diagnostic laboratory tests or histopathologic findings which confirm the preliminary diagnosis, the final diagnosis should be based on clinical criteria. Frequently a definitive diagnosis is established within several years or months after the first manifestations appear. The increased number of cases, recently described worldwide also in the Polish population, indicates that the disease could spread out of endemic areas. The aim of this manuscript is to present the clinical picture, diagnosis criteria and therapeutic approaches of this "international disease" which currently is observed not only in emigrants from Asia but also in native Polish citizens.

A general synthesis of C8-arylpurine phosphoramidites.

PubMed

Vongsutilers, Vorasit; Daft, Jonathan R; Shaughnessy, Kevin H; Gannett, Peter M

2009-09-02

A general scheme for the synthesis of C8-arylpurine phosphoramidites has been developed. C8-Arylation of C8-bromo-2'-deoxyguanosine is the key step and has been achieved through the use of a Suzuki coupling. Since the coupling reaction is conducted under aqueous conditions, it is unnecessary to protect and then deprotect the hydroxyl groups, thus saving several steps and improving overall yields. Once the C8-arylgroup is introduced, the glycosidic bond becomes very sensitive to acid catalyzed cleavage. Protection of the amino groups as the corresponding N,N-dimethylformamidine derivative improves stability of the derivatives. Synthetic C8-arylpurines were successfully used to prepare synthetic oligonucleotides.

Recurrent Pulmonary Aneurysms: Hughes-Stovin Syndrome on the Spectrum of Behçet Disease.

PubMed

Bennji, Sami M; du Preez, Leonard; Griffith-Richards, Stephanie; Smit, Derrick P; Rigby, Jonathan; Koegelenberg, Coenraad F N; Irusen, Elvis M; Allwood, Brian W

2017-11-01

In this report, we describe a male patient who presented with recurrent life-threatening hemoptysis due to the sequential formation of multiple pulmonary aneurysms. Both pulmonary artery coil embolization and right lower lobectomy were performed, with limited success. The patient experienced extensive bilateral femoral DVT extending into the inferior vena cava, with massive hemoptysis, fulfilling the diagnosis of Hughes-Stovin syndrome. A final diagnosis of Behçet disease was made following extensive investigation, and the patient responded well to prednisone 20 mg orally and azathioprine 100 mg orally. Copyright © 2017 American College of Chest Physicians. Published by Elsevier Inc. All rights reserved.

Genetic basis of human complement C8[beta] deficiency

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kaufmann, T.; Rittner, C.; Schneider, P.M.

1993-06-01

The eighth component of human complement (c8) is a serum protein consisting of three chains ([alpha], [beta], and [gamma]) and encoded by three different genes, C8A, C8B, and C8G. C8A and C8B are closely linked on chromosome 1p, whereas C8G is located on chromosome 9q. In the serum the [beta] subunit is non-covalently bound to the disulfide-linked [alpha]-[gamma] subunit. Patients with C8[beta] deficiency suffer from recurrent neisserial infections such as meningitis. Exon-specific polymerase chain reaction (PCR) amplification with primer pairs from the flanking intron sequences was used to amplify all 12 C8B exons separately. No difference regarding the exon sizesmore » was observed in a C8[beta]-deficient patient compared with a normal person. Therefore, direct sequence analysis of all exon-specific PCR products from normal and C8[beta]-deficient individuals was carried out. As a cause for C8[beta] deficiency, we found a single C-T exchange in exon 9 leading to a stop codon. An allele-specific PCR system was designed to detect the normal and the deficiency allele simultaneously. Using this approach as well as PCR typing of the Taql polymorphism located in intron 11, five families with 7 C8[beta]-deficient members were investigated. The mutation was not found to be restricted to one of the two Taql RFLP alleles. The mutant allele was observed in all families investigated and can therefore be regarded as a major cause of C8[beta] deficiency in the Caucasian population. In addition, two C8[beta]-deficient patients were found to be heterozygous for the C-T exchange. The molecular basis of the alleles without this point mutation also causing deficiency has not yet been defined. 23 refs., 4 figs., 3 tabs.« less

Rare esophageal ulcers related to Behçet disease: A case report.

PubMed

Jia, Ning; Tang, Yanping; Liu, Huayi; Li, Yang; Liu, Simiao; Liu, Lei

2017-11-01

The fundamental pathogenesis of Behçet disease (BD) is still unclear and controversial. Many cases of oral aphthous ulcers and genital ulcers related to BD are reported; nevertheless, idiopathic giant esophageal ulcers related to BD are rare. A rare case for esophageal ulcers related to BD is presented. In China, BD is represented with esophageal involvement which is called esophageal BD (EBD). A 56-year-old man diagnosed to the Gastroenterology Department of Integrated Traditional Chinese and Western Medicine Hospital, for multiple discrete, elliptical esophageal ulcers related to BD. The esophageal ulcers were treated with corticosteroid treatment for 12 weeks. The esophageal ulcers were cured. Our report might give further strength to avoiding the erroneous diagnosis or missed diagnosis for EBD, which is different from esophageal carcinoma, esophageal tuberculosis and esophageal Crohns disease.

MMP-8 C-799T and MMP-8 C+17G polymorphisms in mild and severe preeclampsia: Association between MMP-8 C-799T with susceptibility to severe preeclampsia.

PubMed

Rahimi, Ziba; Zangeneh, Maryam; Rezaeyan, Arezoo; Shakiba, Ebrahim; Rahimi, Zohreh

2018-01-01

The aim of present study was to determine the role of matrix metalloproteinase-8 (MMP-8) C-799T (rs11225395) and C+17 (rs2155052) polymorphisms in susceptibility to preeclampsia. In a case-control study, 256 pregnant women including 152 women with preeclampsia (86 women with mild preeclampsia and 66 women with severe preeclampsia) and 104 women with normal pregnancy from Western Iran with Kurdish ethnic background were investigated for MMP-8 C-799T and C + 17G polymorphisms using polymerase chain reaction-restriction fragment length polymorphism method. Comparing the MMP-8 TT genotype with the combined genotype of CC+CT (recessive model) indicated a significantly higher frequency of the MMP-8 TT genotype (47%) in severe preeclamptic patients than that in healthy pregnant women (30.8%) that was associated with 1.99-fold increased risk of severe preeclampsia (95% CI = 1.05-3.77, p = 0.034). The frequency of MMP-8 G allele was 27.3% in all preeclamptic patients compared to 30.2% in controls (p = 0.56). Also, no significant difference was detected comparing the frequency of G allele in mild (26.6%, p = 0.46) and severe preeclamptic patients (28.4%, p = 0.75) with controls (30.2%). Our study demonstrated that the MMP-8 C-799T is associated with the risk of developing severe preeclampsia during pregnancy. However, the MMP-8 C + 17G polymorphism might not be a risk factor for susceptibility to preeclampsia.

Multiple proton decays of 6Be, 8C, 8B(IAS) and excited states in 10C

NASA Astrophysics Data System (ADS)

Sobotka, Lee

2011-10-01

Recent technical advances have allowed for high-order correlation experiments to be done. We have primarily focused on experiments in which the final channels are composed of only alphas and protons. Four cases we have studied are: 6Be, 10C*, 8C, and 8B*(IAS) via 3, 4, 5, and 3-particle correlation measurements, respectively. While the first case had been studied before, our work presents very high statistics in the full Jacobi coordinates (the coordinates needed to describe 3-body decay.) Our study of 10C excited states provides isolatable examples of: correlated 2p decay, from one state, and the decay of another which is unusually highly correlated, a ``ménage a quatre.'' 8C decay presents the only case of sequential 3-body 2p decay steps (i.e. 2p-2p.) The intermediate in this 2-step process is the first example (6Be) mentioned above. Unlike the well-studied second step (6Be decay), the first step in this 2p-2p process provides another example of correlated 2p emission. The decay of 8B(IAS), the isobaric analog of 8C, also decays overwhelmingly by 2p emission, in this case to 6Li(IAS). This IAS-to-IAS 2p decay is one for which decay to the potential 1p intermediates is energetically allowed but isospin forbidden. This represents an expansion, over that originally envisioned by Goldanski, of the conceivable nuclear territory for 2p decay.

Development and application of a UPLC-MS/MS method for the pharmacokinetic study of 10-hydroxy camptothecin and hydroxyethyl starch conjugate in rats.

PubMed

Li, Guofei; Cai, Cuifang; Ren, Tianyang; Tang, Xing

2014-01-01

With the purpose to carry out the pharmacokinetic studies of 10-hydroxy camptothecin (10-HCPT) and hydroxyethyl starch (10-HCPT-HES) conjugate, an ultraperformance liquid chromatography tandem mass spectrometry (UPLC-MS/MS) method has been developed and validated. The analytes, 10-HCPT and the internal standard, Diphenhydramine hydrochloride were extracted with ethyl acetate-isopropanol (95:5, v/v) and separated on an ACQUITY UPLC™ BEH C18 column using a mobile phase composed of acetonitrile and water (containing 0.1% formic acid) with a linear gradient program. With positive ion electrospray ionization (ESI), the analytes were monitored on a triple quadrupole mass spectrometer in the multiple reaction monitoring (MRM) mode. Linear calibration curves were obtained over the concentration ranges of 0.5-2500ng/mL. The intra- and inter-day precisions were less than 9.8% and 10.8%, respectively. The accuracy was within 12.1%. The mean recoveries of 10-HCPT at three concentrations of 2.5, 100, 2000ng/mL were higher than 87.2%. Commercial 10-HCPT injection and 10-HCPT-HES conjugate were administered intravenously at an equal dose of 10-HCPT at 0.5mg/kg. The biological half-life of conjugate was increased significantly from 10min to 3.15h and the bioavailability was 40 times higher than 10-HCPT injection. Consequently, the proposed UPLC-ESI-MS/MS method was proved to be sensitive, specific and reliable to analyze 10-HCPT in biological samples; 10-HCPT and HES conjugate is a promising strategy for delivery of 10-HCPT with prolonged half time and improved bioavailability. Copyright © 2013 Elsevier B.V. All rights reserved.

Solid phase extraction with high polarity Carb/PSA as composite fillers prior to UPLC-MS/MS to determine six bisphenols and alkylphenols in trace level hotpot seasoning.

PubMed

Dong, Hao; Zeng, Xiaofang; Bai, Weidong

2018-08-30

The present study reports an ultra high-performance liquid chromatography tandem mass spectrometry method for the simultaneous determination of six bisphenols (bisphenol A, bisphenol B and bisphenol F) and alkylphenols (4-nonylphenol, 4-n-nonylphenol and octylphenol) in hotpot seasoning. Samples were dispersed in n-hexane after addition of internal standards bisphenol A-d 4 and 4-n-nonylphenol-d 4 . Sample solutions were then centrifuged, and the supernatants purified using solid phase extraction with high polarity Carb/PSA composite fillers. Six target analytes were separated on a Waters ACQUITY BEH C18 column by gradient elution with methanol and 0.05% ammonium hydroxide in water as the mobile phase, and determined under multiple reactions monitoring mode. The limits of detection and quantitation, matrix effect, recovery and precision of the method were investigated. Results were linear in the concentration range 0.1-250 µg/L for all compounds of interest, with R 2  > 0.9950. Limits of detection were in the range 0.1-0.4 μg/kg, and limits of quantitation were between 0.5 μg/kg and 1.0 μg/kg. The mean recoveries for negative samples at three spiked concentrations were in the range 87.9%-102.4%, and the intra-day precision and inter-day precision were in the ranges 2.1-8.2% and 4.8-11.2%, respectively. This method is accurate and sensitive, and had good clean-up characteristics, which might apply to screening and quantitation of target bisphenols and alkylphenols in hotpot seasoning. Copyright © 2018 Elsevier Ltd. All rights reserved.

Simultaneous determination of AM80 (tamibarotene) and WJD-A-1 in rat plasma by ultra high-performance liquid chromatography-tandem mass spectrometry and its application to a pharmacokinetic study.

PubMed

Leng, Ping; Yang, Zhao; Ma, Baohua; Li, Jing; Sun, Jialin; Xie, Yiming; Sun, Yong

2018-03-05

A compound (WJD-A-1) was previously reported as a candidate prodrug of Am80 (tamibarotene), which was approved in Japan in 2005 as a therapeutic agent for recurrent refractory acute promyelocytic leukaemia. A rapid, selective and sensitive ultra high-performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) method was developed for the first time to simultaneously determine WJD-A-1 and its major phase-I metabolites AM80 in rat plasma. After a simple sample preparation procedure by protein precipitation with methanol and acetonitrile, WJD-A-1, AM80 and the internal standard were chromatographed on an ACQUITY UPLC TM BEH C 18 column. The mobile phase consisted of methanol-0.1% formic acid (80:20, v/v) and the flow rate was 0.20 mL/min. The detection was performed on a triple quadrupole tandem mass spectrometer by multiple reaction monitoring (MRM) mode via electrospray ionization (ESI) source. Each plasma sample was chromatographed within 2.6 min. The linear calibration curves for WJD-A-1 and the AM80 were obtained in the concentration range of 5.40-5.40 × 10 3 and 5.08-5.08 × 10 3  ng/mL, respectively (r ≥ 0.99). The intra- and inter-day precision (relative standard deviation, RSD) values were less than 8% and the accuracy (relative error, RE) was within ±6.8%, determined from quality control (QC) samples for the analytes. The method herein described was fully validated and successfully applied to pharmacokinetic study of WJD-A-1 following an intravenous administration of 300 μg/kg WJD-A-1 to rats.

Behçet syndrome: is it one condition?

PubMed

Yazici, H; Ugurlu, S; Seyahi, E

2012-12-01

Behçet's syndrome (BS) is a disease of unknown etiology, and as such, there have been efforts to classify BS within the popular nosological identities of the times such as seronegative spondarthritides, autoimmune, and more recently autoinflammatory diseases. Current evidence suggests that BS does not easily fit into any one of these lumps, while on occasion, it might be impossible to tell BS from Crohn's disease, especially when the main clinical presentation is intestinal ulceration. There are distinct regional differences in disease expression of BS with fewer cases of intestinal disease in the Mediterranean basin and less severe eye disease and less frequent skin pathergy among patients reported from northern Europe or America. The clustering of symptoms, especially with the recently described increased frequency of the acne/arthritis cluster in familial cases, suggests that more than one pathological pathway is involved in what we call BS today. Supportive evidence for this contention also comes from the observations that (a) the genetic component is very complex with perhaps different genetic modes of inheritance in the adult and in the pediatric patients; and (b) there are differing organ responses to one same drug. For example, the anti-TNF agents successfully control the oral ulcers while they have no effect on the pathergy reaction.

New therapeutic solutions for Behçet's syndrome.

PubMed

Vitale, Antonio; Rigante, Donato; Lopalco, Giuseppe; Emmi, Giacomo; Bianco, Maria Teresa; Galeazzi, Mauro; Iannone, Florenzo; Cantarini, Luca

2016-07-01

Behçet's syndrome (BS) is a systemic inflammatory disorder characterized by a wide range of potential clinical manifestations with no gold-standard therapy. However, the recent classification of BS at a crossroads between autoimmune and autoinflammatory syndromes has paved the way to new further therapeutic opportunities in addition to anti-tumor necrosis factor agents. This review provides a digest of all current experience and evidence about pharmacological agents recently described as having a role in the treatment of BS, including interleukin (IL)-1 inhibitors, tocilizumab, rituximab, alemtuzumab, ustekinumab, interferon-alpha-2a, and apremilast. IL-1 inhibitors currently represent the most studied agents among the latest treatment options for BS, proving to be effective, safe and with an acceptable retention on treatment. However, since BS is a peculiar disorder with clinical features responding to certain treatments that in turn can worsen other manifestations, identifying new treatment options for patients unresponsive to the current drug armamentarium is of great relevance. A number of agents have been studied in the last decade showing changing fortunes in some cases and promising results in others. The latter will potentially provide their contribution for better clinical management of BS, improving patients' quality of life and long-term outcome.

Practical comparison of 2.7 microm fused-core silica particles and porous sub-2 microm particles for fast separations in pharmaceutical process development.

PubMed

Abrahim, Ahmed; Al-Sayah, Mohammad; Skrdla, Peter; Bereznitski, Yuri; Chen, Yadan; Wu, Naijun

2010-01-05

Fused-core silica stationary phases represent a key technological advancement in the arena of fast HPLC separations. These phases are made by fusing a 0.5 microm porous silica layer onto 1.7 microm nonporous silica cores. The reduced intra-particle flow path of the fused particles provides superior mass transfer kinetics and better performance at high mobile phase velocities, while the fused-core particles provide lower pressure than sub-2 microm particles. In this work, chromatographic performance of the fused-core particles (Ascentis Express) was investigated and compared to that of sub-2 microm porous particles (1.8 microm Zorbax Eclipse Plus C18 and 1.7 microm Acquity BEH C18). Specifically, retention, selectivity, and loading capacity were systematically compared for these two types of columns. Other chromatographic parameters such as efficiency and pressure drop were also studied. Although the fused-core column was found to provide better analyte shape selectivity, both columns had similar hydrophobic, hydrogen bonding, total ion-exchange, and acidic ion-exchange selectivities. As expected, the retention factors and sample loading capacity on the fused-core particle column were slightly lower than those for the sub-2 microm particle column. However, the most dramatic observation was that similar efficiency separations to the sub-2 microm particles could be achieved using the fused-core particles, without the expense of high column back pressure. The low pressure of the fused-core column allows fast separations to be performed routinely on a conventional LC system without significant loss in efficiency or resolution. Applications to the HPLC impurity profiling of drug substance candidates were performed using both types of columns to validate this last point.

[Content determination of twelve major components in Tibetan medicine Zuozhu Daxi by UPLC].

PubMed

Qu, Yan; Li, Jin-hua; Zhang, Chen; Li, Chun-xue; Dong, Hong-jiao; Wang, Chang-sheng; Zeng, Rui; Chen, Xiao-hu

2015-05-01

A quantitative analytical method of ultra-high performance liquid chromatography (UPLC) was developed for simultaneously determining twelve components in Tibetan medicine Zuozhu Daxi. SIMPCA 12.0 software was used a principal component analysis PCA) and partial small squares analysis (PLSD-DA) on the twelve components in 10 batches from four pharmaceutical factories. Acquity UPLC BEH C15 column (2.1 mm x 100 mm, 1.7 µm) was adopted at the column temperature of 35 °C and eluted with acetonitrile (A) -0.05% phosphate acid solution (B) as the mobile phase with a flow rate of 0. 3 mL · min(-1). The injection volume was 1 µL. The detection wavelengths were set at 210 nm for alantolactone, isoalantolactone and oleanolic; 260 nm for trychnine and brucine; 288 nm for protopine; 306 nm for protopine, resveratrol and piperine; 370 nm for quercetin and isorhamnetin. The results showed a good separation among index components, with a good linearity relationship (R2 = 0.999 6) within the selected concentration range. The average sample recovery rates ranged between 99.44%-101.8%, with RSD between 0.37%-1.7%, indicating the method is rapid and accurate with a good repeatability and stability. The PCA and PLSD-DA analysis on the sample determination results revealed a great difference among samples from different pharmaceutical factories. The twelve components included in this study contributed significantly to the quantitative determination of intrinsic quality of Zuozhu Daxi. The UPLC established for to the quantitative determination of the twelve components can provide scientific basis for the comprehensive quality evaluation of Zuozhu Daxi.

[Epstein-Barr virus-infected T-cell malignancy in an adult patient with Behçet's disease-like symptoms].

PubMed

Ueda, M; Kobayashi, Y; Yoshimori, K; Takahashi, Y; Chikayama, S; Ikeda, M; Uoshima, N; Kimura, S; Tanaka, K; Wada, K; Ozawa, M; Kondou, M; Kawa, K; Inoue, M

1997-08-01

A 20-year-old woman was hospitalized on November 11, 1994 with Behçet's disease-like symptoms (fever, genital ulcer and aphtha in the oral cavity). Bilateral cervical lymph node swelling was also noted and diagnosed as lymphadenitis on biopsy. Chronic active Epstein-Barr virus infection (CAEBV) was diagnosed based on the high titer of antibodies to the EBV capsid antigen, early antigen, and nuclear antigen. She was treated with prednisolone and acyclovir and all symptoms improved. However, ten months after onset of symptoms, T-cell malignancy was diagnosed on bone marrow aspiration, which revealed 34.9% blast cells that had rearrangement of TCR-beta. She died on May 8, 1995, despite anticancer therapy. In analyzing the blast cells, the monoclonal junctional DNA structure of the EBV terminal repeat was analyzed by Southern blotting and provided definitive evidence for the monoclonality of EBV-infected T cells. These findings strongly suggest that EBV plays a pathogenic role in T-cell malignancy. EBV-infected T-cell malignancy, such as this case, is very rare in Japan, especially in adult.

Non-invasive vascular biomarkers in patients with Behçet's disease: review of the data and future perspectives.

PubMed

Protogerou, Athanase D; Nasothimiou, Efthimia G; Sfikakis, Petros P; Tzioufas, Athanasios G

2017-01-01

Vascular inflammation in small to large veins and arteries contributes substantially to mortality above that of the general population in Behçet's disease. Recent data verified also the presence of accelerated classical subclinical arterial damage (atheromatosis, arteriosclerosis, arterial hypertrophy) even in patients free of overt vascular complications, and may be complementary to that of vasculitis. Early detection of such vascular damage might provide helpful pathophysiological insight and potentially even guide treatment management. Herein, we review the existing literature for each one of the most widely applied non-invasive vascular biomarkers (assessing endothelial dysfunction, atheromatosis/hypertrophy, arteriosclerosis and central haemodynamic parameters) that are clinically used in primary cardiovascular prevention. We aim to: (i) identify early pathophysiological vascular pathways, complementary to vasculitis, in the development of vascular complications and (ii) identify gaps in knowledge and suggest future research topics. We identified evidence of proof of concept for some of the widely applied non-invasive vascular biomarkers (carotid plaques, pulse wave velocity, flow mediated dilatation). Yet, several steps in their clinical validation process are lacking. Extensive vascular phenotyping of a large prospective observational patient cohort with the application of these easy-to-use, low-cost, free of any adverse effect, non-invasive methods should be performed in order to test their ability to provide clinically meaningful guidance regarding the prognosis and treatment of Behçet's disease.

Testing of DLR C/C-SiC and C/C for HIFiRE 8 Scramjet Combustor

NASA Technical Reports Server (NTRS)

Glass, David E.; Capriotti, Diego P.; Reimer, Thomas; Kutemeyer, Marius; Smart, Michael K.

2014-01-01

Ceramic Matrix Composites (CMCs) have been proposed for use as lightweight hot structures in scramjet combustors. Previous studies have calculated significant weight savings by utilizing CMCs (active and passive) versus actively cooled metallic scramjet structures. Both a carbon/carbon (C/C) and a carbon/carbon-silicon carbide (C/C-SiC) material fabricated by DLR (Stuttgart, Germany) are being considered for use in a passively cooled combustor design for Hypersonic International Flight Research Experimentation (HIFiRE) 8, a joint Australia / Air Force Research Laboratory hypersonic flight program, expected to fly at Mach 7 for approximately 30 sec, at a dynamic pressure of 55 kilopascals. Flat panels of the DLR C/C and C/C-SiC materials were installed downstream of a hydrogen-fueled, dual-mode scramjet combustor and tested for several minutes at conditions simulating flight at Mach 5 and Mach 6. Gaseous hydrogen fuel was used to fuel the scramjet combustor. The test panels were instrumented with embedded Type K and Type S thermocouples. Zirconia felt insulation was used during some of the tests to reduce heat loss from the back surface and thus increase the heated surface temperature of the C/C-SiC panel approximately 177 C (350 F). The final C/C-SiC panel was tested for three cycles totaling over 135 sec at Mach 6 enthalpy. Slightly more erosion was observed on the C/C panel than the C/C-SiC panels, but both material systems demonstrated acceptable recession performance for the HIFiRE 8 flight.

Testing of DLR C/C-SiC for HIFiRE 8 Scramjet Combustor

NASA Technical Reports Server (NTRS)

Glass, David E.; Capriotti, Diego P.; Reimer, Thomas; Kutemeyer, Marius; Smart, Michael

2013-01-01

Ceramic Matrix Composites (CMCs) have been proposed for hot structures in scramjet combustors. Previous studies have calculated significant weight savings by utilizing CMCs (active and passive) versus actively cooled metallic scramjet structures. Both a C/C and a C/C-SiC material system fabricated by DLR (Stuttgart, Germany) are being considered for use in a passively cooled combustor design for HIFiRE 8, a joint Australia / AFRL hypersonic flight program, expected to fly at Mach 7 for approximately 30 sec, at a dynamic pressure of 55 kPa. Flat panels of the DLR C/C and the C/C-SiC were tested in the NASA Langley Direct Connect Rig (DCR) at Mach 5 and Mach 6 enthalpy for several minutes. Gaseous hydrogen fuel was used to fuel the scramjet combustor. The test panels were instrumented with embedded Type K and Type S thermocouples. Zirconia felt insulation was used in some of the tests to increase the surface temperature of the C/C-SiC panel for approximately 350degF. The final C/C-SiC panel was tested for 3 cycles totaling over 135 sec at Mach 6 enthalpy. Slightly more erosion was observed on the C/C panel than the C/C-SiC panels, but both material systems demonstrated acceptable recession performance for the HIFiRE 8 flight.

Nailfold capillaroscopy in Behçet disease, performed using videodermoscopy.

PubMed

Aytekin, S; Yuksel, E P; Aydin, F; Senturk, N; Ozden, M G; Canturk, T; Turanli, A Y

2014-06-01

Nailfold capillaroscopy is used for the identification of microvascular involvement in many rheumatic and extrarheumatic diseases. To determine the nailfold capillary changes in patients with Behçet disease (BD) by videodermoscopy, i.e. nailfold videocapillaroscopy (NVC). We used a videodermatoscope (Molemax II, × 30 magnification) to perform nailfold capillaroscopy on 40 patients with BD and 40 healthy controls (HC). All nailfold images were evaluated for capillary density, distribution and morphology, assessing features such as enlargement or tortuosity of the capillaries, microhaemorrhages and avascular areas. Enlarged capillaries were detected in 14 patients, microhaemorrhages in 6 patients, and avascular area in 3 patients. There was a statistically significant difference between patients with BD and healthy controls for capillary dilatation and microhaemorrhages (P < 0.05). Capillaroscopic changes were not associated with sex or clinical characteristics. Using NVC, nailfold capillary changes were apparent in patients with BD, but not in HC. NVC could be a useful technique for evaluating microvascular damage in BD. © 2014 British Association of Dermatologists.

Recurrent symptomatic ischemic stroke in a 46-year-old African male revealing Angio-Behçet with severe cardiovascular involvement.

PubMed

Marie, Ba Djibril; Aminata, Diack; Cherif, Mboup Mouhamed; Daouda, Fall Moussa

2017-03-01

Behçet'sdisease (BD) is a chronic, multisystem vasculitis. It is categorized under variable vessel vasculitis in the new Chapel Hill nomenclature as it involves blood vessels of any type and size. It is characterized by relapsing aphthous ulcers commonly occurring in the oral mucosa and genitalia with ocular involvement. Other organ systems may be involved any time throughout the course of the disease. The exact cause is unknown. However, combination of genetic and environmental factors is likely to play a role. Cardiac involvement may occur in the form of intracardiac thrombus, endocarditis, myocarditis, pericarditis, endomyocardial fibrosis, coronary arteritis, myocardial infarction, and valvular disease. We present a case of Angio-Behçet in a 46-year-old African male with severe cardiovascular involvement including pulmonary artery hypertension (PAH), right ventricular failure and left ventricular diastolic dysfunction diagnosed after 2 episodes of symptomatic ischemic stroke resulting from complete occlusion of the right internal carotid artery (ICA) up to its intracranial portion. Immunosuppressive and anticoagulant therapies have induced improvement in cardiac manifestations. Nevertheless, prompt recognition of the primarily vascular manifestation of BD without mucocutaneous manifestations was responsible for considerable delay that did not afford surgical therapy for the carotid occlusion.

Global variation in CYP2C8–CYP2C9 functional haplotypes

PubMed Central

Speed, William C; Kang, Soonmo Peter; Tuck, David P; Harris, Lyndsay N; Kidd, Kenneth K

2009-01-01

We have studied the global frequency distributions of 10 single nucleotide polymorphisms (SNPs) across 132 kb of CYP2C8 and CYP2C9 in ∼2500 individuals representing 45 populations. Five of the SNPs were in noncoding sequences; the other five involved the more common missense variants (four in CYP2C8, one in CYP2C9) that change amino acids in the gene products. One haplotype containing two CYP2C8 coding variants and one CYP2C9 coding variant reaches an average frequency of 10% in Europe; a set of haplotypes with a different CYP2C8 coding variant reaches 17% in Africa. In both cases these haplotypes are found in other regions of the world at <1%. This considerable geographic variation in haplotype frequencies impacts the interpretation of CYP2C8/CYP2C9 association studies, and has pharmacogenomic implications for drug interactions. PMID:19381162

Simultaneous determination of icariin, naringin and osthole in rat plasma by UPLC-MS/MS and its application for pharmacokinetic study after oral administration of Gushudan capsules.

PubMed

Lu, Yuejuan; Li, Ning; Deng, Ying; Zhao, Longshan; Guo, Xingjie; Li, Famei; Xiong, Zhili

2015-07-01

A rapid, sensitive and selective ultra performance liquid chromatography tandem mass spectrometry (UPLC-MS/MS) method was developed and validated for the simultaneous determination of icariin, naringin and osthole in rat plasma. Plasma samples pretreatment involved a one-step liquid-liquid extraction with a mixture of ethyl acetate-methyl tert-butyl ether (3:1, ν/ν). The separation was performed on an ACQUITY UPLC™ BEH C18 column with a gradient mobile phase system of methanol and water. The detection was performed on a triple quadrupole tandem mass spectrometer equipped with electrospray ionization (ESI) by multiple reactions monitoring (MRM), with the transitions at m/z 513.3→366.8 (icariin), m/z 579.3→150.9 (naringin), m/z 245.1→189.0 (osthole) and m/z 237.1→194.1 (IS), respectively. A good linear response was observed over the concentration ranges of 1.06-424ng/ml, 2.10-525ng/ml and 1.05-1.05×10(3)ng/ml with lower limit of quantification (LLOQ) of 1.06, 2.10 and 1.05ng/ml for icariin, naringin and osthole, respectively. The intra- and inter-day precisions (R.S.D.) were within 14.3%, and the accuracy (R.E.) ranged from -4.1% to 4.6% at three quality control levels. The sensitive and selective method was applied to a pharmacokinetic study of icarrin, naringin and osthole in rats after oral administration of Gushudan capsule. Copyright © 2015 Elsevier B.V. All rights reserved.

Development and Validation of a Rapid RP-UPLC Method for the Simultaneous Estimation of Bambuterol Hydrochloride and Montelukast Sodium from Tablets

PubMed Central

Yanamandra, R.; Vadla, C. S.; Puppala, U. M.; Patro, B.; Murthy, Y. L. N.; Parimi, A. R.

2012-01-01

A rapid, simple, sensitive and selective analytical method was developed by using reverse phase ultra performance liquid chromatographic technique for the simultaneous estimation of bambuterol hydrochloride and montelukast sodium in combined tablet dosage form. The developed method is superior in technology to conventional high performance liquid chromatography with respect to speed, resolution, solvent consumption, time, and cost of analysis. Elution time for the separation was 6 min and ultra violet detection was carried out at 210 nm. Efficient separation was achieved on BEH C18 sub-2-μm Acquity UPLC column using 0.025% (v/v) trifluoro acetic acid in water and acetonitrile as organic solvent in a linear gradient program. Resolutions between bambuterol hydrochloride and montelukast sodium were found to be more than 31. The active pharmaceutical ingredient was extracted from tablet dosage from using a mixture of methanol, acetonitrile and water as diluent. The calibration graphs were linear for bambuterol hydrochloride and montelukast sodium in the range of 6.25-37.5 μg/ml. The percentage recoveries for bambuterol hydrochloride and montelukast sodium were found to be in the range of 99.1-100.0% and 98.0-101.6%, respectively. The test solution was found to be stable for 7 days when stored in the refrigerator between 2-8°. Developed UPLC method was validated as per International Conference on Harmonization specifications for method validation. This method can be successfully employed for simultaneous estimation of bambuterol hydrochloride and montelukast sodium in bulk drugs and formulations. PMID:23325991

Mass transfer resistance in narrow-bore columns packed with 1.7 microm particles in very high pressure liquid chromatography.

PubMed

Gritti, Fabrice; Guiochon, Georges

2010-07-30

Surprisingly, the mass transfer kinetic properties of columns packed with superficially porous particles are markedly different from those of columns packed with fully porous particles. The performances of 2.1mmx150mm columns packed with a new type of sub-2microm particles, the superficially porous 1.7microm Kinetex-C(18), and with the classical 1.7microm BEH-C(18) fully porous particles were measured and are discussed. The sample was naphtho[2,3-a]pyrene; the use of different mobile phase compositions allowed a comparison between data measured with retention factors of k(') approximately 2 and k(') approximately 20. The minimum reduced height equivalent to a theoretical plate (HETP) of the two columns were similar, at h(min)=2.0. However, this minimum HETP was observed at a markedly shorter reduced linear velocity for the column packed with totally porous particles, between 5 and 7 for BEH, than for the one packed with shell particles, between 8 and 10 for Kinetex. This result is explained by the combination of (1) a 35% smaller B term for the Kinetex column than for the BEH column, due to the 37% lower porous volume of the former; (2) a larger reduced A term for the Kinetex column (1.6), showing a relatively poorly packed column with significant trans-column velocity biases than for the BEH column (ca. 1.0); and (3) a much lesser dependance of the efficiency on the mobile phase velocity at high velocities for the Kinetex than for the BEH column, when these columns are placed in the oven of the instrument under still-air conditions. The heat friction affects significantly more the efficiency of the BEH column than that of the Kinetex column. This unexpected result is accounted for by the three times smaller heat conductivity of the BEH bed (lambda(BEH) approximately 0.25 W/m/K) than that of the Kinetex bed (lambda(Kinetex) approximately 0.75W/m/K).

21 CFR 74.1208 - D&C Green No. 8.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 21 Food and Drugs 1 2010-04-01 2010-04-01 false D&C Green No. 8. 74.1208 Section 74.1208 Food and... ADDITIVES SUBJECT TO CERTIFICATION Drugs § 74.1208 D&C Green No. 8. (a) Identity. (1) The color additive D&C Green No. 8 is principally the trisodium salt of 8-hydroxy-1,3,6-pyrene-trisulfonic acid. (2) Color...

Colchicine in Behçet syndrome: a longterm survey of patients in a controlled trial.

PubMed

Hamuryudan, Vedat; Hatemi, Gulen; Tascilar, Koray; Yurdakul, Sebahattin; Mat, Cem; Ozyazgan, Yilmaz; Seyahi, Emire; Ugurlu, Serdal; Yazici, Hasan

2014-04-01

To test the hypothesis that colchicine use during early disease decreases immunosuppressive use in Behçet syndrome (BS) in the long term. Patients with BS who participated in a double-blind, placebo-controlled trial of colchicine 16.6±1.1 years ago were evaluated for immunosuppressive use during the posttrial period. We could contact 90/116 patients; 28 (31%) received immunosuppressives during the posttrial period, 14 being from the colchicine arm. Posttrial colchicine use and cumulative duration were similar between patients who received immunosuppressives and those who did not. Continuous use of colchicine, even when initiated at an early disease stage, does not seem to decrease the use of immunosuppressives in the long term.

[Studies on effects of Achyranthes bidentata on tongsaimai pellets main active ingredients chlorogenic acid, isoliquiritin, harpagoside and glycyrrhizin in vivo pharmacokinetics].

PubMed

Cheng, Jian; Di, Liu-Qing; Shan, Jin-Jun; Zhao, Xiao-Li; Kang, An; Bi, Xiao-Lin; Li, Jun-Song

2014-04-01

To study on the effects of Achyranthes bidentata on Tongsaimai pellets main active ingredients chlorogenic acid, isoliquiritin, harpagoside and glycyrrhizin in rats in vivo pharmacokinetic behaviors, a method for the simultaneous determination of chlorogenic acid, isoliquiritin, harpagoside and liquiritigenin in rat plasma was established by UPLC-MS/MS. The analysis was performed on a waters Acquity BEH C18 column (2.1 mm x 100 mm, 1.7 microm) with the mixture of acetonitrile and 0.1% formic acid/water as mobile phase, and the gradient elution at a flow rate of 0.3 mL x min(-1). The analytes were detected by tandem mass spectrometry with the electrospray ionization (ESI) source and in the multiple reaction monitoring (MRM) mode. It turned out that the analytes of Tongsaimai pellets groups C(max) and AUC(Q-infinity) values were higher than that with A. bidentata group, and the C(max) values of chlorogenic acid had significantly difference (P < 0.05), the AUC(0-infinity) values of chlorogenic acid and glycyrrhizin had significantly difference (P < 0.05); The T(max) and CL values of two groups had no significantly difference. Results showed that the established method was specific, rapid, accurate and sensitive for the studies of Tongsaimai pellets four main active ingredients in rat in vivo pharmacokinetic, and A. bidentata have varying degrees of effects on Tongsaimai pellets four main active ingredients in rat in vivo pharmacokinetic behaviors.

Development and validation of an ultra high performance liquid chromatography electrospray ionization tandem mass spectrometry method for the simultaneous determination of selected flavonoids in Ginkgo biloba.

PubMed

Pandey, Renu; Chandra, Preeti; Arya, Kamal Ram; Kumar, Brijesh

2014-12-01

A rapid and sensitive ultra high performance liquid chromatography electrospray ionization tandem mass spectrometry method was developed and validated for the simultaneous determination of 13 flavonoids in leaf, stem, and fruit extracts of male and female trees of Ginkgo biloba to investigate gender- and age-related variations of flavonoids content. Chromatographic separation was accomplished on an Acquity UPLC BEH C18 column (50 mm × 2.1 mm id, 1.7 μm) in 5 min. Quantitation was performed using negative electrospray ionization mass spectrometry in multiple reaction monitoring mode. The calibration curves of all analytes showed a good linear relationship (r(2) ≥ 0.9977) over the concentration range of 1-1000 ng/mL. The precision evaluated by an intra- and interday study showed RSD ≤ 1.98% and good accuracy with overall recovery in the range from 97.90 to 101.09% (RSD ≤ 1.67%) for all analytes. The method sensitivity expressed as the limit of quantitation was typically 0.25-3.57 ng/mL. The results showed that the total content of 13 flavonoids was higher in the leaf extract of an old male Ginkgo tree compared to young female Ginkgo trees. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Determination and pharmacokinetic study of Enasidenib in rat plasma by UPLC-MS/MS.

PubMed

Pang, Ni-Hong; Liu, Qian; Lu, Xiang-Ran; Yang, Su-Fen; Lin, Dong-Dong; Hu, Guo-Xin

2018-04-27

Enasidenib, an oral product for treating Acute Myeloid Leukemia, has been approved by FDA in Aug, 2017. In this study, we set up an ultra-performance liquid chromatography-mass spectrometry (UPLC-MS/MS) method for measuring Enasidenib and imatinib (internal standard, IS), simultaneously. Enasidenib and imatinib were separated on an ACQUITY UPLC BEH C 18 Column (2.1 mm × 50 mm, 1.7 μm, 132 Å). Mass detection was carried out by electrospray ionization in the position mode, and the multiple reaction monitoring transitions were m/z 474.23 → 456.17 and m/z 494.30 → 394.20 for Enasidenib and imatinib, respectively. Linearity (2 - 500 ng·mL -1 , R 2  > 0.999), precision and accuracy (RE < ± 15%), extraction recovery (≥ 96.69%), matrix effect (≥ 96.47%) and stability (RE < ± 10%) were validated which demonstrated the robustness of our method. This rapid, efficient and reliable UPLC-MS/MS method shows specificity and repeatability of Enasidenib in rat plasma and can be used in further pharmacokinetic studies. Copyright © 2018 Elsevier B.V. All rights reserved.

Ultrafast quantification of β-lactam antibiotics in human plasma using UPLC-MS/MS.

PubMed

Carlier, Mieke; Stove, Veronique; De Waele, Jan J; Verstraete, Alain G

2015-01-26

There is an increasing interest in monitoring plasma concentrations of β-lactam antibiotics. The objective of this work was to develop and validate a fast ultra-performance liquid chromatographic method with tandem mass spectrometric detection (UPLC-MS/MS) for simultaneous quantification of amoxicillin, cefuroxime, ceftazidime, meropenem and piperacillin with minimal turn around time. Sample clean-up included protein precipitation with acetonitrile containing 5 deuterated internal standards, and subsequent dilution of the supernatant with water after centrifugation. Runtime was only 2.5 min. Chromatographic separation was performed on a Waters Acquity UPLC system using a BEH C18 column (1.7 μm, 100 mm × 2.1 mm) applying a binary gradient elution of water and methanol both containing 0.1% formic acid and 2 mmol/L ammonium acetate on a Water TQD instrument in MRM mode. All compounds were detected in electrospray positive ion mode and could be quantified between 1 and 100 mg/L for amoxicillin and cefuroxime, between 0.5 and 80 mg/L for meropenem and ceftazidime, and between 1 and 150 mg/L for piperacillin. The method was validated in terms of precision, accuracy, linearity, matrix effect and recovery and has been compared to a previously published UPLC-MS/MS method. Copyright © 2014 Elsevier B.V. All rights reserved.

Complete temperature profiles in ultra-high-pressure liquid chromatography columns.

PubMed

Gritti, Fabrice; Guiochon, Georges

2008-07-01

The temperature profiles were calculated along and across seven packed columns (lengths 30, 50, 100, and 150 mm, i.d., 1 and 2.1 mm, all packed with Acquity UPLC, BEH-C 18 particles, average d(p) approximately 1.7 microm) and their stainless steel tubes (o.d. 4.53 and 6.35 mm). These columns were kept horizontal and sheltered from forced air convection (i.e., under still air conditions), at room temperature. They were all percolated with pure acetonitrile, either under the maximum pressure drop (1034 bar) or at the maximum flow rate (2 mL/min) permitted by the chromatograph. The heat balance equation of chromatographic columns was discretized and solved numerically with minimum approximation. Both the compressibility and the thermal expansion of the eluent were taken into account. The boundary conditions were determined from the experimental measurements of the column inlet pressure and of the temperature profile along the column wall, which were made with a precision better than +/-0.1 K. These calculation results provide the 3-D temperature profiles along and across the columns. The axial and radial temperature gradients are discussed in relationship with the experimental conditions used. The temperature map obtained permits a prediction of the chromatographic data obtained under a very high pressure gradient.

Simultaneous determination of paeoniflorin, albiflorin, ferulic acid, tetrahydropalmatine, protopine, typhaneoside, senkyunolide I in Beagle dogs plasma by UPLC-MS/MS and its application to a pharmacokinetic study after Oral Administration of Shaofu Zhuyu Decoction.

PubMed

Huang, Xiaochen; Su, Shulan; Cui, Wenxia; Liu, Pei; Duan, Jin-ao; Guo, Jianming; Li, Zhenhao; Shang, Erxin; Qian, Dawei; Huang, Zhijun

2014-07-01

In this present study, a sensitive and rapid UPLC-MS/MS method was developed for simultaneous quantification of paeoniflorin, albiflorin, ferulic acid, tetrahydropalmatine, protopine, typhaneoside and senkyunolide I in Beagle dog plasma after oral administration of the Shao-Fu-Zhu-Yu Decoction. Chloramphenicol and clarithromycin were used as internal standards. Plasma samples were processed by protein precipitation with methanol. The separation was performed on an Acquity BEH C18 column (100mm×2.1mm, 1.7μm) at a flow-rate of 0.4mL/min, using 0.1% formic acid-acetonitrile as mobile phase. Method validation was performed as per Food and Drug Administration guidelines and the results met the acceptance criteria. After validation, this method was successfully applied to a pharmacokinetic study. The results showed that the apparent plasma clearance of paeoniflorin, albiflorin, typhaneoside and senkyunolide I were significantly higher than others. Double peak was observed in plasma concentration curves of tetrahydropalmatine, the ferulic acid had a good absorption in Beagle dog plasma, and senkyunolide I was detected in plasma from the first blood sampling time (15min) and rapidly reached Tmax. The compound of typhaneoside has a low bioavailability according to the results. Copyright © 2014. Published by Elsevier B.V.

Cerebral vein thrombosis in a four year old with Behçet's disease.

PubMed

Hacihamdioglu, Duygu Ovunc; Demiriz, Murat; Sobaci, Gungor; Kocaoglu, Murat; Demirkaya, Erkan; Gok, Faysal

2014-01-01

Behçet's disease (BD) is a multisystem disorder. The main pathology in BD is vasculitis that involves arteries and veins of all calibers. Central nervous system involvement occurs in 5-10% of patients. Increased morbidity and mortality is rarely observed in children. The mean age at onset in pediatric BD is approximately 7 years. Neurologic involvement in BD is usually observed after 3-6 years. We report the case of a four-year-old Turkish boy with BD with sagittal sinus thrombosis treated with infliximab. The patient presented papilledema without neurologic signs. Although long-term efficacy evaluations are needed in this case, infliximab therapy may be a good option in childhood BD with refractory sinus thrombosis. This is the youngest case of BD with sagittal sinus thrombosis reported so far. Copyright © 2012 Elsevier España, S.L. All rights reserved.

Electron induced ionization of plasma processing gases: C4F x (x  =  1–8) and the isomers of C4F6 and C4F8

NASA Astrophysics Data System (ADS)

Gupta, Dhanoj; Choi, Heechol; Kwon, Deuk-Chul; Yoon, Jung-Sik; Song, Mi-Young

2018-04-01

The total ionization cross section (Q ion) for C4F x (x  =  1–8) fluorocarbons and the isomers of C4F6 and C4F8 molecules are calculated from ionization threshold to 5 keV using the binary-encounter bethe method. The targets are fully optimized using the Hartree–Fock (HF) method and density function theory (DFT) for their minimum energy structure and orbital parameters. The present Q ion with HF parameters showed good agreement with the experimental data for 1,3-C4F6, 2-C4F6, 2-C4F8 and 1-C4F8. On the other hand, the Q ion with DFT parameters are in good accordance with the recent theoretical results for 1,3-C4F6 and 2-C4F6. The Q ion for c-C4F8 showed much variation among the various results. The isomer effect in Q ion is negligible for the isomers of C4F6 and C4F8 molecules. The calculation of Q ion for C4F, C4F2, C4F3, C4F4, C4F5, c-C4F6, C4F7 and iso-C4F8 is a maiden attempt. The present cross section data are important quantities for low temperature plasma modeling especially related to the fluorocarbon plasmas.

15 CFR 8c.49 - Program accessibility: Discrimination prohibited.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 15 Commerce and Foreign Trade 1 2010-01-01 2010-01-01 false Program accessibility: Discrimination prohibited. 8c.49 Section 8c.49 Commerce and Foreign Trade Office of the Secretary of Commerce ENFORCEMENT OF NONDISCRIMINATION ON THE BASIS OF HANDICAP IN PROGRAMS OR ACTIVITIES CONDUCTED BY THE DEPARTMENT OF COMMERCE § 8c.49...

15 CFR 8c.30 - General prohibitions against discrimination.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 15 Commerce and Foreign Trade 1 2010-01-01 2010-01-01 false General prohibitions against discrimination. 8c.30 Section 8c.30 Commerce and Foreign Trade Office of the Secretary of Commerce ENFORCEMENT OF NONDISCRIMINATION ON THE BASIS OF HANDICAP IN PROGRAMS OR ACTIVITIES CONDUCTED BY THE DEPARTMENT OF COMMERCE § 8c.30...

Schizophrenia and organic brain syndrome with trisomy 8 (group-C trisomy 8 [47, XX, 8+]).

PubMed

Sperber, M A

1975-02-01

A supernumerary autosomal syndrome in the C group of submetacentric autosomes has not yet been delineated phenotypically, although cases of an extra C-group autosome have been reported. Recent technical advances (fluorescence and Giemsa banding) now permit positive identification of each autosome. The present case reports the presence of schizophrenia and organic brain syndrome in association with trisomy 8. It is the sixth case of trisomy 8 reported to date. A stress-diathesis model is used to explain the development of the psychiatric disturbances. The patient's autosomal aberration is regarded as diathetic, and the multiple congenital anomalies, surgical interventions, infections, familial, and other environmental responses as stress. This report provides further data for the phenotypic delineation of a trisomy 8 syndrome.

Ocular Involvement of Behçet's Syndrome: a Comprehensive Review.

PubMed

Ozyazgan, Yilmaz; Ucar, Didar; Hatemi, Gulen; Yazici, Yusuf

2015-12-01

Behçet's syndrome (BS) is a vasculitis involving several organ systems including the eyes. Ocular involvement is one of the most disabling complications of BS, causing loss of vision that may progress to blindness if left untreated. The typical form of ocular involvement is a relapsing and remitting panuveitis and retinal vasculitis. Initial attacks may spontaneously improve and subsequently disappear in a few weeks but tend to recur if left untreated. Destructive and recurrent attacks, especially with posterior segment and retina involvement, may cause irreversible ocular structural changes and permanent damage in sensory retina, resulting in loss of vision. The risk of irreversible damage to ocular tissue which may result in loss of vision warrants early and intensive treatment especially in patients at high risk such as young men who tend to follow an aggressive disease course. The management strategy involves rapid suppression of inflammation during the attacks and prevention of recurrent attacks. Local and systemic measures including immunosuppressives, corticosteroids, and biologic agents are used for this purpose. Surgery may be required in selected cases. The prognosis of eye involvement has greatly improved over the last decades with the effective use of immunosuppressives.

Prevalence of hereditary properdin, C7 and C8 deficiencies in patients with meningococcal infections.

PubMed

Schlesinger, M; Nave, Z; Levy, Y; Slater, P E; Fishelson, Z

1990-09-01

High incidence of hereditary complement (C) deficiencies was found among 101 patients who had a meningococcal disease. This study revealed 11 non-related patients with complete C deficiency: five deficient in C7, three in C8, two in properdin and one in C2. Additional C-deficient individuals, most of them with no history of severe bacterial infections, were detected in family studies. The C8-deficient patients were found to have a selective deficiency of the C8-beta subunit and a reduced expression of the alpha/gamma subunit. Only a few families with properdin deficiency have been described so far. However, it is likely that frequent analysis of the activity of the alternative C pathway in survivors of severe bacterial infections will disclose numerous properdin-deficient patients. All our C7-, C8- and properdin-deficient patients are Sephardic Jews whose families originated from Morocco, Yemen (C7 and C8 deficient) or Tunisia (properdin deficient). This and other findings indicate that the type of complement abnormality found in association with meningococcal infections varies with the ethnic origin of the patient.

Efficacy of combination therapy of anti-TNF-α antibody infliximab and methotrexate in refractory entero-Behçet's disease.

PubMed

Iwata, Shigeru; Saito, Kazuyoshi; Yamaoka, Kunihiro; Tsujimura, Shizuyo; Nawata, Masao; Hanami, Kentaro; Tanaka, Yoshiya

2011-04-01

It is often difficult to manage refractory gastrointestinal tract complications of Behçet's disease (entero-BD) by conventional therapy. In this study, we assessed the short- and long-term efficacy and safety of the combination therapy of infliximab, an anti-tumor-necrosis-factor (TNF)-α antibody, and methotrexate in ten patients with refractory entero-BD refractory to conventional therapies. The short- (weeks) and long-term (by 2 years) effects of infliximab at 3-5 mg/kg body weight every 8 weeks on the clinical course and intestinal manifestations were assessed by abdominal computed tomography (CT) and colonoscopy. The primary endpoint was the rate of disappearance of ileocecal ulceration at 12 months of therapy. All patients showed improvement of gastrointestinal symptoms and disease-associated complications within 4 weeks. Furthermore, the rate of disappearance of ileocecal ulcerations was 50% (5/10 patients) at 6 months and 90% (9/10 patients) at 12 months, and, therefore 90% of patients were satisfied with the primary endpoint. Furthermore, corticosteroid dose was significantly reduced from 22.0 to 1.8 mg/day at 24 months. No severe adverse effects were observed during the 24 months of follow-up. We provide evidence for the rapid and excellent efficacy of infliximab in patients with refractory entero-BD and that the combination of infliximab and methotrexate brings about long-term alleviation of entero-BD and excellent tolerability.

[Determination of six anticoccidials in chicken using QuEChERS combined with ultra high liquid chromatography-high resolution mass spectrometry].

PubMed

Muharem, Muhteber; Yan, Hua; Xu, Shan; Feng, Nan; Hao, Jie; Zhu, Chenqi; Guo, Shuang; Zhang, Zhaohui; Han, Nanyin

2015-11-01

An ultra high liquid chromatography-Q Exactive orbitrap mass spectrometry multi-residue method has been developed for the determination of six anticoccidials residues (dinitlmide, nicarbazin, diclazuril, toltrazuril, monensin and salinomycin) in chicken tissue. Sample preparation was based on QuEChERS method, using 1% (v/v) trichloroacetic acid/acetonitrile aqueous solution (3:7, v/v) as the extraction solvent and salting-out with sodium chloride followed by clean-up with 50 mg/mL primary secondary amine (PSA) +50 mg/mL neutral alumina (Alumina-N) dispersive solid phase extraction (DSPE). The separation of the compounds in liquid chromatography was carried out using a Waters Acquity UPLC BEH C8 column (100 mm x 2.1 mm, 1.7 μm) with mobile phases consisting of methanol-5 mmol/L ammonium acetate aqueous solution in gradient elution. The Q Exactive orbitrap mass spectrometric detection was carried out with positive and negative electrospray ionization simultaneously. The results showed the linear ranges of the six target compounds were as follows: dinitolmide, 1.0-30.0 μg/L; nicarbazin, 0.2-6.0 μg/L; diclazuril and toltrazuril, 2.0-60.0 [μg/L; monensin and salinomycin, 4.0-120.0 μg/L. The external standard method was used for quantification. The spiked recoveries at three levels for the six anticoccidials ranged from 67.7% to 126.8%. The relative standard deviations (RSDs) were ≤ 10.4%. The limits of quantification (LOQs) were as follows: dinitolmide, 2.50 μg/kg; nicarbazin, 0.50 μg/kg; diclazuril and toltrazuril, 5.00 μg/kg; monensin and salinomycin, 20.00 μg/kg. The developed method is easy of operation and of high sensitivity. It can meet the requirements of daily inspection.

21 CFR 74.2708 - D&C Yellow No. 8.

Code of Federal Regulations, 2010 CFR

2010-04-01

... ADDITIVES SUBJECT TO CERTIFICATION Cosmetics § 74.2708 D&C Yellow No. 8. (a) Identity and specifications. The color additive D&C Yellow No. 8 shall conform in identity and specifications to the requirements... coloring externally applied cosmetics in amounts consistent with good manufacturing practice. (c) Labeling...

21 CFR 74.2708 - D&C Yellow No. 8.

Code of Federal Regulations, 2011 CFR

2011-04-01

... ADDITIVES SUBJECT TO CERTIFICATION Cosmetics § 74.2708 D&C Yellow No. 8. (a) Identity and specifications. The color additive D&C Yellow No. 8 shall conform in identity and specifications to the requirements... coloring externally applied cosmetics in amounts consistent with good manufacturing practice. (c) Labeling...

21 CFR 74.2708 - D&C Yellow No. 8.

Code of Federal Regulations, 2012 CFR

2012-04-01

... ADDITIVES SUBJECT TO CERTIFICATION Cosmetics § 74.2708 D&C Yellow No. 8. (a) Identity and specifications. The color additive D&C Yellow No. 8 shall conform in identity and specifications to the requirements... coloring externally applied cosmetics in amounts consistent with good manufacturing practice. (c) Labeling...

21 CFR 74.2708 - D&C Yellow No. 8.

Code of Federal Regulations, 2013 CFR

2013-04-01

... ADDITIVES SUBJECT TO CERTIFICATION Cosmetics § 74.2708 D&C Yellow No. 8. (a) Identity and specifications. The color additive D&C Yellow No. 8 shall conform in identity and specifications to the requirements... coloring externally applied cosmetics in amounts consistent with good manufacturing practice. (c) Labeling...

21 CFR 74.2708 - D&C Yellow No. 8.

Code of Federal Regulations, 2014 CFR

2014-04-01

... ADDITIVES SUBJECT TO CERTIFICATION Cosmetics § 74.2708 D&C Yellow No. 8. (a) Identity and specifications. The color additive D&C Yellow No. 8 shall conform in identity and specifications to the requirements... coloring externally applied cosmetics in amounts consistent with good manufacturing practice. (c) Labeling...

FAS Gene Copy Numbers are Associated with Susceptibility to Behçet Disease and VKH Syndrome in Han Chinese.

PubMed

Yu, Hongsong; Luo, Le; Wu, Lili; Zheng, Minming; Zhang, Lijun; Liu, Yunjia; Li, Hua; Cao, Qingfeng; Kijlstra, Aize; Yang, Peizeng

2015-11-01

Previous studies have identified that disturbed apoptosis was involved in the pathogenesis of Behçet disease (BD) and Vogt-Koyanagi-Harada (VKH) syndrome. This study aims to investigate whether copy number variations of apoptosis-related genes, including FAS, CASPASE8, CASPASE3, and BCL2, are associated with BD and VKH syndrome in Han Chinese. A two-stage association study was performed in 1,014 BD patients, 1,051 VKH syndrome patients, and 2,076 healthy controls. TaqMan(®) Copy Number Assays and real-time PCR were performed. The first-stage study showed that increased frequency of high FAS copy number (>2) was found in BD (P = 1.05 × 10(-3) ) and VKH syndrome (P = 2.56 × 10(-3) ). Replication and combined study confirmed the association of high copy number (>2) of FAS with BD (P = 3.35 × 10(-8) ) and VKH syndrome (P = 9.77 × 10(-8) ). A significant upregulated mRNA expression of FAS was observed in anti-CD3/CD28 antibodies-stimulated CD4(+) T cells from individuals carrying a high gene copy number (>2) as compared to normal diploid 2 copy number carriers (P = 0.004). Moreover, the mRNA expression of FAS both in active patients with BD and VKH syndrome was significantly higher than that in controls (P = 0.001 and P = 0.007, respectively). Our findings suggest that a high copy number of FAS gene confers risk for BD and VKH syndrome. © 2015 WILEY PERIODICALS, INC.

Two human homeobox genes, c1 and c8: structure analysis and expression in embryonic development.

PubMed

Simeone, A; Mavilio, F; Acampora, D; Giampaolo, A; Faiella, A; Zappavigna, V; D'Esposito, M; Pannese, M; Russo, G; Boncinelli, E

1987-07-01

Two human cDNA clones (HHO.c1.95 and HHO.c8.5111) containing a homeobox region have been characterized, and the respective genomic regions have been partially analyzed. Expression of the corresponding genes, termed c1 and c8, was evaluated in different organs and body parts during human embryonic/fetal development. HHO.c1.95 apparently encodes a 217-amino acid protein containing a class I homeodomain that shares 60 out of 61 amino acid residues with the Antennapedia homeodomain of Drosophila melanogaster. HHO.c8.5111 encodes a 153-amino acid protein containing a homeodomain identical to that of the frog AC1 gene. Clones HHO.c1 and HHO.c8 detect by blot-hydridization one and two specific polyadenylylated transcripts, respectively. These are differentially expressed in spinal cord, backbone rudiments, limb buds (or limbs), heart, and skin of human embryos and early fetuses in the 5- to 9-week postfertilization period, thus suggesting that the c1 and c8 genes play a key role in a variety of developmental processes. Together, the results of the embryonic/fetal expression of c1 and c8 and those of two previously analyzed genes (c10 and c13) indicate a coherent pattern of expression of these genes in early human ontogeny.

Trace elements and antioxidant enzymes in Behçet's disease.

PubMed

Saglam, K; Serce, A F; Yilmaz, M I; Bulucu, F; Aydin, A; Akay, C; Sayal, A

2002-07-01

Free oxygen radicals and insufficiency of antioxidant enzymes have been implicated in the pathogenesis of Behçet's disease (BD). Trace elements function as cofactors to antioxidant enzymes. The antioxidant system and trace elements were investigated in many different studies, including BD, but these subjects have not been investigated as a whole in these patients. The aim of the present study was to investigate the antioxidative system and trace elements in BD to contribute to the knowledge of pathogenesis and treatment of this disease. We examined glutathione peroxidase (GSH-Px) and superoxide dismutase (SOD) activities together with selenium (Se), copper (Cu), zinc (Zn), manganese (Mn), and iron (Fe) levels in plasma and erythrocytes of 50 patients with BD and 30 healthy controls. It was found that in patients with BD, erythrocyte GSH-Px and SOD activities and erythrocyte Se, plasma Fe, Mn, and Zn levels were significantly lower than those of controls and that plasma Cu, erythrocyte Zn, and Mn levels were significantly higher in patients with BD. Insufficient antioxidant enzyme activities were observed in patients with BD. The mechanism(s) of this phenomenon is not clear. Therefore, supplementation with trace elements involved in the antioxidative processes may increase scavenger enzyme activities, and consequently, an improvement in clinical symptoms may be expected.

Knitting the Threads of Silk through Time: Behçet's Disease—Past, Present, and Future

PubMed Central

Stack, Austin G.; Fraser, Alexander D.

2017-01-01

Behçet's disease (BD) is a chronic relapsing vasculitis that affects vessels of all types and sizes with a broad spectrum of phenotypic heterogeneity and complex immunopathogenesis. Efforts by the scientific community to resolve the unmet needs of BD and gaps in our knowledge have been hampered by considerable challenges that primarily relate to the rare nature of the disease in many parts of the world and its heterogeneity. Controversies remain in many aspects of the disease including the diagnostic criteria, immunopathogenesis and biomarker discovery, geographical variation, and therapeutic considerations. In this review, we highlight recent advances in our scientific understanding of BD, shed new insights into diagnostic and treatment strategies, and discuss residual gaps in our knowledge that will serve as the basis for current and future research. PMID:29081805

Treatment and outcomes: medical and surgical treatment for intestinal Behçet's disease.

PubMed

Hisamatsu, Tadakazu; Hayashida, Mari

2017-07-01

Behçet's disease (BD) is a chronic relapsing disease involving multiple organ systems. BD is characterized clinically by oral and genital aphthae, cutaneous lesions, and ophthalmological, neurological, and/or gastrointestinal manifestations. It is widely recognized that the presence of intestinal lesions may be a poor prognostic factor in intestinal BD, increasing the risk of surgery and decreasing the quality of life. Despite this, the management of intestinal BD has not been standardized. Empirical therapies including 5-aminosalicylic acid and corticosteroids have been used anecdotally to treat intestinal BD, but recent studies have provided evidence for the efficacy of anti-tumor necrosis factor α monoclonal antibodies. The development of agents targeting tumor necrosis factor α continues, it seems likely that they will change the therapeutic strategy and clinical outcomes of intestinal BD and inflammatory bowel disease. Monitoring disease activity such as endoscopic evaluation will become more important to obtain better outcomes. Here, we review current and future perspectives in the treatment and outcomes of intestinal BD.

Evaluation of Intraocular Inflammation with Laser Flare Photometry in Behçet Uveitis.

PubMed

Yalcindag, Fatime Nilufer; Bingol Kiziltunc, Pinar; Savku, Esra

2017-02-01

To evaluate the association between intraocular inflammation and laser flare photometry measurements in Behçet disease. In total, 45 patients were included in the study. The retrospective chart reviews of patients were performed. The flare levels were compared with the grade of anterior chamber cells, the presence of vitreous cells, the complications of uveitis, and fluorescein angiography scores. The attack group had higher flare intensity; the flare levels were higher in both groups compared with the values of healthy controls. The flare levels were related to the grade of the anterior chamber cells, the presence of vitreous cells and the fluorescein angiography scores. Patients with optic atrophy and/or maculopathy also had higher values. Higher flare values were correlated with poor vision. Laser flare photometry may reduce the necessity of fluorescein angiography in monitoring subclinical inflammation and may be an indicator of posterior segment activity when fluorescein angiography is not applicable.

21 CFR 74.1208 - D&C Green No. 8.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 21 Food and Drugs 1 2011-04-01 2011-04-01 false D&C Green No. 8. 74.1208 Section 74.1208 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES GENERAL LISTING OF COLOR ADDITIVES SUBJECT TO CERTIFICATION Drugs § 74.1208 D&C Green No. 8. (a) Identity. (1) The color additive D&C...

Cytochrome P450 2C8 pharmacogenetics: a review of clinical studies

PubMed Central

Daily, Elizabeth B; Aquilante, Christina L

2009-01-01

Cytochrome P450 (CYP) 2C8 is responsible for the oxidative metabolism of many clinically available drugs from a diverse number of drug classes (e.g., thiazolidinediones, meglitinides, NSAIDs, antimalarials and chemotherapeutic taxanes). The CYP2C8 enzyme is encoded by the CYP2C8 gene, and several common nonsynonymous polymorphisms (e.g., CYP2C8*2 and CYP2C8*3) exist in this gene. The CYP2C8*2 and *3 alleles have been associated in vitro with decreased metabolism of paclitaxel and arachidonic acid. Recently, the influence of CYP2C8 polymorphisms on substrate disposition in humans has been investigated in a number of clinical pharmacogenetic studies. Contrary to in vitro data, clinical data suggest that the CYP2C8*3 allele is associated with increased metabolism of the CYP2C8 substrates, rosiglitazone, pioglitazone and repaglinide. However, the CYP2C8*3 allele has not been associated with paclitaxel pharmacokinetics in most clinical studies. Furthermore, clinical data regarding the impact of the CYP2C8*3 allele on the disposition of NSAIDs are conflicting and no definitive conclusions can be made at this time. The purpose of this review is to highlight these clinical studies that have investigated the association between CYP2C8 polymorphisms and CYP2C8 substrate pharmacokinetics and/or pharmacodynamics in humans. In this review, CYP2C8 clinical pharmacogenetic data are provided by drug class, followed by a discussion of the future of CYP2C8 clinical pharmacogenetic research. PMID:19761371

[Comparison of chemical composition between fresh and processed Bufonis Venenum by UPLC-TQ-MS].

PubMed

Wang, Zi-yue; Wang, Hong-lan; Zhou, Jing; Ma, Hong-yue; Gong, Yan; Yan, Wen-li; Qian, Da-wei

2015-10-01

Toad venom is the Bufo bufo gargarizans or B. melanostictus after the ears of the gland secretion, used in the treatment of various cancers in recent years. Research shows that the main anti-tumor components in bufadienolide. Bufadienolide have free type structure and conjunct type structure. To identify and clarify the difference between bufogenin and bufotoxin contained in Bufonis Venenum, which was from B. bufo gargarizans, an UPLC-TQ-MS method has been established. UPLC-TQ-MS method was used to identify and quantify the major bufadienolides in Bufonis Venenum. UPLC-TQ-MS assay with positive ion mode was performed on a Waters ACQUITY UPLC BEH C, (2.1 mm x 100 mm, 1.7 µm) with the mobile phase consisting of 0. 1% aqueous formic and acidacetonitrile in gradient elution at a flow rate of 0.4 mL · min⁻¹ and the column temperature was set at 35 °C. By comparing their retention time and high resolution mass data of Bufonis Venenum extracts, 37 effective components were primarily identified by MS/MS analysis in positive ion mode. Twenty-six of them were free-type bufadienolides (bufogenin), 11 of them were conjugated bufadienolides. There were significant differences in the main composition between fresh and processed Bufonis Venenum. The study found that the chemical composition of toad venom through great changes after processing, conjunct type content is much less, free type content as well change.

[Determination of 6 kinds of plant growth regulator in bean sprout by ultra high performance liquid chromatography-tandem mass spectrometry].

PubMed

Liu, Ping; Fan, Sai; Wu, Guohua; Zhao, Rong; Liu, Wei; Zhao, Xudong

2016-05-01

A method for the simultaneous determination of 6 plant growth regulator (PGR) residues in bean sprout was developed by ultra high performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS). 6-Benzylaminopurine, isopentennyladenine, 4-chlorophenoxyacetic acid, 4-fluorophenoxyacetic acid, indole-3- acetic acid and indole-3-butyric acid were concerned. Bean sprout samples were extracted by acetonitrile and QuEChERS extraction kit, purified by C18 powers. After centrifugation, the sample liquids was diluted 10 times by ultrapure water. The chromatographic analysis was carried out on an waters acquity UPLC BEH C18 column( 100 mm x 2.1 mm, 1.7 microm). The analyzer confirmed and quantified by mass spectrum of triple quadrupole in the multiple reaction monitoring (MRM) mode and quantified by matrix-matched external standard method. The calibration curves showed good linearity in each range with correlation coefficients greater than 0.998. 3 levels spiked recoveries were carried out using blank bean sprout extraction as substrate, the recoveries ranged from 84.2% to 107.5%, the relative standard deviations (RSDs) ranged from 3.08% to 12.71%. The qualitative limits of detections (S/N = 3) were 0.03-3.0 microg/kg and the quantitative limits(S/N = 10) were 0.1-10.0 microg/kg for the 6 PGRs. The method is simple and easy to operate, with less organic reagent, high sensitivity and good stability. It is suitable for the detection of 6 kinds of plant growth regulators in bean sprouts.

Ethnicity and association with disease manifestations and mortality in Behçet's disease.

PubMed

Savey, Lea; Resche-Rigon, Mathieu; Wechsler, Bertrand; Comarmond, Cloé; Piette, Jean Charles; Cacoub, Patrice; Saadoun, David

2014-03-27

Behçet's disease (BD) significantly increases morbidity and mortality. BD mainly affects young adults with a peculiar geographical distribution. It has been suggested that BD varies in its phenotypic expression in different ethnic groups. We investigated potential ethnicity-related differences relative to phenotype and prognosis of BD patients in a French multiethnic country. We included 769 consecutive patients fulfilling the international criteria of classification for BD, in the 3 largest ethnic groups of our cohort [European (n = 369), North African (n = 350) and sub Saharan African (n = 50)]. Factors that affect prognosis were assessed by multivariate analysis. 535 (69.6%) patients were male and the median (IQR) age at diagnosis was of 30.9 (24.9-37.2) years. Sub Saharan African BD patients had a higher frequency of CNS involvement (48% vs 32.3% vs 29.5%, p = 0 .035), a higher rate of death (12% vs 6% vs 3.5%, p = 0.029) and a lower frequency of HLA B51 allele (29.4% vs 49.2% vs 55.8%, p = 0.009) compared to those from North Africa and Europe, respectively. Multivariate analysis showed that male gender (HR: 5.01, CI: 1.51-16.65), cardiovascular involvement (HR: 2.24, CI: 1.15-4.36), and sub Saharan African origin (HR 2.62 (0.98-6.97) were independently associated with mortality. The 15-year mortality rate was of 19%, 9% and 6% in sub Saharan African, North African and European BD patients, respectively (p = 0.015). We reported ethnicity-related differences with respect to phenotype of BD. Sub Saharan Africans patients exhibited a worse prognosis.

Development and validation of an ultra high performance liquid chromatography tandem mass spectrometry method for simultaneous determination of sulfonamides, quinolones and benzimidazoles in bovine milk.

PubMed

Hou, Xiao-Lin; Chen, Guo; Zhu, Li; Yang, Ting; Zhao, Jian; Wang, Lei; Wu, Yin-Liang

2014-07-01

A simple, sensitive and reliable analytical method was developed for the simultaneous determination of 38 veterinary drugs (18 sulfonamides, 11 quinolones and 9 benzimidazoles) and 8 metabolites of benzimidazoles in bovine milk by ultra high performance liquid chromatography-positive electrospray ionization tandem mass spectrometry (UHPLC-ESI-MS/MS). Samples were extracted with acidified acetonitrile, cleaned up with Oasis(®) MCX cartridges, and analyzed by LC-MS/MS on an Acquity UPLC(®) BEH C18 column with gradient elution. The method allows such multi-analyte measurements within a 13min runtime while the specificity is ensured through the MRM acquisition mode. The method was validated according to the European Commission Decision 2002/657/EC determining specificity, decision limit (CCα), detection capability (CCβ), recovery, precision, linearity and stability. For compounds which have MRLs in bovine milk, the CCα values fall into a range from 11 to 115μg/kg, and the CCβ values fall within a range of 12-125μg/kg. For compounds which have not MRLs in bovine milk, the CCα values fall into a range from 0.01 to 0.08μg/kg, and the CCβ values fall within a range of 0.02-0.11μg/kg. The mean recoveries of the 46 analytes were between 87 and 119%. The calculated RSD values of repeatability and within-laboratory reproducibility experiments were below 11% and 15% for the 46 compounds, respectively. The method was demonstrated to be suitable for the simultaneous determination of sulfonamides, quinolones and benzimidazoles in bovine milk. Copyright © 2014 Elsevier B.V. All rights reserved.

Analysis of perfluorinated chemicals in umbilical cord blood by ultra-high performance liquid chromatography/tandem mass spectrometry.

PubMed

Lien, Guang-Wen; Wen, Ting-Wen; Hsieh, Wu-Shiun; Wu, Kuen-Yuh; Chen, Chia-Yang; Chen, Pau-Chung

2011-03-15

Perfluorinated compounds (PFCs) can cross the placental barrier and enter fetal circulation. This study aimed at developing a fast and sensitive ultra-high performance liquid chromatography/tandem mass spectrometry method for the determination of twelve perfluorinated compounds in cord blood. Samples were processed with protein precipitation using formic acid and methanol, mixed with stable isotope labeled standard, followed by sonication and centrifugation, and were analyzed using a Waters ACQUITY UPLC coupled with a Waters Quattro Premier XE triple-quadrupole mass spectrometer. The instrument was operated in selected reaction monitoring (SRM) with negative electrospray ionization. Using BEH C(18) column (2.1 mm×50 mm, 1.7 μm) with 10-mM N-methylmorpholine/methanol gradient elution provided a fast chromatographic separation (5.5 min) and sharp peaks. Intra- and inter-day calibration bias was less than 7% and intra- and inter-day calibration of relative standard deviations were within 0.02-8.22% for all the analytes and concentrations. The recoveries of PFCs spiked into bovine serum ranged from 85 to 104% with relative standard deviations from 0.02 to 6.37%. The limits of quantitation (LOQs), defined as a signal-to-noise ratio of ten, ranged from 0.15 to 3.1 ng/mL for the twelve PFCs. Perfluorooctanoic acid (PFOA), perfluorooctyl sulfonate (PFOS), perfluoroundecanoic acid (PFUA) and perfluorononanoic acid (PFNA) were detected in up to 68% of umbilical cord plasma (n=444) in Taiwan Birth Panel Study and the health effect of these chemicals on children developmental deserves further investigation. Copyright © 2011 Elsevier B.V. All rights reserved.

Use of chiral derivatization for the determination of dichlorprop in tea samples by ultra performance LC with fluorescence detection.

PubMed

Inoue, Koichi; Prayoonhan, Nuntawat; Tsutsui, Haruhito; Sakamoto, Tasuku; Nishimura, Maiko; Toyo'oka, Toshimasa

2013-04-01

Dichlorprop is available for agricultural use as a chiral pesticide. In this study, the stereoselective determination of dichlorprop enantiomers in tea samples such as green, black, jasmine, and oolong was developed by ultra performance LC with fluorescence spectrometry after covalent chiral derivatization. The separation was achieved on an Acquity BEH C18 column with the mobile phase consisting of 0.1% formic acid in acetonitrile/water at a flow rate of 0.4 mL/min. In the covalent chiral derivatization using (S)-(+)-4-(N,N-dimethylaminosulfonyl)-7-(3-aminopyrrolidin-1-yl)-2,1,3-benzoxadiazole, the peak resolution between the S and R-dichlorprop enantiomers was 2.6. LODs and LOQs values were 10 and 50 ng/mL standard solution. The linearity of the calibration curves yielded the coefficients (r(2) > 0.99, ranging from 0.05 to 5 μg/mL) of determination of each of the dichlorprop enantiomers. SPE extraction was used for the sample preparation of dichlorprop in various tea samples. Recoveries were in the range of 82.4-97.6% with associated precision values (within-day: 82.4-95.8%, n = 6, and between-day: 83.7-97.6% for 3 days) for repeatability and reproducibility. Based on this result, our method has been proven to be highly efficient and suitable for the routine assay of dichlorprop enantiomers in various tea samples. We propose that the ultra performance LC assay after covalent chiral derivatization would be the renewed tools in the era of chiral stationary platform for chiral pesticide residues in foods. © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Analysis of drugs of abuse in human plasma using microextraction by packed sorbents and ultra-high-performance liquid chromatography.

PubMed

Fernández, P; González, M; Regenjo, M; Ares, A M; Fernández, A M; Lorenzo, R A; Carro, A M

2017-02-17

A miniaturized and simple method based on digitally programmed microextraction by packed sorbent (eVol ® -MEPS) coupled to ultra-performance liquid chromatography (UPLC) has been developed for quantitative determination of three synthetic cathinones and seven conventional drugs of abuse and metabolites. The influence of several extraction parameters, such as washing and elution solvents were tested. In addition important variables affecting MEPS performance, namely sample volume, sorbent drying time, washing solvent volume, elution volume, number of extraction cycles, sorbent phase and pH, were evaluated using an asymmetrical screening design. The optimal experimental conditions involved 300μL of plasma, loading 10×100μL of sample through a C8/SCX sorbent in a MEPS syringe placed in the semi-automatic eVol ® system, washing using 150μL H 2 O:MeOH (90:10, v/v), drying for 0.5min and elution using 200μL dichloromethane:2-propanol:ammonium hydroxide (78:20:2, v/v/v). The drugs separation was achieved using an ACQUITY BEH Shield RP18 column (2.1mm×100mm×1.7μm) in 3min. Under optimized conditions the proposed method was validated in terms of selectivity, linearity, limits of detection (LOD) and quantitation (LOQ), precision and matrix effect, using standard addition calibration. The combination of MEPS and UPLC provides a method for the primary screening of the analytes in 18min with excellent recoveries at three concentration levels, ranging between 80 and 104% (relative standard deviation <11%). The developed methodology has been successfully applied to plasma samples from polydrug abusers. Copyright © 2017 Elsevier B.V. All rights reserved.

Spacecraft Maximum Allowable Concentrations (SMACs) for C3 to C8 Aliphatic Saturated Aldehydes

NASA Technical Reports Server (NTRS)

Langford, Shannon D.

2007-01-01

Spacecraft maximum allowable concentrations (SMACs) for C3 to C8, straight-chain, aliphatic aldehydes have been previously assessed and have been documented in volume 4 of Spacecraft Maximum Allowable Concentrations for Selected Airborne Contaminants (James, 2000). These aldehydes as well as associated physical properties are shown in Table 1. The C3 to C8 aliphatic aldehydes can enter the habitable compartments and contaminate breathing air of spacecraft by several routes including incomplete oxidation of alcohols in the Environmental Control and Life Support System (ECLSS) air revitalization subsystem, as a byproduct of human metabolism, through materials off-gassing, or during food preparation. These aldehydes have been detected in the atmosphere of manned space vehicles in the past. Analysis performed by NASA of crew cabin air samples from the Russian Mir Space Station revealed the presence of C3 to C8 aldehydes at concentrations peaking at approximately 0.1 mg/cu m.

40 CFR 721.10024 - 10H-Phenothiazine, ar-(C9-rich C8-10-branched alkyl) derivs.

Code of Federal Regulations, 2010 CFR

2010-07-01

... 40 Protection of Environment 30 2010-07-01 2010-07-01 false 10H-Phenothiazine, ar-(C9-rich C8-10... New Uses for Specific Chemical Substances § 721.10024 10H-Phenothiazine, ar-(C9-rich C8-10-branched... substance identified as 10H-phenothiazine, ar-(C9-rich C8-10-branched alkyl) derivs (PMN P-01-771; CAS No...

One year in review 2017: Behçet's syndrome.

PubMed

Hatemi, Gulen; Seyahi, Emire; Fresko, Izzet; Talarico, Rosaria; Hamuryudan, Vedat

2017-01-01

A meta-analysis showed that methodological differences in prevalence studies such as a sample survey design or census design may be responsible for some of the variance in BS prevalence reported across countries, in addition to a true geographic variation. Efforts towards developing a data driven core set of outcome measures for clinical trials is continuing. Multimodal imaging using color fundus photography, fluorescein angiography, and optical coherence tomography is essential in visualising diagnostic features, detecting structural changes, and monitoring disease activity and response to treatment in Behçet's uveitis. Haemoptysis could also be due to bronchial artery enlargement in BS patients with pulmonary artery involvement and can be effectively treated with embolisation. Recent studies shed light on the link between immune system and thrombosis: fibrin clots seemed to be structurally different and plasmin resistant in BS. Newer genetic associations using immunochip were determined, but HLA-B51 is still the principal genetic link. Various studies on micro-RNA's, important molecules of immune regulation were published and discussed. Anti-TNF agents are still the key biologics for the treatment of various manifestations of BS. Two Phase III trials enrolling a small number of BS patients have shown the efficacy of adalimumab in the treatment of non-infectious, non-anterior uveitis. Interferon-alpha was found to induce long-lasting drug free remissions in a retrospective study. Small observational studies with non-TNF biologics such as ustekinumab, anakinra and canakinumab report beneficial results which await confirmation with further studies.

Nailfold capillaroscopy in Behçet's disease, analysis of 128 patients.

PubMed

Movasat, Atusa; Shahram, Farhad; Carreira, Patricia E; Nadji, Abdolhadi; Akhlaghi, Maassoomeh; Naderi, Nassim; Davatchi, Fereydoun

2009-05-01

The aims of this study were to find the characteristics and prevalence of nailfold capillary changes in a large series of patients with Behçet's disease (BD) and to analyze their possible relation to other clinical characteristics of the disease. We performed nailfold capillaroscopy in 128 randomly selected patients fulfilling the international classification criteria for BD. Capillaroscopy was done in eight fingers with a x3.2 microscopy. All patients were questioned for history of Raynaud's phenomenon, ischemic ulcers, smoking, and hypertension. A computerized form including demographic, clinical, and para-clinical features was used to collect data. Univariate and multivariate logistic regressions were used to analyze the relation between capillaroscopic findings and disease characteristics. Odds ratio and a confidence interval at 95% (CI) were calculated for each item. The mean age of the patients was 37 +/- 10 years, and the male to female ratio was 1.56:1. Capillaroscopy was abnormal in 51 patients (40%, CI 8.5). Enlarged capillaries were seen in 33 patients (26%, CI 7.6), hemorrhages in 21 (16%, CI 6.4), and capillary loss only in one patient. In univariate logistic regression analysis, the presence of enlarged capillaries was associated with lower age at disease onset (OR = 0.9, CI 0.9-1; p = 0.04), hypertension (OR = 4.2, CI 1.5-11.4; p = 0.006), superficial phlebitis (OR = 5.5, CI 1.2-24.4; p = 0.03), and negative pathergy test (OR = 0.4, CI 0.2-0.9; p = 0.04). The presence of hemorrhages tended to be associated with articular symptoms (p = 0.05). Multivariate analysis also confirmed the association of enlarged capillaries with lower age at disease onset (p = 0.01), hypertension (p = 0.001), and superficial phlebitis (p = 0.03). Nailfold abnormalities, mainly enlarged capillaries, are frequent in patients with BD. Our results suggest that these abnormalities may be related to other vascular features of the disease such as superficial phlebitis, but it

Rapid chiral separation of atenolol, metoprolol, propranolol and the zwitterionic metoprolol acid using supercritical fluid chromatography-tandem mass spectrometry - Application to wetland microcosms.

PubMed

Svan, Alfred; Hedeland, Mikael; Arvidsson, Torbjörn; Jasper, Justin T; Sedlak, David L; Pettersson, Curt E

2015-08-28

A method for enantiomeric separation of the three β-blocking agents atenolol, metoprolol, propranolol and the zwitterionic metoprolol acid, a major metabolite of both metoprolol and in environmental matrices also atenolol, has been developed. By use of supercritical fluid chromatography and the polysaccharide-based Chiralpak(®) IB-3, all four compounds were simultaneously enantiomerically separated (Rs>1.5) within 8min. Detection was performed using tandem mass spectrometry, and to avoid isobaric interference between the co-eluting metoprolol and metoprolol acid, the achiral column Acquity(®) UPC(2) BEH 2-EP was attached ahead of to the chiral column. Carbon dioxide with 18% methanol containing 0.5% (v/v) of the additives trifluoroacetic acid and ammonia in a 2:1 molar ratio were used as mobile phase. A post column make-up flow (0.3mL/min) of methanol containing 0.1% (v/v) formic acid was used to enhance the positive electrospray ionization. Detection was carried out using a triple quadrupole mass spectrometer operating in the selected reaction monitoring mode, using one transition per analyte and internal standard. The method was successfully applied for monitoring the enantiomeric fraction change over time in a laboratory scale wetland degradation study. It showed good precision, recovery, sensitivity and low effect of the sample matrix. Copyright © 2015. Published by Elsevier B.V.

New insights of HLA class I association to Behçet's disease in Portuguese patients.

PubMed

Bettencourt, A; Pereira, C; Carvalho, L; Carvalho, C; Patto, J V; Bastos, M; Silva, A M; Barros, R; Vasconcelos, C; Paiva, P; Costa, L; Costa, P P; Mendonça, D; Correia, J; Silva, B M

2008-10-01

Human leukocyte antigen (HLA)-B*51 is a well-known genetic factor associated with Behçet's disease (BD). To analyse the influence of HLA-B*51 and other HLA class I alleles in BD susceptibility in a Portuguese population and its association with disease severity, we studied 78 BD patients and 208 healthy controls. The patients were classified into two severity groups as described by Gul et al. As expected, a higher frequency of HLA-B*51 was found. The frequency of HLA-Cw*16 alleles was significantly higher in patients. Regarding severity, HLA-B*27 frequency was higher in the severe group compared with controls and with the mild group. Thus, HLA-B*51 and HLA-Cw*16 seem to confer susceptibility to BD in this patients. HLA-B*27 may be important as a prognostic factor.

26 CFR 1.381(c)(8)-1 - Installment method.

Code of Federal Regulations, 2014 CFR

2014-04-01

... 26 Internal Revenue 4 2014-04-01 2014-04-01 false Installment method. 1.381(c)(8)-1 Section 1.381... (CONTINUED) INCOME TAXES (CONTINUED) Insolvency Reorganizations § 1.381(c)(8)-1 Installment method. (a... the installment method, then the acquiring corporation shall be treated as the distributor or...

26 CFR 1.381(c)(8)-1 - Installment method.

Code of Federal Regulations, 2012 CFR

2012-04-01

... 26 Internal Revenue 4 2012-04-01 2012-04-01 false Installment method. 1.381(c)(8)-1 Section 1.381... (CONTINUED) INCOME TAXES (Continued) Insolvency Reorganizations § 1.381(c)(8)-1 Installment method. (a... the installment method, then the acquiring corporation shall be treated as the distributor or...

26 CFR 1.381(c)(8)-1 - Installment method.

Code of Federal Regulations, 2013 CFR

2013-04-01

... 26 Internal Revenue 4 2013-04-01 2013-04-01 false Installment method. 1.381(c)(8)-1 Section 1.381... (CONTINUED) INCOME TAXES (CONTINUED) Insolvency Reorganizations § 1.381(c)(8)-1 Installment method. (a... the installment method, then the acquiring corporation shall be treated as the distributor or...

26 CFR 1.381(c)(8)-1 - Installment method.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 26 Internal Revenue 4 2010-04-01 2010-04-01 false Installment method. 1.381(c)(8)-1 Section 1.381... (CONTINUED) INCOME TAXES Insolvency Reorganizations § 1.381(c)(8)-1 Installment method. (a) Carryover... corporation has elected under section 453 and the regulations thereunder to report on the installment method...

26 CFR 1.381(c)(8)-1 - Installment method.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 26 Internal Revenue 4 2011-04-01 2011-04-01 false Installment method. 1.381(c)(8)-1 Section 1.381... (CONTINUED) INCOME TAXES Insolvency Reorganizations § 1.381(c)(8)-1 Installment method. (a) Carryover... corporation has elected under section 453 and the regulations thereunder to report on the installment method...

Lattice dynamics of a rotor-stator molecular crystal: Fullerene-cubane C60ṡC8H8

NASA Astrophysics Data System (ADS)

Bousige, Colin; Rols, Stéphane; Cambedouzou, Julien; Verberck, Bart; Pekker, Sándor; Kováts, Éva; Durkó, Gábor; Jalsovsky, István; Pellegrini, Éric; Launois, Pascale

2010-11-01

The dynamics of fullerene-cubane (C60ṡC8H8) cocrystal is studied combining experimental [x-ray diffuse scattering, quasielastic and inelastic neutron scattering (INS)] and simulation (molecular dynamics) investigations. Neutron scattering gives direct evidence of the free rotation of fullerenes and of the libration of cubanes in the high-temperature phase, validating the “rotor-stator” description of this molecular system. X-ray diffuse scattering shows that orientational disorder survives the order/disorder transition in the low-temperature phase, although the loss of fullerene isotropic rotational diffusion is featured by the appearance of a 2.2 meV mode in the INS spectra. The coupling between INS and simulations allows identifying a degeneracy lift of the cubane librations in the low temperature phase, which is used as a tool for probing the environment of cubane in this phase and for getting further insights into the phase transition mechanism.

Behçet's disease: review with emphasis on dermatological aspects*

PubMed Central

Scherrer, Maria Antonieta Rios; Rocha, Vanessa Barreto; Garcia, Lucas Campos

2017-01-01

Behçet's disease is a systemic vasculitis characterized by attacks of acute inflammation, which can affect almost every vascularized area of the body. There is a close correlation between the geographical distribution of HLA-B51 and its prevalence. In the etiopathogenesis there are indications of genetic susceptibility associated with environmental influence. Among the involved genes are those that encompass innate and adaptive immunities. Polymorphisms and epistatic interactions in several genes are described, as well as the presence of imbalance lineage between HLA-B51 and A (MICA). Herpes simplex and Streptococcus sanguinis may be important extrinsic factors. An increase of Th1 response and of IL-21 is observed. The production of IL-21 is positively related to Th17 cells and negatively to T-regs. The mucocutaneous manifestations are Behcet´s disease markers, and their earlier onset indicates a worse prognosis. Recurrent oral ulcers have varied sizes and arrangements, genital ulcers are recurrent, leaving scars, skin lesions are multivaried, and pathergy, although not so frequent, is important for the diagnosis. There are numerous attempts to validate indexes that can evaluate the disease activity and among them the Mucocutaneous Activity Index. This is a specific score that can help with therapeutic decisions and to reduce morbidity, but still lacks validation. The clinical manifestations of other organs are described as well as treatment options. PMID:28954091

[Determination of 11 industrial antioxidants in the aqueous simulants by ultra-performance liquid chromatography-tandem mass spectrometry].

PubMed

Fan, Sai; Zou, Jianhong; Li, Liping; Zhang, Nan; Liu, Wei; Li, Bing; Zhao, Xudong; Wu, Guohua; Xue, Ying; Zhao, Rong

2014-09-01

An ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) method has been developed to identify and determine 11 industrial antioxidants in the aqueous simulants. A ProElut PLS SPE column was used for the enrichment, and an ACQUITY UPLC BEH C18 UPLC column (100 mm x 2.1 mm, 1.7 μm) was used for separation by the gradient elution with pure water and acetonitrile as the mobile phases. The MS/MS detection was performed with an electrospray ionization (ESI) source in negative mode. The external standard method was used for quantitation in the present study. The linear ranges of the 11 analytes were from 5.0 to 100 μg/L. The coefficients of correlation were greater than 0.995. The recoveries of blank aqueous simulants fortified with the 11 analytes at the levels of 5.0, 10.0 and 20.0 μg/L were 61.4% to 109.4% with the relative standard deviations varied from 3.9% to 18.2% (n = 6). The LODs and LOQs of the 11 analytes in aqueous simulants were 0.2-1.0 μg/L and 0.5-3.0 μg/L, respectively. This method is highly sensitive and accurate, and can be applied to the determination of the 11 trace industrial antioxidants in the aqueous simulants.

Simultaneous determination of eight bioactive components of Qishen Yiqi dripping pills in rat plasma using UFLC-MS/MS and its application to a pharmacokinetic study.

PubMed

Shao, Yaping; Zhang, Wen; Tong, Ling; Huang, Jingyi; Li, Dongxiang; Nie, Wei; Zhu, Yan; Li, Yunfei; Lu, Tao

2017-08-01

In this study, a rapid and reliable ultra-fast liquid chromatography-tandem mass spectrometry method was developed and validated for the simultaneous determination of eight active ingredients, including astragaloside IV, ononin, tanshinol, protocatechualdehyde, protocatechuic acid, salvianolic acid D, rosmarinic acid and ginsenoside Rg 1 , in rat plasma. The plasma samples were pretreated by protein precipitation with acetonitrile. Chromatographic separation was performed on a Waters Acquity UPLC® BEH C 18 column (1.7 μm particles, 2.1 × 100 mm). The mobile phase consisted of 0.1% aqueous formic acid (A)-acetonitrile with 0.1% formic acid (B) at a flow rate of 0.4 mL/min. Quantification was performed on a triple quadruple tandem mass spectrometry with electrospray ionization by multiple reaction monitoring both in the negative and in the positive ion mode. The lower limit of quantification of tanshinol was 2.0 ng/mL and the others were 5.0 ng/mL. The extraction recoveries, matrix effects, intra- and inter-day precision and accuracy of eight tested components were all within acceptable limits. The validated method was successfully applied to the pharmacokinetic study of the eight active constituents after intragastric administration of three doses (1.0, 3.0, 6.0 g/kg body weight) of Qishen Yiqi Dripping Pills to rats. Copyright © 2017 John Wiley & Sons, Ltd.

Simultaneous determination of pyrroquinazoline alkaloids and flavonoids in Adhatoda beddomei and Adhatoda vasica and their marketed herbal formulations using ultra-high-performance liquid chromatography coupled with triple quadrupole linear ion trap mass spectrometry.

PubMed

Singh, Awantika; Kumar, Sunil; Bajpai, Vikas; Kumar, Brijesh

2017-03-01

Adhatoda beddomei and Adhatoda vasica leaf, known as 'Vasaka' and/or 'Vasa' in Ayurveda and 'Malabar nut' in English, is an official drug in the Indian Pharmacopoeia. The medicinal properties of these plants are due to the presence of pyrroquinazoline alkaloids. An UHPLC-ESI/MS/MS method in both positive and negative electrospray ionization in multiple-reaction-monitoring mode was developed and validated for the estimation of alkaloids and flavonoids in Adhatoda species and their marketed herbal formulations. Chromatographic separation was achieved on an Acquity UPLC® BEH C 18 -column using a gradient elution with 0.1% formic acid in water and methanol. The developed method was validated as per International Conference on Harmonization guidelines and found to be accurate with overall recovery in the range 94.2-105.0% (RSD ≤ 1.71%), precise (RSD ≤ 3.44%) and linear (R 2  ≥ 0.9992) over the concentration range of 0.5-1000 ng/mL. The total content of alkaloids and flavonoids were highest in the chloroform and aqueous fraction of A. vasica leaf, respectively. The results indicated that the developed method was simple, rapid, sensitive, selective and accurate for the estimation of multiple bioactive constituents in crude mixture, and therefore could make a contribution to the quality control of Adhatoda species and its derived herbal formulations. Copyright © 2016 John Wiley & Sons, Ltd.

Determination of rutin in rat plasma by ultra performance liquid chromatography tandem mass spectrometry and application to pharmacokinetic study.

PubMed

Chen, Mengchun; Zhang, Xiaoqian; Wang, Hao; Lin, Baoli; Wang, Shuanghu; Hu, Guoxin

2015-04-01

A sensitive and rapid ultra performance liquid chromatography tandem mass spectrometry (UPLC-MS-MS) method for the determination of rutin in rat plasma was developed and validated. After addition of tolbutamide as internal standard (IS), protein precipitation by acetonitrile was used as sample preparation. The chromatographic separation was performed on an Acquity UPLC BEH C18 column (2.1 × 50 mm, 1.7 μm particle size), using acetonitrile-0.1% formic acid as the mobile phase with gradient elution, delivered at a flow-rate of 0.4 mL/min. Mass spectrometric analysis was performed using a XEVO TQD mass spectrometer coupled with an electro-spray ionization (ESI) source in the positive ion mode. The MRM transitions of m/z 610.91→302.98 and m/z 271.2→155.1 were used to quantify for rutin and tolbutamide, respectively. This assay method has been fully validated in terms of specificity, linearity, recovery and matrix effect, accuracy, precision and stability. Calibration curves were linear in the concentration ranges of 25-2000 ng/mL for rutin. Only 3 min was needed for an analytical run. This developed method was successfully used for determination of rutin in rat plasma for pharmacokinetic study. © The Author 2014. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Simultaneous determination of acetaminophen and dihydrocodeine in human plasma by UPLC-MS/MS: Its pharmacokinetic application.

PubMed

Qiu, Xiangjun; Lou, Dan; Su, Ding; Liu, Zebin; Gao, Pengtao; Zhang, Nan-sheng

2015-06-15

An ultra performance liquid chromatography tandem mass spectrometry (UPLC-MS/MS) method was developed and validated to determine acetaminophen (AAP) and dihydrocodeine (DHC) in human plasma simultaneously. Plasma samples were prepared using protein precipitation with acetonitrile, the two analytes and the internal standard midazolam were separated on an Acquity UPLC BEH C18 column and mass spectrometric analysis was performed using a QTrap5500 mass spectrometer coupled with an electro-spray ionization (ESI) source in the positive ion mode. The MRM transitions of m/z 151.2→110.0 and m/z 302.3→199.2 were used to quantify for AAP and DHC, respectively. The linearity of this method was found to be within the concentration range of 50-10000ng/mL for AAP, and 1-100ng/mL for DHC in human plasma, respectively. The lower limit of quantification (LLOQ) was 50ng/mL and 1ng/mL for AAP and DHC in human plasma, respectively. The relative standard deviations (RSD) of intra and inter precision were less than 10% for both AAP and DHC. The analysis time of per sample was 1.0min. The developed and validated method was successfully applied to a pharmacokinetic study of AAP (500mg) with DHC (20mg) capsule in Chinese healthy volunteers (N=20). Copyright © 2015 Elsevier B.V. All rights reserved.

[Rapidly identify oligosaccharides in Morinda officinalis by UPLC-Q-TOF-MSE].

PubMed

Hao, Qing-Xiu; Kang, Li-Ping; Zhu, Shou-Dong; Yu, Yi; Hu, Ming-Hua; Ma, Fang-Li; Zhou, Jie; Guo, Lan-Ping

2018-03-01

In this paper, an approach was applied for separation and identification of oligosaccharides in Morinda officinalis How by Ultra performance liquid chromatography/quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF-MS) with collision energy. The separation was carried out on an ACQUITY UPLC BEH Amide C₁₈(2.1mm×100 mm，1.7 μm) with gradient elution using acetonitrile(A) and water(B) containing 0.1% ammonia as mobile phase at a flow rate of 0.2 mL·min⁻¹. The column temperature was maintained at 40 °C. The information of accurate mass and characteristic fragment ion were acquired by MSE in ESI negative mode in low and high collision energy. The chemical structures and formula of oligosaccharides were obtained and identified by the software of UNIFI and Masslynx 4.1 based on the accurate mass, fragment ions, neutral losses, mass error, reference substance, isotope information, the intensity of fragments, and retention time. A total of 19 inulin oligosaccharide structures were identified including D(+)-sucrose, 1-kestose, nystose, 1F-fructofuranosyl nystose and other inulin oligosaccharides (DP 5-18). This research provided important information about the inulin oligosaccharides in M. officinalis. The results would provide scientific basis for innovative utilization of M. officinalis. Copyright© by the Chinese Pharmaceutical Association.

[Determination of strobilurin fungicides in fruits and their mass fragmentation routes by ultra performance liquid chromatography-tandem mass spectrometry].

PubMed

Zhou, Yao; Yang, Huiqin; Shi, Yiyin; Chen, Jiaxian; Zhu, Jian; Deng, Xiaojun; Guo, Dehua

2017-09-08

A method was developed for the simultaneous determination of six strobilurin fungicide ( E -metominostrobin, azoxystrobin, kresoxim-methyl, picoxystrobin, pyraclostrobin and trifloxystrobin) residues in orange, banana, apple and pineapple samples by ultra performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS). The fragmentation routes of all the compounds were explained by the aid of a fragment predicting software ACD Lab/MS Fragmenter. The samples were extracted by acetonitrile, then cleaned up by amino solid phase extraction cartridges (SupelClean LC-NH 2 ). The extracts were separated on a ACQUITY UPLC BEH C 18 column (50 mm×2.1 mm, 1.7 μm) with gradient elution. Acetonitrile containing 0.1% (v/v) formic acid and 10 mmol/L ammonium acetate containing 0.1% (v/v) formic acid were used as mobile phases. The samples were detected by electrospray ionization (ESI)-MS/MS in positive ion and multiple reaction monitoring (MRM) mode, quantified by external standard method. Good linearities were obtained in the range of 5-100 μg/L (for pyraclostrobin, 1-20 μg/L) with correlation coefficients ( r 2 ) greater than 0.999. The recoveries ranged from 60.4% to 120% with the relative standard deviations between 2.15% and 15.1% ( n =6). The developed method can meet the inspection of the six strobilurin residues in the orange, banana, apple and pineapple samples.

[Simultaneous determination of sixteen perfluorinated organic compounds in surface water by solid phase extraction and ultra performance liquid chromatography with electrospray ionization tandem mass spectrometry].

PubMed

Zhang, Ming; Tang, Fangliang; Yu, Yayun; Chen, Feng; Xu, Jianfen; Ye, Yonggen

2014-05-01

A high-throughput detection method has been developed for the determination of sixteen perfluorinated organic compounds (PFCs) in surface water by solid phase extraction-ultra performance liquid chromatography coupled with electrospray ionization tandem mass spectrometry (SPE-UPLC-ESI-MS/MS). The water samples were concentrated and purified through WAX solid phase extraction cartridges. The UPLC separation was performed on an ACQUITY UPLC BEH C18 column utilizing a gradient elution program of methanol (containing 2 mmol/L ammonium acetate) and water (containing 2 mmol/L ammonium acetate) as the mobile phases at a flow rate of 0.4 mL/min. The MS/MS detection was performed under negative electrospray ionization ( ESI ) in multiple reaction monitoring (MRM) mode. Good linearities were observed in the range of 0.5-100 gg/L or 1.0 - 100 microg/L with correlation coefficients from 0.998 7 to 0.999 9. The limits of detection (LODs) for the sixteen perfluorinated organic compounds were in the range of 0.06-0.46 ng/L. The recoveries ranged from 67.6% to 103% with the relative standard deviations between 2.94% and 12.0%. This method was characterized by high sensitivity and precision, extensive range and high speed, and can be applied for the analysis of PFC contaminants in surface water.

Simultaneous determination of ambroxol and salbutamol in human plasma by ultra-performance liquid chromatography-tandem mass spectrometry and its application to a pharmacokinetic study.

PubMed

Guo, Zhening; Chen, Yangsheng; Ding, Xiaoliang; Huang, Chenrong; Miao, Liyan

2016-11-01

A rapid, selective and sensitive liquid chromatography-tandem mass spectrometry assay method was developed for simultaneous determination of ambroxol and salbutamol in human plasma using citalopram hydrobromide as internal standard (IS). The sample was alkalinized with ammonia water (33:67, v/v) and extracted by single liquid-liquid extraction with ethyl acetate. Separation was achieved on Waters Acquity UPLC BEH C 18 column using a gradient program at a flow rate of 0.2 mL/min. Detection was performed using electrospray ionization in positive ion multiple reaction monitoring mode by monitoring the ion transitions m/z 378.9 → 263.6 (ambroxol), m/z 240.2 → 147.7 (salbutamol) and m/z 325.0 → 261.7 (IS). The total analytical run time was relatively short (3 min). Calibration curves were linear in the concentration range of 0.5-100.0 ng/mL for ambroxol and 0.2-20.0 ng/mL for salbutamol, with intra- and inter-run precision (relative standard deviation) <15% and accuracy (relative error) ranging from 97.7 to 112.1% for ambroxol and from 94.5 to 104.1% for salbutamol. The method was successfully applied in a clinical pharmacokinetic study of the compound ambroxol and salbutamol tablets. Copyright © 2016 John Wiley & Sons, Ltd.

SPE-UPLC-MS/MS assay for determination of letrozole in human plasma and its application to bioequivalence study in healthy postmenopausal Indian women.

PubMed

Vanol, Pravin G; Singhal, Puran; Shah, Priyanka A; Shah, Jaivik V; Shrivastav, Pranav S; Sanyal, Mallika

2016-08-01

A rapid and sensitive ultra performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) method is described for determination of letrozole in human plasma. Following solid phase extraction (SPE) of letrozole and letrozole-d4 on Orochem DVB-LP cartridges, chromatography was performed on Acquity UPLC BEH C 18 (50 mm×2.1 mm, 1.7 µm) column using methanol-0.1% formic acid in water (85:15, v/v) as the mobile phase. Detection was carried out on a triple quadrupole mass spectrometer with an electrospray source, operated under positive ionization mode. Quantitation of letrozole and letrozole-d4 was done using multiple reaction monitoring (MRM) following the transitions at m/z 286.2→217.0 and m/z 290.2→221.0, respectively. The calibration plots were linear through the concentration range of 0.10-100 ng/mL ( r 2 ≥0.9990) using 100 µL human plasma. The extraction recovery of letrozole ranged from 94.3% to 96.2% and the intra-batch and inter-batch precision was ≤5.2%. The method was successfully applied to a bioequivalence study of letrozole after oral administration of 2.5 mg tablet formulation to 16 healthy postmenopausal Indian women. The assay reproducibility was also established through incurred sample reanalysis (ISR) of 74 subject samples.

A rapid UPLC-MS/MS assay for eicosanoids in human plasma: Application to evaluate niacin responsivity.

PubMed

Miller, Tricia M; Poloyac, Samuel M; Anderson, Kacey B; Waddell, Brooke L; Messamore, Erik; Yao, Jeffrey K

2017-01-18

A rapid and sensitive method using ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) was developed to simultaneously quantify hydroxyeicosatetraenoic (HETE), dihydroxyeicosatrienoic (DiHETrE), epoxyeicosatrienoic acid (EET), and prostaglandin metabolites of arachidonic acid in human plasma. Sample preparation consisted of solid phase extraction with Oasis HLB (30mg) cartridges for all metabolites. Separation of HETEs, EETs, and DiHETrEs was achieved on an Acquity UPLC BEH C18, 1.7µm (100×2.1mm) reversed-phase column (Waters Corp, Millford, MA) with negative electrospray ionization mass spectrometric detection. A second injection of the same extracted sample allowed for separation and assessment of prostaglandin metabolites under optimized UPLC-MS/MS conditions. Additionally, the endogenous levels of these metabolites in five different matrices were determined in order to select the optimal matrix for assay development. Human serum albumin was shown to have the least amount of endogenous metabolites, a recovery efficiency of 79-100% and a matrix effect of 71 - 100%. Linear calibration curves ranging from 0.416 to 66.67ng/ml were validated. Inter-assay and intra-assay variance was less than 15% at most concentrations. This method was successfully applied to quantify metabolite levels in plasma samples of healthy control subjects receiving niacin administration to evaluate the association between niacin administration and eicosanoid plasma level response. Published by Elsevier Ltd.

Determination of Asymmetric and Symmetric Dimethylarginine in Serum from Patients with Chronic Kidney Disease: UPLC-MS/MS versus ELISA.

PubMed

Boelaert, Jente; Schepers, Eva; Glorieux, Griet; Eloot, Sunny; Vanholder, Raymond; Lynen, Frédéric

2016-05-13

Asymmetric dimethylarginine (ADMA), an endogenous inhibitor of nitric oxide (NO) synthesis, and its structural isomer symmetric dimethylarginine (SDMA) are uremic toxins accumulating in chronic kidney disease (CKD) patients. The objective of this study was to develop and validate a robust UPLC-MS/MS method for the simultaneous determination of ADMA and SDMA in human serum. Chromatographic separation after butyl ester derivatization was achieved on an Acquity UPLC BEH C18 column, followed by tandem mass spectrometric detection. After validation, the applicability of the method was evaluated by the analysis of serum samples from 10 healthy controls and 77 CKD patients on hemodialysis (CKD5HD). Both ADMA (0.84 ± 0.19 µM vs. 0.52 ± 0.07 µM) and SDMA concentrations (2.06 ± 0.82 µM vs. 0.59 ± 0.13 µM) were significantly (p < 0.001) elevated in CKD5HD patients compared to healthy controls. In general, low degrees of protein binding were found for both ADMA and SDMA. In addition, an established commercially available ELISA kit was utilized on the same samples (n = 87) to compare values obtained both with ELISA and UPLC-MS/MS. Regression analysis between these two methods was significant (p < 0.0001) but moderate for both ADMA (R = 0.78) and SDMA (R = 0.72).

Quantification of amlodipine and atorvastatin in human plasma by UPLC-MS/MS method and its application to a bioequivalence study.

PubMed

Rezk, Mamdouh R; Badr, Kamal A

2018-07-01

A robust, rapid and sensitive UPLC-MS/MS method has been developed, optimized and validated for the determination of amlodipine (AML) and atorvastatin (ATO) in human plasma using eplerenone as an internal standard (IS). Multiple-reaction monitoring in positive electrospray ionization mode was utilized in Xevo TQD LC-MS/MS. Double extraction was used in sample preparation using diethyl ether and ethyl acetate. The prepared samples were analyzed using an Acquity UPLC BEH C 18 (50 × 2.1 mm, 1.7 μm) column. Ammonium formate and acetonitrile, pumped isocraticaly at a flow rate of 0.25 mL/min, were used as a mobile phase. Method validation was done as per the US Food and Drug Administration guidelines. Linearity was achieved in the range of 0.1-10 ng/mL for AML and 0.05-50 ng/mL for ATO. Intra-day and inter-day accuracy and precision were calculated and found to be within the acceptable range. A short run time, of <1.5 min, permits analysis of a large number of plasma samples per batch. The developed and validated method was applied to estimate AML and ATO in a bioequivalence study in healthy human volunteers. Copyright © 2018 John Wiley & Sons, Ltd.

Quantitative determination of triterpenoids and formononetin in rhizomes of black cohosh (Actaea racemosa) and dietary supplements by using UPLC-UV/ELS detection and identification by UPLC-MS.

PubMed

Avula, Bharathi; Wang, Yan-Hong; Smillie, Troy J; Khan, Ikhlas A

2009-03-01

A UPLC-UV/ELSD method has been developed for analysis of major triterpenoids and formononetin in ACTAEA RACEMOSA L. (family Ranunculaceae) samples. The best results were obtained with an Acquity UPLC BEH C18 (100 mmx2.1 mm, i. d., 1 microm) column system using gradient elution with a mobile phase consisting of water and acetonitrile:methanol (7:3) at a constant flow rate of 0.3 mL/min. Owing to their low UV absorption, the triterpene saponins were detected by evaporative light scattering. Within 5.5 minutes, three main triterpenoid glycosides [cimiracemoside A, 23- EPI-26-deoxyactein, and actein] and an isoflavonoid, formononetin, could be separated, with detection limits of 5, 5, 10, and 0.01 microg/mL, respectively. The method was successfully used to analyze different Actaea racemosa market products as well as to distinguish between two other ACTAEA species. There was a significant variability in the amounts of the selected triterpene glycosides for the products containing black cohosh and rhizomes of black cohosh. The isoflavone formononetin was not detected in the samples analyzed. LC-MS coupled with the electrospray ionization (ESI) interface method is described for the identification of formononetin and triterpenoid glycosides in plant samples and dietary supplements that claim to contain black cohosh and different species of Actaea.

Determination and pharmacokinetic study of pirfenidone in rat plasma by UPLC-MS/MS.

PubMed

Sun, Wei; Jiang, Zhe-li; Zhou, Lei; Chen, Rui-min; Wang, Zhe; Li, Wan-shu; Jiang, Shuo-min; Hu, Guo-xin; Chen, Rui-jie

2015-02-15

A rapid, sensitive and selective ultra-performance liquid chromatography tandem mass spectrometry (UPLC-MS/MS) was developed and validated for the determination and pharmacokinetic investigation of pirfenidone in rat plasma. Sample preparation was accomplished through a simple one-step deproteinization procedure with 0.2 mL of acetonitrile to a 0.1 mL plasma sample. Plasma samples were separated by UPLC on an Acquity UPLC BEH C18 column using a mobile phase consisting of acetonitrile-0.1% formic acid in water with gradient elution. The total run time was 3.0 min and the elution of pirfenidone was at 1.39 min. The detection was performed on a triple quadrupole tandem mass spectrometer in the multiple reaction-monitoring (MRM) mode using the respective transitions m/z 186.2→92.1 for pirfenidone and m/z 237.1→194.2 for carbamazepine (IS), respectively. The calibration curve was linear over the range of 5-2000 ng/mL with a lower limit of quantitation (LLOQ) of 5 ng/mL. Mean recovery of pirfenidone in plasma was in the range of 80.4-84.3%. Intra-day and inter-day precision were both <12.1%. This method was successfully applied in pharmacokinetic study after oral administration of 10.0mg/kg pirfenidone in rats. Copyright © 2015 Elsevier B.V. All rights reserved.

[Screening and confirmation of 24 hormones in cosmetics by ultra high performance liquid chromatography-linear ion trap/orbitrap high resolution mass spectrometry].

PubMed

Li, Zhaoyong; Wang, Fengmei; Niu, Zengyuan; Luo, Xin; Zhang, Gang; Chen, Junhui

2014-05-01

A method of ultra high performance liquid chromatography-linear ion trap/orbitrap high resolution mass spectrometry (UPLC-LTQ/Orbitrap MS) was established to screen and confirm 24 hormones in cosmetics. Various cosmetic samples were extracted with methanol. The extract was loaded onto a Waters ACQUITY UPLC BEH C18 column (50 mm x 2.1 mm, 1.7 microm) using a gradient elution of acetonitrile/water containing 0.1% (v/v) formic acid for the separation. The accurate mass of quasi-molecular ion was acquired by full scanning of electrostatic field orbitrap. The rapid screening was carried out by the accurate mass of quasi-molecular ion. The confirmation analysis for targeted compounds was performed with the retention time and qualitative fragments obtained by data dependent scan mode. Under the optimal conditions, the 24 hormones were routinely detected with mass accuracy error below 3 x 10(-6) (3 ppm), and good linearities were obtained in their respective linear ranges with correlation coefficients higher than 0.99. The LODs (S/N = 3) of the 24 compounds were < or = 10 microg/kg, which can meet the requirements for the actual screening of cosmetic samples. The developed method was applied to screen the hormones in 50 cosmetic samples. The results demonstrate that the method is a useful tool for the rapid screening and identification of the hormones in cosmetics.

UPLC-MS-MS Method for the Determination of Vilazodone in Human Plasma: Application to a Pharmacokinetic Study.

PubMed

El-Bagary, Ramzia; Hashem, Hanaa; Fouad, Marwa; Tarek, Sally

2016-09-01

A sensitive, rapid and simple liquid chromatographic-electrospray ionization tandem mass spectrometric (LC-ESI-MS-MS) method was developed for the quantitative determination of vilazodone in human plasma and for the study of the pharmacokinetic behavior of vilazodone in healthy Egyptian volunteers. With escitalopram as internal standard (IS), liquid-liquid extraction was used for the purification and preconcentration of analytes from human plasma matrix using diethyl ether. The separation was performed on an Acquity UPLC BEH shield RP C18 column (1.7 µm, 2.1 × 150 mm). Isocratic elution was applied using methanol-0.2% formic acid (90:10, v/v). Detection was performed on a triple-quadrupole tandem mass spectrometer with multiple reaction monitoring mode via an electrospray ionization source at m/z 442.21 → 155.23 for vilazodone and m/z 325.14 → 109.2 for escitalopram. Linear calibration curves were obtained over the range of 1-200 ng/mL with the lower limit of quantification at 1 ng/mL. The intra- and inter-day precision showed relative standard deviation ≤3.3%. The total run time was 1.5 min. This method was successfully applied for clinical pharmacokinetic investigation, and a preliminary metabolic study was also carried out. © The Author 2016. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

21 CFR 74.2208 - D&C Green No. 8.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 21 Food and Drugs 1 2011-04-01 2011-04-01 false D&C Green No. 8. 74.2208 Section 74.2208 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES GENERAL LISTING OF COLOR....1208(a)(1) and (b). (b) Uses and restrictions. D&C Green No. 8 may be safely used for coloring...

21 CFR 74.2208 - D&C Green No. 8.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 21 Food and Drugs 1 2010-04-01 2010-04-01 false D&C Green No. 8. 74.2208 Section 74.2208 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES GENERAL LISTING OF COLOR....1208(a)(1) and (b). (b) Uses and restrictions. D&C Green No. 8 may be safely used for coloring...

15 CFR 8c.3 - Definitions.

Code of Federal Regulations, 2014 CFR

2014-01-01

... BASIS OF HANDICAP IN PROGRAMS OR ACTIVITIES CONDUCTED BY THE DEPARTMENT OF COMMERCE § 8c.3 Definitions..., walks, parking lots, rolling stock or other conveyances, or other real or personal property. Individual with handicaps means any person who has a physical or mental impairment that substantially limits one...

Isotropic C6, C8 and C10 interaction coefficients for CH 4, C 2H 6, C 3H 8, n-C 4H 10 and cyclo- C3H 6

NASA Astrophysics Data System (ADS)

Thomas, Gerald F.; Mulder, Fred; Meath, William J.

1980-12-01

The non-empirical generalized Kirkwood, Unsöld, and the single-Δ Unsöld methods (with double-zeta quality SCF wave-functions) are used to calculate isotropic dispersion (and induction) energy coefficients C2n, with n ⩽ 5, for interactions involving ground state CH 4, C 2H 6, C 3H 8, n-C 4H 10 and cyclo-C 3H 6. Results are also given for the related multipole polarizabilities α l, multipole sums S1/(0) and S1(-1) which are evaluated using sum rules, and the permanent multipole moments. for l = 1 (dipole) to l = 3 (octupole). Estimates of the reliability of the non-empirical methods, for the type of molecules considered, are obtained by a comparison with accurate literature values of α 1S1(-1) and C6. This, and the asymptotic properties of the multipolar expansion of the dispersion energy, the use to discuss recommended representation for the isotropic long range interaction energies through R-10 where R is the intermolecular separation.

Simultaneous determination of kolliphor HS15 and miglyol 812 in microemulsion formulation by ultra-high performance liquid chromatography coupled with nano quantity analyte detector.

PubMed

Zhang, Honggen; Wang, Zhenyu; Liu, Oscar

2016-02-01

A novel method for simultaneous determination of kolliphor HS15 and miglyol 812 in microemulsion formulation was developed using ultra-high performance liquid chromatography coupled with a nano quantitation analytical detector (UHPLC-NQAD). All components in kolliphor HS15 and miglyol 812 were well separated on an Acquity BEH C 18 column. Mobile phase A was 0.1% trifluoroacetic acid (TFA) in water and mobile phase B was acetonitrile. A gradient elution sequence was programed initially with 60% organic solvent, slowly increased to 100% within 8 min. The flow rate was 0.7 mL/min. Good linearity ( r >0.95) was obtained in the range of 27.6-1381.1 μg/mL for polyoxyl 15 hydroxystearate in kolliphor HS15, 0.8-202.0 μg/mL for caprylic acid triglyceride and 2.7-221.9 μg/mL for capric acid triglyceride in miglyol 812. The relative standard deviations (RSD) ranged from 0.6% to 1.7% for intra-day precision and from 0.4% to 2.7% for inter-day precision. The overall recoveries (accuracy) were 99.7%-101.4% for polyoxyl 15 hydroxystearate in kolliphor HS15, 96.7%-99.6% for caprylic acid triglyceride, and 94.1%-103.3% for capric acid triglyceride in miglyol 812. Quantification limits (QL) were determined as 27.6 μg/mL for polyoxyl 15 hydroxystearate in kolliphor HS15, 0.8 μg/mL for caprylic acid triglyceride, and 2.7 μg/mL for capric acid triglyceride in miglyol 812. No interferences were observed in the retention time ranges of kolliphor HS15 and miglyol 812. The method was validated in terms of specificity, linearity, precision, accuracy, QL, and robustness. The proposed method has been applied to microemulsion formulation analyses with good recoveries (82.2%-103.4%).

40 CFR 721.10022 - Benzenamine, N-phenyl-, ar′-(C9-rich C8-10-branched alkyl) derivs.

Code of Federal Regulations, 2010 CFR

2010-07-01

... Significant New Uses for Specific Chemical Substances § 721.10022 Benzenamine, N-phenyl-, ar′-(C9-rich C8-10... chemical substance identified as benzenamine, N-phenyl-, ar′-(C9-rich C8-10-branched alkyl) derivs (PMN P...

Long-term tropospheric trend of octafluorocyclobutane (c-C4F8 or PFC-318)

NASA Astrophysics Data System (ADS)

Oram, D. E.; Mani, F. S.; Laube, J. C.; Newland, M. J.; Reeves, C. E.; Sturges, W. T.; Penkett, S. A.; Brenninkmeijer, C. A. M.; Röckmann, T.; Fraser, P. J.

2011-07-01

Air samples collected at Cape Grim, Tasmania between 1978 and 2008 and during a series of more recent aircraft sampling programmes have been analysed to determine the atmospheric abundance and trend of octafluorocyclobutane (-C4F8 or PFC-318). c-C4F8 has an atmospheric lifetime in excess of 3000 yr and a global warming potential (GWP) of 10 300 (100 yr time horizon), making it one of the most potent greenhouse gases detected in the atmosphere to date. The abundance of c-C4F8 in the Southern Hemisphere has risen from 0.35 ppt in 1978 to 1.2 ppt in 2010, and is currently increasing at a rate of around 0.03 ppt yr-1. It is the third most abundant perfluorocarbon (PFC) in the present day atmosphere, behind CF4 (~75 ppt) and C2F6 (~4 ppt). The origin of c-C4F8 is unclear. Using a 2-D global model to derive top-down global emissions based on the Cape Grim measurements yields a recent (2007) emission rate of around 1.1 Gg yr-1 and a cumulative emission up to and including 2007 of 38.1 Gg. Emissions reported on the EDGAR emissions database for the period 1986-2005 represent less than 1 % of the top-down emissions for the same period, which suggests there is a large unaccounted for source of this compound. It is also apparent that the magnitude of this source has varied considerably over the past 30 yr, declining sharply in the late 1980s before increasing again in the mid-1990s.

Long-term tropospheric trend of octafluorocyclobutane (c-C4F8 or PFC-318)

NASA Astrophysics Data System (ADS)

Oram, D. E.; Mani, F. S.; Laube, J. C.; Newland, M. J.; Reeves, C. E.; Sturges, W. T.; Penkett, S. A.; Brenninkmeijer, C. A. M.; Röckmann, T.; Fraser, P. J.

2012-01-01

Air samples collected at Cape Grim, Tasmania between 1978 and 2008 and during a series of more recent aircraft sampling programmes have been analysed to determine the atmospheric abundance and trend of octafluorocyclobutane (c-C4F8 or PFC-318). c-C4F8 has an atmospheric lifetime in excess of 3000 yr and a global warming potential (GWP) of 10 300 (100 yr time horizon), making it one of the most potent greenhouse gases detected in the atmosphere to date. The abundance of c-C4F8 in the Southern Hemisphere has risen from 0.35 ppt in 1978 to 1.2 ppt in 2010, and is currently increasing at a rate of around 0.03 ppt yr-1. It is the third most abundant perfluorocarbon (PFC) in the present day atmosphere, behind CF4 (~75 ppt) and C2F6 (~4 ppt). Although a number of potential sources of c-C4F8 have been reported, including the electronics and semi-conductor industries, there remains a large discrepancy in the atmospheric budget. Using a 2-D global model to derive top-down global emissions based on the Cape Grim measurements yields a recent (2007) emission rate of around 1.1 Gg yr-1 and a cumulative emission up to and including 2007 of 38.1 Gg. Emissions reported on the EDGAR emissions database for the period 1986-2005 represent less than 1% of the top-down emissions for the same period, which suggests there is a large unaccounted for source of this compound. It is also apparent that the magnitude of this source has varied considerably over the past 30 yr, declining sharply in the late 1980s before increasing again in the mid-1990s.

17 CFR 240.15c1-8 - Sales at the market.

Code of Federal Regulations, 2014 CFR

2014-04-01

... 17 Commodity and Securities Exchanges 4 2014-04-01 2014-04-01 false Sales at the market. 240.15c1-8 Section 240.15c1-8 Commodity and Securities Exchanges SECURITIES AND EXCHANGE COMMISSION... Securities Exchange Act of 1934 Rules Relating to Over-The-Counter Markets § 240.15c1-8 Sales at the market...

15 CFR 8c.3 - Definitions.

Code of Federal Regulations, 2011 CFR

2011-01-01

... more major life activities. (4) “Is regarded as having an impairment” means— (i) Has a physical or... BASIS OF HANDICAP IN PROGRAMS OR ACTIVITIES CONDUCTED BY THE DEPARTMENT OF COMMERCE § 8c.3 Definitions... skills to have an equal opportunity to participate in, and enjoy the benefits of, programs or activities...

40 CFR 180.1250 - C8, C10, and C12 fatty acid monoesters of glycerol and propylene glycol; exemption from the...

Code of Federal Regulations, 2010 CFR

2010-07-01

... 40 Protection of Environment 23 2010-07-01 2010-07-01 false C8, C10, and C12 fatty acid monoesters..., C10, and C12 fatty acid monoesters of glycerol and propylene glycol; exemption from the requirement of a tolerance. The C8, C10, and C12 straight-chain fatty acid monoesters of glycerol (glycerol...

40 CFR 180.1250 - C8, C10, and C12 fatty acid monoesters of glycerol and propylene glycol; exemption from the...

Code of Federal Regulations, 2011 CFR

2011-07-01

... 40 Protection of Environment 24 2011-07-01 2011-07-01 false C8, C10, and C12 fatty acid monoesters..., C10, and C12 fatty acid monoesters of glycerol and propylene glycol; exemption from the requirement of a tolerance. The C8, C10, and C12 straight-chain fatty acid monoesters of glycerol (glycerol...

CYP2C8 activity recovers within 96 hours after gemfibrozil dosing: estimation of CYP2C8 half-life using repaglinide as an in vivo probe.

PubMed

Backman, Janne T; Honkalammi, Johanna; Neuvonen, Mikko; Kurkinen, Kaisa J; Tornio, Aleksi; Niemi, Mikko; Neuvonen, Pertti J

2009-12-01

Gemfibrozil 1-O-beta-glucuronide is a mechanism-based inhibitor of cytochrome P450 2C8. We studied the recovery of CYP2C8 activity after discontinuation of gemfibrozil treatment using repaglinide as a probe drug, to estimate the in vivo turnover half-life of CYP2C8. In a randomized five-phase crossover study, nine healthy volunteers ingested 0.25 mg of repaglinide alone or after different time intervals after a 3-day treatment with 600 mg of gemfibrozil twice daily. The area under the plasma concentration-time curve (AUC) from time 0 to infinity of repaglinide was 7.6-, 2.9-, 1.4- and 1.0-fold compared with the control phase when it was administered 1, 24, 48, or 96 h after the last gemfibrozil dose, respectively (P < 0.001 versus control for 1, 24, and 48 h after gemfibrozil). Thus, a strong CYP2C8 inhibitory effect persisted even after gemfibrozil and gemfibrozil 1-O-beta-glucuronide concentrations had decreased to less than 1% of their maximum (24-h dosing interval). In addition, the metabolite to repaglinide AUC ratios indicated that significant (P < 0.05) inhibition of repaglinide metabolism continued up to 48 h after gemfibrozil administration. Based on the recovery of repaglinide oral clearance, the in vivo turnover half-life of CYP2C8 was estimated to average 22 +/- 6 h (mean +/- S.D.). In summary, CYP2C8 activity is recovered gradually during days 1 to 4 after gemfibrozil discontinuation, which should be considered when CYP2C8 substrate dosing is planned. The estimated CYP2C8 half-life will be useful for in vitro-in vivo extrapolations of drug-drug interactions involving induction or mechanism-based inhibition of CYP2C8.

One year in review 2016: Behçet's syndrome.

PubMed

Hatemi, Gulen; Seyahi, Emire; Fresko, Izzet; Talarico, Rosaria; Hamuryudan, Vedat

2016-01-01

Several articles highlighting the epidemiology, pathogenesis, clinical features, treatment modalities and disease assessment of Behçet's syndrome (BS) have been published during the last year. Clinical and radiological features of lower extremity deep vein thrombosis due to BS can be quite different than those found in thrombosis due to other causes; additionally, frequency of post-thrombotic syndrome is significantly increased in BS. Some clinical and colonoscopic features are useful in differentiating BS from Crohn's disease. Barkhof criteria may be helpful in differentiating neurologic involvement due to BS from multiple sclerosis. Anatomical localization of papulopustular lesions but not histology has been found to be helpful in differentiating papulopustular lesions of BS from those found in acne vulgaris. Several studies looked at the ovarian reserve with contradicting results. A population-based cohort study found higher risk of hematological malignancies only among female BS patients living in Taiwan. The role of genetic factors and environment is discussed and both autoimmune and autoinflammatory features are underlined in the pathogenesis of BS. New data on the epistatic interactions between ERAP and HLA B51 is available and information on the microbiome have started to appear. New uncontrolled data suggest beneficial effects of anti-TNFs for refractory extra-ocular complications of BS such as pulmonary artery, gastrointestinal and central nervous system involvement. Uncontrolled studies suggest promising results with interleukin-1 inhibition but gevokizumab, a humanised anti IL-1β antibody, failed to meet the primary endpoint of time to first ocular exacerbation in a phase III trial. The debate on anticoagulation continues with new observational data.

Azathioprine in severe uveitis of Behçet's disease.

PubMed

Saadoun, D; Wechsler, B; Terrada, C; Hajage, D; Le Thi Huong, D; Resche-Rigon, M; Cassoux, N; Le Hoang, P; Amoura, Z; Bodaghi, B; Cacoub, P

2010-12-01

To investigate the efficacy and tolerance of azathioprine in severe uveitis related to Behçet's disease (BD). We reported 157 consecutive patients with severe uveitis (active posterior uveitis or panuveitis) fulfilling the international criteria for BD and treated with corticosteroids (0.5-1 mg/kg/day) and azathioprine (2.5 mg/kg/day). Long-term outcome and factors associated with complete remission were assessed. Mean±SD age at diagnosis was 29.9±10.1 years, with 71.3% men. At baseline, 59 patients (37.6%) had loss of useful vision, 54 (34.4%) had retinal vasculitis, 66 (42.0%) had panuveitis, and 132 (84.1%) had bilateral uveitis. Following azathioprine therapy, 81 patients (51.6%) were complete responders, 65 (41.4%) were partial responders, and 11 (7%) were nonresponders. The visual acuity significantly improved (P<0.001), and a significant decrease in the mean oral prednisone dosage (55.3 to 10.5 mg/day; P<0.001) was observed after therapy. Patients with retinal vasculitis (odds ratio [OR] 0.45 [95% confidence interval (95% CI) 0.2-0.9], P=0.02) and severe visual loss (OR 0.28 [95% CI 0.2-0.7], P<0.0001) at diagnosis were less likely to be complete responders. Azathioprine was well tolerated, with only 3 withdrawals due to hepatotoxic effects (n=2) and bacterial septicemia (n=1). Azathioprine represents an effective and safe therapy in patients with severe uveitis of BD. Copyright © 2010 by the American College of Rheumatology.

Characterization of [8-ethyl]-chlorophyll c3 from Emiliania huxleyi.

PubMed

Álvarez, Susana; Zapata, Manuel; Garrido, José L; Vaz, Belén

2012-06-04

We report herein the isolation and complete characterization of a member of the chlorophyll c family, designated as [8-ethyl]-chlorophyll c(3) ([8-ethyl]-chl c(3)). Structural elucidation of this pigment rested on the analysis of mono- and bidimensional NMR, UV-VIS spectroscopy and ESI-MS data, and the configuration at the 13(2) position on chiral HPLC analysis.

[Simultaneous determination of ten major compounds including iridoid glycosides and phenolic acids in Pterocephalus hookeri by UPLC-PDA].

PubMed

Tang, Ce; Wen, Jian; Wang, Jing; Zhao, Ke-Hui; Fan, Gang; Meng, Xian-Li; Zou, Zhong-Mei; Zhang, Yi

2017-04-01

This study is to develop an UPLC-PDA method for determination of 10 major components in Pterocephalus. The UPLC-PDA assay was performed on a Waters Acquity UPLCR BEH C₁₈（2.1 mm ×100 mm,1.7 μm）, and the column temperature was at 30 ℃. The mobile phase consists of water containing 0.2% phosphoric acid (A) and acetonitrile (B) in gradient elution at a flow rate of 0.4 mL•min⁻¹. The detection wave length was set at 237 and 325 nm, and the injection volume was 1 μL in the UPLC system. The linear range of 10 detected compounds were good (r≥0.999 7), and the overall recoveries ranged from 96.30% to 103.0%, with the RSD ranging from 0.72% to 2.9%. The method was simple, accurate and reproducible, which can be used for the simultaneous determination of the content of ten major components in P. hookeri. Copyright© by the Chinese Pharmaceutical Association.

[Analysis of picric acid and picramic acid in water samples by ultra performance hydrophilic interaction chromatography-tandem mass spectrometry].

PubMed

Qian, Feizhong; Zhu, Libo; Xu, Nengbin; Feng, Jiayong; Hong, Zhengfang; Xu, Lihong; Chen, Zhongquan; Wang, Shengle

2014-05-01

An ultra performance liquid chromatography/tandem mass spectrometry (UPLC-MS/ MS) method was developed for the determination of picric acid and its reductive transformation product picramic acid in aqueous samples. A hydrophilic interaction liquid chromatography (HILIC) column (Acquity UPLC BEH HILIC; 100 mm x 2.1 mm, 1.7 microm) was used for the separation. Surface water samples could be injected into the UPLC system just after being filtered through a 0.2 microm membrane. The satisfactory recoveries of picric acid and picramic acid were in the range of 89% - 107%. Waste water samples were purified by solid phase extraction (SPE), and then were analyzed. The recoveries of picric acid and picramic acid in waste water were 72%-101%. The reproducibility of the method was good with the RSDs of 4.9% - 14.7%. The limits of detection (LODs) of picric acid and picramic acid were 0.1 microg/L and 0.3 microg/L, respectively. This proposed method is rapid, highly specific and suitable for the confirmation and quantitative determination of picric acid and picramic acid in surface water and waste water.

15N nuclear magnetic resonance studies on the tautomerism of 8-hydroxy-2'-deoxyguanosine, 8-hydroxyguanosine, and other C8-substituted guanine nucleosides.

PubMed

Cho, B P; Kadlubar, F F; Culp, S J; Evans, F E

1990-01-01

The favored tautomeric and ionic structures were examined for the oxidative DNA damage adduct 8-hydroxy-2'-deoxyguanosine and its RNA analogue 8-hydroxyguanosine by 15N NMR spectroscopy. In addition, 15N chemical shifts and coupling constants from 13 different guanine nucleosides, including a wide variety of C8 substitutions (OH, SH, Br, OCH2C6H5, OCH3, SCH3, and SO2CH3), have been analyzed with respect to their tautomeric structures. A -98.5-Hz proton-nitrogen coupling constant observed for the N7 resonance of 8-hydroxyguanosine in dimethyl sulfoxide was evidence for 8-keto substitution, which is contrary to the structure implied by the generally used nomenclature. The pH dependence of 15N NMR spectra of 8-hydroxyguanosine in aqueous solution showed downfield shifts of the N1 and N7 resonances that were greater than 50 ppm, which indicated the conversion from a neutral 6,8-diketo to a 6-enolate-8-keto (pKa1 = 8.6) and finally to a 6,8-dienolate structure (pKa2 = 11.7). There was no evidence of an 8-enol substituent in the absence of ionization. It is proposed that the syn conformation of these oxidized bases in duplex DNA and RNA can be further stabilized by abnormal hydrogen bonding or mispairing that involves N7-H. The combined data show that 15N NMR is a sensitive probe to examine tautomerism of the guanine ring system. The analysis indicates that the change from a single to a double bond for the C8 substituent, and the accompanying removal of the normal double bond between N7 and C8 on the imidazole ring system, has no detectable effect on the tautomerism at the N1-O6 site of the pyrimidine ring system for both the 8-keto and 8-thio substitutions. In addition, large differences in electronegativity of the C8 substituents do not alter the N1-O6 tautomerism.

Subdural hematoma in infants without accidental or nonaccidental injury: benign external hydrocephalus, a risk factor.

PubMed

Ghosh, Partha S; Ghosh, Debabrata

2011-10-01

Benign external hydrocephalus (BEH) is considered a self-limiting condition in infants. Subdural hematoma (SDH) in infants without a history of trauma indicates nonaccidental injury (NAI). The authors studied whether SDH can complicate BEH without apparent trauma. Out of 45 children younger than 3 years with nontraumatic SDH, 9 (7 boys) with mean age 6 months had BEH as risk factor. Symptoms included increasing head size (8), fussiness, and irritability (3). Three had up-gaze restriction, 1 axial hypotonia, and 6 normal examination. Neuroimaging showed prominent extra-axial spaces; SDH was bilateral (6), subacute (5). Other etiological workup for SDH was negative except NAI in 1. Two required evacuation of SDH and subdural-peritoneal shunt; others managed conservatively. Development was normal in 8 on follow-up. On follow-up imaging of 8, SDH completely resolved in 3, markedly reduced in 3, and remained stable in 2. BEH is a risk factor for SDH in infants, thus not always benign.

Transcatheter aortic valve-in-valve implantation for severe bioprosthetic stenosis after Bentall operation using a homograft in a patient with Behçet's disease.

PubMed

Joo, Hyung Joon; Hong, Soon Jun; Yu, Cheol Woong

2015-03-01

A 43-year-old man presented with severe aortic stenosis. Eight years previously, he had undergone primary surgical aortic valve replacement (AVR) for severe aortic regurgitation, but one year later developed cardiac arrest and complete atrioventricular block as a result of non-bacterial thrombotic endocarditis with severe valvular dehiscence. Following the diagnosis of prosthetic valve failure caused by Behçet's disease, the patient underwent a Bentall operation using 23 mm aortic homograft with permanent pacemaker implantation and coronary artery bypass grafting. Subsequently, he was stable with steroid administration and azathioprine for seven years after the second operation, but recently suffered from severe dyspnea and chest pain. Echocardiography revealed the development of severe aortic stenosis. A preprocedural evaluation demonstrated a porcelain aorta with severe calcification in the previous homograft valve on computed tomography, and critical stenosis at the ostium of the left circumflex artery on coronary angiography. After percutaneous coronary intervention for the ostium of the left circumflex artery, a transcatheter AVR was successfully performed using a 26 mm Edwards SAPIEN XT valve. The patient recovered without any complications after the procedure. This is the first report of a successful transcatheter aortic valve-in valve implantation for severe homograft aortic stenosis after a Bentall operation, using a homograft, in a patient with Behçet's disease.

The recovery of bladder epithelial hyperplasia caused by a melamine diet-induced bladder calculus in mice.

PubMed

Sun, Ying; Jiang, Yi-Na; Xu, Chang-Fu; Du, Yun-Xia; Zhang, Jiao-Jiao; Yan, Yang; Gao, Xiao-Li

2014-02-01

Applying a model of bladder epithelial hyperplasia (BEH) caused by melamine-induced bladder calculus (BC), the recovery of BEH after melamine withdrawal was investigated. One experiment, comprising untreated, melamine and recovery groups, was conducted in Balb/c mice. Each group included 4 subgroups. Mice were fed normal-diet in untreated or a melamine-diet in other groups. The melamine-diet was then substituted with normal-diet in recovery group. Both of BC and BEH were observed after 14 and 56 days of melamine-diet. The BC is relatively uniform at the same melamine-diet durations. The BEH was diffuse with many mitotic figures, 4-7 rows of nuclei, and well-defined umbrella/intermediate cells. No marked differences in BEH degree were observed in the two different melamine-diet durations. On 4-42 days after melamine withdrawal, BC was not found, as the progressive regression with complete regression of BEH was observed, along with well-defined ageing/apoptotic cells in the superficial regions of BEH regression tissue. Conclusion, the melamine-induced BEH is relatively uniform, may be self-limiting in rows of nuclei, and can return to normal. Melamine withdrawal duration is critical for the BEH regression. Tissue of the BEH and its regression is ideal for exploring the renewal as well as growth biology of mammalian urothelium. Crown Copyright © 2013. Published by Elsevier Ltd. All rights reserved.

Electron scattering by the hydrocarbons C4H6,C5H8 , and C6H10

NASA Astrophysics Data System (ADS)

Kiataki, Matheus B.; Pastega, Diego F.; Bettega, Márcio H. F.

2017-10-01

We report calculated elastic integral and differential cross sections for electron collisions with the hydrocarbons 1,3-butadiene (C4H6 ), 2-methyl-1,3-butadiene (C5H8 ), and 2,3-dimethyl-1,3-butadiene (C6H10 ) for impact energies up to 15 eV. Our calculations were performed with the Schwinger Multichannel Method with pseudopotentials, in the static-exchange and static-exchange plus polarization approximations. These molecules differ for the presence of one methyl group, in the case of C5H8 , and two methyl groups, in the case of C6H10 in substitution of one and two hydrogen atoms in C4H6 , respectively (methylation effect). For the polar molecule 2-methyl-1,3-butadiene, we included the Born closure procedure in order to account for the long-range potential. We found two π* shape resonances in the integral cross section of each one of the molecules studied. The present results are also compared with the experimental values for the resonances positions and with total cross sections available in the literature. In particular, we show that the minimum in the total cross section of C5H8 located at around 1.6 eV and assigned by the authors as a Ramsauer-Townsend minimum is, actually, a valley between the two π* shape resonances. Also for the C5H8 molecule, the enhancement in the total cross section below 1.6 eV is the tail of the low-lying shape resonance and not an effect due to its permanent dipole moment, as suggested by the authors. We discuss the influence of the methylation effect in the shape and magnitude of the elastic cross sections and also in the location of the π* shape resonances of these hydrocarbons.

Tratamento endovascular de aneurisma de aorta abdominal com erosão de vértebra lombar associada à doença de Behçet: relato de caso

PubMed Central

de Souza, Nathalia Leslie Albanez Rodrigues; Siqueira, Daniel Emílio Dalledone; Cantador, Alex Aparecido; Rossetti, Leandro Pablos; Molinari, Giovani José Dal Poggetto; Guillaumon, Ana Terezinha

2017-01-01

Resumo A doença de Behçet é uma doença sistêmica, multifatorial e autoimune com diversas manifestações clínicas, entre elas o acometimento vascular. Aneurisma de aorta associado a erosão de vértebra lombar é condição rara na literatura, existindo apenas quatro relatos de caso nas bases de dados da PubMed. O presente artigo relata o caso de paciente do sexo feminino com diagnóstico de Doença de Behçet de longa data e aneurisma sacular de aorta abdominal infrarrenal com erosão de vértebra lombar. O caso foi tratado por meio de técnica endovascular com colocação de endoprótese monoilíaca e enxerto fêmoro-femoral cruzado, devido a limitações anatômicas da bifurcação aórtica. O artigo aborda a raridade desse tipo de apresentação da doença e o desfecho do tratamento e apresenta revisão da literatura sobre esse tema. PMID:29930640

X-Ray study of hetero ring flexibility in norbornane, norbornene-fused 1,3-oxazin-2-thiones Structure of 5,8-methano- r-4-phenyl-c-4a, c-5,6,7, c-8, c- 8a-hexahydro-4H- 1 ,3-benzoxazin-2 (3H)-thione

NASA Astrophysics Data System (ADS)

Kálmán, A.; Argay, Gy.; Stájer, G.; Bernáth, G.

1991-08-01

The structure of S,8-methano- r-4-phenyl c4a, c5,6,7 c8 c8ahexahydro4 H 1,3 -benzoxazin- 2 (3 H)-thione (C 15H 17N0S, M r=259.37) has been established by X-ray crystallography from diffractometer data: it crystallizes in the monoclinic space group P2 1/n with a=6.150(2) Å, b=9.655(1) Å, c=22.093(4) Å,β=96.75(2)† V=1302.7(8) Å 3,4,D c=1.32gcm -3and p( Cu K) =20.4cm -. The structure has been solved by direct methods, refined to R=0.050 for 2193 observed reflections. The X-ray analysis substantiated the structure: the NMR spectra in- dicated that the 4-phenyl group assumes an exo-equatorial position. The puckering parameters of D. Cremer, J.A. Pople, J. Am. Chem. Soc., 97 (1975), 1354 (ref.1), of the distorted hetero ring (a transitional form between E 4-envelope, ( 5S 4-screw-boat) show that, depending on the positions of the hetero atoms, both the norbornane, norbornene skeletons markedly alter the characteristic transitional ( 5E/ 5H 6) shape of the 1,3-oxazine ring observed in other saturated, partly saturated l,3-benzoxazin-2-ones, analogous thiones.

Medullary ischemia due to vertebral arteritis associated with Behçet syndrome: a case report.

PubMed

Kaido, Takanobu; Otsuki, Taisuke; Ogawa, Masafumi; Takahashi, Akio; Kaneko, Yuu; Yamamoto, Toshiyuki; Nakata, Yasuhiro

2012-09-01

Here we report an extremely rare case of Behçet syndrome (BS) that showed acute onset of Wallenberg syndrome and was treated successfully by corticosteroids. A 51-year-old woman with BS had a sudden onset of Wallenberg syndrome. Three days after the onset, she was transferred to our institute. In the magnetic resonance imaging (MRI) study on admission, T2-weighted and fluid-attenuated inversion recovery images showed a high intensity area in the left paramedian region of the medulla oblongata. Contrast-enhanced T1-weighted images showed enhancement in the vessel wall of the left vertebral artery. We diagnosed her as having Wallenberg syndrome due to the acute vertebral arteritis associated with BS. After initiation of high-dose steroid therapy, her symptoms gradually improved. Two months after admission, she was discharged from our institute with mild hemihypesthesia. We hypothesized that vertebral arteritis due to BS had caused hypoperfusion of the medullary perforators causing Wallenberg syndrome in our patient.

Development and validation of a UHPLC-MS/MS method for simultaneous quantitation the plasma concentration of Sabarubicin and its alcohol metabolite M3 in Chinese small cell lung cancer patients.

PubMed

Zhang, Yan; Liu, Peng; Li, Ning; Wu, Di; Feng, Yun; Song, Yuanyuan; Shi, Yuankai; Han, Xiaohong

2016-07-01

To support a novel anthracycline agent - Sabarubicin's pharmacokinetics study in Chinese small cell lung cancer patients, a rapid, sensitive, and high throughput ultra-performance liquid chromatography tandem mass spectrometry method using Doxorubicin hydrochloride as internal standard (IS) was developed and validated for simultaneously quantifying Sabarubicin and its alcohol metabolite M3 in human plasma. Plasma samples were pre-extracted with n-hexane to remove hydrophobic interferences and the target compounds were extracted into a 1ml mixture of chloroform and isopropanol (1:1, v/v) and separated on an ACQUITY UPLC BEH Shield RP18 (100mm×2.1mm, 1.7μm) column with gradient mobile phase composed of acetonitrile and water containing 0.1% formic acid. Detection was performed by electrospray ionization in the positive ionization mode under multiple reaction monitoring of the transitions at m/z 644→130 for Sabarubicin, m/z 646→333.2 for M3, and m/z 544→360 for IS. For Sabarubicin and M3, calibration curves over 2-400ng/ml and 0.5-100ng/ml could achieve excellent linearity respectively(r>0.99). Intra- and inter-day precisions were 1.5%-9.1% and 2.2%-12.8%, and accuracy were -9.6% to 0.7% and -4.8% to 5.9% for Sabarubicin and M3 respectively at four concentration levels. The mean recovery for Sabarubicin was 62.4%, 71.9% for M3, and 58.8% for IS. This method was completely validated and successfully applied in the pharmacokinetics study of Sabarubicin and M3 in Chinese small cell lung cancer patients. Copyright © 2016 Elsevier B.V. All rights reserved.

Molecular structure of Ti8C12 and related complexes.

PubMed Central

Pauling, L

1992-01-01

Application of valence-bond theory leads to the assignment to the molecule Ti8C12 of a cubic structure, point group Ohm3m, with 8 Ti at the cube corners, +/-(x x x, x, x x [symbol, see text]) where x = 1.78 A, and with 12 C in pairs in the cube faces, +/-(0 y z, [symbol, see text], 0, y z [symbol, see text]) where y = 1.78 A and z = 0.71 A. The Ti-C and C-C bonds have bond number 4/3, corresponding to resonance of single and double bonds in 2:1 ratio. PMID:11607323

Ethnicity and association with disease manifestations and mortality in Behçet’s disease

PubMed Central

2014-01-01

Background Behçet’s disease (BD) significantly increases morbidity and mortality. BD mainly affects young adults with a peculiar geographical distribution. It has been suggested that BD varies in its phenotypic expression in different ethnic groups. Methods We investigated potential ethnicity-related differences relative to phenotype and prognosis of BD patients in a French multiethnic country. We included 769 consecutive patients fulfilling the international criteria of classification for BD, in the 3 largest ethnic groups of our cohort [European (n = 369), North African (n = 350) and sub Saharan African (n = 50)]. Factors that affect prognosis were assessed by multivariate analysis. Results 535 (69.6%) patients were male and the median (IQR) age at diagnosis was of 30.9 (24.9-37.2) years. Sub Saharan African BD patients had a higher frequency of CNS involvement (48% vs 32.3% vs 29.5%, p = 0 .035), a higher rate of death (12% vs 6% vs 3.5%, p = 0.029) and a lower frequency of HLA B51 allele (29.4% vs 49.2% vs 55.8%, p = 0.009) compared to those from North Africa and Europe, respectively. Multivariate analysis showed that male gender (HR: 5.01, CI: 1.51-16.65), cardiovascular involvement (HR: 2.24, CI: 1.15-4.36), and sub Saharan African origin (HR 2.62 (0.98-6.97) were independently associated with mortality. The 15-year mortality rate was of 19%, 9% and 6% in sub Saharan African, North African and European BD patients, respectively (p = 0.015). Conclusion We reported ethnicity-related differences with respect to phenotype of BD. Sub Saharan Africans patients exhibited a worse prognosis. PMID:24674137

Risk factors and outcomes of acute lower gastrointestinal bleeding in intestinal Behçet's disease.

PubMed

Park, Jihye; Cheon, Jae Hee; Park, Yong Eun; Lee, Yoon Jee; Lee, Hyun Jung; Park, Soo Jung; Hong, Sung Pil; Kim, Tae Il; Kim, Won Ho

2017-05-01

Intestinal Behçet's disease (BD) can cause acute lower gastrointestinal bleeding, which is sometimes fatal. We aimed to identify the risk factors and outcomes of acute lower gastrointestinal bleeding and factors associated with rebleeding in intestinal BD patients. Of the total of 588 intestinal BD patients, we retrospectively reviewed the medical records of 66 (11.2%) patients with acute lower gastrointestinal bleeding and compared them with those of 132 matched patients without bleeding. The baseline characteristics were comparable between the bleeding group (n = 66) and the non-bleeding group (n = 132). On multivariate analysis, the independent factors significantly associated with lower gastrointestinal bleeding were older age (>52 years) (hazard ratio [HR] 2.2, 95% confidence interval [CI] 1.058-4.684, p = 0.035) and a nodular ulcer margin (HR 7.1, 95% CI 2.084-24.189, p = 0.002). Rebleeding occurred in 23 patients (34.8%). Female patients (p = 0.044) and those with previous use of corticosteroids or azathioprine (p = 0.034) were more likely to develop rebleeding. On multivariate analysis, only use of steroids or azathioprine was significantly associated with rebleeding (HR 3.2, 95% CI 1.070-9.462, p = 0.037). Age >52 years and the presence of a nodular margin of the ulcer were found to be related to increased risk of bleeding in patients with intestinal BD. Rebleeding is not uncommon and not effectively prevented with currently available medications. Further studies are warranted to identify effective measures to decrease rebleeding in intestinal BD.

Biological treatments in Behçet's disease: beyond anti-TNF therapy.

PubMed

Caso, Francesco; Costa, Luisa; Rigante, Donato; Lucherini, Orso Maria; Caso, Paolo; Bascherini, Vittoria; Frediani, Bruno; Cimaz, Rolando; Marrani, Edoardo; Nieves-Martín, Laura; Atteno, Mariangela; Raffaele, Carmela G L; Tarantino, Giusyda; Galeazzi, Mauro; Punzi, Leonardo; Cantarini, Luca

2014-01-01

Behçet's disease (BD) is universally recognized as a multisystemic inflammatory disease of unknown etiology with chronic course and unpredictable exacerbations: its clinical spectrum varies from pure vasculitic manifestations with thrombotic complications to protean inflammatory involvement of multiple organs and tissues. Treatment has been revolutionized by the progressed knowledge in the pathogenetic mechanisms of BD, involving dysfunction and oversecretion of multiple proinflammatory molecules, chiefly tumor necrosis factor- (TNF-) α, interleukin- (IL-) 1β, and IL-6. However, although biological treatment with anti-TNF-α agents has been largely demonstrated to be effective in BD, not all patients are definite responders, and this beneficial response might drop off over time. Therefore, additional therapies for a subset of refractory patients with BD are inevitably needed. Different agents targeting various cytokines and their receptors or cell surface molecules have been studied: the IL-1 receptor has been targeted by anakinra, the IL-1 by canakinumab and gevokizumab, the IL-6 receptor by tocilizumab, the IL12/23 receptor by ustekinumab, and the B-lymphocyte antigen CD-20 by rituximab. The aim of this review is to summarize all current experiences and the most recent evidence regarding these novel approaches with biological drugs other than TNF-α blockers in BD, providing a valuable addition to the actually available therapeutic armamentarium.

Determination of itraconazole and its photodegradation products with kinetic evaluation by ultra-performance liquid chromatography/tandem mass spectrometry.

PubMed

Kryczyk, Agata; Żmudzki, Paweł; Hubicka, Urszula

2016-11-01

A simple and reproducible UPLC-MS/MS method for the determination of itraconazole (ITZ) and its photodegradation products formed during exposure to UV-A radiation was developed. Chromatographic separations were carried out using an Acquity UPLC BEH C 18 column (2.1 × 100 mm, 1.7 μm particle size). The column was maintained at 40°C, and eluted under gradient conditions from 100% to 50% of eluent A over 13 min, at a flow rate of 0.3 mL min -1 . Eluent A was 0.1% (v/v) formic acid in water; eluent B was 0.1% (v/v) formic acid in acetonitrile. The linear regression analysis for the calibration curve showed a good linear correlation over the concentration range 0.0066-0.15 mg mL -1 with determination coefficient > 0.99. The activities of some photocatalysts during degradation process of ITZ were compared. It was found that indirect photodegradation of ITZ was more effective than direct photolysis. Under our experimental conditions the photodegradation rate constant depended on the applied catalysts with catalytic activity decreasing in the following pattern: FeCl 3  > TiO 2 /FeCl 3  > TiO 2 . The kinetic analysis of the photodegradation data revealed that the degradation of the ITZ follows first-order kinetics. The photodegradation products of ITZ were identified, and their fragmentation pathways, derived from MS/MS data, were proposed. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

75 FR 8796 - Civil Penalties Under ERISA Section 502(c)(8)

Federal Register 2010, 2011, 2012, 2013, 2014

2010-02-26

...-AB31 Civil Penalties Under ERISA Section 502(c)(8) AGENCY: Employee Benefits Security Administration... procedures relating to the assessment of civil penalties by the Department of Labor under section 502(c)(8...). However, section 102(b)(1)(C) of the Worker, Retiree, and Employer Recovery Act of 2008, Public Law 110...

Ultra-high Performance Liquid Chromatography Tandem Mass-Spectrometry for Simple and Simultaneous Quantification of Cannabinoids

PubMed Central

Jamwal, Rohitash; Topletz, Ariel R.; Ramratnam, Bharat; Akhlaghi, Fatemeh

2017-01-01

Cannabis is used widely in the United States, both recreationally and for medical purposes. Current methods for analysis of cannabinoids in human biological specimens rely on complex extraction process and lengthy analysis time. We established a rapid and simple assay for quantification of Δ9-tetrahydrocannabinol (THC), cannabidiol (CBD), 11-hydroxy Δ9-tetrahydrocannabinol (11-OH THC) and 11-nor-9-carboxy-Δ9-tetrahydrocannbinol (THC-COOH) in human plasma by U-HPLC-MS/MS using Δ9-tetrahydrocannabinol-D3 as the internal standard. Chromatographic separation was achieved on an Acquity BEH C18 column using a gradient comprising of water (0.1% formic acid) and methanol (0.1% formic acid) over a 6 min run-time. Analytes from 200 µL plasma were extracted using acetonitrile (containing 1% formic acid and THC-D3). Mass spectrometry was performed in positive ionization mode, and total ion chromatogram was used for quantification of analytes. The assay was validated according to guidelines set forth by Food and Drug Administration of United States. An eight-point calibration curve was fitted with quadratic regression (r2>0.99) from 1.56 to 100 ng mL−1 and a lower limit of quantification (LLOQ) of 1.56 ng mL−1 was achieved. Accuracy and precision calculated from six calibration curves was between 85 to 115% while the mean extraction recovery was >90% for all the analytes. Several plasma phospholipids eluted after the analytes thus did not interfere with the assay. Bench-top, freeze-thaw, auto-sampler and short-term stability ranged from 92.7 to 106.8% of nominal values. Application of the method was evaluated by quantification of analytes in human plasma from six subjects. PMID:28192758

40 CFR Appendix 8 to Subpart A of... - Reference C16-C18 Internal Olefin Drilling Fluid Formulation

Code of Federal Regulations, 2014 CFR

2014-07-01

... Drilling Fluid Formulation 8 Appendix 8 to Subpart A of Part 435 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) EFFLUENT GUIDELINES AND STANDARDS (CONTINUED) OIL AND GAS EXTRACTION POINT...—Reference C16-C18 Internal Olefin Drilling Fluid Formulation The reference C16-C18 internal olefin drilling...

40 CFR Appendix 8 to Subpart A of... - Reference C16-C18 Internal Olefin Drilling Fluid Formulation

Code of Federal Regulations, 2012 CFR

2012-07-01

... Drilling Fluid Formulation 8 Appendix 8 to Subpart A of Part 435 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) EFFLUENT GUIDELINES AND STANDARDS (CONTINUED) OIL AND GAS EXTRACTION POINT...—Reference C16-C18 Internal Olefin Drilling Fluid Formulation The reference C16-C18 internal olefin drilling...

40 CFR Appendix 8 to Subpart A of... - Reference C16-C18 Internal Olefin Drilling Fluid Formulation

Code of Federal Regulations, 2013 CFR

2013-07-01

... Drilling Fluid Formulation 8 Appendix 8 to Subpart A of Part 435 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) EFFLUENT GUIDELINES AND STANDARDS (CONTINUED) OIL AND GAS EXTRACTION POINT...—Reference C16-C18 Internal Olefin Drilling Fluid Formulation The reference C16-C18 internal olefin drilling...

Decomposed Fragment Identification in C_8F_18 RF Plasma for a-C:F Film Production

NASA Astrophysics Data System (ADS)

Sakai, Yosuke; Tazawa, Shota; Bratescu, Maria; Suda, Yoshiyuki; Sugawara, Hirotake

2004-09-01

Amorphous fluorocarbon polymer (a-C:F) film shows excellent insulation properties such as low dielectric constant (<2.5), high dielectric strength (>2 MV/cm), low surface energy, and chemical inertness. Therefore, we have studied this film for a purpose of an additional insulator to enhance the breakdown voltage in an alternative to a SF6 gas insulation system. The films are prepared using a C_8F_18 vapor RF plasma. When per-fluorocarbon, such as C_8F_18 as source gases, then the deposition rate becomes roughly two orders of magnitude higher than that obtained from conventional low molecular-weight source monomers (CF_4, C_2F_6, C_3F_6, and C_4F_8) [1]. The breakdown voltage (V_s) of N_2, Ar and He gases between the a-C:F film coated Al sphere-sphere electrodes for a gas pressure (p) times gap length (d), pd=0.1-100 Torr¥cm, was studied as well. Then, Vs between the a-C:F film coated electrodes was a several times higher than that between the Al electrodes in the present pd range[2]. In this work, the decomposed species of C_8F_18 in the plasma were identified using emission spectra from the plasma and Quadra-pole mass spectrograph, and the reason why the high deposition rate was obtained was discussed. The physical and chemical properties of a-C:F film was analyzed. [1] C.P.Lungu, et.al., Jpn. J. Appl. Phys. 38 (12B) L1544 - L1546 (1999) [2] C.Biloiu, et.al., Jpn. J. Appl. Phys. 42 (2B) L 201- L203 (2003) Work supported by Grant-in-Aid for Scientific Research (B), JSPS.

Detection of 22 antiepileptic drugs by ultra-performance liquid chromatography coupled with tandem mass spectrometry applicable to routine therapeutic drug monitoring.

PubMed

Shibata, Mai; Hashi, Sachiyo; Nakanishi, Haruka; Masuda, Satohiro; Katsura, Toshiya; Yano, Ikuko

2012-12-01

The purpose of this study was to develop an ultra-performance liquid chromatography tandem mass spectrometry (UPLC-MS/MS) method of 22 antiepileptics for routine therapeutic monitoring. The antiepileptics used in the analyses were carbamazepine, carbamazepine-10,11-epoxide, clobazam, N-desmethylclobazam, clonazepam, diazepam, N-desmethyldiazepam, ethosuximide, felbamate, gabapentin, lamotrigine, levetiracetam, N-desmethylmesuximide, nitrazepam, phenobarbital, phenytoin, primidone, tiagabine, topiramate, valproic acid, vigabatrin and zonisamide. After protein precipitation of 50 μL plasma with methanol, the supernatant was diluted with water or was evaporated to dryness and reconstituted with mobile phase in the case of benzodiazepines. Separation was achieved on an Acquity UPLC BEH C₁₈ column with a gradient mobile phase of 10 mm ammonium acetate containing 0.1% formic acid and methanol at a flow rate of 0.4 mL/min. An Acquity TQD instrument in multiple reaction monitoring mode with ion mode switching was used for detection. All antiepileptics were detected and quantified within 10 min, with no endogenous interference. All the calibration curves showed good linearity in the therapeutic range (r²  < 0.99). The precision and accuracy values for intra- and inter-assays were within ±15% except for phenobarbital and tiagabine. A good correlation was observed between the concentration of clinical samples measured by the new method described here and the conventional methods. The values of carbamazepine and phenytoin by UPLC-MS/MS were lower than those detected by the immunoassays, which might be caused by the cross-reaction of antibodies with their metabolites. In conclusion, we developed a simple and selective UPLC-MS/MS method suitable for routine therapeutic monitoring of antiepileptics. Copyright © 2012 John Wiley & Sons, Ltd.

Muscle, skin and core temperature after -110°c cold air and 8°c water treatment.

PubMed

Costello, Joseph Thomas; Culligan, Kevin; Selfe, James; Donnelly, Alan Edward

2012-01-01

The aim of this investigation was to elucidate the reductions in muscle, skin and core temperature following exposure to -110°C whole body cryotherapy (WBC), and compare these to 8°C cold water immersion (CWI). Twenty active male subjects were randomly assigned to a 4-min exposure of WBC or CWI. A minimum of 7 days later subjects were exposed to the other treatment. Muscle temperature in the right vastus lateralis (n=10); thigh skin (average, maximum and minimum) and rectal temperature (n=10) were recorded before and 60 min after treatment. The greatest reduction (P<0.05) in muscle (mean ± SD; 1 cm: WBC, 1.6 ± 1.2°C; CWI, 2.0 ± 1.0°C; 2 cm: WBC, 1.2 ± 0.7°C; CWI, 1.7 ± 0.9°C; 3 cm: WBC, 1.6 ± 0.6°C; CWI, 1.7 ± 0.5°C) and rectal temperature (WBC, 0.3 ± 0.2°C; CWI, 0.4 ± 0.2°C) were observed 60 min after treatment. The largest reductions in average (WBC, 12.1 ± 1.0°C; CWI, 8.4 ± 0.7°C), minimum (WBC, 13.2 ± 1.4°C; CWI, 8.7 ± 0.7°C) and maximum (WBC, 8.8 ± 2.0°C; CWI, 7.2 ± 1.9°C) skin temperature occurred immediately after both CWI and WBC (P<0.05). Skin temperature was significantly lower (P<0.05) immediately after WBC compared to CWI. The present study demonstrates that a single WBC exposure decreases muscle and core temperature to a similar level of those experienced after CWI. Although both treatments significantly reduced skin temperature, WBC elicited a greater decrease compared to CWI. These data may provide information to clinicians and researchers attempting to optimise WBC and CWI protocols in a clinical or sporting setting.

The origin of Behçet's disease geoepidemiology: possible role of a dual microbial-driven genetic selection.

PubMed

Piga, Matteo; Mathieu, Alessandro

2014-01-01

It is recognised that the genetic profiles that give rise to chronic inflammatory diseases, under the influence of environmental agents, might have been implicated in the host defence mechanism against lethal infections in the past. Behçet's disease (BD) is an immune-mediated inflammatory disease, expressed as vasculitis, triggered by environmental factors in genetically susceptible individuals. We carried out a review of published data to draw up an evolutionary adaptation model, as Author's perspective, for genetic susceptibility factors and inflammatory immune response involved in BD pathogenesis. Two lethal infectious agents, Plasmodium Falciparum and Yersinia Pestis, are proposed as the putative driving forces that favoured the fixing of the major genetic susceptibility factors to BD, thus determining its geoepidemiology. Further studies are needed to confirm the validity of this evolutionary model which includes and integrates the key insights of previous hypotheses.

Isothermal fatigue behavior of a (90)(sub 8) SiC/Ti-15-3 composite at 426 C

NASA Technical Reports Server (NTRS)

Gayda, John; Gabb, Timothy P.

1991-01-01

The transverse fatigue behavior of a unidirectional, SiC/Ti-15-3 composite (35 v/o SiC, (90)(sub 8)) was evaluated at 426 C. The fatigue behavior of the composite along the fiber direction (0)(sub 8) and of unreinforced Ti-15-3 alloy were also studied for comparison purposes. The (90)(sub 8) composite fatigue life was much shorter then (0)(sub 8) life. Further, (90)(sub 8) fatigue life was also found to be far lower than that of the unreinforced Ti-15-3 alloys. A simple one-dimensional model for (90)(sub 8) fatigue behavior indicated that the short life of the composite in this orientation resulted, in large part, from weak fiber-matrix bond strength. This conclusion was supported by fractographic evidence showing numerous initiation sites along the fiber-matrix interfaces.

40 CFR 721.10025 - 10H-Phenothiazine, ar, ar′-(C9-rich C8-10-branched alkyl) derivs.

Code of Federal Regulations, 2010 CFR

2010-07-01

... 40 Protection of Environment 30 2010-07-01 2010-07-01 false 10H-Phenothiazine, ar, arâ²-(C9-rich... Significant New Uses for Specific Chemical Substances § 721.10025 10H-Phenothiazine, ar, ar′-(C9-rich C8-10... chemical substances identified as 10H-phenothiazine, ar, ar′-(C9-rich C8-10-branched alkyl) derivs (PMN P...

Interfacial Electronic Structures of Photodetectors Based on C8BTBT/Perovskite.

PubMed

Li, Lin; Tong, Sichao; Zhao, Yuan; Wang, Can; Wang, Shitan; Lyu, Lu; Huang, Yingbao; Huang, Han; Yang, Junliang; Niu, Dongmei; Liu, Xiaoliang; Gao, Yongli

2018-06-07

Comprehensive measurements of ultraviolet photoemission spectroscopy, X-ray photoemission spectroscopy, X-ray diffraction, and atomic force microscopy are adopted to investigate the corelevance of energy level alignment, molecular orientation, and film growth of Au/C8BTBT/perovskite interfaces. A small energy offset of valence band maximum of 0.06 eV between perovskite and C8BTBT makes hole transportation feasible. About 0.65 eV upward shift of energy levels is observed with the deposition of the Au film on C8BTBT, which enhances hole transportation to the Au electrode. The observations from the interface analysis are supported by a prototype photodetector of Au (80 nm)/C8BTBT (20 nm)/perovskite (100 nm) that exhibits excellent performances whose responsivity can reach up to 2.65 A W -1 , 4 times higher than the best CH 3 NH 3 PbI 3 photodetectors.

Copper Causes Regiospecific Formation of C4F8-Containing Six-Membered Rings and their Defluorination/Aromatization to C4F4-Containing Rings in Triphenylene/1,4-C4F8I2 Reactions

DOE Office of Scientific and Technical Information (OSTI.GOV)

Rippy, Kerry C.; Bukovsky, Eric V.; Clikeman, Tyler T.

The presence of Cu in reactions of triphenylene (TRPH) and 1,4-C4F8I2 at 360 °C led to regiospecific substitution of TRPH ortho C(β) atoms to form C4F8-containing rings, completely suppressing substitution on C(α) atoms. In addition, Cu caused selective reductive-defluorination/aromatization (RD/A) to form C4F4- containing aromatic rings. Without Cu, the reactions of TRPH and 1,4- C4F8I2 were not regiospecific and no RD/A was observed. These results, supported by DFT calculations, are the first examples of Cupromoted (i) regiospecific perfluoroannulation, (ii) preparative C–F activation, and (iii) RD/A. HPLC-purified products were characterized by X-ray diffraction, low-temperature PES, and 1H/19F NMR.

The C8 health project: design, methods, and participants.

PubMed

Frisbee, Stephanie J; Brooks, A Paul; Maher, Arthur; Flensborg, Patsy; Arnold, Susan; Fletcher, Tony; Steenland, Kyle; Shankar, Anoop; Knox, Sarah S; Pollard, Cecil; Halverson, Joel A; Vieira, Verónica M; Jin, Chuanfang; Leyden, Kevin M; Ducatman, Alan M

2009-12-01

The C8 Health Project was created, authorized, and funded as part of the settlement agreement reached in the case of Jack W. Leach, et al. v. E.I. du Pont de Nemours & Company (no. 01-C-608 W.Va., Wood County Circuit Court, filed 10 April 2002). The settlement stemmed from the perfluorooctanoic acid (PFOA, or C8) contamination of drinking water in six water districts in two states near the DuPont Washington Works facility near Parkersburg, West Virginia. This study reports on the methods and results from the C8 Health Project, a population study created to gather data that would allow class members to know their own PFOA levels and permit subsequent epidemiologic investigations. Final study participation was 69,030, enrolled over a 13-month period in 2005-2006. Extensive data were collected, including demographic data, medical diagnoses (both self-report and medical records review), clinical laboratory testing, and determination of serum concentrations of 10 perfluorocarbons (PFCs). Here we describe the processes used to collect, validate, and store these health data. We also describe survey participants and their serum PFC levels. The population geometric mean for serum PFOA was 32.91 ng/mL, 500% higher than previously reported for a representative American population. Serum concentrations for perfluorohexane sulfonate and perfluorononanoic acid were elevated 39% and 73% respectively, whereas perfluorooctanesulfonate was present at levels similar to those in the U.S. population. This largest known population study of community PFC exposure permits new evaluations of associations between PFOA, in particular, and a range of health parameters. These will contribute to understanding of the biology of PFC exposure. The C8 Health Project also represents an unprecedented effort to gather basic data on an exposed population; its achievements and limitations can inform future legal settlements for populations exposed to environmental contaminants.

Heats of Formation for Cyclic C4Fn, n=4-8, and their Cations

NASA Technical Reports Server (NTRS)

Bauschlicher, Charles W., Jr.; Ricca, Alessandra; Arnold, James (Technical Monitor)

2000-01-01

Heats of formation for cyclic C4F8 and C4F8+ are determined at the G3MP2 level. The several decomposition pathways are investigated. The calculations confirm that C4F8+ rearranges and its decomposition is responsible for both the C2F4+ and C3F5+ species observed in experiment. The heats of formation are presented for C4Fn and C4Fn+, n = 4-8.

Stability-indicating UPLC method for determining related substances and degradants in dronedarone.

PubMed

Pydimarry, Surya Prakash Rao; Cholleti, Vijay Kumar; Vangala, Ranga Reddy

2014-08-01

A simple, sensitive and reproducible method was developed on ultra-performance liquid chromatography coupled with photodiode array detection for the quantitative determination of dronedarone hydrochloride (DRO) in drug substance and pharmaceutical dosage forms. The method is applicable for the quantification of related substances and assays of drug substances. Chromatographic separation was achieved on Acquity UPLC BEH C8 100 mm, 2.1 mm and 1.7 µm columns, using gradient elution within a short run time of 10.0 min. The eluted compounds were monitored at 288 nm, the flow rate was 0.5 mL/min and the column oven temperature was maintained at 40°C. The resolution of DRO and 11 impurities (potentials and by-products) was greater than 2.0 for all pairs of components. The high correlation coefficient value (>0.9995) indicates the clear correlations between the concentrations of investigated compound and their peak areas within the test ranges. The repeatability and intermediate precision, expressed by the relative standard deviation, were less than 2.5%. The accuracy and validity of the method were further ascertained by performing recovery studies via a spike method. The accuracy of the method, expressed as relative error, was satisfactory. No interference was observed from concomitant substances normally added to the tablets. DRO was subjected to the stress conditions of oxidative, acid, base, hydrolytic, thermal and photolytic degradation. DRO was found to degrade significantly in acid and base stress conditions and to remain stable in thermal, photolytic degradation, oxidative and hydrolytic conditions. The degradation products were well resolved from primary peak and its impurities, proving that the method is stability indicating. The developed method was validated as per International Conference on Harmonization guidelines with respect to specificity, limit of detection, limit of quantification, linearity, accuracy, precision, solution stability and robustness

Solution structure of an artificial Fe8S8 ferredoxin: the D13C variant of Bacillus schlegelii Fe7S8 ferredoxin.

PubMed

Aono, S; Bentrop, D; Bertini, I; Cosenza, G; Luchinat, C

1998-12-01

The solution structure of the D13C variant of the thermostable Fe7S8 ferredoxin from Bacillus schlegelii has been determined by 1H-NMR spectroscopy in its oxidized form. In a variable-temperature NMR study the D13C variant was as thermostable (up to 90 degrees C) as the wild-type protein (WT). Seventy-five out of 77 amino acid residues and 81% of all theoretically expected proton resonances in the D13C Fe8S8 protein have been assigned. Its structure was determined through torsion angle dynamics calculations with the program DYANA, using 935 meaningful NOEs (from a total of 1251), hydrogen bond constraints, and NMR-derived dihedral angle constraints for the cluster-ligating cysteines. Afterwards, restrained energy minimization and restrained molecular dynamics were applied to each conformer of the family. The final family of 20 structures has RMSD values from the mean structure of 0.055 nm for the backbone atoms and of 0.099 nm for all heavy atoms. The overall folding of the WT is maintained in the mutant, except for the immediate vicinity of the new cysteine, which becomes much more similar to native Fe8S8 proteins. The two residues at positions 11 and 12, which constitute an insertion with respect to all known Fe8S8 proteins, assume a conformation that does not prevent the preceding and following residues from folding like in native Fe8S8 proteins. Clear evidence for the existence of two conformations involving almost half of the amino acid residues was found. The two conformations are structurally indistinguishable. Temperature-dependent NMR experiments show that one of them is thermodynamically more stable than the other.

F-8C adaptive flight control laws

NASA Technical Reports Server (NTRS)

Hartmann, G. L.; Harvey, C. A.; Stein, G.; Carlson, D. N.; Hendrick, R. C.

1977-01-01

Three candidate digital adaptive control laws were designed for NASA's F-8C digital flyby wire aircraft. Each design used the same control laws but adjusted the gains with a different adaptative algorithm. The three adaptive concepts were: high-gain limit cycle, Liapunov-stable model tracking, and maximum likelihood estimation. Sensors were restricted to conventional inertial instruments (rate gyros and accelerometers) without use of air-data measurements. Performance, growth potential, and computer requirements were used as criteria for selecting the most promising of these candidates for further refinement. The maximum likelihood concept was selected primarily because it offers the greatest potential for identifying several aircraft parameters and hence for improved control performance in future aircraft application. In terms of identification and gain adjustment accuracy, the MLE design is slightly superior to the other two, but this has no significant effects on the control performance achievable with the F-8C aircraft. The maximum likelihood design is recommended for flight test, and several refinements to that design are proposed.

Histamine and tele-methylhistamine quantification in cerebrospinal fluid from narcoleptic subjects by liquid chromatography tandem mass spectrometry with precolumn derivatization.

PubMed

Croyal, Mikaël; Dauvilliers, Yves; Labeeuw, Olivier; Capet, Marc; Schwartz, Jean-Charles; Robert, Philippe

2011-02-01

An ultra-performance liquid chromatography tandem mass spectrometry (UPLC™-MS/MS) assay was developed for the simultaneous analysis of histamine, its major metabolite tele-methylhistamine, and an internal standard (N-tele-(R)-α-dimethylhistamine) from human cerebrospinal fluid (CSF) samples. The method involves derivatization of primary amines with 4-bromobenzenesulfonyl chloride and subsequent analysis by reversed phase liquid chromatography with mass spectrometry detection and positive electrospray ionization. The separation of derivatized biogenic amines was achieved within 3.5 min on an Acquity® BEH C(18) column by elution with a linear gradient of acetonitrile/water/formic acid (0.1%). The assay was linear in the concentration range of 50-5000 pM for each amine (5.5-555 pg/ml for histamine and 6.25-625 pg/ml for tele-methylhistamine). For repeatability and precision determination, coefficients of variation (CVs) were less than 11.0% over the tested concentration ranges, within acceptance criteria. Thus, the developed method provides the rapid, easy, highly sensitive, and selective requirement to quantify these amines in human CSF. No significant difference was found in the mean ± standard error levels of these amines between a group of narcoleptic patients (histamine=392 ± 64 pM, tele-methylhistamine=2431 ± 461 pM, n=7) and of neurological control subjects (histamine=402 ± 72 pM, tele-methylhistamine=2209 ± 463 pM, n=32). Copyright © 2010 Elsevier Inc. All rights reserved.

[Determination of eleven fluorescent whitening agents in paper food packaging materials by UPLC-FLD/PDA with series double-detector].

PubMed

Wang, Tianjiao; Wu, Pinggu; Hu, Zhengyan; Wang, Liyuan; Tang, Jun; Jiang, Wei; Wang, Zhiyuan

2016-07-01

To establish a new qualitative and quantitative ultraperformance liquid chromatography-fluorescence detector / photodiode array detector with series double-detector method for the determination of eleven fluorescent whitening agents in paper food packaging materials. The sample was extracted with 40%acetonitrile water solution, separated by Waters ACQUITY UPLC BEH C_(18)column( 1. 7μm, 2. 1 mm × 100 mm) and eluted gradient. The excitation wavelength and emission wavelength of fluorescence detector( FLD) were 350 nm and 430 nm, and the wavelength of photodiode array detector( PDA) was 350 nm. The detectors were used in series to achieve qualitative and quantitative detection. In the substrates of paper cups, paper bowls, paper trays and paper boxes, those eleven fluorescent whitening agents were separated properly. For both detectors, in the linear range of 25- 1000 ng / m L, the correlation coefficient was greater than 0. 99, and the recoveries of spiked recoveries were between 82. 2%- 104. 1% with the RSD less than 10%( n = 6). The detection limits ofthose eleven fluorescent whitening agents were 0. 20- 0. 28 mg / kg for FLD and 1. 4- 2. 5mg / kg for PDA. The eleven fluorescent whitening agents could be separated properly with complete separation, good shapes and high recovery rate. This method is easy to operate also. Thus it's an effective method to detect the fluorescent whitening agents in paper food packaging materials.

Simultaneous determination of 30 ginsenosides in Panax ginseng preparations using ultra performance liquid chromatography

PubMed Central

Park, Hee-Won; In, Gyo; Han, Sung-Tai; Lee, Myoung-Woo; Kim, So-Young; Kim, Kyung-Tack; Cho, Byung-Goo; Han, Gyeong-Ho; Chang, Il-Moo

2013-01-01

A quick and simple method for simultaneous determination of the 30 ginsenosides (ginsenoside Ro, Rb1, Rb2, Rc, Rd, Re, Rf, Rg1, 20(S)-Rg2, 20(R)-Rg2, 20(S)-Rg3, 20(R)-Rg3, 20(S)-Rh1, 20(S)-Rh2, 20(R)-Rh2, F1, F2, F4, Ra1, Rg6, Rh4, Rk3, Rg5, Rk1, Rb3, Rk2, Rh3, compound Y, compound K, and notoginsenoside R1) in Panax ginseng preparations was developed and validated by an ultra performance liquid chromatography photo diode array detector. The separation of the 30 ginsenosides was efficiently undertaken on the Acquity BEH C-18 column with gradient elution with phosphoric acids. Especially the chromatogram of the ginsenoside Ro was dramatically enhanced by adding phosphoric acid. Under optimized conditions, the detection limits were 0.4 to 1.7 mg/L and the calibration curves of the peak areas for the 30 ginsenosides were linear over three orders of magnitude with a correlation coefficients greater than 0.999. The accuracy of the method was tested by a recovery measurement of the spiked samples which yielded good results of 89% to 118%. From these overall results, the proposed method may be helpful in the development and quality of P. ginseng preparations because of its wide range of applications due to the simultaneous analysis of many kinds of ginsenosides. PMID:24235860

Gas chromatography and ultra high performance liquid chromatography tandem mass spectrometry methods for the determination of selected endocrine disrupting chemicals in human breast milk after stir-bar sorptive extraction.

PubMed

Rodríguez-Gómez, R; Zafra-Gómez, A; Camino-Sánchez, F J; Ballesteros, O; Navalón, A

2014-07-04

In the present work, two specific, accurate and sensitive methods for the determination of endocrine disrupting chemicals (EDCs) in human breast milk are developed and validated. Bisphenol A and its main chlorinated derivatives, five benzophenone-UV filters and four parabens were selected as target analytes. The method involves a stir-bar sorptive extraction (SBSE) procedure followed by a solvent desorption prior to GC-MS/MS or UHPLC-MS/MS analysis. A derivatization step is also necessary when GC analysis is performed. The GC column used was a capillary HP-5MS with a run time of 26min. For UHPLC analysis, the stationary phase was a non-polar Acquity UPLC(®) BEH C18 column and the run time was 10min. In both cases, the analytes were detected and quantified using a triple quadrupole mass spectrometer (QqQ). Quality parameters such as linearity, accuracy (trueness and precision), sensitivity and selectivity were examined and yielded good results. The limits of quantification (LOQs) ranged from 0.3 to 5.0ngmL(-1) for GC and from 0.2 to 1.0ngmL(-1) for LC. The relative standard deviation (RSD) was lower than 15% and the recoveries ranged from 92 to 114% in all cases, being slightly unfavorable the results obtained with LC. The methods were satisfactorily applied for the determination of target compounds in human milk samples from 10 randomly selected women. Copyright © 2014 Elsevier B.V. All rights reserved.

Simultaneous determination of four alkaloids in Lindera aggregata by ultra-high-pressure liquid chromatography-tandem mass spectrometry.

PubMed

Han, Zheng; Zheng, Yunliang; Chen, Na; Luan, Lianjun; Zhou, Changxin; Gan, Lishe; Wu, Yongjiang

2008-11-28

A new separation and quantification method using liquid chromatography under ultra-high-pressure in combination with tandem mass spectrometry (MS/MS) was developed for simultaneous determination of four alkaloids in Lindera aggregata. The analysis was performed on an Acquity UPLC BEH C(18) column (50mmx2.1mm, 1.7microm particle size; Waters, Milford, MA, USA) utilizing a gradient elution profile and a mobile phase consisting of (A) water containing 10mM ammonium acetate adjusted to pH 3 with acetic acid and (B) acetonitrile. An electrospray ionization (ESI)-tandem interface in the positive mode was employed prior to mass spectrometric detection. The calibration curve was linear over the range of 17.1-856ng for boldine, 42.4-2652ng for norboldine, 6.1-304ng for reticuline and 0.5-50ng for linderegatine, respectively. The average recoveries ranged from 99.2 to 101.4% with RSDs< or =2.7%. Then, four L. aggregata samples from different batches were analyzed using the established method. The results indicated that ultra-high-pressure liquid chromatography-tandem mass spectrometry provided improved chromatographic parameters resulting in significantly increased sample throughput including lower solvent consumption and lower limits of quantitation (LOQs) for most of target analytes compared to previous method employing conventional high-performance liquid chromatography (HPLC) separation. So, the established method was validated, sensitive and reliable for the determination of four alkaloids in L. aggregata.

Rapid and sensitive determination of major polyphenolic components in Euphoria longana Lam. seeds using matrix solid-phase dispersion extraction and UHPLC with hybrid linear ion trap triple quadrupole mass spectrometry.

PubMed

Rathore, Atul S; Sathiyanarayanan, L; Deshpande, Shreekant; Mahadik, Kakasaheb R

2016-11-01

A rapid and sensitive method for the extraction and determination of four major polyphenolic components in Euphoria longana Lam. seeds is presented for the first time based on matrix solid-phase dispersion extraction followed by ultra high performance liquid chromatography with hybrid triple quadrupole linear ion trap mass spectrometry. Matrix solid-phase dispersion method was designed for the extraction of Euphoria longana seed constituents and compared with microwave-assisted extraction and ultrasonic-assisted extraction methods. An Ultra high performance liquid chromatography with hybrid triple quadrupole linear ion-trap mass spectrometry method was developed for quantitative analysis in multiple-reaction monitoring mode in negative electrospray ionization. The chromatographic separation was accomplished using an ACQUITY UPLC BEH C 18 (2.1 mm × 50 mm, 1.7 μm) column with gradient elution of 0.1% aqueous formic acid and 0.1% formic acid in acetonitrile. The developed method was validated with acceptable linearity (r 2 > 0.999), precision (RSD ≤ 2.22%) and recovery (RSD ≤ 2.35%). The results indicated that matrix solid-phase dispersion produced comparable extraction efficiency compared with other methods nevertheless was more convenient and time-saving with reduced requirements on sample and solvent volumes. The proposed method is rapid and sensitive in providing a promising alternative for extraction and comprehensive determination of active components for quality control of Euphoria longana products. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Quantitative determination of chromium picolinate in animal feeds by solid phase extraction and liquid chromatography-tandem mass spectrometry.

PubMed

Han, Miaomiao; Tian, Ying; Li, Zhen; Chen, Yiqiang; Yang, Wenjun; Zhang, Liying

2017-12-01

Chromium picolinate is one of the important Cr 3+ resources and is widely used in animal production. A convenient, reliable and rapid liquid chromatography-tandem mass spectrometry (LC-MS/MS) method was developed and validated for the quantitative determination of chromium picolinate in animal feeds. Feed samples were extracted with acetonitrile and subsequently cleaned up by solid phase extraction cartridges Supelclean™ LC-18. Chromium picolinate was efficiently separated with a Waters ACQUITY UPLC ® BEH C18 column, ionized with electrospray ion source in positive mode (ESI + ), and quantitatively determined by tandem mass spectrometry in multiple reaction monitoring mode. Standard calibration curve of chromium picolinate in the concentration range from 0.5 to 1000ng/mL was obtained with good linearity correlation coefficient (R 2 =0.9982). Average recoveries ranged from 95.37%∼105.54%, as detected by spiking 0.02∼640mg/kg of chromium picolinate in complete feed, concentrated feed and premix. Intra-day and inter-day coefficient of variation were 0.59%∼6.67% and 2.36%∼6.97%, respectively. The limits of quantitation were 0.02mg/kg, 0.025mg/kg, and 2mg/kg for complete feed, concentrated feed, and premix, respectively. Actual sample analysis indicated that the developed method can be an effective tool to monitoring CrPic content in animal feed. Copyright © 2017. Published by Elsevier B.V.

Development and Validation of a UHPLC UV Method for the In-Process Control of Bosentan Monohydrate Synthesis.

PubMed

Jatczak, Marta; Sidoryk, Katarzyna; Kossykowska, Magdalena; Łuniewski, Wojciech; Zagrodzka, Joanna; Lipiec-Abramska, Elżbieta

2016-01-01

Bosentan monohydrate (4- tert -butyl- N -[6-(2-hydroxyethoxy)-5-(2-methoxyphenoxy)-2-(pyrimidin-2-yl) pyrimidin-4-yl]benzene-1-sulfonamide monohydrate) is a dual endothelin receptor antagonist (ERA) applied in the treatment of pulmonary arterial hypertension. To achieve effective process control of the bosentan monohydrate synthesis, it was necessary to develop a selective and not highly time-consuming method for ultra-high performance liquid chromatography (UHPLC). The method is characterized by adequate sensitivity, reproducibility and selectivity for the determination of bosentan monohydrate and related compounds from all synthetic stages. The UHPLC separation was carried out by reversed phase chromatography on the Acquity BEH C18 column (100 mm × 2.1 mm, 1.7 µm) with a mobile phase composed of solvent A (0.1 %, v/v, acetic acid in water) and solvent B (methanol), in the gradient mode at the flow rate of 0.4 mL min -1 . Limits of detection and quantification for the compounds were ≤0.1 µg mL -1 and 0.3 µg mL -1 , respectively. The linearity for all related compounds was investigated as in the range for the active pharmaceutical ingredient (API) and as in the range for the in-process control. The developed method was validated according to the current guidelines, proving the suitability of the method for its intended purpose.

The relation of neutrophil-to-lymphocyte ratio, platelet-to-lymphocyte ratio, and mean platelet volume with the presence and severity of Behçet's syndrome.

PubMed

Alan, Sevil; Tuna, Serpil; Türkoğlu, Elif Betül

2015-12-01

Behçet's syndrome (BS) is associated with chronic inflammation and endothelial dysfunction. Although there have been extensive investigations on neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), and mean platelet volume (MPV) in many diseases, their roles in BS is unclear. The purpose of the present study was to evaluate NLR, PLR, and MPV levels in BS patients and explore their clinical significance. The study included 254 patients with BS and 173 healthy individuals. Age, sex, age of onset, duration of disease, smoking, Behçet activity score, total white blood counts, neutrophil, platelet, and T lymphocyte counts of the patients were recorded. White blood cell (WBC), neutrophil, platelet, NLR, and PLR were significantly higher in patients with BS when compared with healthy controls (all p < 0.001). Lymphocyte counts and MPVs of the BS group were not statistically different from healthy controls (all p > 0.05). In the BS group, PLR and MPV were significantly different among the three severity groups (p = 0.037 and p = 0.016, respectively). We showed that any laboratory markers were not associated with joint, eye, central nervous system, large vessel, or gastrointestinal involvement in BS. NLR was shown to be an independent factor for BS by multivariate analysis. We suggest that NLR can be considered to be a diagnostic criterion of BS given the support of the findings from larger prospective studies. Copyright © 2015. Published by Elsevier Taiwan.

Interferon alfa-2b, colchicine, and benzathine penicillin versus colchicine and benzathine penicillin in Behçet's disease: a randomised trial.

PubMed

Demiroglu, H; Ozcebe, O I; Barista, I; Dündar, S; Eldem, B

2000-02-19

Sight-threatening eye involvement is a serious complication of Behçet's disease. Extraocular complications such as arthritis, vascular occlusive disorders, mucocutaneous lesions, and central-nervous-system disease may lead to morbidity and even death. We designed a prospective study in newly diagnosed patients without previous eye disease to assess whether prevention of eye involvement and extraocular manifestations, and preservation of visual acuity are possible with combination treatments with and without interferon alfa-2b. Patients were randomly assigned 3 million units interferon alfa-2b subcutaneously every other day for the first 6 months plus 1.5 mg colchicine orally daily and 1.2 million units benzathine penicillin intramuscularly every 3 weeks (n=67), or colchicine and benzathine penicillin alone (n=68). The primary endpoint was visual-acuity loss. Analysis was by intention to treat. Significantly fewer patients who were treated with interferon had eye involvement than did patients who did not receive interferon (eight vs 27, relative risk 0.21 [95% CI 0.09-0.50], p<0.001). Ocular attack rate was 0.2 (SD 0.62) per year with interferon therapy and 1.02 (1.13) without interferon therapy (p=0.0001). Visual-acuity loss was significantly lower among patients treated with interferon than in those without interferon (two vs 13, relative risk 0.13 [95% CI 0.03-0.60], p=0.003). Arthritis episodes, vascular events, and mucocutaneous lesions were also less frequent in patients treated with interferon than in those not receiving interferon. No serious side-effects were reported. Therapy with interferon alfa-2b, colchicine, and benzathine penicillin seems to be an effective regimen in Behçet's disease for the prevention of recurrent eye attacks and extraocular complications, and for the protection of vision.

Short-term to Long-term Results of Ahmed Glaucoma Valve Implantation for Uveitic Glaucoma Secondary to Behçet Disease.

PubMed

Yakin, Mehmet; Eksioglu, Umit; Sungur, Gulten; Satana, Banu; Demirok, Gulizar; Ornek, Firdevs

2017-01-01

To evaluate short-term to long-term outcomes of Ahmed glaucoma valve (AGV) implantation in the management of uveitic glaucoma (UG) secondary to Behçet disease (BD). A retrospective chart review of 47 eyes of 35 patients with UG secondary to BD who underwent AGV implantation was conducted. Success was defined as having an intraocular pressure (IOP) between 6 and 21 mm Hg with (qualified success) or without (complete success) antiglaucomatous medications and without need for further glaucoma surgery. Mean postoperative follow-up was 57.72±26.13 months. Mean preoperative IOP was 35.40±8.33 mm Hg versus 12.28±2.90 mm Hg at the last follow-up visit (P<0.001). Mean number of preoperative topical antiglaucomatous medications was 2.96±0.29 versus 0.68±1.12 at the last follow-up visit (P<0.001). In all eyes, IOP could be maintained between 6 and 21 mm Hg with or without antiglaucomatous medications during follow-up. The cumulative probability of complete success was 46.8% at 6 months, 40.4% at 12 months, and 35.9% at 36 months, and the cumulative probability of eyes without complication was 53.2% at 6 months, 46.5% at 12 months, and 39.6% at 24 months postoperatively based on Kaplan-Meier survival analysis. No persistent or irreparable complications were observed. This study includes one of the largest series of AGV implantation in the management of UG with the longest follow-up reported. AGV implantation can be considered as a primary surgical option in the management of UG secondary to BD with 100% total success rate (with or without medications).

Muscle, Skin and Core Temperature after −110°C Cold Air and 8°C Water Treatment

PubMed Central

Costello, Joseph Thomas; Culligan, Kevin; Selfe, James; Donnelly, Alan Edward

2012-01-01

The aim of this investigation was to elucidate the reductions in muscle, skin and core temperature following exposure to −110°C whole body cryotherapy (WBC), and compare these to 8°C cold water immersion (CWI). Twenty active male subjects were randomly assigned to a 4-min exposure of WBC or CWI. A minimum of 7 days later subjects were exposed to the other treatment. Muscle temperature in the right vastus lateralis (n = 10); thigh skin (average, maximum and minimum) and rectal temperature (n = 10) were recorded before and 60 min after treatment. The greatest reduction (P<0.05) in muscle (mean ± SD; 1 cm: WBC, 1.6±1.2°C; CWI, 2.0±1.0°C; 2 cm: WBC, 1.2±0.7°C; CWI, 1.7±0.9°C; 3 cm: WBC, 1.6±0.6°C; CWI, 1.7±0.5°C) and rectal temperature (WBC, 0.3±0.2°C; CWI, 0.4±0.2°C) were observed 60 min after treatment. The largest reductions in average (WBC, 12.1±1.0°C; CWI, 8.4±0.7°C), minimum (WBC, 13.2±1.4°C; CWI, 8.7±0.7°C) and maximum (WBC, 8.8±2.0°C; CWI, 7.2±1.9°C) skin temperature occurred immediately after both CWI and WBC (P<0.05). Skin temperature was significantly lower (P<0.05) immediately after WBC compared to CWI. The present study demonstrates that a single WBC exposure decreases muscle and core temperature to a similar level of those experienced after CWI. Although both treatments significantly reduced skin temperature, WBC elicited a greater decrease compared to CWI. These data may provide information to clinicians and researchers attempting to optimise WBC and CWI protocols in a clinical or sporting setting. PMID:23139763

Rapid and sensitive ultra-high-pressure liquid chromatography method for quantification of antichagasic benznidazole in plasma: application in a preclinical pharmacokinetic study.

PubMed

Davanço, Marcelo Gomes; de Campos, Michel Leandro; Peccinini, Rosângela Gonçalves

2015-07-01

Benznidazole (BNZ) and nifurtimox are the only drugs available for treating Chagas disease. In this work, we validated a bioanalytical method for the quantification of BNZ in plasma aimed at improving sensitivity and time of analysis compared with the assays already published. Furthermore, we demonstrated the application of the method in a preclinical pharmacokinetic study after administration of a single oral dose of BNZ in Wistar rats. A Waters® Acquity UHPLC system equipped with a UV-vis detector was employed. The method was established using an Acquity® UHPLC HSS SB C18 protected by an Acquity® UHPLC HSS SB C18 VanGuard guard column and detection at 324 nm. The mobile phase consisted of ultrapure water-acetonitrile (65:35), and elution was isocratic. The mobile phase flow rate was 0.55 mL/min, the volume of injection was 1 μL, and the run time was just 2 min. The samples were kept at 25°C until injection and the column at 45°C for the chromatographic separation. The sample preparation was performed by a rapid protein precipitation with acetonitrile. The linear concentration range was 0.15-20 µg/mL. The pharmacokinetic parameters of BNZ in rats were determined and the method was considered sensitive, fast and suitable for application in pharmacokinetic studies. Copyright © 2014 John Wiley & Sons, Ltd.

35 GHz ENDOR characterization of the "very rapid" signal of xanthine oxidase reacted with 2-hydroxy-6-methylpurine (13C8): evidence against direct Mo-C8 interaction.

PubMed

Manikandan, P; Choi, E Y; Hille, R; Hoffman, B M

2001-03-21

Xanthine oxidase is a molybdenum-containing enzyme that catalyzes the hydroxylation of xanthine and a wide variety of other aromatic heterocycles. In the course of the reaction with xanthine and substrates such as 2-hydroxy-6-methylpurine (HMP), the enzyme gives rise to a Mo(V) EPR signal, denoted "very rapid", that arises from an authentic catalytic intermediate. The two alternative catalytic mechanisms proposed for this enzyme differ critically in whether the distance between Mo and C8 of the purine nucleus in this intermediate is short enough to admit a direct bonding interaction. To examine this distance, we have performed 13C ENDOR measurements of the "very rapid" EPR signal generated by xanthine oxidase during reaction with 13C8-HMP. The resulting (13)C8 hyperfine tensor, A = [10.2(1), 7.0(1), 6.5(1)] MHz, is discussed in the framework of a detailed consideration of factors involved in extracting metrical parameters from an anisotropic hyperfine interaction composed of contributions from multiple sources, in particular, the effect of the local contributions from spin density on (13)C8. The analysis presented here gives a Mo...C distance whose value is expected to be ca. 2.7-2.9 A in the "very rapid" intermediates formed with both xanthine and HMP, consistent with plausible bond lengths for a Mo-O-C8 fragment where C8 is a trigonal-planar aromatic carbon. The difference from earlier conclusions is explained. The data thus do not support the existence of a direct Mo-C bond in the signal-giving species. This conclusion supports a mechanism that does not involve such an interaction and which begins with base-assisted nucleophilic attack of the Mo(VI)-OH group on the C-8 of substrate, with concomitant hydride transfer to the Mo=S group to give Mo(IV)-SH; the EPR-active "very rapid" species then forms by one-electron oxidation and deprotonation to yield the EPR-detectable Mo(V)OS(OR) species. We further discuss the complexities and limitations of the semiempirical

Identity of the segment of human complement C8 recognized by complement regulatory protein CD59.

PubMed

Lockert, D H; Kaufman, K M; Chang, C P; Hüsler, T; Sodetz, J M; Sims, P J

1995-08-25

CD59 antigen is a membrane glycoprotein that inhibits the activity of the C5b-9 membrane attack complex (MAC), thereby protecting human cells from lysis by human complement. The inhibitory function of CD59 derives from its capacity to interact with both the C8 and C9 components of MAC, preventing assembly of membrane-inserted C9 polymer. MAC-inhibitory activity of CD59 is species-selective and is most effective when both C8 and C9 derive from human or other primate plasma. Rabbit C8 and C9, which can substitute for human C8 and C9 in MAC, mediate virtually unrestricted lysis of human cells expressing CD59. In order to identify the segment of human C8 that is recognized by CD59, recombinant peptides containing human or rabbit C8 sequence were expressed in Escherichia coli and purified. CD59 was found to specifically bind to a peptide corresponding to residues 334-385 of the human C8 alpha-subunit, and to require a disulfide bond between Cys345 and Cys369. No specific binding was observed to the corresponding sequence from rabbit C8 alpha (residues 334-386). To obtain functional evidence that this segment of human C8 alpha is selectively recognized by CD59, recombinant C8 proteins were prepared by co-transfecting COS-7 cells with human/rabbit chimeras of the C8 alpha cDNA, and cDNAs encoding the C8 beta and C8 gamma chains. Hemolytic activity of MAC formed with chimeric C8 was analyzed using target cells reconstituted with CD59. These experiments confirmed that CD59 recognizes a conformationally sensitive epitope that is within a segment of human C8 alpha internal to residues 320-415. Our data also suggest that optimal interaction of CD59 with this segment of human C8 alpha is influenced by N-terminal flanking sequence in C8 alpha and by human C8 beta, but is unaffected by C8 gamma.

Cold-induced vasodilation during single digit immersion in 0°C and 8°C water in men and women.

PubMed

Tyler, Christopher James; Reeve, Tom; Cheung, Stephen S

2015-01-01

The present study compared the thermal responses of the finger to 0 and 8°C water immersion, two commonly used temperatures for cold-induced vasodilation (CIVD) research. On two separate and counterbalanced occasions 15 male and 15 female participants immersed their index finger in 20°C water for 5 min followed by either 0 or 8°C water for 30 min. Skin temperature, cardiovascular and perceptual data were recorded. Secondary analyses were performed between sexes and comparing 0.5, 1 and 4°C CIVD amplitude thresholds. With a 0.5°C threshold, CIVD waves were more prevalent in 8°C (2 (1-3) than in 0°C (1.5 (0-3)), but the amplitude was lower (4.0 ± 2.3 v 9.2 ± 4.0°C). Mean, minimum and maximum finger temperatures were lower in 0°C during the 30 min immersion, and CIVD onset and peak time occurred later in 0°C. Thermal sensation was lower and pain sensation was higher in 0°C. There were no differences between males and females in any of the physiological or CIVD data with the exception of SBP, which was higher in males. Females reported feeling higher thermal sensations in 8°C and lower pain sensations in 0°C and 8°C compared to males. Fewer CIVD responses were observed when using a 4°C (1 (0-3)) threshold to quantify a CIVD wave compared to using a 1°C (2 (0-3)) or 0.5°C (2 (0-3)) amplitude. In conclusion, both 0 and 8 °C can elicit CIVD but 8°C may be more suitable when looking to optimise the number of CIVD waves while minimising participant discomfort. The CIVD response to water immersion does not appear to be influenced by sex. Researchers should consider the amplitude threshold that was used to determine a CIVD wave when interpreting previous data.

Off-Label Uses of Anti-TNF Therapy in Three Frequent Disorders: Behçet's Disease, Sarcoidosis, and Noninfectious Uveitis

PubMed Central

Sánchez-Cano, Daniel; Callejas-Rubio, José Luis; Ruiz-Villaverde, Ricardo; Ríos-Fernández, Raquel; Ortego-Centeno, Norberto

2013-01-01

Tumoral necrosis factor α plays a central role in both the inflammatory response and that of the immune system. Thus, its blockade with the so-called anti-TNF agents (infliximab, etanercept, adalimumab, certolizumab pegol, and golimumab) has turned into the most important tool in the management of a variety of disorders, such as rheumatoid arthritis, spondyloarthropatties, inflammatory bowel disease, and psoriasis. Nonetheless, theoretically, some other autoimmune disorders may benefit from these agents. Our aim is to review these off-label uses of anti-TNF blockers in three common conditions: Behçet's disease, sarcoidosis, and noninfectious uveitis. Due to the insufficient number of adequate clinical trials and consequently to their lower prevalence compared to other immune disorders, this review is mainly based on case reports and case series. PMID:23983404

Downhill oesophageal variceal bleeding: A rare complication in Behçet's disease-related superior vena cava syndrome.

PubMed

Ennaifer, Rym; B'chir Hamzaoui, Saloua; Larbi, Thara; Romdhane, Hayfa; Abdallah, Maya; Bel Hadj, Najet; M'rad, Sander

2015-03-01

Behçet's disease (BD) is a multisystemic disorder that involves vessels of all sizes. Superior vena cava (SVC) thrombosis is a rare complication that can lead to the development of various collateral pathways. A 31-year-old man presented with SVC syndrome. He had a history of recurrent genital aphthosis. Computed tomography revealed extensive thrombosis of the right internal jugular, axillary, and subclavian veins with collateral circulation. The patient was diagnosed with BD, and he was started on anticoagulation and immunosuppressive therapy. One week later, he presented with haematemesis. Upper gastrointestinal endoscopy disclosed varices in the upper third of the oesophagus with stigmata of recent bleeding. Portal hypertension was ruled out. Anticoagulation therapy was discontinued. He was discharged on immunosuppressive therapy. Bleeding from downhill oesophageal varices should be suspected in any patient presenting with upper gastrointestinal bleeding and a history of SVC syndrome due to BD. Copyright © 2015 Arab Journal of Gastroenterology. Published by Elsevier B.V. All rights reserved.

[Serum pharmacochemistry of Qinbai Qingfei concentrated pellets based on UPLC-Q-TOF-MS].

PubMed

Liu, Ye; Wei, Wen-Feng; Huo, Jin-Hai; Wang, Wei-Ming

2017-02-01

To analyze the main components of Qinbai Qingfei concentrated pellets in rat serum with UPLC-Q-TOF-MS technology and serum pharmacochemistry theory. After gavage administration with Qinbai Qingfei concentrated pellets, blood was collected from hepatic portal vein. ACQUITY UPLC BEH C₁₈(2.1 mm×100 mm, 1.7 μm) was used, with 0.1% formic acid agueous solution(A)-0.1%formic acid and acetonitrile(B) as the mobile phase for gradient elution. The flow rate was 0.3 mL•min⁻¹, the column temperature was maintained at 35 ℃. Through the comparative analysis fingerprints of Qinbai Qingfei concentrated pellets, drug containing-serum and blank serum, and with the help Peakview and Metabolitepilot software, components in serum were defined. A total of 28 compounds were identified, including 18 prototypes and 10 metabolites. As a result, UPLC-Q-TOF-MS technology and serum pharmacochemistry theory were applied to comprehensively expound Qinbai Qingfei concentrated pellets'constituents migrating to rat serum, and provide scientific basis for further studies for in vivo metabolic process and effective material base. Copyright© by the Chinese Pharmaceutical Association.

LC-MS/MS assay for the quantitation of the tyrosine kinase inhibitor neratinib in human plasma.

PubMed

Kiesel, Brian F; Parise, Robert A; Wong, Alvin; Keyvanjah, Kiana; Jacobs, Samuel; Beumer, Jan H

2017-02-05

Neratinib is an orally available tyrosine kinase inhibitor targeting HER2 (ERBB2) and EGFR (ERBB). It is being clinically evaluated for the treatment of breast and other solid tumors types as a single agent or in combination with other chemotherapies. In support of several phase I/II clinical trials investigating neratinib combinations, we developed and validated a novel LC-MS/MS assay for the quantification of neratinib in 100μL of human plasma with a stable isotopic internal standard. Analytes were extracted from plasma using protein precipitation and evaporation of the resulting supernatant followed by resuspension. Chromatographic separation was achieved using an Acquity UPLC BEH Shield RP18 column and a gradient methanol-water mobile phase containing 10% ammonium acetate. An ABI 4000 mass spectrometer and electrospray positive mode ionization were used for detection. The assay was linear from 2 to 1,000ng/mL and proved to be accurate (98.9-106.5%) and precise (<6.2%CV), and met the FDA guidance for bioanalytical method validation. This LC-MS/MS assay will be an essential tool to further define the pharmacokinetics of neratinib. Copyright © 2016 Elsevier B.V. All rights reserved.

8. Historic American Buildings Survey, Gift of Thomas C. Vint, ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

8. Historic American Buildings Survey, Gift of Thomas C. Vint, Chief of Design and Construction, National Park Service, Washington, D.C., late 19th century view, photocopied 1960, VIEW OF CONSTRUCTION - Mormon Tabernacle, Temple Square, Salt Lake City, Salt Lake County, UT

8-Nitro-cGMP promotes bone growth through expansion of growth plate cartilage.

PubMed

Hoshino, Marie; Kaneko, Kotaro; Miyamoto, Yoichi; Yoshimura, Kentaro; Suzuki, Dai; Akaike, Takaaki; Sawa, Tomohiro; Ida, Tomoaki; Fujii, Shigemoto; Ihara, Hideshi; Tanaka, Junichi; Tsukuura, Risa; Chikazu, Daichi; Mishima, Kenji; Baba, Kazuyoshi; Kamijo, Ryutaro

2017-09-01

In endochondral ossification, growth of bones occurs at their growth plate cartilage. While it is known that nitric oxide (NO) synthases are required for proliferation of chondrocytes in growth plate cartilage and growth of bones, the precise mechanism by which NO facilitates these process has not been clarified yet. C-type natriuretic peptide (CNP) also positively regulate elongation of bones through expansion of the growth plate cartilage. Both NO and CNP are known to use cGMP as the second messenger. Recently, 8-nitro-cGMP was identified as a signaling molecule produced in the presence of NO in various types of cells. Here, we found that 8-nitro-cGMP is produced in proliferating chondrocytes in the growth plates, which was enhanced by CNP, in bones cultured ex vivo. In addition, 8-nitro-cGMP promoted bone growth with expansion of the proliferating zone as well as increase in the number of proliferating cells in the growth plates. 8-Nitro-cGMP also promoted the proliferation of chondrocytes in vitro. On the other hand, 8-bromo-cGMP enhanced the growth of bones with expansion of hypertrophic zone of the growth plates without affecting either the width of proliferating zone or proliferation of chondrocytes. These results indicate that 8-nitro-cGMP formed in growth plate cartilage accelerates chondrocyte proliferation and bone growth as a downstream molecule of NO. Copyright © 2017. Published by Elsevier Inc.

Global microRNA profiling of peripheral blood mononuclear cells in patients with Behçet's disease.

PubMed

Erre, Gian Luca; Piga, Matteo; Carru, Ciriaco; Angius, Andrea; Carcangiu, Laura; Piras, Marco; Sotgia, Salvatore; Zinellu, Angelo; Mathieu, Alessandro; Passiu, Giuseppe; Pescatori, Mario

2015-01-01

To explore the post-transcriptional regulation of the peripheral blood mononuclear cells (PBMCs) transcriptome by microRNAs in Behçet's disease (BD). Using TaqMan Low Density Array-based microRNAs expression profiling, the expression of 750 mature human microRNAs in PBMCs from 5 BD patients and 3 healthy controls (HC) was compared. The expression of deregulated microRNAs was then validated by quantitative real time-polymerase chain reaction (qRT-PCR), in 42 BD patients and 8 HC. In the initial screening, 13 microRNAs appeared deregulated in BD vs HC. Among them, the differential expression of miR-720 and miR-139-3p was confirmed by qRT-PCR, (p<0.05 and FDR<5%). Areas under the receiver operating characteristic curve for miR-139-3p, miR-720 and miR-139-3p+miR-720 in the validation cohort were 0.84, 0.87 and 0.92 respectively, indicating good discrimination between BD patients and HC. Post-hoc analysis showed that 9 out of 13 microRNAs from the discovery phase were significantly upregulated in active vs. quiescent BD, suggesting inflammation as a key regulator of microRNAs machinery in BD. In silico analysis revealed that several BD candidate susceptibility genes are predicted target of significantly deregulated microRNAs in active BD. A significant enrichment in microRNAs targeting elements of the Toll-like receptor (TLR) and T-cell receptor signalling pathways was also assumed. miR199-3p and miR720 deserve further confirmation as biomarkers of BD in larger studies. PBMCs from active BD displayed a unique signature of microRNAs which may be implicated in regulation of innate immunity activation and T-cell function.

40 CFR Appendix 8 to Subpart A of... - Reference C16-C18 Internal Olefin Drilling Fluid Formulation

Code of Federal Regulations, 2010 CFR

2010-07-01

... 40 Protection of Environment 29 2010-07-01 2010-07-01 false Reference C16-C18 Internal Olefin Drilling Fluid Formulation 8 Appendix 8 to Subpart A of Part 435 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) EFFLUENT GUIDELINES AND STANDARDS OIL AND GAS EXTRACTION POINT SOURCE CATEGORY...

40 CFR Appendix 8 to Subpart A of... - Reference C16-C18 Internal Olefin Drilling Fluid Formulation

Code of Federal Regulations, 2011 CFR

2011-07-01

... 40 Protection of Environment 30 2011-07-01 2011-07-01 false Reference C16-C18 Internal Olefin Drilling Fluid Formulation 8 Appendix 8 to Subpart A of Part 435 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) EFFLUENT GUIDELINES AND STANDARDS OIL AND GAS EXTRACTION POINT SOURCE CATEGORY...

Development of a stability-indicating UPLC method for determining olanzapine and its associated degradation products present in active pharmaceutical ingredients and pharmaceutical dosage forms.

PubMed

Krishnaiah, Ch; Vishnu Murthy, M; Kumar, Ramesh; Mukkanti, K

2011-03-25

A simple, sensitive and reproducible ultra performance liquid chromatography (UPLC) coupled with a photodiode array detector method was developed for the quantitative determination of olanzapine (OLN) in API and pharmaceutical dosage forms. The method is applicable to the quantification of related substances and assays of drug substances. Chromatographic separation was achieved on Acquity UPLC BEH 100-mm, 2.1-mm, and 1.7-μm C-18 columns, and the gradient eluted within a short runtime, i.e., within 10.0 min. The eluted compounds were monitored at 250 nm, the flow rate was 0.3 mL/min, and the column oven temperature was maintained at 27°C. The resolution of OLN and eight (potential, bi-products and degradation) impurities was greater than 2.0 for all pairs of components. The high correlation coefficient (r(2)>0.9991) values indicated clear correlations between the investigated compound concentrations and their peak areas within the test ranges. The repeatability and intermediate precision, expressed by the RSD, were less than 2.4%. The accuracy and validity of the method were further ascertained by performing recovery studies via a spike method. The accuracy of the method expressed as relative error was satisfactory. No interference was observed from concomitant substances normally added to the tablets. The drug was subjected to the International Conference on Harmonization (ICH)-prescribed hydrolytic, oxidative, photolytic and thermal stress conditions. The performance of the method was validated according to the present ICH guidelines for specificity, limit of detection, limit of quantification, linearity, accuracy, precision, ruggedness and robustness. Copyright © 2010 Elsevier B.V. All rights reserved.

Development and validation of a sensitive UPLC-MS/MS instrumentation and alkaline nitrobenzene oxidation method for the determination of lignin monomers in wheat straw.

PubMed

Zheng, Mengjing; Gu, Shubo; Chen, Jin; Luo, Yongli; Li, Wenqian; Ni, Jun; Li, Yong; Wang, Zhenlin

2017-06-15

A method to determine the lignin monomers (p-hydroxybenzaldehyde, vanillin and syringaldehyde) in plant cell wall of wheat internode was developed and validated using a high-throughput nitrobenzene oxidation step and ultra performance liquid chromatography tandem mass spectrometry (UPLC-MS/MS) for quantification. UPLC analyses were carried out using an reversed phase C 18 column (ACQUITY UPLC BEH, 1.7μm, 2.1×100mm) and gradient elution with water and acetonitrile. This method was completely validated in terms of analyzing speed, linearity, sensitivity, limits of detection (LODs) and limits of quantification (LOQs).The three lignin monomers were successfully separated within 6min and only 2min were required to regain its equilibrium. The method linearity with regression coefficients values (R2) greater than 0.997. Additionally, LODs ranged from 0.21 to 0.89μgL -1 and LOQs ranged from 0.69 to 2.95μgL -1 . The applicability of this analytical approach for determining the three lignin monomers was confirmed by the successful analysis of real samples of wheat stem internodes. The nitrobenzene oxidation method was used for the analysis of lignin monomers. We have optimized the treatment temperature (170°C, 1h) and realized the high-throughput using the microwave digestion instrument. Recovery of this extraction method ranged from 68.4% to 77.7%. The analysis result showed that the guaiacyl unit (G) was the major component of lignin and there was a higher content of the syringyl unit (S) than that of the hydroxybenzyl unit (H). Copyright © 2017. Published by Elsevier B.V.

Effect of the CYP2C8 genotype on the pharmacokinetics and pharmacodynamics of repaglinide.

PubMed

Tomalik-Scharte, Dorota; Fuhr, Uwe; Hellmich, Martin; Frank, Dorothee; Doroshyenko, Oxana; Jetter, Alexander; Stingl, Julia C

2011-05-01

The pharmacokinetics of repaglinide shows pronounced interindividual variability, for which several reasons have been considered, including interactions with drugs inhibiting CYP2C8 and CYP2C8 genetic polymorphism. However, existing data on the role of genetic polymorphisms in repaglinide disposition are not fully consistent. We studied the effect of CYP2C8*3 on the pharmacokinetics and pharmacodynamics of repaglinide in 29 healthy whites carrying CYP2C8*3/*3 (n = 4), CYP2C8*1/*3 (n = 13), or CYP2C8*1/*1 (n = 12). After administration of a single dose of 2 mg of repaglinide, blood was drawn for assessment of repaglinide pharmacokinetics and pharmacodynamics, and urine was collected to quantify the main repaglinide metabolites M1 and M4 up to 24 h postdose. Repaglinide and the metabolites were quantified by liquid chromatography-tandem mass spectrometry. Considering only the effect of CYP2C8*3, the mean (95% confidence interval) area under the time-concentration curve (AUC) from zero to infinity of repaglinide was 72.4 (6.7-138.0), 97.2 (59.2-135.2), and 105.9 (52.4-159.3) ng · ml(-1) · h and the maximal concentration (C(max)) was 38.5 (3.8-73.2), 50.3 (37.5-63.0), and 60.3 (31.5-89.1) ng · ml(-1), respectively, in carriers of CYP2C8*3/*3, CYP2C8*1/*3, and CYP2C8*1/*1 [p > 0.05, one-way analysis of variance (ANOVA)]. In addition, for urinary metabolite excretion and pharmacodynamic parameters, i.e., mean and maximal changes in insulin and glucose concentration, no significant differences between CYP2C8 genotypes were observed. Likewise, no significant effects on the pharmacokinetics or pharmacodynamics were observed when AUC and C(max) of repaglinide were corrected for reported effects of the SLCO1B1 521T>C polymorphism or when both polymorphisms were tested in a two-way ANOVA. In conclusion, CYP2C8*3 does not seem to play an important role in the pharmacokinetics and pharmacodynamics of repaglinide given in a therapeutic dose.

Exacerbation of Behçet's syndrome and familial Mediterranean fever with menstruation.

PubMed

Guzelant, Gul; Ozguler, Yesim; Esatoglu, Sinem Nihal; Karatemiz, Guzin; Ozdogan, Huri; Yurdakul, Sebahattin; Yazici, Hasan; Seyahi, Emire

2017-01-01

Menstruation triggers several conditions such as migraine, recurrent aphthous stomatitis and acne vulgaris in healthy individuals. There is evidence that Behçet's syndrome (BS) and familial Mediterranean fever (FMF) may exacerbate during menstruation. The aim is to assess whether BS and FMF patients experience menstrual flares. Females of reproductive age with BS and FMF seen consecutively at the outpatient clinic of Cerrahpasa Medical Faculty at Istanbul, as well as apparently healthy hospital workers were studied using a standardised questionnaire. BS patients were asked whether they experienced increased skin-mucosa lesions during the menstrual period. A similar questionnaire assessing this time the frequency of abdominal pain, chest pain and fever attacks was given to the patients with FMF. The healthy controls received both questionnaires. A total of 200 BS patients, 240 FMF patients and 250 healthy controls were studied. The most commonly reported symptom among both BS patients (51%) and healthy controls (62%) was the acneiform lesion. At least 79% patients with FMF reported attacks with menstruation, notably abdominal pain which, majority thought, could be differentiated from dysmenorrhea. Additionally, 76% of healthy controls reported having abdominal pain consistent most probably with dysmenorrhea. This survey showed that, in 68% of the patients with BS at least one skin mucosa lesion was exacerbated with menstruation, this was most commonly acneiform lesion. Menstruation had a slightly stronger effect on FMF, triggering at least one symptom in 79%. The main limitation of the study was the self-reported assessment methodology.

CYP2C8 Genotype Significantly Alters Imatinib Metabolism in Chronic Myeloid Leukaemia Patients.

PubMed

Barratt, Daniel T; Cox, Hannah K; Menelaou, Andrew; Yeung, David T; White, Deborah L; Hughes, Timothy P; Somogyi, Andrew A

2017-08-01

The aims of this study were to determine the effects of the CYP2C8*3 and *4 polymorphisms on imatinib metabolism and plasma imatinib concentrations in chronic myeloid leukaemia (CML) patients. We genotyped 210 CML patients from the TIDELII trial receiving imatinib 400-800 mg/day for CYP2C8*3 (rs11572080, rs10509681) and *4 (rs1058930). Steady-state trough total plasma N-desmethyl imatinib (major metabolite):imatinib concentration ratios (metabolic ratios) and trough total plasma imatinib concentrations were compared between genotypes (one-way ANOVA with Tukey post hoc). CYP2C8*3 (n = 34) and *4 (n = 15) carriers had significantly higher (P < 0.01) and lower (P < 0.01) metabolic ratios, respectively, than CYP2C8*1/*1 (n = 147) patients (median ± standard deviation: 0.28 ± 0.08, 0.18 ± 0.06 and 0.22 ± 0.08, respectively). Plasma imatinib concentrations were consequently > 50% higher for CYP2C8*1/*4 than for CYP2C8*1/*1 and CYP2C8*3 carriers (2.18 ± 0.66 vs. 1.45 ± 0.74 [P < 0.05] and 1.36 ± 0.98 μg/mL [P < 0.05], respectively). CYP2C8 genotype significantly alters imatinib metabolism in patients through gain- and loss-of-function mechanisms.

Role of gemfibrozil as an inhibitor of CYP2C8 and membrane transporters.

PubMed

Tornio, Aleksi; Neuvonen, Pertti J; Niemi, Mikko; Backman, Janne T

2017-01-01

Cytochrome P450 (CYP) 2C8 is a drug metabolizing enzyme of major importance. The lipid-lowering drug gemfibrozil has been identified as a strong inhibitor of CYP2C8 in vivo. This effect is due to mechanism-based inhibition of CYP2C8 by gemfibrozil 1-O-β-glucuronide. In vivo, gemfibrozil is a fairly selective CYP2C8 inhibitor, which lacks significant inhibitory effect on other CYP enzymes. Gemfibrozil can, however, have a smaller but clinically meaningful inhibitory effect on membrane transporters, such as organic anion transporting polypeptide 1B1 and organic anion transporter 3. Areas covered: This review describes the inhibitory effects of gemfibrozil on CYP enzymes and membrane transporters. The clinical drug interactions caused by gemfibrozil and the different mechanisms contributing to the interactions are reviewed in detail. Expert opinion: Gemfibrozil is a useful probe inhibitor of CYP2C8 in vivo, but its effect on membrane transporters has to be taken into account in study design and interpretation. Moreover, gemfibrozil could be used to boost the pharmacokinetics of CYP2C8 substrate drugs. Identification of gemfibrozil 1-O-β-glucuronide as a potent mechanism-based inhibitor of CYP2C8 has led to recognition of glucuronide metabolites as perpetrators of drug-drug interactions. Recently, also acyl glucuronide metabolites of clopidogrel and deleobuvir have been shown to strongly inhibit CYP2C8.

Simultaneous determination of 11 designated hallucinogenic phenethylamines by ultra-fast liquid chromatography with fluorescence detection.

PubMed

Min, Jun Zhe; Shimizu, Yoshiha; Toyo'oka, Toshimasa; Inagaki, Shinsuke; Kikura-Hanajiri, Ruri; Goda, Yukihiro

2008-10-01

To avoid the spreading of illegal drugs, a designated drug regulation system was introduced along with revision of the Pharmaceutical Affairs Law in Japan in 2006, and 32 substances including phenethylamine-type drugs were listed in April 2007. In this study, a new simultaneous determination method, based on ultra-fast liquid chromatography coupled with fluorescence detection (UFLC-FL), was developed for the 11 designated phenethylamine drugs. The phenethylamines were labeled with 4-(N,N-dimethylaminosulfonyl)-7-fluoro-2,1,3-benzoxadiazole (DBD-F) at 60 degrees C for 2h in 0.1M borax (pH 9.3). The resulting 11 fluorophores were completely separated by reversed-phase chromatography using an ACQUITY UPLC BEH C(18) column (2.1 mm x 100 mm 1.7 microm) and fluorometrically detected at 550 nm (excitation at 450 nm). The calibration curves obtained from the peak areas versus the injection amounts of the phenethylamines showed a good linearity. The limits of detection (signal-to-noise ratio of 3: S/N=3) on the chromatogram were in the range from 10 fmol (PMMA) to 2.5pmol (MMDA-2). Good accuracy (%) and precision (CV) by intra-day assay and inter-day assay were also obtained using the present procedure. The method was applied to the qualitative and quantitative analyses of phenethylamine in real products obtained from the Japanese market. As the results, BDB (0.24 mg/mg), MMDA-2 (0.98 mg/mL) and 2C-I (0.016 mg/mg) were identified from the different products (powder, liquid and mushroom like). Because the procedure is simple, selective and sensitive, the present method seems to be useful for the qualitative and quantitative analyses of the designated phenethylamines in various samples including biological specimens.

Oxidation of Slurry Aluminide Coatings on Cast Stainless Steel Alloy CF8C-Plus at 800oC in Water Vapor

DOE Office of Scientific and Technical Information (OSTI.GOV)

Haynes, James A; Armstrong, Beth L; Dryepondt, Sebastien N

A new, cast austenitic stainless steel, CF8C-Plus, has been developed for a wide range of high temperature applications, including diesel exhaust components, turbine casings and turbocharger housings. CF8C-Plus offers significant improvements in creep rupture life and creep rupture strength over standard CF8C steel. However, at higher temperatures and in more aggressive environments, such as those containing significant water vapor, an oxidation-resistant protective coating will be necessary. The oxidation behavior of alloys CF8C and CF8C-Plus with various aluminide coatings were compared at 800oC in air plus 10 vol% water vapor. Due to their affordability, slurry aluminides were the primary coating systemmore » of interest, although chemical vapor deposition (CVD) and pack cementation coatings were also compared. Additionally, a preliminary study of the low cycle fatigue behavior of aluminized CF8C-Plus was conducted at 800oC. Each type of coating provided substantial improvements in oxidation behavior, with simple slurry aluminides showing very good oxidation resistance after 4,000 h testing in water vapor. Preliminary low cycle fatigue results indicated that thicker aluminide coatings degraded high temperature fatigue properties of CF8C-Plus, whereas thinner coatings did not. Results suggest that appropriately designed slurry aluminide coatings are a viable option for economical, long-term oxidation protection of austenitic stainless steels in water vapor.« less

Cast CF8C-Plus Stainless Steel for Turbocharger Applications

DOE Office of Scientific and Technical Information (OSTI.GOV)

Maziasz, P.J.; Shyam, A.; Evans, N.D.

2010-06-30

The purpose of this Cooperative Research and Development Agreement (CRADA) project is to provide the critical test data needed to qualify CF8C-Plus cast stainless steel for commercial production and use for turbocharger housings with upgraded performance and durability relative to standard commercial cast irons or stainless steels. The turbocharger technologies include, but are not limited to, heavy-duty highway diesel engines, and passenger vehicle diesel and gasoline engines. This CRADA provides additional critical high-temperature mechanical properties testing and data analysis needed to quality the new CF8C-Plus steels for turbocharger housing applications.

Acquisition of C1 inhibitor by Bordetella pertussis virulence associated gene 8 results in C2 and C4 consumption away from the bacterial surface

PubMed Central

Hovingh, Elise S.; Kuipers, Betsy; Pinelli, Elena; Rooijakkers, Suzan H. M.

2017-01-01

Whooping cough, or pertussis, is a contagious disease of the respiratory tract that is re-emerging worldwide despite high vaccination coverage. The causative agent of this disease is the Gram-negative Bordetella pertussis. Knowledge on complement evasion strategies of this pathogen is limited. However, this is of great importance for future vaccine development as it has become apparent that a novel pertussis vaccine is needed. Here, we unravel the effect of Virulence associated gene 8 (Vag8) of B. pertussis on the human complement system at the molecular level. We show that both recombinant and endogenously secreted Vag8 inhibit complement deposition on the bacterial surface at the level of C4b. We reveal that Vag8 binding to human C1-inhibitor (C1-inh) interferes with the binding of C1-inh to C1s, C1r and MASP-2, resulting in the release of active proteases that subsequently cleave C2 and C4 away from the bacterial surface. We demonstrate that the depletion of these complement components in the bacterial surrounding and subsequent decreased deposition on B. pertussis leads to less complement-mediated bacterial killing. Vag8 is the first protein described that specifically prevents C1s, C1r and MASP-2 binding to C1-inh and thereby mediates complement consumption away from the bacterial surface. Unravelling the mechanism of this unique complement evasion strategy of B. pertussis is one of the first steps towards understanding the interactions between the first line of defense complement and B. pertussis. PMID:28742139

Acquisition of C1 inhibitor by Bordetella pertussis virulence associated gene 8 results in C2 and C4 consumption away from the bacterial surface.

PubMed

Hovingh, Elise S; van den Broek, Bryan; Kuipers, Betsy; Pinelli, Elena; Rooijakkers, Suzan H M; Jongerius, Ilse

2017-07-01

Whooping cough, or pertussis, is a contagious disease of the respiratory tract that is re-emerging worldwide despite high vaccination coverage. The causative agent of this disease is the Gram-negative Bordetella pertussis. Knowledge on complement evasion strategies of this pathogen is limited. However, this is of great importance for future vaccine development as it has become apparent that a novel pertussis vaccine is needed. Here, we unravel the effect of Virulence associated gene 8 (Vag8) of B. pertussis on the human complement system at the molecular level. We show that both recombinant and endogenously secreted Vag8 inhibit complement deposition on the bacterial surface at the level of C4b. We reveal that Vag8 binding to human C1-inhibitor (C1-inh) interferes with the binding of C1-inh to C1s, C1r and MASP-2, resulting in the release of active proteases that subsequently cleave C2 and C4 away from the bacterial surface. We demonstrate that the depletion of these complement components in the bacterial surrounding and subsequent decreased deposition on B. pertussis leads to less complement-mediated bacterial killing. Vag8 is the first protein described that specifically prevents C1s, C1r and MASP-2 binding to C1-inh and thereby mediates complement consumption away from the bacterial surface. Unravelling the mechanism of this unique complement evasion strategy of B. pertussis is one of the first steps towards understanding the interactions between the first line of defense complement and B. pertussis.

Inner and outer segment junction (IS/OS line) integrity in ocular Behçet's disease.

PubMed

Yüksel, Harun; Türkcü, Fatih M; Sahin, Muhammed; Cinar, Yasin; Cingü, Abdullah K; Ozkurt, Zeynep; Sahin, Alparslan; Ari, Seyhmus; Caça, Ihsan

2014-08-01

In this study, we examined the spectral domain optical coherence tomography (OCT) findings of ocular Behçet's disease (OB) in patients with inactive uveitis. Specifically, we analyzed the inner and outer segment junction (IS/OS line) integrity and the effect of disturbed IS/OS line integrity on visual acuity. Patient files and OCT images of OB patients who had been followed-up between January and June of the year 2013 at the Dicle University Eye Clinic were evaluated retrospectively. Sixty-six eyes of 39 patients were included the study. OCT examination of the patients with inactive OB revealed that approximately 25% of the patients had disturbed IS/OS and external limiting membrane (EML) line integrity, lower visual acuity (VA), and lower macular thickness than others. Linear regression analysis revealed that macular thickness was not an independent variable for VA. In contrast, the IS/OS line integrity was an independent variable for VA in inactive OB patients. In this study, we showed that the IS/OS line integrity was an independent variable for VA in inactive OB patients. Further prospective studies are needed to evaluate the integrity of the IS/OS line in OB patients.

miR-150 Regulates Memory CD8 T Cell Differentiation via c-Myb.

PubMed

Chen, Zeyu; Stelekati, Erietta; Kurachi, Makoto; Yu, Sixiang; Cai, Zhangying; Manne, Sasikanth; Khan, Omar; Yang, Xiaolu; Wherry, E John

2017-09-12

MicroRNAs play an important role in T cell responses. However, how microRNAs regulate CD8 T cell memory remains poorly defined. Here, we found that miR-150 negatively regulates CD8 T cell memory in vivo. Genetic deletion of miR-150 disrupted the balance between memory precursor and terminal effector CD8 T cells following acute viral infection. Moreover, miR-150-deficient memory CD8 T cells were more protective upon rechallenge. A key circuit whereby miR-150 repressed memory CD8 T cell development through the transcription factor c-Myb was identified. Without miR-150, c-Myb was upregulated and anti-apoptotic targets of c-Myb, such as Bcl-2 and Bcl-xL, were also increased, suggesting a miR-150-c-Myb survival circuit during memory CD8 T cell development. Indeed, overexpression of non-repressible c-Myb rescued the memory CD8 T cell defects caused by overexpression of miR-150. Overall, these results identify a key role for miR-150 in memory CD8 T cells through a c-Myb-controlled enhanced survival circuit. Copyright © 2017 The Author(s). Published by Elsevier Inc. All rights reserved.

The C8-binding protein of human erythrocytes: interaction with the components of the complement-attack phase.

PubMed Central

Schönermark, S; Filsinger, S; Berger, B; Hänsch, G M

1988-01-01

C8-binding protein is an intrinsic membrane protein of the human erythrocyte. It inhibits the complement (C5b-9)-mediated lysis in a species-restricting manner. In the present study we incorporated C8bp, isolated from human erythrocytes, into sheep erythrocytes (SRBC). SRBC, normally sensitive to lysis by human C5b-9, became insensitive to lysis. Furthermore, we found that C8bp is incorporated into the membrane-attack complex C5b-9, most probably by interacting with C8, since C8bp has an affinity for C8, particularly for the C8 alpha-gamma-subunit. Antibodies to C8bp react with the C8 alpha-subunits and with C9, pointing to the possibility of a partial homology between these proteins. Images Figure 4 Figure 6 Figure 7 PMID:3366469

An outcome survey of 43 patients with Budd-Chiari syndrome due to Behçet's syndrome followed up at a single, dedicated center.

PubMed

Seyahi, Emire; Caglar, Erkan; Ugurlu, Serdal; Kantarci, Fatih; Hamuryudan, Vedat; Sonsuz, Abdullah; Melikoglu, Melike; Yurdakul, Sebahattin; Yazici, Hasan

2015-04-01

Behçet's syndrome (BS) is a well-recognized cause of Budd-Chiari syndrome (BCS); however, information about its clinical characteristics and outcome is limited. We reviewed the records of about 9000 patients with BS registered at the multidisciplinary Behçet's syndrome outpatient clinic at Cerrahpasa Medical Faculty between July 1977 and October 2013. We identified 43 (40 M/3 F) patients who were diagnosed as having BCS. Their outcome was evaluated between September 2012 and October 2013. In total, 33 patients (77%) had presented with liver-related symptoms (Group I), while 10 (23%) were asymptomatic for liver disease (Group II). This latter group had presented with symptoms related to the presence of major vessel disease such as fever, leg swelling, or dyspnea. The site of venous obstruction determined in 41 patients was inferior vena cava (IVC) and hepatic veins combined in 25 (61%), IVC alone in 12 (29%), and only hepatic veins in 4 patients (10%). The number of patients with concurrent obstruction in the hepatic veins and the IVC was less in Group II than in Group I (3/10 vs 22/31, p = 0.06). A total of 20 (19 M/1 F) patients (47%) had died at a median of 10 months after diagnosis. Mortality was significantly lower in Group II (10%) than in Group I (58%), (p = 0.011). By the end of the survey, 23 patients were alive, of whom 21 could be re-evaluated at the clinic. BCS associated with BS is usually due to IVC thrombosis with or without hepatic vein thrombosis. Silent cases exist and have a better prognosis. The mortality rate among the patients symptomatic for liver disease remains high. Copyright © 2014 Elsevier Inc. All rights reserved.

Mutations in C8ORF37 cause Bardet Biedl syndrome (BBS21)

PubMed Central

Heon, Elise; Kim, Gunhee; Qin, Sophie; Garrison, Janelle E.; Tavares, Erika; Vincent, Ajoy; Nuangchamnong, Nina; Scott, C. Anthony; Slusarski, Diane C.; Sheffield, Val C.

2016-01-01

Bardet Biedl syndrome (BBS) is a multisystem genetically heterogeneous ciliopathy that most commonly leads to obesity, photoreceptor degeneration, digit anomalies, genito-urinary abnormalities, as well as cognitive impairment with autism, among other features. Sequencing of a DNA sample from a 17-year-old female affected with BBS did not identify any mutation in the known BBS genes. Whole-genome sequencing identified a novel loss-of-function disease-causing homozygous mutation (K102*) in C8ORF37, a gene coding for a cilia protein. The proband was overweight (body mass index 29.1) with a slowly progressive rod-cone dystrophy, a mild learning difficulty, high myopia, three limb post-axial polydactyly, horseshoe kidney, abnormally positioned uterus and elevated liver enzymes. Mutations in C8ORF37 were previously associated with severe autosomal recessive retinal dystrophies (retinitis pigmentosa RP64 and cone-rod dystrophy CORD16) but not BBS. To elucidate the functional role of C8ORF37 in a vertebrate system, we performed gene knockdown in Danio rerio and assessed the cardinal features of BBS and visual function. Knockdown of c8orf37 resulted in impaired visual behavior and BBS-related phenotypes, specifically, defects in the formation of Kupffer’s vesicle and delays in retrograde transport. Specificity of these phenotypes to BBS knockdown was shown with rescue experiments. Over-expression of human missense mutations in zebrafish also resulted in impaired visual behavior and BBS-related phenotypes. This is the first functional validation and association of C8ORF37 mutations with the BBS phenotype, which identifies BBS21. The zebrafish studies hereby show that C8ORF37 variants underlie clinically diagnosed BBS-related phenotypes as well as isolated retinal degeneration. PMID:27008867

Comprehensive Proteoform Characterization of Plasma Complement Component C8αβγ by Hybrid Mass Spectrometry Approaches

NASA Astrophysics Data System (ADS)

Franc, Vojtech; Zhu, Jing; Heck, Albert J. R.

2018-03-01

The human complement hetero-trimeric C8αβγ (C8) protein assembly ( 150 kDa) is an important component of the membrane attack complex (MAC). C8 initiates membrane penetration and coordinates MAC pore formation. Here, we charted in detail the structural micro-heterogeneity within C8, purified from human plasma, combining high-resolution native mass spectrometry and (glyco)peptide-centric proteomics. The intact C8 proteoform profile revealed at least 20 co-occurring MS signals. Additionally, we employed ion exchange chromatography to separate purified C8 into four distinct fractions. Their native MS analysis revealed even more detailed structural micro-heterogeneity on C8. Subsequent peptide-centric analysis, by proteolytic digestion of C8 and LC-MS/MS, provided site-specific quantitative profiles of different types of C8 glycosylation. Combining all this data provides a detailed specification of co-occurring C8 proteoforms, including experimental evidence on N-glycosylation, C-mannosylation, and O-glycosylation. In addition to the known N-glycosylation sites, two more N-glycosylation sites were detected on C8. Additionally, we elucidated the stoichiometry of all C-mannosylation sites in all the thrombospondin-like (TSP) domains of C8α and C8β. Lastly, our data contain the first experimental evidence of O-linked glycans located on C8γ. Albeit low abundant, these O-glycans are the first PTMs ever detected on this subunit. By placing the observed PTMs in structural models of free C8 and C8 embedded in the MAC, it may be speculated that some of the newly identified modifications may play a role in the MAC formation. [Figure not available: see fulltext.

Quantification of 21 antihypertensive drugs in serum using UHPLC-MS/MS.

PubMed

Gundersen, Per Ole M; Helland, Arne; Spigset, Olav; Hegstad, Solfrid

2018-04-28

Poor drug adherence in hypertensive patients can lead to treatment failure and increased cardiovascular morbidity, as well as increased costs to society. An analytical method based on ultra-performance liquid chromatography tandem mass spectrometry (UPLC-MSMS) was developed and validated for use in routine therapeutic drug monitoring (TDM). The method includes 21 antihypertensive drugs or active metabolites from the groups beta blockers (n=5), calcium antagonists (n=5), angiotensin II receptor antagonists (n=4), angiotensin converting enzyme (ACE) inhibitors (n=3) and diuretics (n = 3), in addition to one α1-selective alpha blocker. A 200 µL serum sample was handled automatically using a pipetting robot. Protein precipitation was performed with 600 µL of 1% formic acid in acetonitrile (v:v) and phospholipid removal was carried out using a Waters OSTRO™ 96-well plate. After evaporation and reconstitution the eluent was injected thrice with different inlet and mass spectrometric methods to cover the different physico-chemical properties of the drugs and the variations in therapeutic concentration ranges between drugs. Acquity UPLC BEH C18 (2.1x50mm, 1.7 µm) column equipped with a corresponding pre-column was used for chromatographic separation. For every analyte an isotopically labelled analogue served as internal standard, except for lisinopril where enalaprilat-d5 was used. Accuracies were in the range of -13.7 to 13.2% and intra-day and inter-day precisions in the range of 1.1 to 10.5%. The linearity within the calibration ranges expressed as coefficient of determination was higher than 0.995 for all compounds. Matrix effects and recovery efficiencies were within acceptable limits. The limits of quantitation varied from 0.02 to 10.7 µg/L. The stability of the drugs in serum at different conditions was tested. Diltiazem was not stable at 4-8 °C with up to 23.5 % loss after six days. Degradation of atenolol, irbesartan, bendroflumethiazide

The structural proteins of epidemic and historical strains of Zika virus differ in their ability to initiate viral infection in human host cells.

PubMed

Bos, Sandra; Viranaicken, Wildriss; Turpin, Jonathan; El-Kalamouni, Chaker; Roche, Marjolaine; Krejbich-Trotot, Pascale; Desprès, Philippe; Gadea, Gilles

2018-03-01

Mosquito-borne Zika virus (ZIKV) recently emerged in South Pacific islands and Americas where large epidemics were documented. In the present study, we investigated the contribution of the structural proteins C, prM and E in the permissiveness of human host cells to epidemic strains of ZIKV. To this end, we evaluated the capacity of the epidemic strain BeH819015 to infect epithelial A549 and neuronal SH-SY5Y cells in comparison to the African historical MR766 strain. For that purpose, we generated a molecular clone of BeH819015 and a chimeric clone of MR766 which contains the BeH819015 structural protein region. We showed that ZIKV containing BeH819015 structural proteins was much less efficient in cell-attachment leading to a reduced susceptibility of A549 and SH-SY5Y cells to viral infection. Our data illustrate a previously underrated role for C, prM, and E in ZIKV epidemic strain ability to initiate viral infection in human host cells. Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.

Partial discharges and breakdown in C3F8

NASA Astrophysics Data System (ADS)

Koch, M.; Franck, C. M.

2014-10-01

Traditional search processes of gases or gas mixtures for replacing SF6 involve time consuming measurements of partial discharges and breakdown behaviour for several voltage waveforms and different field configurations. Recently a model for prediction of this behaviour for SF6 was described in literature. The model only requires basic properties of the gas such as the critical field strength and the effective ionization coefficient, which can be obtained by swarm parameter measurements, and thermodynamic properties, which can be calculated. In this paper, we show for the well-known and electronegative gas octafluoropropane (C3F8) that it is possible to transfer the model developed for SF6 to this gas to describe the breakdown behaviour of C3F8. Thus the model can be beneficial in the screening process of new insulation gases.

Epidemiology and management of neuropsychiatric disorders in Behçet's syndrome.

PubMed

Talarico, Rosaria; Palagini, Laura; d'Ascanio, Anna; Elefante, Elena; Ferrari, Claudia; Stagnaro, Chiara; Tani, Chiara; Gemignani, Angelo; Mauri, Mauro; Bombardieri, Stefano; Mosca, Marta

2015-03-01

Behçet's syndrome (BS) is a systemic, chronic, relapsing vasculitis, typically characterized by recurrent orogenital ulcers, ocular inflammation and skin manifestations; articular, vascular, gastroenteric and neurological involvement may also occur. Besides the other clinical features of BS, it seems relatively frequent that patients with BS develop a neurobehavioural syndrome, characterized by euphoria, bipolar disorders and paranoid attitudes, loss of insight/disinhibition, and indifference to their disease, defined as 'neuro-psycho-BS'. To date, the pathogenetic mechanism underlying neuro-psycho-BS has not been determined. It may be secondary to organic neurological involvement, or it may be related to poor quality of life and the relapsing course of the disease. Another engaging theory suggests that it could be related to the frequent observation of psychiatric symptoms during relapses or, in some cases, in the phases preceding reactivation of the disease; these elements suggest that psychiatric disorders in BS could represent a crucial element, whether a psychiatric subset or a distinct clinical feature of the disease. Moreover, it has been reported that cognitive impairment in BS can be seen with or without central nervous system involvement. Globally, psychiatric symptoms have been described as being multifaceted, ranging from anxiety disorders to depressive-bipolar disorders or to psychotic ones. In addition, some psychological characteristics of BS patients seem to predispose them to maladaptive stress management, which may lead to stress-related disorders, including anxiety and depression. Therefore, the aims of this review are to explore the epidemiology of neuro-psycho-BS by evaluating the relationship between the stress system and the multifaceted psychiatric manifestations in BS, and to summarize the therapeutic strategy used.

The prevalence of Behçet's disease in Korea: data from Health Insurance Review and Assessment Service from 2011 to 2015.

PubMed

Kim, Ji Na; Kwak, Sang Gyu; Choe, Jung-Yoon; Kim, Seong-Kyu

2017-01-01

The aim of this study is to identify the prevalence of Behçet's disease (BD) from data in the Healthcare Bigdata Hub of the Health Insurance Review & Assessment (HIRA) Service from 2011 to 2015 in Korea. This study collected information on primary and auxiliary diagnoses of BD (M352) by physicians according to the Korean Standard Classification of Diseases (KCD) codes. The prevalence of BD was assessed on the basis of age, sex, and geographical distribution. We used time series analysis, using the ARIMA model for the expected prevalence of BD from 2016 to 2025. The overall prevalence of BD was gradually increased, ranging from 32.8 to 35.7 per 100,000 population over the study period. The male to female ratio of BD ranged from 0.54:1 to 0.56:1, revealing a female predominance from 2011 to 2015. Among five districts in Korea, the prevalence in the Seoul Metropolitan district was the highest, with a slowly increasing trend for the study period, accounting for about 60.3% of total BD patients. The expected prevalence of BD patients was estimated to range from 36.9 (95% CI 35.0 - 39.0) to 44.7 (95% CI 40.2 - 49.6) between 2016 and 2025. This study found that the overall prevalence of BD is estimated to be approximately 35.0 per 100,000 population, with female predominance, and predicts gradually increased prevalence of BD in Korea.

Determination of a highly selective mixed-affinity sigma receptor ligand, in rat plasma by ultra performance liquid chromatography mass spectrometry and its application to a pharmacokinetic study

PubMed Central

Jamalapuram, Seshulatha; Vuppala, Pradeep K.; Mesangeau, Christophe; McCurdy, Christopher R.; Avery, Bonnie A.

2014-01-01

A selective, rapid and sensitive ultra performance liquid chromatography mass spectrometry (UPLC/MS) method was developed and validated to quantitate a highly selective mixed-affinity sigma receptor ligand, CM156 (3-(4-(4-cyclohexylpiperazin-1-yl)butyl)benzo[d] thiazole-2(3H)-thione), in rat plasma. CM156 and the internal standard (aripiprazole) were extracted from plasma samples by a single step liquid–liquid extraction using chloroform. The analysis was carried out on an ACQUITY UPLCTM BEH HILIC column (1.7 µm, 2.1 mm × 50 mm) with isocratic elution at flow rate of 0.2 mL/min using 10 mM ammonium formate in 0.1% formic acid and acetonitrile (10:90) as the mobile phase. The detection of the analyte was performed on a mass spectrometer operated in selected ion recording (SIR) mode with positive electrospray ionization (ESI). The validated analytical method resulted in a run time of 4 min and the retention times observed were 2.6 ± 0.1 and 2.1 ± 0.1 min for CM156 and the IS, respectively. The calibration curve exhibited excellent linearity over a concentration range of 5–4000 ng/mL with the lower limit of quantification of 5 ng/mL. The intra- and inter-day precision values were below 15% and accuracy ranged from −6.5% to 5.0%. The mean recovery of CM156 from plasma was 96.8%. The validated method was applied to a pilot intravenous pharmacokinetic study in rats. PMID:22406103

Behçet's syndrome: a critical digest of the 2012-2013 literature.

PubMed

Hatemi, Gulen; Seyahi, Emire; Fresko, Izzet; Hamuryudan, Vedat

2013-01-01

Recent work on the epidemiology of Behçet's syndrome confirm the previous contention that the prevalence increases from North to South and that the disease follows a more severe course in patients with an early age of onset, also when specifically studied in patients with eye and gastrointestinal involvement. Imputation analyses of genome wide association studies revealed new associations such as ERAP-1, CCR1-CCR3, KLRC4 and STAT4. Further work suggested that the BS associated variant of STAT4 is not related to the previously reported one associated with autoimmune diseases such as rheumatoid arthritis and systemic lupus erythematosus. The prognosis of eye involvement seems to have improved over the last decade with better visual acuity and less frequent severe complications in patients reported in the 2000s compared to the 1990s. Immunosuppresssives and corticosteroids were observed to improve the outcome of cardiac involvement in BS. Recurrence and complications were common in these patients when surgery was performed without immunosuppressives. The cognitive dysfunction in BS patients with neurological involvement seemed to be severely impaired and worse than that of multiple sclerosis patients, suggesting a more severe 'frontal'-executive dysfunction. Gastrointestinal involvement seemed to be brought to a remission in the majority of BS within 5 years, with about one fourth of the patients following a relapsing or chronic disease course. TNF-α inhibitors have become standard treatment for patients resistant to conventional immunosuppressives. Switching to another biologic can be effective when the first or even the second biologic agent fails or is stopped due to adverse events.

Post-thrombotic syndrome and venous disease-specific quality of life in patients with vascular Behçet's disease.

PubMed

Alibaz-Oner, Fatma; Aldag, Belgin; Aldag, Mustafa; Unal, A Ugur; Mutiş, Aydan; Toptas, Tayfur; Ergun, Tulin; Direskeneli, Haner

2016-07-01

Deep venous thrombosis (DVT) is the most common form of vascular involvement in Behçet's disease (BD). Chronic post-thrombotic syndrome (PTS) develops in up to one-half of patients with DVT and is associated with impaired quality of life (QoL). There are no data on the severity of DVT-related PTS and its effect on QoL in patients with vascular BD (VBD). We aimed to evaluate PTS and venous disease-specific QoL in patients with VBD. This study included 50 patients (41 men, nine women) with VBD and 31 individuals matched for age and gender (22 men, nine women) with DVT associated with non-BD causes. The Villalta scale was used to assess PTS. The Venous Disability Score and the Venous Clinical Severity Score were used for the assessment of venous disease. Venous disease-specific QoL was measured through Venous Insufficiency Epidemiological and Economic Study Quality of Life/Symptom (VEINES-QoL/Sym) questionnaire. The Behçet Syndrome Activity Score (BSAS) questionnaire was used to assess disease activity. We observed a significantly lower risk of PTS together with significantly better VEINES-QoL/Sym, and Venous Disability Score in the VBD group compared with the non-BD group. When VBD patients with PTS were compared with patients without PTS, VEINES-QoL/Sym, and Venous Clinical Severity Score were significantly worse. BSAS was also significantly higher in patients with PTS. An inverse correlation was found between the VEINES-QoL and the BSAS in multivariate analysis. There were no differences between anticoagulant users and nonusers regarding the presence of PTS and scores of all of the venous assessment tools. We found lower PTS risk and better venous disease-specific QoL, symptom severity, and venous disability scores in VBD patients compared with the non-BD group. Venous disease-specific QoL negatively correlated with disease activity. Effective control of vascular inflammation through treatment in VBD might explain lower rates of PTS and better venous Qo

C8 cross transfer for the treatment of caudal brachial plexus avulsion in three dogs.

PubMed

Moissonnier, Pierre; Carozzo, Claude; Thibaut, Jean-Laurent; Escriou, Catherine; Hidalgo, Antoine; Blot, Stéphane

2017-01-01

To evaluate the cervical nerve 8 cross-transfer technique (C8CT) as a part of surgical treatment of caudal brachial plexus avulsion (BPA) in the dog. Case series. Client-owned dogs suspected to have caudal BPA based on neurological examination and electrophysiological testing (n = 3). The distal stump of the surgically transected contralateral C8 ventral branch (donor) was bridged to the proximal stump of the avulsed C8 ventral branch (recipient) and secured with 9-0 polypropylene suture under an operating microscope. A carpal panarthrodesis was performed on the injured limb after C8CT. Surgical exploration confirmed avulsion of nerve roots C7, C8, and T1 in all cases. There was no evidence of an iatrogenic effect on the donor forelimb. Gradual improvement in function of the affected forelimb occurred in all dogs, with eventual recovery of voluntary elbow extension. Reinnervation was evident in EMG recordings 6 months postoperatively in all three dogs. Stimulation of the donor C8 ventral branch led to motor evoked potentials in the avulsed side triceps brachialis and radial carpus extensor muscles. Variable functional outcome was observed in the 3 dogs during clinical evaluation 3-4 years after surgery. Digital abrasion wounds, distal interphalangeal infectious arthritis, and self-mutilation necessitated distal phalanx amputation of digits 3 and 4 in 2 dogs. C8CT provided partial reconnection of the donor C8 ventral branch to the avulsed brachial plexus in the 3 dogs of this series. Reinnervation resulted in active elbow extension and promoted functional recovery in the affected limb. © 2017 The American College of Veterinary Surgeons.

8. Historic American Buildings Survey, James C. Massey, Photographer November, ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

8. Historic American Buildings Survey, James C. Massey, Photographer November, 1959 INTERIOR LOOKING TO REAR. - Provident Life & Trust Company Bank, 407-409 Chestnut Street, Philadelphia, Philadelphia County, PA

Quantification of phenolic acids and their methylates, glucuronides, sulfates and lactones metabolites in human plasma by LC-MS/MS after oral ingestion of soluble coffee.

PubMed

Marmet, Cynthia; Actis-Goretta, Lucas; Renouf, Mathieu; Giuffrida, Francesca

2014-01-01

Chlorogenic acids and derivatives like phenolic acids are potentially bioactive phenolics, which are commonly found in many foods. Once absorbed, chlorogenic and phenolic acids are highly metabolized by the intestine and the liver, producing glucuronidated and/or sulphated compounds. These metabolites were analyzed in human plasma using a validated liquid chromatography-electrospray ionization-tandem mass spectrometry (LC-ESI-MS/MS) method. After protein precipitation, phenolic acids and their metabolites were extracted by using ethanol and chromatographic separation was achieved by reversed-phase using an Acquity UPLC BEH C18 column combined with a gradient elution system using 1% acetic acid aqueous solution and 1% acetic acid with 100% acetonitrile. The method was able to quantify 56 different compounds including 24 phenolic acids, 4 lactones, 15 sulfates and 13 glucuronides metabolites between 5 and 1000nM in plasma for most of them, except for m-dihydrocoumaric acid, 5-ferulloylquinic-glucuronide, 4-methoxycinnamic acid, 3-phenylpropionic acid, 3-(4-methoxyphenyl)propionic acid (25 to 1000nM) and p-dihydrocoumaric acid (50-1000nM). Values of repeatability and intermediate reproducibility were below 15% of deviation in general, and maximum 20% for the lowest concentrations. The validated method was successfully applied to quantify phenolic acids and their metabolites in plasma obtained after oral ingestion of soluble coffee. In conclusion, the developed and validated method is proved to be very sensitive, accurate and precise for the quantification of these possible dietary phenols. Copyright © 2013 Elsevier B.V. All rights reserved.

Quantitative determination of dopamine in human plasma by a highly sensitive LC-MS/MS assay: Application in preterm neonates.

PubMed

Zhang, Daping; Wu, Lei; Chow, Diana S-L; Tam, Vincent H; Rios, Danielle R

2016-01-05

The determination of dopamine facilitates better understanding of the complex brain disorders in the central nervous system and the regulation of endocrine system, cardiovascular functions and renal functions in the periphery. The purpose of this study was to develop a highly sensitive and reliable assay for the quantification of dopamine in human neonate plasma. Dopamine was extracted from human plasma by strong cation exchange (SCX) solid phase extraction (SPE), and subsequently derivatized with propionic anhydride. The derivatized analyte was separated by a Waters Acquity UPLC BEH C18 column using gradient elution at 0.4 ml/min with mobile phases A (0.2% formic acid in water [v/v]) and B (MeOH-ACN [v/v, 30:70]). Analysis was performed under positive electrospray ionization tandem mass spectrometer (ESI-MS/MS) in the multiple reaction monitoring (MRM) mode. The stable and relatively non-polar nature of the derivatized analyte enables reliable quantification of dopamine in the range of 10-1000 pg/ml using 200 μl of plasma sample. The method was validated with intra-day and inter-day precision less than 7%, and the intra-day and inter-day accuracy of 91.9-101.9% and 92.3-102.6%, respectively. The validated assay was applied to quantify dopamine levels in two preterm neonate plasma samples. In conclusion, a sensitive and selective LC-MS/MS method has been developed and validated, and successfully used for the determination of plasma dopamine levels in preterm neonates. Copyright © 2015 Elsevier B.V. All rights reserved.

Pharmacokinetic determination of ephedrine in Herba Ephedrae and Wu Tou Tang decoctions in rats using ultra performance liquid chromatography tandem mass spectrometry.

PubMed

Zheng, Zhijie; Yan, Tongmeng; Chen, Weiying; Ye, Ling; Tang, Lan; Liu, Zhongqiu

2012-08-01

A rapid and sensitive ultra performance liquid chromatography tandem mass spectrometry method was developed and validated for the determination and quantification of ephedrine in rat plasma samples. An Acquity UPLC BEH C18 column (1.7 μm, 2.1 mm × 50 mm) was used for chromatographic separation. Electrospray ionization in the positive mode was used, and the precursor-fragment ion pairs of m/z 166/148 and m/z 289/97 were adopted to characterize ephedrine and testosterone (internal standard), respectively. The method was validated using 10, 100 and 500 ng/mL of ephedrine. It demonstrated adequate levels of precision and accuracy, matrix effect, extraction recovery and stability. Linearity over the concentration range of 0.5-2000 ng/mL was acceptable with a correlation coefficient (r²) better than 0.990. To determine the pharmacokinetic behaviour of this sympathomimetic compound in the Sprague-Dawley rats, ephedrine hydrochloride, Herba Ephedrae single-herb and Wu Tou Tang decoctions were administered orally, and ephedrine hydrochloride was also administered by intravenous injection, and blood samples were collected over 24 h. Ephedrine was measured in plasma and pharmacokinetic parameters were determined by using the standard non-compartmental method and calculated by using Practical Pharmacokinetic Program-Version 87/97. The AUC(0-t) and T(max) values were significantly different (p < 0.05). Ephedrine AUC(0-t) values were significantly lower following the Wu Tou Tang decoction compared to the other oral treatments, suggesting that some components in the decoction may reduce the bioavailability of ephedrine.

Simultaneous detection of 15 antibiotic growth promoters in bovine muscle, blood and urine by UPLC-MS/MS.

PubMed

Wang, Zhi; Shi, Zongwei; Xi, Cunxian; Wang, Guomin; Cao, Shurui; Zhang, Lei; Tang, Bobin; Mu, Zhaode

2017-12-01

An analytical method was established for the rapid detection of antibiotic growth promoters (AGPs) in bovine muscle, and bovine blood and bovine urine, using ultra high performance liquid chromatography tandem mass spectrometry (UPLC-MS/MS). After the addition of an aqueous solution of EDTA-Na 2 , the pH of bovine urine samples was directly adjusted to 5.2 by acetic acid-ammonium acetate and purified by HLB solid-phase extraction cartridge; bovine muscle and bovine blood samples processing were extracted with acetonitrile (ACN) and ACNwater (90:10; v/v) without any purification step. The samples were then centrifuged, concentrated and analysed by UPLC-MS/MS on an ACQUITY UPLC® BEH C18 column using gradient elution. The developed method was validated and mean recovery percentages at three spiked levels were 74-119%, 76-115% and 76-119%, respectively, in bovine muscle, bovine blood, and bovine urine. The relative standard deviation (RSD) ranged from 1.0% to 14.7% in spiked bovine muscle, bovine blood and bovine urine. The limits of detection (LOD) of all analytes were in the ranges 0.11-3.82 µg kg -1 , 0.10-2.49 µg kg -1 and 0.06-4.53 µg kg -1 in bovine muscle, bovine blood, and bovine urine, respectively. The method was sensitive, accurate and was applied to monitor real samples. To the best of our knowledge, this is first method available for simultaneous determination of several classes of APGs in bovine muscle, and bovine blood and bovine urine.

Development of Simultaneous Analysis of Thirteen Bioactive Compounds in So-Cheong-Ryong-Tang Using UPLC-DAD

PubMed Central

2018-01-01

So-Cheong-Ryong-Tang, which is a standardized Korean medicine of the National Health Insurance, is a traditional prescription for the treatment of allergic rhinitis, bronchitis, and bronchial asthma. Simultaneous analysis and development of SCRT is essential for its stability, efficacy, and risk management. In this study, a simple, reliable, and accurate method using ultrahigh-performance liquid chromatography (UPLC) fingerprinting with a diode array detector (DAD) was developed for the simultaneous analysis. The chromatographic separation of the analytes was performed by an ACQUITY UPLC BEH C18 column (1.7 μM, 2.1 × 100 mm, Waters) with a mobile phase of water containing 0.01% (v/v) phosphoric acid and acetonitrile containing 0.01% (v/v) phosphoric acid. The flow rate and detection wavelength were set at 0.4 mL/min and 215, 230, 254, and 280 nm. All calibration curves of the thirteen components showed good linearity (R2 > 0.999). The limit of detection and limit of quantification ranged 0.001–0.360 and 0.004–1.200 µg/mL, respectively. The relative standard deviation (RSD) of intra- and interday was less than 2.60%, and the recoveries were within the range 76.08–103.79% with an RSD value of 0.03–1.50%. The results showed that the developed method was simple, reliable, accurate, sensitive, and precise for the quantification of bioactive components of SCRT. PMID:29854559

Validated UPLC-MS/MS method for determination of moclobemide in human brain cell supernatant and its application to bidirectional transport study.

PubMed

Li-Bo, Dai; Miao, Yan; Huan-De, Li; Ping-Fei, Fang; Feng, Wang; Yang, Deng

2013-09-01

A simple and sensitive analytical method based on ultraperformance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) has been developed for determination of moclobemide in human brain cell monolayer as an in vitro model of blood-brain barrier. Brucine was employed as the internal standard. Moclobemide and internal standard were extracted from cell supernatant by ethyl acetate after alkalinizing with sodium hydroxide. The UPLC separation was performed on an Acquity UPLC(TM) BEH C18 column (50 × 2.1 mm, 1.7 µm, Waters, USA) with a mobile phase consisting of methanol-water (29.5:70.5, v/v); the water in the mobile phase contained 0.05% ammonium acetate and 0.1% formic acid. Detection of the analytes was achieved using positive ion electrospray via multiple reaction monitoring mode. The mass transitions were m/z 269.16 → 182.01 for moclobemide and m/z 395.24 → 324.15 for brucine. The extraction recovery was 83.0-83.4% and the lower limit of quantitation (LLOQ) was 1.0 ng/mL for moclobemide. The method was validated from LLOQ to 1980 ng/mL with a coefficient of determination greater than 0.999. Intra- and inter-day accuracies of the method at three concentrations ranged from 89.1 to 100.9% for moclobemide with precision of 1.1-9.6%. This validated method was successfully applied to bidirectional transport study of moclobemide blood-brain barrier permeability. Copyright © 2013 John Wiley & Sons, Ltd.

Automatic and rapid identification of glycopeptides by nano-UPLC-LTQ-FT-MS and proteomic search engine.

PubMed

Giménez, Estela; Gay, Marina; Vilaseca, Marta

2017-01-30

Here we demonstrate the potential of nano-UPLC-LTQ-FT-MS and the Byonic™ proteomic search engine for the separation, detection, and identification of N- and O-glycopeptide glycoforms in standard glycoproteins. The use of a BEH C18 nanoACQUITY column allowed the separation of the glycopeptides present in the glycoprotein digest and a baseline-resolution of the glycoforms of the same glycopeptide on the basis of the number of sialic acids. Moreover, we evaluated several acquisition strategies in order to improve the detection and characterization of glycopeptide glycoforms with the maximum number of identification percentages. The proposed strategy is simple to set up with the technology platforms commonly used in proteomic labs. The method allows the straightforward and rapid obtention of a general glycosylated map of a given protein, including glycosites and their corresponding glycosylated structures. The MS strategy selected in this work, based on a gas phase fractionation approach, led to 136 unique peptides from four standard proteins, which represented 78% of the total number of peptides identified. Moreover, the method does not require an extra glycopeptide enrichment step, thus preventing the bias that this step could cause towards certain glycopeptide species. Data are available via ProteomeXchange with identifier PXD003578. We propose a simple and high-throughput glycoproteomics-based methodology that allows the separation of glycopeptide glycoforms on the basis of the number of sialic acids, and their automatic and rapid identification without prior knowledge of protein glycosites or type and structure of the glycans. Copyright © 2016 Elsevier B.V. All rights reserved.

Infliximab for uveitis of Behçet's syndrome: a trend for earlier initiation.

PubMed

Guzelant, Gul; Ucar, Didar; Esatoglu, Sinem Nihal; Hatemi, Gulen; Ozyazgan, Yilmaz; Yurdakul, Sebahattin; Seyahi, Emire; Yazici, Hasan; Hamuryudan, Vedat

2017-01-01

The prognosis of uveitis in Behçet's syndrome (BS) has improved over decades. Whether this is related to the use of more aggressive management strategies is not known. This is a retrospective study of BS patients who received infliximab (IFX) for refractory eye disease between 2003-2015. The patients were divided into two groups according to the date of onset of in IFX treatment as before and after 2013. We compared the two groups in terms of disease characteristics at the onset of IFX treatment and response to treatment. There were 43 patients in the old and 14 patients in the new group. The duration of uveitis and previous immunosuppressive treatment before the initiation of IFX were significantly shorter in the new group compared to the old group (p=0.043 and p=0.028, respectively). The baseline visual acuity (VA) at the initiation of IFX was better in the new group, but this was only significant for the left eye. Treatment with IFX was effective in both groups in preserving VA and this was more pronounced in the new group. Attack frequency under IFX was significantly lower in the new group (p<0.001). IFX seems to be initiated earlier and also in less severe cases during the course of BS uveitis than before. Despite the few numbers of patients and relatively short duration of follow-up, our results give a hint that this change has improved the outcome.

8. VIEW OF 'TRIUMPH' CORN SHELLER (C. O. Bartlett & ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

8. VIEW OF 'TRIUMPH' CORN SHELLER (C. O. Bartlett & Snow Co., Cleveland), LOCATED IN THE BASEMENT, USED TO REMOVE CORN KENNELS FROM THE COB. Photographer: Louise Taft Cawood, July 1986 - Alexander's Grist Mill, Lock 37 on Ohio & Erie Canal, South of Cleveland, Valley View, Cuyahoga County, OH

The prolyl isomerase Pin1 modulates development of CD8+ cDC in mice.

PubMed

Barberi, Theresa J; Dunkle, Alexis; He, You-Wen; Racioppi, Luigi; Means, Anthony R

2012-01-01

Pin1 has previously been described to regulate cells that participate in both innate and adaptive immunity. Thus far, however, no role for Pin1 has been described in modulating conventional dendritic cells, innate antigen presenting cells that potently activate naïve T cells, thereby bridging innate and adaptive immune responses. When challenged with LPS, Pin1-null mice failed to accumulate spleen conventional dendritic cells (cDC). Analysis of steady-state spleen DC populations revealed that Pin1-null mice had fewer CD8+ cDC. This defect was recapitulated by culturing Pin1-null bone marrow with the DC-instructive cytokine Flt3 Ligand. Additionally, injection of Flt3 Ligand for 9 days failed to induce robust expansion of CD8+ cDC in Pin1-null mice. Upon infection with Listeria monocytogenes, Pin1-null mice were defective in stimulating proliferation of adoptively transferred WT CD8+ T cells, suggesting that decreases in Pin1 null CD8+ cDC may affect T cell responses to infection in vivo. Finally, upon analyzing expression of proteins involved in DC development, elevated expression of PU.1 was detected in Pin1-null cells, which resulted from an increase in PU.1 protein half-life. We have identified a novel role for Pin1 as a modulator of CD8+ cDC development. Consistent with reduced numbers of CD8+ cDC in Pin1-null mice, we find that the absence of Pin1 impairs CD8+ T cell proliferation in response to infection with Listeria monocytogenes. These data suggest that, via regulation of CD8+ cDC production, Pin1 may serve as an important modulator of adaptive immunity.

The Role of CYP2C8 and CYP2C9 Genotypes in Losartan-Dependent Inhibition of Paclitaxel Metabolism in Human Liver Microsomes.

PubMed

Mukai, Yuji; Senda, Asuna; Toda, Takaki; Eliasson, Erik; Rane, Anders; Inotsume, Nobuo

2016-06-01

The aim of the present study was to further investigate a previously identified metabolic interaction between losartan and paclitaxel, which is one of the marker substrates of CYP2C8, by using human liver microsomes (HLMs) from donors with different CYP2C8 and CYP2C9 genotypes. Although CYP2C8 and CYP2C9 exhibit genetic linkage, previous studies have yet to determine whether losartan or its active metabolite, EXP-3174 which is specifically generated by CYP2C9, is responsible for CYP2C8 inhibition. Concentrations of 6α-hydroxypaclitaxel and EXP-3174 were measured by high-performance liquid chromatography after incubations with paclitaxel, losartan or EXP-3174 in HLMs from seven donors with different CYP2C8 and CYP2C9 genotypes. The half maximal inhibitory concentration (IC50 ) values were not fully dependent on CYP2C8 genotypes. Although the degree of inhibition was small, losartan significantly inhibited the production of 6α-hydroxypaclitaxel at a concentration of 1 μmol/L in only HL20 with the CYP2C8*3/*3 genotype. HLMs with either CYP2C9*2/*2 or CYP2C9*1/*3 exhibited a lower losartan intrinsic clearance (Vmax /Km ) than other HLMs including those with CYP2C9*1/*1 and CYP2C9*1/*2. Significant inhibition of 6α-hydroxypaclitaxel formation by EXP-3174 could only be found at levels that were 50 times higher (100 μmol/L) than the maximum concentration generated in the inhibition study using losartan. These results suggest that the metabolic interaction between losartan and paclitaxel is dependent on losartan itself rather than its metabolite and that the CYP2C8 inhibition by losartan is not affected by the CYP2C9 genotype. Further study is needed to define the effect of CYP2C8 genotypes on losartan-paclitaxel interaction. © 2015 Nordic Association for the Publication of BCPT (former Nordic Pharmacological Society).

C20H4(C4F8)3: a fluorine-containing annulated corannulene that is a better electron acceptor than C60.

PubMed

Kuvychko, Igor V; Dubceac, Cristina; Deng, Shihu H M; Wang, Xue-Bin; Granovsky, Alexander A; Popov, Alexey A; Petrukhina, Marina A; Strauss, Steven H; Boltalina, Olga V

2013-07-15

At sixes and sevens: The reaction of corannulene with 35 equivalents of 1,4-C4F8I2 is an efficient and a relatively selective process that yields two main products in which six H atoms are substituted with three C4F8 moieties that form six- and seven-membered rings. Low-temperature photoelectron spectroscopy showed the electron affinity of the major isomer (shown) exceeds that of C60 (2.74±0.02 and 2.689±0.008 eV, respectively). Copyright © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

42 CFR 68c.8 - What does the CIR-LRP provide to participants?

Code of Federal Regulations, 2012 CFR

2012-10-01

... 42 Public Health 1 2012-10-01 2012-10-01 false What does the CIR-LRP provide to participants? 68c.8 Section 68c.8 Public Health PUBLIC HEALTH SERVICE, DEPARTMENT OF HEALTH AND HUMAN SERVICES FELLOWSHIPS, INTERNSHIPS, TRAINING NATIONAL INSTITUTE OF CHILD HEALTH AND HUMAN DEVELOPMENT CONTRACEPTION AND...

42 CFR 68c.8 - What does the CIR-LRP provide to participants?

Code of Federal Regulations, 2010 CFR

2010-10-01

... 42 Public Health 1 2010-10-01 2010-10-01 false What does the CIR-LRP provide to participants? 68c.8 Section 68c.8 Public Health PUBLIC HEALTH SERVICE, DEPARTMENT OF HEALTH AND HUMAN SERVICES FELLOWSHIPS, INTERNSHIPS, TRAINING NATIONAL INSTITUTE OF CHILD HEALTH AND HUMAN DEVELOPMENT CONTRACEPTION AND...

8. Historic American Buildings Survey, Arthur C. Haskell, Photographer. July ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

8. Historic American Buildings Survey, Arthur C. Haskell, Photographer. July 1934. (i) Paneled fireplace end, S.E. Room, second floor. - Captain Samuel Trevett House, 65 Washington Street, Marblehead, Essex County, MA

Differential CXC and CX3C Chemokine Expression Profiles in Aqueous Humor of Patients With Specific Endogenous Uveitic Entities.

PubMed

El-Asrar, Ahmed M Abu; Berghmans, Nele; Al-Obeidan, Saleh A; Gikandi, Priscilla W; Opdenakker, Ghislain; Van Damme, Jo; Struyf, Sofie

2018-05-01

To determine the levels of the neutrophil chemoattractants CXCL1, CXCL2, CXCL5, CXCL6, and CXCL8, the T helper 1 chemoattractants CXCL9, CXCL10 and CXCL11, the lymphoid chemokines CXCL12 and CXCL13 and the soluble form of the transmembrane chemokines CXCL16 and CX3CL1, in aqueous humor samples from patients with specific uveitic entities. Aqueous humor samples from patients with active uveitis associated with Behçet's disease (n = 13), sarcoidosis (n = 8), HLA-B27-related inflammation (n = 12), Vogt-Koyanagi-Harada (VKH) disease (n = 12), and healthy controls (n = 9) were assayed with the use of a multiplex assay. All chemoattractant levels were significantly higher in all patients than in the controls. The levels of all neutrophil chemoattractants and CXCL10, CXCL16, and CX3CL1 were significantly higher in nongranulomatous uveitis (Behçet's disease and HLA-B27-associated uveitis) than in granulomatous uveitis (sarcoidosis and VKH disease), whereas the levels of the B cell chemoattractant CXCL13 were significantly higher in granulomatous uveitis than in nongranulomatous uveitis. CXCL13 levels were highest in the patients with VKH disease. CXCL9, CXCL11, and CXCL12 levels did not differ significantly. Inflammation in nongranulomatous uveitis appears to be driven by neutrophils and T helper 1 lymphocytes, whereas B lymphocytes may contribute to the inflammatory process in granulomatous uveitis, particularly in VKH disease.

Outcome Measures Used in Clinical Trials for Behçet Syndrome: A Systematic Review

PubMed Central

Hatemi, Gulen; Merkel, Peter A.; Hamuryudan, Vedat; Boers, Maarten; Direskeneli, Haner; Aydin, Sibel Z.; Yazici, Hasan

2015-01-01

Behçet syndrome (BS) is a multisystem vasculitis that is most active during young adulthood, causing serious disability and significant impairment in quality of life. Differences in the disease course, severity, and organ involvement between patients, depending on the age at presentation and sex, makes it impossible to determine a single management strategy. The diversity and variability in the outcome measures used in clinical trials in BS makes it difficult to compare the results or inform physicians about the best management strategy for individual patients. There is a large unmet need to determine or develop validated outcome measures for use in clinical trials in BS that are acceptable to researchers and regulatory agencies. We conducted a systematic review to describe the outcomes and outcome measures that have been used in clinical trials in BS. This review revealed the diversity and variability in the outcomes and outcome measures and the lack of standard definitions for most outcomes and rarity of validated outcome tools for disease assessment in BS. This systematic literature review will identify domains and candidate instruments for use in a Delphi exercise, the next step in the development of a core set of outcome measures that are properly validated and widely accepted by the collaboration of researchers from many different regions of the world and from different specialties, including rheumatology, ophthalmology, dermatology, gastroenterology, and neurology. PMID:24488418

Outcome measures used in clinical trials for Behçet syndrome: a systematic review.

PubMed

Hatemi, Gulen; Merkel, Peter A; Hamuryudan, Vedat; Boers, Maarten; Direskeneli, Haner; Aydin, Sibel Z; Yazici, Hasan

2014-03-01

Behçet syndrome (BS) is a multisystem vasculitis that is most active during young adulthood, causing serious disability and significant impairment in quality of life. Differences in the disease course, severity, and organ involvement between patients, depending on the age at presentation and sex, makes it impossible to determine a single management strategy. The diversity and variability in the outcome measures used in clinical trials in BS makes it difficult to compare the results or inform physicians about the best management strategy for individual patients. There is a large unmet need to determine or develop validated outcome measures for use in clinical trials in BS that are acceptable to researchers and regulatory agencies. We conducted a systematic review to describe the outcomes and outcome measures that have been used in clinical trials in BS. This review revealed the diversity and variability in the outcomes and outcome measures and the lack of standard definitions for most outcomes and rarity of validated outcome tools for disease assessment in BS. This systematic literature review will identify domains and candidate instruments for use in a Delphi exercise, the next step in the development of a core set of outcome measures that are properly validated and widely accepted by the collaboration of researchers from many different regions of the world and from different specialties, including rheumatology, ophthalmology, dermatology, gastroenterology, and neurology.

8. Historic American Buildings Survey Arthur C. Haskell, Photographer Aug. ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

8. Historic American Buildings Survey Arthur C. Haskell, Photographer Aug. 30, 1938 (h) INT.- NORTH WALL, SOUTHEAST ROOM, 1st. FLOOR - Captain William Wildes House, 872 Commercial Street, Weymouth, Norfolk County, MA