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Sample records for acquity beh c8

  1. 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...

  2. 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...

  3. 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...

  4. Analytic Empirical Potentials for BeH^+, BeD^+, and BeT^+ Including up to 4TH Order QED in the Long-Range and Predictions for the Halo Nucleonic Molecules 11BeH^+ and 14BeH^+.

    NASA Astrophysics Data System (ADS)

    Li Chun Fong, Lena C. M.; Lach, Grzegorz; Le Roy, Robert J.; Dattani, Nikesh S.

    2015-06-01

    The 13.81(8)s half-life of the halo nucleonic atom 11Be is orders of magnitude longer than those for any other halo nucleonic atom known, and makes Be-based diatomics the most promising candidates for the formation of the first halo nucleonic molecules. However, the 4e^- species LiH and BeH^+ are some of the first molecules for which the highest accuracy ab initio methods are not accessible, so empirical potential energy functions will be important for making predictions and for benchmarking how ab initio calculations break down at this transition from 3e^- to 4e^-. BeH^+ is also very light, and has one of the most extensive data sets involving a tritium isotopologue, making it a very useful benchmark for studying Born-Oppenheimer breakdown. We therefore seek to determine an empirical analytic potential energy function for BeH^+ that has as much precision as possible. To this end, all available spectroscopic data for all stable isotopologues of BeH^+ are analyzed in a standard direct-potential-fit procedure that uses least-squares fits to optimize the parameters defining an analytic potential. The ``Morse/Long-range'' (MLR) model used for the potential energy function incorporates the inverse-power long-range tail required by theory, and the calculation of the leading long-range coefficients C_4, C_6, C_7, and C_8 include non-adiabatic terms, and up to 4th order QED corrections. As a by-product, we have calculated some fundamental properties of 1e^- systems with unprecedented precision, such as the dipole, quadrupole, octupole, non-adiabatic, and mixed higher order polarizabilities of hydrogen, deuterium, and tritium. We provide good first estimates for the transition energies for the halo nucleonic species 11BeH^+ and 14BeH^+.

  5. 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... health, or the conservation of grant funds....

  6. 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... health, or the conservation of grant funds....

  7. Multiple Intracranial Aneurysms Associated with Behçet's Disease

    PubMed Central

    Ha, Sangwoo; Kim, Jaeho; Kim, Chong-gue

    2016-01-01

    Behçet's disease is an inflammatory disorder involving multiple organs. Its cause is still unknown, but vasculitis is the major pathologic characteristic. The common vascular lesions associated with Behçet's disease are aneurysm formation, arterial or venous occlusive diseases, and varices. Arterial aneurysms mostly occur in large arteries. Intracranial aneurysms hardly occur with Behçet's disease. We would like to present a 41-year-old female patient with Behçet's disease who showed symptoms of severe headache due to subarachnoid hemorrhage. Brain computed tomography revealed multiple aneurysms. We also present a literature review of intracranial arterial aneurysms associated with Behçet's disease. PMID:27114964

  8. The Anharmonic Force Field of BeH2 Revisited

    NASA Technical Reports Server (NTRS)

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

    2003-01-01

    The anharmonic force field of BeH2 has been calculated near the basis set and n-particle space limits. The computed antisymmetric stretch frequencies of BeH2 and BeD2 are in excellent agreement with recent high-resolution gas-phase measurements. The agreement between theory and experiment for the other spectroscopic constants is also excellent, except for omega(sub 3) and X(sub 33) for BeH2 and G(sub 22) for BeD2. It is concluded that further experimental work is needed in order to resolve these discrepancies.

  9. Behçet's syndrome in pregnancy

    PubMed Central

    Martineau, Marcus; Haskard, Dorian O; Nelson-Piercy, Catherine

    2010-01-01

    Behçet's syndrome (BS), a systemic inflammatory disease characterized by oral and genital ulceration, eye inflammation and arthritis, usually presents in the third and fourth decades of life, but is rare in pregnancy. BS is not usually associated with a detrimental effect on pregnancy outcome. In most women BS is reported to improve in pregnancy, although it may not always follow a similar course in successive pregnancies and it is not possible to predict the course of BS in a particular pregnancy. Many of the drug therapies used to treat BS are safe to use in pregnancy and in the breastfeeding mother. These include corticosteroids, azathioprine, calcineurin inhibitors and probably colchicine. Experience with use of biologics in pregnancy is increasing. Drugs used in the management of BS that should be avoided in women planning a pregnancy include methotrexate, mycophenolate mofetil, thalidomide, cyclophosphamide and chlorambucil.

  10. Behçet's disease physiopathology: a contemporary review.

    PubMed

    Zeidan, Mohamad J; Saadoun, David; Garrido, Marlene; Klatzmann, David; Six, Adrien; Cacoub, Patrice

    2016-12-01

    Behçet's disease, also known as the Silk Road Disease, is a rare systemic vasculitis disorder of unknown etiology. Recurrent attacks of acute inflammation characterize Behçet's disease. Frequent oral aphthous ulcers, genital ulcers, skin lesions and ocular lesions are the most common manifestations. Inflammation is typically self-limiting in time and relapsing episodes of clinical manifestations represent a hallmark of Behçet's disease. Other less frequent yet severe manifestations that have a major prognostic impact involve the eyes, the central nervous system, the main large vessels and the gastrointestinal tract. Behçet's disease has a heterogeneous onset and is associated with significant morbidity and premature mortality. This study presents a current immunological review of the disease and provides a synopsis of clinical aspects and treatment options. PMID:26868128

  11. Pulmonary artery aneurysms in Behçet's disease.

    PubMed

    Yilmaz, Sema; Cimen, Kadriye Akar

    2010-08-01

    Behçet's disease is the most common cause of pulmonary artery aneurysms. Pulmonary artery aneurysms are rare, but they are life-threatening because of their high tendency to rupture. However, there is also a chance that the aneurysms may completely resolve with immunosuppressive therapy. A 30-year-old man was admitted with chest pain, painful oral and genital ulcers, skin rash, weakness, and intermittent hemoptysis. He had a history of Behçet's disease for 6 years. The chest radiography showed a round opacity superior part of hilus on right. The helical thoracic computed tomography (CT) angiography demonstrated pulmonary aneurysms associated with Behçet's disease. The patient was successfully treated with colchicine, corticosteroids, and cyclophosphamide. A discussion about pulmonary artery aneurysms associated with Behçet's disease is provided in this case. PMID:19693504

  12. Serum IL-17A in Behçet's disease

    PubMed Central

    Cengiz, Fatma Pelin; Erdem, Gul Bahar

    2015-01-01

    Introduction Behçet's disease is a chronic multisystem disease with spontaneous remissions and relapses. Several studies show that autoimmune mechanisms play an important role in the development of Behçet's disease. Activation of T cells and neutrophils is important in the pathogenesis of the disease. Interleukin 17 (IL-17) is a new cytokine that induces several types of cells to secrete proinflammatory cytokines in many inflammatory and autoimmune diseases. Aim This study evaluated the serum levels of IL-17A in active and stable Behçet's disease patients. Material and methods Seventy-six patients who had active clinic findings of Behçet's disease were enrolled in our study. Seventy age- and sex-matched controls were also enrolled. Serum IL-17 levels were studied in peripheral venous blood samples. Results No significant differences were found between active Behçet's disease patients and controls in terms of serum IL-17A (p > 0.05). Conclusions These results suggest that IL-17A serum levels do not play an important role in active Behçet's disease. PMID:26759544

  13. Low Level Laser Therapy to Reduce Recurrent Oral Ulcers in Behçet's Disease

    PubMed Central

    Babu, D. B. Gandhi; Chavva, Sunanda; Waghray, Shefali

    2016-01-01

    Behçet's disease (BD) is a chronic, relapsing multisystemic vascular condition. Behçet's disease was described by Hulusi Behçet in 1937. This rare multisystem relapsing-remitting inflammatory disease is poorly understood but is thought to be an autoimmune inflammatory vasculitic process in a genetically predisposed population. Diagnosis of Behçet's disease is based on International Criteria of Behçet's Disease (ICBD). The present paper describes a case report of Behçet's syndrome where aphthous stomatitis was treated with low level laser therapy. PMID:27555969

  14. Low Level Laser Therapy to Reduce Recurrent Oral Ulcers in Behçet's Disease.

    PubMed

    Babu, D B Gandhi; Chavva, Sunanda; Waghray, Shefali; Allam, Neeharika Satya Jyothi; Kondaiah, Marella

    2016-01-01

    Behçet's disease (BD) is a chronic, relapsing multisystemic vascular condition. Behçet's disease was described by Hulusi Behçet in 1937. This rare multisystem relapsing-remitting inflammatory disease is poorly understood but is thought to be an autoimmune inflammatory vasculitic process in a genetically predisposed population. Diagnosis of Behçet's disease is based on International Criteria of Behçet's Disease (ICBD). The present paper describes a case report of Behçet's syndrome where aphthous stomatitis was treated with low level laser therapy. PMID:27555969

  15. [Neurological manifestations of Behçet's disease].

    PubMed

    Bousser, M G; Rougemont, D; Youl, B D; Wechsler, B

    1988-01-01

    Characterised classically by the association of buccal and genital ulceration and uveitis with hypopyon, Behçet's disease has many other manifestations, amongst which the neurological ones (often referred to as Neuro-Behçet) are important in view of their frequency and their gravity. Anatomically, it produces a subacute haemorrhagic and necrotising meningo-encephalitis, which most typically effects the hypothalamus and brainstem. Clinically, there is extreme polymorphism, central manifestations being the most frequent: seizures, organic brain syndromes, disorders of consciousness, aphasia, hemiplegia, cranial nerve palsies, pseudobulbar and extrapyramidal syndromes and meningism. The peripheral nerves and muscles are rarely affected. Alongside Neuro-Behçet per se, attention has recently been directed to the various cerebro-vascular manifestations, dominated by venous thrombosis. A review of the principal neurological manifestations is given, with comment on anatomico-pathological aspects, clinical presentation, investigational techniques, diagnostic difficulties, prognosis, and treatment. PMID:3049880

  16. 26 CFR 301.6231(c)-8 - Prompt assessment.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ..., see § 301.6231(c)-8T contained in 26 CFR part 1, revised April 1, 2001. ... 26 Internal Revenue 18 2011-04-01 2011-04-01 false Prompt assessment. 301.6231(c)-8 Section 301... AND ADMINISTRATION PROCEDURE AND ADMINISTRATION Assessment In General § 301.6231(c)-8...

  17. 26 CFR 301.6231(c)-8 - Prompt assessment.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ..., see § 301.6231(c)-8T contained in 26 CFR part 1, revised April 1, 2001. ... 26 Internal Revenue 18 2012-04-01 2012-04-01 false Prompt assessment. 301.6231(c)-8 Section 301... AND ADMINISTRATION PROCEDURE AND ADMINISTRATION Assessment In General § 301.6231(c)-8...

  18. 26 CFR 301.6231(c)-8 - Prompt assessment.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ..., see § 301.6231(c)-8T contained in 26 CFR part 1, revised April 1, 2001. ... 26 Internal Revenue 18 2014-04-01 2014-04-01 false Prompt assessment. 301.6231(c)-8 Section 301... AND ADMINISTRATION PROCEDURE AND ADMINISTRATION Assessment In General § 301.6231(c)-8...

  19. Behçet's disease and the alimentary tract

    PubMed Central

    Parkin, J. V.; Wight, D. G. D.

    1975-01-01

    Two patients with perforation of the alimentary tract in Behçet's disease are described. One of these is believed to be the first recorded case of oesophageal perforation in this condition, while the second is one of the few survivors of bowel perforation. The literature, aetiology and treatment are reviewed. ImagesFig. 1Fig. 2Fig. 3 PMID:1197160

  20. The great masquerader: Behçet's disease

    PubMed Central

    Nordstrom, Edra; Fischer, Monika

    2014-01-01

    This report describes the case of a 44-year-old Caucasian woman of Northern European descent with a medical history of pyoderma gangrenosum, chronic abdominal pain and erythema nodosum which required intermittent use of high-dose steroids that failed to improve her symptoms. The patient was initially diagnosed with Crohn's disease and most recently with sclerosing mesenteritis. She presented to the hospital with worsening abdominal pain. She was found to have recurrent painful aphthous oral, genital and perianal ulcers and a clinical diagnosis of Behçet's disease was made. Her hospitalisation was complicated by haemoptysis, and bronchoscopy revealed alveolar haemorrhage. Treatment was initiated with three days of pulse intravenous solumedrol 1 g/day and cyclophosphamide at 700 mg/m2. The case had a favourable outcome despite the initial diagnostic challenges. This report emphasises that systemic diseases, including Behçet's disease, can have variable presentations and can be frequently misdiagnosed. PMID:24748137

  1. Colonic perforation in Behçet’s syndrome

    PubMed Central

    Dowling, Catherine M; Hill, Arnold DK; Malone, Carmel; Sheehan, John J; Tormey, Shona; Sheahan, Kieran; McDermott, Enda; O’Higgins, Niall J

    2008-01-01

    A 17-year-old gentleman was admitted to our hospital for headache, the differential diagnosis of which included Behçet’s syndrome (BS). He developed an acute abdomen and was found to have air under the diaphragm on erect chest X-ray. Subsequent laparotomy revealed multiple perforations throughout the colon. This report describes an unusual complication of Behcets syndrome occurring at the time of presentation and a review of the current literature of reported cases. PMID:19030217

  2. Recurrent right atrial thrombosis due to Behçet disease.

    PubMed

    Kuno, Toshiki; Tamura, Yuichi; Ono, Tomohiko; Murata, Mitsushige; Kuwana, Masataka; Satoh, Toru; Fukuda, Keiichi

    2014-10-01

    Behçet disease is a rare condition sometimes associated with chronic cardiac inflammation followed by myocardial dysfunction and vascular inflammation. We report a case of recurrent right atrial thrombus due to Behçet disease despite continued anticoagulation therapy. The thrombus disappeared after the initiation of immunosuppressive therapy. To avoid a progression to thrombus or cardiac dysfunction in this recurrent case, the early identification of cardiac involvement of Behçet disease using echocardiography and/or cardiac magnetic resonance imaging might be important. Combined immunosuppressive therapy with prednisone and cyclophosphamide might be needed to treat recurrent thrombosis due to Behçet disease. PMID:25174856

  3. Behçet's disease associated with amyloidosis in Turkey and in the world.

    PubMed Central

    Dilşen, N; Koniçe, M; Aral, O; Erbengi, T; Uysal, V; Koçak, N; Ozdogan, E

    1988-01-01

    The association of amyloidosis with Behçet's disease has infrequently been reported in published works. Twenty four such cases have been observed in the world, of which 12 are from Turkey, including eight of ours. In all our eight cases renal biopsy showed amyloidosis of type AA. Behçet's disease of male preponderance, long duration, complete type, multiple organ involvement, and positive skin pathergy test were the main characteristics of all 24 cases of Behçet's disease with amyloidosis. We conclude that amyloidosis associated with Behçet's disease is a secondary AA amyloidosis occurring as an intrinsic manifestation of Behçet's disease. Images PMID:3281606

  4. Dermographism and atopy in patients with Behçet's disease.

    PubMed

    Dinç, A; Karaayvaz, M; Caliskaner, A Z; Pay, S; Erdem, H; Turan, M

    2000-01-01

    Dermographism is the appearance of whealing and erythema within minutes in a site where skin has been exposed to pressure or mechanical irritation. In our clinical observations, dermographism seems to be frequent in patients with Behçet's disease. Since the prevalence of allergic responses is reportedly increased in vasculitic syndromes, we aimed to assess dermographism and atopy in a group of Behçet's patients. The study group comprised 30 consecutive patients with Behçet's disease. The study was carried out in two parts: elicited dermographism and atopy tests. In the first part, dermographism was investigated in the study group (Behçet's patients) and 230 healthy controls. In the second part, the study group, 30 healthy controls and 17 patients with allergic bronchial asthma were evaluated for specific and nonspecific atopy. Dermographism was found to be increased in patients with Behçet's disease. Peripheral blood eosinophil count, serum total IgE and nasal eosinophil scores were similar in patients with Behçet's disease and healthy controls. Although blood eosinophil count and serum total IgE levels were higher in allergic bronchial asthma patients than in Behçet's patients, the difference was significant only in the former. Skin prick test was positive in three of the patients with Behçet's disease and in six healthy controls. The difference was statistically insignificant (p > 0.05). None of the Behçet's disease patients had pathergy or a pathergy-like reaction at the site of the skin prick test after 48 h. In conclusion, our results confirm the general impression that dermographism is common in patients suffering from Behçet's disease. PMID:11206938

  5. Cubic C8 : An Observable Allotrope of Carbon?

    PubMed

    Sharapa, Dmitry; Hirsch, Andreas; Meyer, Bernd; Clark, Timothy

    2015-07-20

    Ab initio and DFT calculations are used to investigate the structure, electronic properties, spectra and reactivity of cubic C8 , which is predicted to be aromatic according to Hirsch's rule. Although highly strained and with a small amount of diradical character, the carbon cube represents a surprisingly deep minimum and should therefore be observable as an isolated molecule. It is, however, predicted to be very reactive, both with itself and triplet oxygen. Calculated IR, Raman, and UV/Vis spectra are provided to aid identification of cubic C8 should it be synthesized. PMID:26013967

  6. Gastrointestinal Behçet's disease: a review.

    PubMed

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

    2015-04-01

    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

  7. 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

  8. [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. PMID:24434015

  9. Immunopathogenesis of ocular Behçet's disease.

    PubMed

    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

  10. Metallization and superconductivity of BeH2 under high pressure

    NASA Astrophysics Data System (ADS)

    Wang, Ziwei; Yao, Yansun; Zhu, Li; Liu, Hanyu; Iitaka, Toshiaki; Wang, Hui; Ma, Yanming

    2014-03-01

    Pressure-induced metallization and potential superconductivity of BeH2 has been a topic of interest. In the present study, we extensively explored the crystal structures of BeH2 in a wide pressure range of 0-300 GPa using an unbiased structure searching method coupled with first-principles density functional calculations. A series of pressure-induced structural transformations are predicted for BeH2, as Ibam (α phase) → P-3m1 (phase II) → R-3m (phase III) → Cmcm (phase IV). Calculated pressures of phase transition are 25, 140, and 202 GPa, respectively. The phase II is isostructural to the well-known 1T structure of transition metal dichalcogenides, which is composed of covalent bonded BeH2 slabs stacked along the perpendicular direction by van der Waals forces. The phase III is constructed by the same BeH2 slabs, but differs from the phase II in the stacking sequence. The α phase, phase II, and phase III all have insulating electronic states while their band gaps decrease as pressure increases. We predicted that BeH2 reaches a metallic state by a III → IV phase transition, instead of a direct band gap closure in phase III. The phase IV has a three-dimensional extended Be-H network formed by edge-sharing BeH8 polyhedrons with delocalized electrons. Electron-phonon coupling calculations implemented using linear response theory on the metallic BeH2 predict a large electron-phonon coupling parameter of 0.63, leading to an estimation of superconducting transition temperature (Tc) of ˜38 K at 250 GPa.

  11. Two distinct abnormalities in patients with C8 alpha-gamma deficiency. Low level of C8 beta chain and presence of dysfunctional C8 alpha-gamma subunit.

    PubMed Central

    Tedesco, F; Roncelli, L; Petersen, B H; Agnello, V; Sodetz, J M

    1990-01-01

    The sera from three C8 alpha-gamma deficient patients previously reported to have a selective C8 alpha-gamma defect were analyzed by SDS-PAGE and Western blot using two polyclonal antisera to C8 alpha-gamma and a monoclonal antibody to C8 alpha. All three sera exhibited C8 alpha-gamma bands that dissociated into alpha and gamma chains under reducing conditions. Quantitation of the alpha-gamma subunit in these sera by a sensitive ELISA revealed an amount approximately 1% of that found in normal human serum. A similar assay performed with a specific antiserum to C8 beta showed unexpectedly low levels of C8 beta in these sera, which were confirmed by hemolytic titration of C8 beta. The remarkable differences between C8 alpha-gamma and C8 beta in the C8 alpha-gamma deficient sera was that in spite of their comparable immunochemical levels, C8 beta still exhibited functional activity whereas C8 alpha-gamma was totally inactive. That the residual C8 alpha-gamma was inactive was also proved by its inability to show lytic bands in an overlay system after SDS-PAGE and subsequent removal of SDS. The implications of these findings for a novel concept of C8 deficiency are discussed. Images PMID:2394837

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

    PubMed

    Düzgün, Nurşen; Küçükşahin, Orhan; Atasoy, Kayhan Çetin; Togay Işıkay, Canan; Gerede, Demet Menekşe; Erden, Ayşe; Sahap, Seda Kaynak; Ibiş, 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

  13. 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

  14. 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...

  15. 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...

  16. Interleukin-1 Inhibition in Behçet's disease.

    PubMed

    Vitale, Antonio; Rigante, Donato; Lopalco, Giuseppe; Selmi, Carlo; Galeazzi, Mauro; Iannone, Florenzo; Cantarini, Luca

    2016-01-01

    Behçet's disease (BD) is a systemic inflammatory disorder characterized by a protean clinical spectrum and an enigmatic pathogenesis. After being classified as an autoimmune disorder, spondyloarthritis and vasculitis, today BD is considered at the crossroad between autoimmune and auto-inflammatory syndromes. Many pathogenetic, clinical and therapeutic clues support this recent interpretation, enabling novel treatment choices such as interleukin (IL)-1 inhibition. Thus, in the last decade the IL-1 receptor antagonist anakinra and the anti-IL-1β monoclonal antibody canakinumab were increasingly administered in BD patients resistant to standard therapies, leading to interesting results and intriguing new pathogenetic implications. However, further studies are essential to both establish how the innate and acquired immune systems interact in BD patients and identify the best way of administering anti-IL-1 agents with regard to dosage, interval of administration, and organ response. PMID:27228638

  17. The C8 Health Project: Design, Methods, and Participants

    PubMed Central

    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.

    2009-01-01

    Background 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. Objectives 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. Methods 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. Results 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. Conclusions 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

  18. [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. PMID:26611428

  19. A rare case of peripheral ulcerative keratitis associated with Behçet's disease.

    PubMed

    Ji, Yong-Sok; Yoon, Kyung Chul

    2014-08-01

    We report a rare case of peripheral ulcerative keratitis (PUK) associated with Behçet's disease. A 34-year-old female presented with right ocular pain persisting for 8 months. The patient had been treated for previously diagnosed Behçet's disease. The corrected visual acuity was 20/32 in the right eye. Ocular examination revealed mild conjunctival hyperemia and a deep ulcerative lesion with perilesional haziness in the peripheral cornea. Autoimmune screening and corneal culture were negative. One month following treatment with topical and systemic immunosuppressants, the symptom had resolved. Slit-lamp examination showed a healed corneal lesion, and visual acuity improved to 20/20. Despite its rare occurrence, PUK can develop in patients with Behçet's disease. Therefore, patients presenting PUK require examination for Behçet's disease using a systemic evaluation. PMID:24493356

  20. R-matrix calculation of bound and resonant states of BeH

    NASA Astrophysics Data System (ADS)

    Chakrabarti, K.; Tennyson, Jonathan

    2014-12-01

    Bound and resonant states of BeH are studied using the diatomic UK molecular R-matrix codes together with a Slater basis set for the BeH+ target states. Bound and resonant states of BeH are determined from an e-BeH+ collisional calculation. The calculations are repeated for 40 internuclear distances in the range 1.5-6.0 a 0 to yield bound state and resonance curves for BeH. Additionally, we also obtain the resonance widths in the range of the inter-nuclear distances considered. The data obtained may be useful for modeling various e-BeH+ collision-induced processes, particularly dissociative recombination and dissociative excitation.

  1. R-matrix calculation of bound and resonant states of BeH

    NASA Astrophysics Data System (ADS)

    Chakrabarti, K.; Tennyson, Jonathan

    2015-12-01

    Bound and resonant states of BeH are studied using the diatomic UK molecular R-matrix codes together with a Slater basis set for the BeH+ target states. Bound and resonant states of BeH are determined from an e-BeH+ collisional calculation. The calculations are repeated for 40 internuclear distances in the range 1.5-6.0 a 0 to yield bound state and resonance curves for BeH. Additionally, we also obtain the resonance widths in the range of the inter-nuclear distances considered. The data obtained may be useful for modeling various e-BeH+ collision-induced processes, particularly dissociative recombination and dissociative excitation.

  2. Infliximab is a plausible alternative for neurologic complications of Behçet disease

    PubMed Central

    Zeydan, Burcu; Uygunoglu, Ugur; Saip, Sabahattin; Demirci, Onat N.; Seyahi, Emire; Ugurlu, Serdal; Hamuryudan, Vedat; Siva, Aksel

    2016-01-01

    Objective: We evaluated the effectiveness of infliximab in patients with neuro-Behçet syndrome for whom other immunosuppressive medications had failed. Methods: Patients whose common immunosuppressive medications fail in recurrent neuro-Behçet syndrome need an alternative. We report our experience with the tumor necrosis factor α blocker infliximab for long-term treatment of neuro-Behçet syndrome. We recruited patients within a multidisciplinary referral practice of Behçet disease and prospectively followed everyone with a neurologic symptom(s). Patients (n = 16) with ≥2 neurologic bouts (excluding purely progressive disease) while on another immunosuppressive treatment were switched to and successfully sustained on infliximab (5 mg/kg in weeks 0, 2, and 6, then once every 8 weeks; minimum follow-up duration ≥12 months). Infliximab was stopped within 2 months after initiation in one patient because of pulmonary and CNS tuberculosis. Results: Patients had stepwise worsening due to relapses in the Expanded Disability Status Scale modified for neuro-Behçet syndrome before switching to infliximab (median score of 5.0, range 2.0–7.0; median neuro-Behçet syndrome duration 29.1 months, range 5.0–180.7). Median duration of preinfliximab immunosuppressive medication use was 20.0 months (range 3.0–180.7). In all 15 patients, during infliximab treatment (median score 4.0, range 2.0–7.0; median duration 39.0 months, range 16.0–104.9 months), neurologic relapses were completely aborted and there was no further disability accumulation. Conclusion: We observed a significant beneficial effect of infliximab in neuro-Behçet syndrome. Classification of evidence: This study provides Class IV evidence that for patients with neuro-Behçet syndrome whose other immunosuppressive medications failed, infliximab prevents further relapses and stabilizes disability. PMID:27458602

  3. [Vasculo-Behçet's disease with superior sagittal sinus thrombosis--case report (author's transl)].

    PubMed

    Ueda, T; Gondo, M; Kitano, I; Kinoshita, K; Kikuchi, I

    1982-04-01

    The patient is a 30-year-old man who has suffered from recurrent attacks of tonsilitis, oral aphthae and scrotal ulcerations, erythema nodosum and thrombophlebitis. In April, 1980, he gradually developed headache and visual disturbance. On April 14, 1980, he was pointed out remarked bilateral choked disc by an ophthalmologist and then admitted to the Miyazaki Medical College Hospital. On admission to our service, he showed atypical symptoms of Behçet's disease, namely, oral aphthae and scrotal ulcerations, erythema nodosum and bilateral choked disc. Laboratory data demonstrated hyperimmunoglobulinemia, increased clotting factors and decreased fibrinolytic activity. Immunogenetically, HLA BW51 type was demonstrated. The angiograms showed complete obstructions of the superior sagittal sinus and the common trunk of the femoral artery. Histological examination of the skin lesion demonstrated atypical chronic inflammation and thrombophlebitis. A diagnosis of atypical Vasculo-Behçet's disease was made. The response to the steroid therapy was dramatic, though the fibrinolytic drugs, anticoagulants and vasodilators were not effective. Thrombophlebitis is a well recognized complication of Behçet's disease occurring in major vessels, however thrombosis of the dural sinus has rarely reported. This case may be the first one which had superior sagittal sinus thrombosis with Vasculo-Behçet's disease in literature. We discussed the mechanism of the thrombogenesis, the relationship to HLA, the coexistence of Neuro-Behçet's disease and the therapy of Vasculo-Behçet's disease. PMID:7093071

  4. Cyclic disulfide C8 iminoporfiromycin: nucleophilic activation of a porfiromycin.

    PubMed

    Lee, Sang Hyup; Kohn, Harold

    2004-04-01

    The clinical success of mitomycin C (1) and its associated toxicities and resistance have led to efforts to prepare semisynthetic analogues (i.e., KW-2149 (3), BMS-181174 (4)) that have improved pharmacological profiles. In this study, we report the preparation and evaluation of the novel 7-N-(1'-amino-4',5'-dithian-2'-yl)porfiromycin C(8) cyclized imine (6) and its reference compound, 7-N-(1'-aminocyclohex-2'-yl)porfiromycin C(8) cyclized imine (13). Porfiromycin 6 contains a disulfide unit that, upon cleavage, may provide thiol(s) that affect drug reactivity. We demonstrated that phosphines dramatically accelerated 6 activation and solvolysis in methanolic solutions ("pH 7.4") compared with 13. Porfiromycins 6 and 13 efficiently cross-linked EcoRI-linearized pBR322 DNA upon addition of Et3P. We found enhanced levels of interstrand cross-link (ISC) adducts for 6 and 13 compared with porfiromycin (7) and that 6 was more efficient than 13. The large Et3P-mediated rate enhancements for the solvolysis of 6 compared with 13 and a N(7)-substituted analogue of 1, and the increased levels of ISC adducts for 6 compared with 13 and 7 are attributed to a nucleophile-assisted disulfide cleavage process that permits porfiromycin activation and nucleophile (MeOH, DNA) adduction. The in vitro antiproliferative activities of 6 and 13 using the A549 tumor cell line (lung adenocarcinoma) were determined under aerobic and hypoxic conditions and then compared with 7. Both 6 and 13 were more cytotoxic than 7, with 13 being more potent than 6. The C(8) iminoporfiromycins 6 and 13 displayed anticancer profiles similar to 3. PMID:15053618

  5. Colon Perforation and Budd-Chiari Syndrome in Behçet’s Disease

    PubMed Central

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

    2015-01-01

    Patient: Female, 38 Final Diagnosis: Behçet’s disease Symptoms: Severe abdominal pain • fever Medication: — Clinical Procedure: Parsiyel colectomy Specialty: Surgery Objective: Unusual clinical course Background: 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. Case Report: 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. Conclusions: 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. PMID:25934795

  6. Cell-mediated immune functions and immunoregulatory cells in Behçet's syndrome.

    PubMed Central

    Victorino, R M; Ryan, P; Hughes, G R; Hodgson, H J

    1982-01-01

    Lymphocyte responsiveness to mitogens (phytohaemagglutinin (PHA), concanavalin A (Con A), and pokeweed mitogen (PWM)), T-cell subsets (T mu and T gamma) and short-lived suppressor cell activity were investigated in the peripheral blood of seven patients with Behçet's syndrome and compared to normal individuals and patients with systemic lupus erythematosus (SLE). Amongst patients with Behçet's syndrome, responses to mitogens PHA and Con A were normal or slightly reduced; numbers of circulating T gamma cells were unaltered whereas T mu cells were reduced (P less than 0 . 05) compared with normal individuals. This was in contrast to SLE where a marked reduction in responses to PHA and Con A was found with reduced T gamma cell but normal T mu cell numbers. Although the mean suppressor cell activity in the Behçet's group was significantly reduced, all patients had values within the normal range, in contrast with SLE where the reduction was much more marked and most patients had values below the normal range. In conclusion, the pattern of alteration in T mu and T gamma cells in Behçet's syndrome is distinct from that in SLE, and the reduction of short-lived suppressor cell activity is only mild in Behçet's syndrome but marked in SLE. PMID:6211313

  7. Layered structure and re-entrant disproportionation observed in crystalline BeH2 under pressure

    NASA Astrophysics Data System (ADS)

    Pépin, Charles M.; Loubeyre, Paul

    2016-06-01

    The phase diagram of the Be-H system is measured up to 100 GPa. BeH2 is the only stoichiometry observed. Three crystalline phases are identified using synchrotron x-ray diffraction. The I b a m structure, already known at ambient pressure, is stable up to 27 GPa. The P 41212 structure, isotypical to the crystoballite-low SiO2 structure, is stable above 600 K over the same pressure range. The well-known P 3 ¯m 1 layered structure of transition metal dichalcogenides is stable above 80 GPa, making BeH2 a quasi-two-dimensional hydride. Surprisingly, between 27 and 72 GPa, a miscibility gap opens up in the Be-H system and an equilibrium between pure Be and pure H is observed. That is at odds with the current prevailing view of an increase in solubility of H in metals under pressure and contradicts calculations of stable compounds in the Be-H system.

  8. Behçet's disease complicated by pylephlebitis and hepatic abscesses.

    PubMed

    Gelber, A C; Schachna, L; Mitchell, L; Schwartzman, G; Hartnell, G; Geschwind, J F

    2001-01-01

    A 22 year old man presented with fever, abdominal pain, weight loss and diarrhea. Past medical history revealed recurrent aseptic meningitis, uveitis, and erythema nodosum. Further inquiry unveiled a prominent history of oral aphthous ulcers; all features of Behçet's disease. Imaging revealed mesenteric arteritis and pylephlebitis, septic thrombophlebitis of the portal vein, a previously unrecognized complication of Behçet's disease, with multiple intrahepatic abscesses. Portal venography demonstrated an extensively diseased, expanded, and obstructed portal venous system. Blood cultures and portal vein aspirate yielded polymicrobial flora. Percutaneous intraportal thrombolytic therapy and mechanical thrombectomy were attempted to restore flow to the portal venous system. This distinctly rare manifestation of Behçet's Disease, pylephlebitis, may result from ischemic injury and structural compromise of the bowel mucosa, resulting from underlying vasculitis. PMID:11760402

  9. 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. PMID:27375145

  10. Behçet disease in association with Budd-Chiari syndrome and multiple thrombosis - Case report*

    PubMed Central

    Bittencourt, Maraya de Jesus Semblano; Dias, Carolina Moraes; Lage, Thaiane Lima; Barros, Renata Silva; Paz, Otávio Augusto Gomes; Vieira, Waldonio de Brito

    2013-01-01

    Behçet's disease is a chronic inflammatory disease of unknown aetiology, characterized by recurrent oral and genital aphthous ulcerations, uveitis, skin lesions and other multisystem affections associated with vasculitis. Different types of vessels, predominantly veins, can be affected in Behçet's disease. The frequency of vascular lesions in Behçet's disease, such as superficial and deep venous thromboses, arterial aneurysms and occlusions, ranges between 7-29%. Budd-Chiari syndrome is a rare and serious complication of Behçet's disease and implies thrombosis of the hepatic veins and/or the intrahepatic or suprahepatic inferior vena cava. We report a case of a 25-year-old man with Behçet's disease that developed Budd-Chiari syndrome. The correlation of dermatological, pathological and imaging studies confirmed the diagnosis. PMID:23793200

  11. [Neurologic manifestations of Behçet's disease].

    PubMed

    Wechsler, B; Gerber, S; Vidailhet, M; Dormont, D

    1999-11-01

    Neurological involvement in Behçet's disease, the cause of the disease's severe functional sequellae, is reported in 5.3 to 30% of cases. Coagulation disorders have been reported but they cannot explain the different thrombotic manifestations which are probably the consequence of an abnormal response of the vascular endothelial cells. Neurological manifestations include: a) dural sinus thrombosis which can be diagnosed by angio-MRI and whose prognosis is improved with the use of anticoagulants; b) exceptional lesions to arteries supplying the brain; c) aseptic meningitis and meningo-encephalitis; and d) exceptionally, solitary spinal cord involvement and peripheral disease. Neurological involvement can occur early or late after development of skin and mucosal signs and when inaugural make mislead diagnosis. The spinal tap usually gives objective evidence of lymphocyte meningitis. MRI is nonspecific, but the T2 and Flair sequences can evidence hypersignal areas, preferentially in the brain stem, basal nuclei, and subtentorial white matter with no preference for the periventricular regions. Spontaneous aggravation is the rule and the neurological prognosis is severe (dementia, pseudo-bulbar syndrome, loss of independence). Treatment is similar to that used for vasculitis and is aimed initially at reducing the inflammation with corticosteroids and at preventing relapse with the adjunction of an immunosuppressor. Results are better when treatment begins early; restitutio ad integrum has been observed. Duration of treatment is poorly defined: immunosuppressors have been proposed for a minimal duration of 2 years; corticosteroid therapy can be tapered off but interruption would expose to relapse. A maintenance therapy is advisable and, in our opinion, should be proposed indefinitely combining colchicine (1 to 2 mg/d), anti-aggregate doses of aspirin, and low-dose corticosteroids (1/10 mg/kg/d). PMID:10637671

  12. Behçet's ulcerations in the lower extremity: A case report.

    PubMed

    Clark, Seth N; Hronek, Anna L; Hodge, Nan E; Soloman, Nehad; Vaughn, Teri L

    2015-09-01

    Behçet's Disease is a syndrome characterized by recurrent, painful oral aphthous ulcers, in conjunction with 2 or more systemic manifestations - a common systemic manifestation of the disease being cutaneous lesions, which often present as papules that ulcerate to form ulcerations which exhibit the same pathergy phenomenon as pyoderma gangrenosum and are thus difficult to heal. We present a case of a type 2 diabetic male with previously undiagnosed Behçet's Disease who presented to clinic with an atypical lower extremity wound. Due to the atypical nature of the patient's wound, combined with information from the patient regarding the history of the wound and other illnesses he had, the wound was biopsied and the results from the biopsy combined with clinical suspicion yielded a diagnosis of Behçet's Disease. After understanding the nature of the wound, management of the ulceration was adjusted appropriately so as to properly treat the patient with both local wound care and medical management for the disease. Patient was referred to rheumatology for further workup and long-term management of Behçet's Disease. Correct identification and treatment of the systemic disease, as well as the lower extremity ulcerations, in patients with Behçet's Disease are critical to avoid organ and limb-threatening complications. Had the diagnosis of Behçet's not been made in this case, the patient's wound would have been at increased risk of disease-related complications - ranging from non-healing ulceration leading to amputation to renal failure to loss of eyesight. PMID:25802130

  13. Isolated optic neuropathy in a case of Behçet's disease.

    PubMed

    Cetin, Ebru N; Yaylali, Volkan; Yildirim, Cem

    2011-04-01

    A 57-year-old male with a 1-year history of recurrent oral ulceration and papulopustular lesions presented with acute visual loss in his left eye. He had an oedematous disc without any signs of uveitis. Laboratory work-up regarding infectious diseases was negative. The patient was diagnosed with acute optic neuropathy secondary to Behçet's disease. Systemic steroid and colchicine treatments were started but his vision did not improve. Isolated optic neuropathy is rare in Behçet's disease and early treatment with high-dose steroids may not be successful in some cases. PMID:21264492

  14. Chylothorax bilatéral au cours de la maladie de Behçet

    PubMed Central

    Zemed, Naaima; Amangar, Nadia; Herrak, Laila; Elftouh, Mustapha

    2015-01-01

    L'atteinte médiastino-pulmonaire de la maladie de Behçet est représentée essentiellement par la thrombose de la veine cave supérieure et l'angéite pulmonaire. L'association de la maladie et du chylothorax est rare, sa prise en charge n'est pas codifiée. Nous rapportant un cas clinique concernant la survenue d'un chylothorax bilatéral secondaire à une thrombose cave supérieure dans un contexte de maladie de Behçet. PMID:26185561

  15. Neuro-Behçet disease presented diplopia with hemiparesis following minor head trauma

    PubMed Central

    Choi, Ja Yun; Park, Sun Young; Hwang, In Ok

    2012-01-01

    Behçet disease (BD) is rare in childhood. We report a 9-year-old boy with neuro-Behçet disease who presented diplopia and weakness on the left side after a cerebral concussion. Brain magnetic resonance imaging (MRI) revealed hyperintensity of the right mesodiencephalic junction on T2-weighted and fluid attenuated inversion recovery images. Prednisolone administration resulted in complete remission and normalization of abnormal MRI finding. Brain MRI is a useful diagnostic tool when the neurological sign is the first symptom of subclinical BD. PMID:23049594

  16. Life threatening chylous pleural and pericardial effusion in a patient with Behçet's syndrome.

    PubMed Central

    Cöplü, L; Emrí, S; Selçuk, Z T; Kalyoncu, F; Balkanci, F; Sahín, A A; Bariş, Y I

    1992-01-01

    Chylothorax and chylopericardium secondary to thrombosis of the superior vena cava and the innominate and subclavian veins were diagnosed in a patient with Behçet's syndrome. Immunosuppressive treatment, diet, and underwater seal drainage led to a diminished volume of pleural fluid and pericardial fluid and to a diminished concentration of triglyceride in them; pleurodesis with tetracycline was then performed. Images PMID:1539151

  17. Tonsillectomy to Effectively Treat a Patient with Behçet's Disease.

    PubMed

    Nanke, Yuki; Kobasigawa, Tsuyoshi; Yoda, Keiko; Yamanaka, Hisashi; Kotake, Shigeru

    2016-01-01

    Behçet's disease (BD) is a polysymptomatic and recurrent systemic vasculitis with a chronic course and unknown cause. We herein report a 27-year-old woman who had suffered from a recurrent fever and tonsillitis for nearly ten years with BD for who tonsillectomy was effective. PMID:26935374

  18. Fullerene and corannulene derivatives acting as insulators of Cl(-) and BeH2.

    PubMed

    Marín-Luna, Marta; Alkorta, Ibon; Elguero, José; Mó, Otilia; Yáñez, Manuel

    2016-02-17

    The capacity of corannulene and its benzo-derivatives CxH10 (x = 20-60) as prototypes of non-planar π-aromatic systems which mimic the end of carbon nanotubes to act as insulators between BeH2 and Cl(-) chemical entities has been explored by means of M06-2x/cc-pVDZ and M06-2x/6-311+G(d) calculations. For the sake of completeness, the set investigated includes also fullerene, C60. All these aromatic derivatives lead to stable binary complexes either with BeH2 or halogen (Cl(-)) anions. For BeH2, however, only the complexes in which the interaction involves the convex face of the aromatic system are stable. No significant changes are observed when the binding energies (BEs) of the BeH2 complexes are compared to those involving planar aromatic compounds, but the ones involving Cl(-) with the concave face of the aromatic moiety can be very large, because its curvature favors many contacts of the anion with the carbon atoms of the π-aromatic system. The formation of these binary complexes changes to a large extent the electrostatic potential on the free face of the aromatic system leading to a mutual reinforcement of both interactions, the beryllium bond and the interaction with Cl(-), when the ternary complexes are formed. As a result, the BEs for the triads are larger than the sum of the BEs of the corresponding binary complexes and the distances between the aromatic subunit and BeH2 or Cl(-) become shorter in the triads than in the binary complexes. A MBIE analysis also indicates that the enhanced stability of ternary complexes arises mainly from the reinforcement of the beryllium bonds as well as from the three-body terms. An exploration of all the minima for BeH2:C60H10:Cl(-) shows that BeH2 binds preferentially to the peripheral aromatic rings than those in the more curved region. PMID:26845429

  19. Evaluation of CYP2C8 inhibition in vitro: utility of montelukast as a selective CYP2C8 probe substrate.

    PubMed

    VandenBrink, Brooke M; Foti, Robert S; Rock, Dan A; Wienkers, Larry C; Wahlstrom, Jan L

    2011-09-01

    Understanding the potential for cytochrome P450 (P450)-mediated drug-drug interactions is a critical step in the drug discovery process. Although in vitro studies with CYP3A4, CYP2C9, and CYP2C19 have suggested the presence of multiple binding regions within the P450 active site based on probe substrate-dependent inhibition profiles, similar studies have not been performed with CYP2C8. The ability to understand CYP2C8 probe substrate sensitivity will enable appropriate in vitro and in vivo probe selection. To characterize the potential for probe substrate-dependent inhibition with CYP2C8, the inhibition potency of 22 known inhibitors of CYP2C8 were measured in vitro using four clinically relevant CYP2C8 probe substrates (montelukast, paclitaxel, repaglinide, and rosiglitazone) and amodiaquine. Repaglinide exhibited the highest sensitivity to inhibition in vitro. In vitro phenotyping indicated that montelukast is an appropriate probe for CYP2C8 inhibition studies. The in vivo sensitivities of the CYP2C8 probe substrates cerivastatin, fluvastatin, montelukast, pioglitazone, and rosiglitazone were determined in relation to repaglinide on the basis of clinical drug-drug interaction (DDI) data. Repaglinide exhibited the highest sensitivity in vivo, followed by cerivastatin, montelukast, and pioglitazone. Finally, the magnitude of in vivo CYP2C8 DDI caused by gemfibrozil-1-O-β-glucuronide was predicted. Comparisons of the predictions with clinical data coupled with the potential liabilities of other CYP2C8 probes suggest that montelukast is an appropriate CYP2C8 probe substrate to use for the in vivo situation. PMID:21697463

  20. Les manifestations ophtalmologiques de la maladie de Behçet, à propos de 33 cas

    PubMed Central

    Andaloussi, Idriss Benatiya; Alami, Bouchra; Abdellaoui, Meryem; Bhallil, Salima; Bono, Wafae; Tahri, Hicham

    2012-01-01

    Les manifestations ophtalmologiques au cours de la maladie de Behçet sont dominées par les uvéites, les vascularites rétiniennes et les thromboses veineuses rétiniennes. Nous rapportons une étude rétrospective portant sur tous les malades atteints de la maladie de Behçet, hospitalisés au sein du service d'Ophtalmologie de Fès de Janvier 2007 à Décembre 2009. Au total ce sont 33 patients qui sont inclut dans l'étudeLa moyenne d’âge est de 28,4 ans. Le délai moyen de consultation varie entre 1 jour et 3 ans. L'atteinte oculaire est bilatérale chez 26 patients (78,8% des yeux). L'AV est très basse avant le traitement: 28,8% à moins de 1/10. Les manifestations oculaires sont dominées par l'uvéite avec 77,3%, suivie de la vascularite rétinienne 54, 5% et la maculopathie 51, 5%. Le pourcentage des yeux dont l'AV était inférieur à 1/10 est passé à 19,7% après traitement. La fréquence de l'atteinte oculaire au cours de la maladie de Behçet est diversement appréciée selon les auteurs et selon le mode de recrutement des patients: elle va de 29% à 100%. L'atteinte uvéale est la plus fréquente des manifestations ophtalmologiques. Les lésions vasculaires rétiniennes sont dominées par la vascularite rétinienne essentiellement la périphlébite aussi bien au pôle postérieur qu’à la périphérie rétinienne. En l'absence de traitement et de mauvaise observance, le pronostic oculaire de la maladie de Behçet est très mauvais. La cécité s'installe dans 13 à 32%. Les manifestations ophtalmologiques au cours de la maladie de Behçet ont une valeur considérable, tant sur le plan diagnostique que pronostique. Notre étude a permis de décrire les aspects cliniques de l'atteinte oculaire de la maladie de Behçet dans un service d'Ophtalmologie tertiaire au Maroc. PMID:23396991

  1. Nqrs Data for C8H9KO6 [C8H5KO4·2(H2O)] (Subst. No. 1092)

    NASA Astrophysics Data System (ADS)

    Chihara, H.; Nakamura, N.

    This document is part of Subvolume A `Substances Containing Ag … C10H15' of Volume 48 `Nuclear Quadrupole Resonance Spectroscopy Data' of Landolt-Börnstein - Group III `Condensed Matter'. It contains an extract of Section `3.2 Data tables' of the Chapter `3 Nuclear quadrupole resonance data' providing the NQRS data for C8H9KO6 [C8H5KO4·2(H2O)] (Subst. No. 1092)

  2. Role of Cytochrome P450 2C8 in Drug Metabolism and Interactions.

    PubMed

    Backman, Janne T; Filppula, Anne M; Niemi, Mikko; Neuvonen, Pertti J

    2016-01-01

    During the last 10-15 years, cytochrome P450 (CYP) 2C8 has emerged as an important drug-metabolizing enzyme. CYP2C8 is highly expressed in human liver and is known to metabolize more than 100 drugs. CYP2C8 substrate drugs include amodiaquine, cerivastatin, dasabuvir, enzalutamide, imatinib, loperamide, montelukast, paclitaxel, pioglitazone, repaglinide, and rosiglitazone, and the number is increasing. Similarly, many drugs have been identified as CYP2C8 inhibitors or inducers. In vivo, already a small dose of gemfibrozil, i.e., 10% of its therapeutic dose, is a strong, irreversible inhibitor of CYP2C8. Interestingly, recent findings indicate that the acyl-β-glucuronides of gemfibrozil and clopidogrel cause metabolism-dependent inactivation of CYP2C8, leading to a strong potential for drug interactions. Also several other glucuronide metabolites interact with CYP2C8 as substrates or inhibitors, suggesting that an interplay between CYP2C8 and glucuronides is common. Lack of fully selective and safe probe substrates, inhibitors, and inducers challenges execution and interpretation of drug-drug interaction studies in humans. Apart from drug-drug interactions, some CYP2C8 genetic variants are associated with altered CYP2C8 activity and exhibit significant interethnic frequency differences. Herein, we review the current knowledge on substrates, inhibitors, inducers, and pharmacogenetics of CYP2C8, as well as its role in clinically relevant drug interactions. In addition, implications for selection of CYP2C8 marker and perpetrator drugs to investigate CYP2C8-mediated drug metabolism and interactions in preclinical and clinical studies are discussed. PMID:26721703

  3. Elucidation of the preferred routes of C8-vinyl reduction in chlorophyll and bacteriochlorophyll biosynthesis

    PubMed Central

    Canniffe, Daniel P.; Chidgey, Jack W.; Hunter, C. Neil

    2014-01-01

    Most of the chlorophylls and bacteriochlorophylls utilized for light harvesting by phototrophic organisms carry an ethyl group at the C8 position of the molecule, the product of a C8-vinyl reductase acting on a chlorophyll/bacteriochlorophyll biosynthetic precursor. Two unrelated classes of C8-vinyl reductase are known to exist, BciA and BciB, found in the purple phototroph Rhodobacter sphaeroides and the cyanobacterium Synechocystis sp. PCC6803 respectively. We constructed strains of each bacterium with the native C8-vinyl reductase swapped for the other class of the enzyme, and combined these replacements with a series of deletions of the native bch and chl genes. In vivo data indicate that the preferred substrates for both classes of the enzyme is C8-vinyl chlorophyllide, with C8-vinyl protochlorophyllide reduced only under conditions in which this pigment accumulates as a result of perturbed formation of chlorophyllide. PMID:24942864

  4. Clinical and Pathological Manifestations with Differential Diagnosis in Behçet's Disease

    PubMed Central

    Kokturk, Aysin

    2012-01-01

    Behçet's disease is a multisystemic inflammatory disease of unknown etiology which usually occurs as a trait of symptoms: aphthous stomatitis, genital ulcerations, and ocular disease. At the beginning of the disease the diagnosis is uncertain because of various clinical manifestations and a long period up to the full clinical picture manifestation. Since neither the laboratory data nor the histopathological signs are truly pathognomonic in Behçet's disease, the differential diagnosis depends on a careful evaluation of the medical history and meticulous physical examination to detect concomitant systemic manifestations. Sometimes, some laboratory test may help establish the diagnosis. Subspecialty referral to ophthalmology, rheumatology, neurology, and gastroenterology should be considered when indicated. PMID:22191082

  5. Managing Behçet’s disease: An update on current and emerging treatment options

    PubMed Central

    van Daele, P LA; Kappen, J H; van Hagen, P M; van Laar, J AM

    2009-01-01

    Behçet’s disease is an autoinflammatory vasculitis of unknown origin characterized by recurrent oral and genital ulcers, uveitis, arthritis and skin lesions. Additionally, involvement of the gastrointestinal tract, central nervous system and large vessels may occur. The disease is prevalent in countries along the ancient Silk Road from Eastern Asia to the Mediterranean Basin. Many treatment modalities are currently available. The choice of treatment depends on organ involvement and severity of disease. Topical treatment with corticosteroids is often sufficient for mucocutaneous involvement, however for more severe disease with vasculitis or neurological involvement a more aggressive approach is warranted. Newer drugs (biologicals) influencing cytokines and thereby T-cell function are promising with an acceptable side effect profile. Unfortunately, reimbursement of the costs of biologicals for rare disease is still a problem in various countries. In this report we discuss the current treatment modalities for Behçet’s disease. PMID:19536320

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

    PubMed Central

    Figus, Michele; Posarelli, Chiara; 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

  7. [Arterial aneurysm in Behçet's disease. Report of 5 cases].

    PubMed

    Ben Taarit, C; Turki, S; Ben Maïz, H

    2001-12-01

    Behçet's disease is a systemic vasculitis generally involving the venous system. Arterial manifestations, usually aneurysm or more rarely occlusion, are less common. We analysed 5 cases of Behçet's disease with arterial aneurysm complications. There were 4 men and 1 woman, mean age 34.6 years. Mean delay to arterial complications was 7.8 years after the first sign of the disease. Four patients showed evidence aneurysms of the pulmonary arteries. One patient developed an aneurysm of the aortic and iliac artery. Phlebitis was associated with arterial involvement in 4 patients. Combined corticosteroid and cyclophosphamide therapy enabled regression of pulmonary aneurysms in 2 patients. One patient was operated, outcome was favorable. Histology showed fragmentation of the media associated with vasculitis. Two patients with pulmonary aneurysms died of massive hemoptysis. PMID:11917664

  8. Human CYP2C8: structure, substrate specificity, inhibitor selectivity, inducers and polymorphisms.

    PubMed

    Lai, Xin-Sheng; Yang, Li-Ping; Li, Xiao-Tian; Liu, Jun-Ping; Zhou, Zhi-Wei; Zhou, Shu-Feng

    2009-11-01

    Human CYP2C8 is a key member of the CYP2C family and metabolizes more than 60 clinical drugs. A number of active site residues in CYP2C8 have been identified based on homology modeling and site-directed mutagenesis studies. In the structure of CYP2C8, the large active site cavity exhibits a trifurcated topology that approximates a T or Y shape, which is consistent with the finding that CYP2C8 can efficiently oxidize relatively large substrates such as paclitaxel and cerivastatin. The active site cavity of CYP2C8 contains at least 48 amino acid residues and many of them are important for substrate binding. The structures of CYP2C8 in complex with distinct ligands have revealed that the enzyme can bind divergent substrates and inhibitors without extensive conformational changes. CYP2C8 is a major catalyst in the metabolism of paclitaxel, amodiaquine, troglitazone, amiodarone, verapamil and ibuprofen, with a secondary role in the biotransformation of cerivastatin and fluvastatin. CYP2C8 also metabolises endogenous compounds such as retinoids and arachidonic acid. Many drugs are inhibitors of CYP2C8 and inhibition of this enzyme may result in clinical drug interactions. The pregnane X receptor, constitutive androstane receptor, and glucocorticoid receptor are likely to involve the regulation of CYP2C8. A number of genetic mutations in the CYP2C8 gene have been identified in humans and some of them have functional impact on the clearance of drugs. Further studies are needed to delineate the role of CYP2C8 in drug development and clinical practice. PMID:20214592

  9. Preclinical Evaluation of Liposomal C8 Ceramide as a Potent anti-Hepatocellular Carcinoma Agent

    PubMed Central

    Lv, Huiqing; Zhang, Zhongmin; Wu, Xiaoyu; Wang, Yaoxia; Li, Chenglin; Gong, Weihong; Gui, Liang; Wang, Xin

    2016-01-01

    Hepatocellular carcinoma (HCC) remains a global health threat. The search for novel anti-HCC agents is urgent. In the current study, we synthesized a liposomal C8 ceramide, and analyzed its anti-tumor activity in pre-clinical HCC models. The liposomal C8 (ceramide) potently inhibited HCC cell (HepG2, SMMC-7721 and Huh-7 lines) survival and proliferation, more efficiently than free C8 ceramide. Yet, non-cancerous HL7702 human hepatocytes were resistant to the liposomal C8 treatment. Liposomal C8 activated caspase-dependent apoptosis in HCC cells, and HCC cytotoxicity by liposomal C8 was significantly attenuated with co-treatment of caspase inhibitors. At the molecular level, we showed that liposomal C8 activated ASK1 (apoptosis signal-regulating kinase 1)-JNK (Jun N-terminal protein kinase) signaling in HCC cells. On the other hand, JNK pharmacological inhibition or dominant negative mutation, as well as ASK1 shRNA-knockdown remarkably inhibited liposomal C8-induced apoptosis in HCC cells. Further studies showed that liposomal C8 inhibited AKT-mTOR (mammalian target of rapamycin) activation in HCC cells. Restoring AKT-mTOR activation by introducing a constitutively-active AKT alleviated HepG2 cytotoxicity by liposomal C8. In vivo, intravenous (i.v.) injection of liposomal C8 significantly inhibited HepG2 xenograft growth in severe combined immuno-deficient (SCID) mice, and mice survival was significantly improved. These preclinical results suggest that liposomal C8 could be further studied as a valuable anti-HCC agent. PMID:26727592

  10. Genetic Polymorphisms of CYP2C8 in the Czech Republic

    PubMed Central

    Buzkova, Helena; Matouskova, Olga; Perlik, Frantisek

    2012-01-01

    Aim: CYP2C8 represents 7% of the hepatic cytochrome system and metabolizes around 5% of drugs in phase I processes. It also plays a significant role in metabolism of endogenous compounds. More than 20 single-nucleotide polymorphisms (SNPs) have been noted, mainly in exons 3, 5, and 8. The most studied SNPs may lead to decreased enzyme activity and may have impact on drug metabolism. Variant alleles are called CYP2C8*2 (I269F), CYP2C8*3 (R139K, K399R), and CYP2C8*4(I264M). Our aim was to investigate the frequency of major functional SNPs among the Czech population. Material and methods: DNA was isolated from whole blood of 161 healthy, young, and unrelated subjects (94 men and 67 women, aged from 23 to 28 years). The genotypes of polymorphic positions CYP2C8*2, CYP2C8*3 (G416A, A1196G), and CYP2C8*4 were determined by polymerase chain reaction–restriction fragment length polymorphism. Results and conclusion: Observed allele frequencies were 10.9%, 5.9%, and 0.3% for the alleles CYP2C8*3, CYP2C8*4, and CYP2C8*2, respectively. Both CYP2C8*3 (G416A, A1196G) alleles have been found in complete linkage disequilibrium. The allele distribution complies well with Hardy–Weinberg equilibrium. Allele frequencies of functionally important CYP2C8 variants in the Czech population are similar to that of other Caucasian populations. PMID:22313047

  11. Preclinical Evaluation of Liposomal C8 Ceramide as a Potent anti-Hepatocellular Carcinoma Agent.

    PubMed

    Lv, Huiqing; Zhang, Zhongmin; Wu, Xiaoyu; Wang, Yaoxia; Li, Chenglin; Gong, Weihong; Gui, Liang; Wang, Xin

    2016-01-01

    Hepatocellular carcinoma (HCC) remains a global health threat. The search for novel anti-HCC agents is urgent. In the current study, we synthesized a liposomal C8 ceramide, and analyzed its anti-tumor activity in pre-clinical HCC models. The liposomal C8 (ceramide) potently inhibited HCC cell (HepG2, SMMC-7721 and Huh-7 lines) survival and proliferation, more efficiently than free C8 ceramide. Yet, non-cancerous HL7702 human hepatocytes were resistant to the liposomal C8 treatment. Liposomal C8 activated caspase-dependent apoptosis in HCC cells, and HCC cytotoxicity by liposomal C8 was significantly attenuated with co-treatment of caspase inhibitors. At the molecular level, we showed that liposomal C8 activated ASK1 (apoptosis signal-regulating kinase 1)-JNK (Jun N-terminal protein kinase) signaling in HCC cells. On the other hand, JNK pharmacological inhibition or dominant negative mutation, as well as ASK1 shRNA-knockdown remarkably inhibited liposomal C8-induced apoptosis in HCC cells. Further studies showed that liposomal C8 inhibited AKT-mTOR (mammalian target of rapamycin) activation in HCC cells. Restoring AKT-mTOR activation by introducing a constitutively-active AKT alleviated HepG2 cytotoxicity by liposomal C8. In vivo, intravenous (i.v.) injection of liposomal C8 significantly inhibited HepG2 xenograft growth in severe combined immuno-deficient (SCID) mice, and mice survival was significantly improved. These preclinical results suggest that liposomal C8 could be further studied as a valuable anti-HCC agent. PMID:26727592

  12. [Articular manifestations of Behçet's disease. Apropos of 65 cases].

    PubMed

    Imbert, I; Legros, P; Prigent, D; Bergaoui, N; Sekkat, A; Chaouni-Berbich, A; Roux, H

    1987-02-01

    The authors, in a series of 65 cases of Behçet's disease, notice 53% of rheumatological manifestations which are third in line after aphthosis and ocular disease. In order of decreasing frequency, it concerns arthritis (mono, oligo or poly-arthritis), arthralgias with an almost identical frequency, sacroiliitis, extraarticular involvement. These rheumatological manifestations are readily associated with necrotic pseudo-folliculitis and cutaneous aphthosis. PMID:3563385

  13. What the Cardiologist Should Know About Cardiac Involvement in Behçet Disease.

    PubMed

    Veilleux, Simon-Pierre; O'Connor, Kim; Couture, Christian; Pagé, Sylvain; Voisine, Pierre; Poirier, Paul; Dubois, Michelle; Sénéchal, Mario

    2015-12-01

    Behçet disease (BD) is a chronic multisystem inflammatory vasculitis affecting mainly young adults and is characterized by a remitting-relapsing course. In North America, the prevalence is 5.2 per 100,000 population. It is believed that cardiac involvement is one of the most severe complications in patients with BD despite its sporadic occurrence, being greatly correlated with mortality. PMID:26215987

  14. Spontaneous aortic pseudoaneurysm rupture into the sigmoid colon in Behçet’s disease patient

    PubMed Central

    Lee, Su Lim; Ku, Young Mi; Won, Yoodong

    2015-01-01

    Behçet’s disease (BD) is a multisystem autoimmune disorder characterized by recurrent orogenital ulcers, uveitis, and skin lesions. The vascular manifestations include thrombophlebitis, stenosis, occlusion, and pseudoaneurysm. BD infrequently precipitates aortic pseudoaneurysm rupture into the sigmoid mesocolon and lumen of the adjacent colon. Here we report an extremely rare case of spontaneous abdominal aortic pseudoaneurysm rupture via the sigmoid mesocolon into the lumen of the sigmoid colon in a 37-year-old patient with BD. PMID:26675745

  15. [Peripheral arterial pseudo-aneurysm in Behçet's disease: Report of two cases].

    PubMed

    Abissegue, Y; Ouldsalek, E; Lyazidi, Y; El Ochi, M R; El Fatemi, B; Chtata, H T; Bensaid, Y; Taberkant, M

    2016-05-01

    Behçet's disease is a systemic vasculitis of unknown etiopathogenesis. Arterial events such as pseudo-aneurysms are rare and may be the mode of occurrence of the disease. These pseudo-aneurysms tend, regardless of size, to progress rapidly to life-threatening rupture. We report two cases of arterial pseudo-aneurysms that ruptured. Treatment consisted of surgical repair in one case and arterial ligation in the other; the postoperative course was uneventful in both cases. PMID:26947054

  16. Neuro-Behçet, pseudotumor cerebri and ocular signs: a rare association

    PubMed Central

    Rodrigues, Maria Inês; Loureiro, Cláudia; Geraldo Couceiro, Ana; Reis Ferreira, Cidalina; Monteiro-Grillo, Manuel

    2013-01-01

    Introduction: The central nervous system involvement in Behçet’s disease occurs in 5–30% of cases. The diagnosis of pseudotumor cerebri is even rarer (only 22 cases reported worldwide). Purpose: To emphasize the importance of differential diagnosis in a case of pseudotumor cerebri in the context of ocular inflammation. Methods: V.A.V.R., a 31 year old female, was diagnosed with pan-uveitis on the left eye associated with recurrent bipolar aphthosis. During the etiological investigation, there was an onset of a left hemiparesis and facial palsy. Results: The central nervous system (CNS) neuroradiological investigation revealed a space-occupying lesion within the right hemisphere with intense signal enhancement with gadolinium. It globally reached the nucleo-basal structures and induced deviation of the middle structures (including homolateral ventricle). Cytochemical analysis of cerebrospinal fluid (CSF) was negative for atypical cells. The ophthalmological features regressed with the corticosteroid and immunosuppressive therapy instituted. The final diagnosis was of pseudotumor cerebri in the context of Behçet’s disease. Conclusion: In Behçet’s disease, a cerebral space-occupying lesion should lead to a diagnosis of pseudotumor cerebri. The correct diagnosis will determine an appropriate therapy and may prevent an inappropriate neurosurgical approach. The cortico and immunotherapy allowed a substantial regression of the lesion.

  17. Cytomorphometric Characteristics of Buccal Mucosal Cells in Behçet's Disease Patients

    PubMed Central

    Aktunc, Erol; Oz, Zehra Safi; Bektas, Sibel; Altinyazar, Cevdet; Koca, Rafet; Bostan, Serdar

    2016-01-01

    Background. The aim of this study was to compare the cytomorphometric characteristics of the buccal cells of Behçet's disease patients with those of healthy controls. Methods. This case-control study compared a group of 30 patients with Behçet's disease with an age- and gender-matched control group of 30 healthy individuals. The buccal mucosal smears were stained using the Papanicolaou technique for cytomorphometric analyses. The nuclear and cytoplasmic areas were evaluated using digital image analysis; the ratio of nuclear to cytoplasmic areas and nuclear roundness are presented. Results. The nuclear and cytoplasmic areas of the BD patients' cells were significantly smaller than those of the healthy controls' cells, while the nucleus-to-cytoplasm ratio and neutrophil infiltration rate did not differ significantly between the groups. However, the nuclear area, cytoplasmic area, nucleus-to-cytoplasm ratio, and nuclear roundness factor were significantly higher in patients without aphthae. The neutrophil infiltration rate did not differ significantly in patients with or without aphthae. Conclusion. Behçet's disease can produce cytomorphometric changes in buccal cells that are detectable by exfoliative cytology and cytomorphometric analysis techniques. PMID:27088074

  18. The immunogenetics of Behçet's disease: A comprehensive review.

    PubMed

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

    2015-11-01

    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

  19. 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...

  20. 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...

  1. 42 CFR 68c.8 - What does the CIR-LRP provide to participants?

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 42 Public Health 1 2011-10-01 2011-10-01 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...

  2. 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...

  3. 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...

  4. 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...

  5. 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...

  6. Targeting of Splice Variants of Human Cytochrome P450 2C8 (CYP2C8) to Mitochondria and Their Role in Arachidonic Acid Metabolism and Respiratory Dysfunction*

    PubMed Central

    Bajpai, Prachi; Srinivasan, Satish; Ghosh, Jyotirmoy; Nagy, Leslie D.; Wei, Shouzou; Guengerich, F. Peter; Avadhani, Narayan G.

    2014-01-01

    In this study, we found that the full-length CYP2C8 (WT CYP2C8) and N-terminal truncated splice variant 3 (∼44-kDa mass) are localized in mitochondria in addition to the endoplasmic reticulum. Analysis of human livers showed that the mitochondrial levels of these two forms varied markedly. Molecular modeling based on the x-ray crystal structure coordinates of CYP2D6 and CYP2C8 showed that despite lacking the N-terminal 102 residues variant 3 possessed nearly complete substrate binding and heme binding pockets. Stable expression of cDNAs in HepG2 cells showed that the WT protein is mostly targeted to the endoplasmic reticulum and at low levels to mitochondria, whereas variant 3 is primarily targeted to mitochondria and at low levels to the endoplasmic reticulum. Enzyme reconstitution experiments showed that both microsomal and mitochondrial WT CYP2C8 efficiently catalyzed paclitaxel 6-hydroxylation. However, mitochondrial variant 3 was unable to catalyze this reaction possibly because of its inability to stabilize the large 854-Da substrate. Conversely, mitochondrial variant 3 catalyzed the metabolism of arachidonic acid into 8,9-, 11,12-, and 14,15-epoxyeicosatrienoic acids and 20-hydroxyeicosatetraenoic acid when reconstituted with adrenodoxin and adrenodoxin reductase. HepG2 cells stably expressing variant 3 generated higher levels of reactive oxygen species and showed a higher level of mitochondrial respiratory dysfunction. This study suggests that mitochondrially targeted variant 3 CYP2C8 may contribute to oxidative stress in various tissues. PMID:25160618

  7. Oral infection control to assist infliximab therapy in a Behçet's disease patient with severe eye inflammation in response to dental treatment: a case report

    PubMed Central

    Kudo, Chieko; Wakabayashi, Hiroshi; Shimoe, Masayuki; Kobayashi, Hiroya; Ito, Takashi; Ohkawa, Toshinori; Isoshima-Nakamura, Arisa; Mineshiba, Junji; Yoshioka, Norie; Nawachi, Kumiko; Maeda, Hiroshi; Matsuo, Toshihiko; Makino, Hirofumi; Takashiba, Shogo

    2014-01-01

    Key Clinical Message We report a case of Behçet's disease which was aggravated by psychological stress and oral infection. The control of oral infection under medical and dental collaboration is important for providing Behçet's disease patients with the optimal medical care and for facilitating the relief of the primary disease. PMID:25548630

  8. Beryllium monohydride (BeH): Where we are now, after 86 years of spectroscopy

    NASA Astrophysics Data System (ADS)

    Dattani, Nikesh S.

    2015-05-01

    BeH is one of the most important benchmark systems for ab initio methods and for studying Born-Oppenheimer breakdown. However the best empirical potential and best ab initio potential for the ground electronic state to date give drastically different predictions in the long-range region between where the highest measurements have been made, and the dissociation energy; a region which is about ∼1000 cm-1 for 9BeH, ∼ 3000 cm-1 for 9BeD, and ∼13 000 cm-1 for 9BeT. Improved empirical potentials and Born-Oppenheimer breakdown corrections have now been built in this work for the ground electronic states X (12Σ+) of all three isotopologues. The predicted dissociation energy for 9BeH from the new empirical potential is now in agreement with the current best ab initio prediction in all 5 digits of the former's precision, while the previous best empirical potential was in disagreement by 74 cm-1. The previous best empirical potential predicted the existence of unobserved vibrational levels for all three isotopologues, and the current best ab initio study also predicted the existence of all of these levels, and 7 more in total. With the exception of two, the present empirical potential agrees with the existence of all of the ab initio potentials' extra levels not predicted by the earlier empirical potential. With one exception, all energy spacings between vibrational energy levels for which measurements have been made, are predicted with an agreement of better than 1 cm-1 between the new empirical potential and the current best ab initio potential, but some predictions for unobserved levels are still in great disagreement, and the equilibrium bond lengths are different by orders of magnitude.

  9. Intracardiac thrombus in Behçet's disease: four new cases and a comprehensive literature review.

    PubMed

    Aksu, Tolga; Tufekcioglu, Omac

    2015-07-01

    Behçet's disease (BD) is a multisystem inflammatory disorder. Intracardiac thrombus formation (ICTF) is an uncommon but important complication of BD. To highlight recent insights into this disease, we aimed to review ICTF and other systemic involvements associated with ICTF in BD. We conducted a comprehensive review of the relevant literature in MEDLINE and EMBASE from 1966 to 2014 to analyze cumulated data about ICTF in BD. We aimed to evaluate 93 cases of BD with ICT (group 1), four of which have been recently identified and have not been discussed in the relevant literature yet, and to compare the frequency of pulmonary, venous and arterial involvements in group 1 and general Behçet population (group 2). The right heart was the most common site of ICTF in group 1. Pulmonary involvement, venous involvement (especially venous thrombosis) and arterial involvement were more frequent in group 1 than in group 2 (56 vs. 0.7 %, 42 vs. 10 % and 38 vs. 0.8 %, respectively, p < 0.0001). The diagnosis of BD should be considered if a patient presents with a mass in the right-sided cardiac chambers, even in the absence of the characteristic clinical manifestations of the illness. This approach is particularly applicable if the patient is a young man from the Mediterranean basin or the Middle East. All Behçet patients with ICTF must be investigated with thoracic computed tomography for pulmonary and arterial involvements and lower extremity venous Doppler ultrasonography for venous thrombosis, regardless of whether they are symptomatic for these systems. PMID:25381640

  10. Fluorescein and indocyanine green angiography findings in Behçet’s disease

    PubMed Central

    Atmaca, L S; Sonmez, P A

    2003-01-01

    Aim: To evaluate and compare the fluorescein (FA) and indocyanine green angiographic (ICGA) findings, and to investigate the choroidal involvement in Behçet’s disease. Methods: FA and ICGA were performed on 112 eyes of 62 patients with Behçet’s disease, between November 1993 and July 2002, using Topcon IMAGEnet Digital System. Patients were aged 16–50 years; 48 (77.4%) were male and 14 (22.6%) were female. Results: FA showed dye leakage from retinal vessels in 57 (50.9%) eyes, cystoid macular oedema in 18 eyes (16.1%), optic disc oedema in four eyes (3.6%), disc neovascularisation in three eyes (2.7%), and retinal neovascularisation in two eyes (1.8%). ICGA showed hyperfluorescent lesions in 40 eyes (35.7%), hypofluorescent lesions in 17 eyes (15.2%), hyperfluorescent and hypofluorescent lesions in 12 (10.7%) eyes, ICG leakage from choroidal vessels in 11 eyes (9.8%), irregular filling of choriocapillaris in five eyes (4.5%), and choroidal filling defect in four eyes (3.6%). Hyperfluorescent and hypofluorescent lesions which were seen in 53 out of 69 eyes (76.8%) on ICGA, were not visible on FA. 55 eyes (49.1%) showed hyperfluorescence on the disc on both FA and ICGA, whereas 36 (32.1%) showed hyperfluorescence only on FA. Conclusion: The hyperfluorescence and/or hypofluorescence, irregular filling of the choriocapillaris, choroidal filling defect, and ICG leakage from choroidal vessels seen only on ICGA may suggest choroidal involvement in Behçet’s disease. PMID:14660454

  11. Is mean platelet volume a new activity criteria in Behçet's disease?

    PubMed

    Uzkeser, Hulya; Haliloglu, Sema; Cayir, Yasemin; Bilen, Nurhan; Karaaslan, Yasar; Kosar, Ali; Carlioglu, Ayse

    2015-10-01

    The aim of this study was to assess mean platelet volume (MPV) and its relationship with disease activity in patients with Behçet's disease. Thirty-six patients with an age of 38.9 ± 11 (mean ± SD) years and 40 controls aged 36.5 ± 12 (mean ± SD) years were enrolled the study. Demographic data, erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), MPV, clinical findings such as oral aphthae, genital aphthae, erythema nodosum, acne, central nervous system involvement, uveitis, arthritis and arthralgia were all recorded. The MPV value in patients with Behçet's disease was 8.06 ± 1.0 (mean ± SD) and the MPV value of the control participants was 7.45 ± 0.6 (mean ± SD). MPV was statistically higher in patients with Behçet's disease than in the controls (P = 0.003). There were also significant differences between patients and controls according to ESR and CRP values (P < 0.001 and P = 0.001, respectively). MPV was positively correlated with arthralgia (P < 0.001, r = 0.438), arthritis (P = 0.008, r = 0.307), erythema nodosum (P = 0.002, r =  0.354), central nervous system involvement (P = 0.002, r = 0.357), acne (P = 0.008, r = 0.312), genital aphthae (P < 0.001, r = 0.401) and oral aphthae (P = 0.001 r = 0.377). MPV can be easily obtained from the patients. It was a cheap and practical method. In the future, MPV may be used as a new marker to detect the activation of BD. PMID:26196194

  12. 16. East side of Building C8, from southeast facing northwest. ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    16. East side of Building C-8, from southeast facing northwest. Replicates historic view at GA-2309-7. - Clark Howell Homes (Public Housing), Bounded by North Avenue, Lovejoy Street, Mills Street & Luckie Street, Atlanta, Fulton County, GA

  13. Pulmonary Nodules as an Initial Manifestation of Behçet's Disease

    PubMed Central

    Malekmohammad, M.; Emamifar, A.

    2014-01-01

    Behçet's disease (BD) is a systemic vasculopathy, characterized by recurrent oral aphthae, genital ulcers, uveitis, and skin lesions. Although vascular involvement, including venous and arteries of any size, is a usual manifestation, cases with pulmonary thrombosis as the initial symptom are not common in the absence of pulmonary artery aneurysm (PAA). This report describes a 36-year-old man with recurrent fever, nonmassive hemoptysis, and persistent cough with lung nodules in CT scan who had undergone open lung biopsy. On the basis of morphological findings, BD was suggested and more precise evaluation confirmed the diagnosis. PMID:25436168

  14. A rare case of Behçet disease with generalised myositis, cardiomyositis and necrotising fasciitis.

    PubMed

    Ng, Felix; Chiong, Fabian Joon Kiong; Buchanan, Russell; Burrell, Louise M

    2016-01-01

    Behçet disease (BD) is a rare relapsing, multisystem vasculitis characterised by recurrent oral and genital ulcers, and uveitis. As an autoimmune small vessel vasculitis, BD can involve other organs including the skin, joints, nervous system, kidney and the gastrointestinal tract. This report describes a 40-year-old woman who presented with an uncommon feature of BD, namely myositis, and who went on to develop myocarditis and polymicrobial necrotising fasciitis. To the best of our knowledge, this is the first reported case of an immunocompromised-associated infection occurring in BD without concurrent immunosuppressive therapy. PMID:26740268

  15. A Case of Behçet’s Disease with Superior and Inferior Vena Caval Occlusion

    PubMed Central

    Yoo, Wan-Hee; Moon, Jin-Seong; Kim, Sung-Il; Kim, Wan-Uk; Min, Jun-Gi; Park, Sung-Hwan; Lee, Sang-Heon; Cho, Chul-Soo; Kim, Ho-Yeon

    1998-01-01

    Behçet’s disease is a chronic multisystemic disorder involving many organs and characterized by recurrent oral and genital ulcers and relapsing iritis. A case of BD with large vein thrombosis involving superior and inferior vena cava is presented. Large vein thrombosis in BD is not commonly developed and most commonly observed in the inferior or superior vena cava. A review of the literature emphasizes the rarity of the combined superior and inferior vena caval occlusion. Existence of extensive large vein occlusion in BD is associated with limited therapy and poor prognosis. PMID:9735671

  16. Similarities and differences between Behçet's disease and Crohn's disease

    PubMed Central

    Yazısız, Veli

    2014-01-01

    Behçet’s disease (BD) is a chronic inflammatory condition with multisystem involvement. Approximately 10%-15% of patients present with gastrointestinal involvement. Involved sites and the endoscopic view usually resemble Crohn’s disease (CD). In addition to intestinal involvement, oral mucosa, the eyes, skin, and joints are commonly affected. No pathognomonic laboratory test is available for the diagnosis of either disease. Management approaches are also similar in various aspects. Differentiating BD from CD is highly challenging. In this article, the similarities and differences between BD and CD in terms of epidemiology, etiopathogenesis, clinical and imaging findings, and histopathological and therapeutic approaches are reviewed. PMID:25133025

  17. Cardiac pathology and modern therapeutic approach in Behçet disease.

    PubMed

    Cocco, Giuseppe; Jerie, Paul

    2014-01-01

    Behçet disease (BD) is an enigmatic inflammatory disorder with multisystemic complications which is endemic in some countries but can be seen in the entire world. Valid diagnostic criteria are available. The pathology is related to a specific perivasculitis with involvement of both arteries and veins of all sizes. Minor arterial and cardiac involvement is frequent in BD but is usually asymptomatic. In exceptional cases cardiac symptoms may be the 1st manifestation of BD. The prevalence of severe cardiac complications (cardio-Behçet) should be < 10%. An impressive therapeutic improvement has been achieved by using appropriate catheterization techniques, coronary and intra-arterial stents, colchicine, drug-response modifying drugs and immunotherapy but, still cardio-Behçet has a poor prognosis. Efforts are undertaken to improve morbidity and prognosis with the use of newer drugs. An important part of the complications in BD are related to the frequent thromboembolic complications and there is high possibility that newer oral anticoagulants will be superior to the classical anticoagulants presently used. Available biologic agents have already been frequently used and seem to have improved the prognosis, but efforts are undertaken to find newer biologic agents with better therapeutic performance and less side-effects. Summarizing as much as possible the effects of the presently used biotherapy in BD, interferon-alpha is effective against many ocular, genital and perhaps vascular manifestations, but its effectiveness is limited by frequent adverse-effects (even if not dangerous for the cardiovascular system). Infliximab is a valid option in the therapy of ocular and cutaneous manifestations but it is less convincing in the therapy of vascular manifestations in vascular- and neuro-Behçet; furthermore, side-effects, including severe cardiovascular complications, are seen in a minority of patients; perhaps worse, infliximab seems to loose efficacy in the long

  18. A giant pseudoaneurysm of the left anterior descending coronary artery related to Behçet disease.

    PubMed

    Calafiore, Antonio M; Al Helali, Sumaya; Iaco', Angela L; Sheickh, Azmat A; Kheirallah, Hatim; Di Mauro, Michele

    2015-03-01

    We report the case of a young patient with a recent diagnosis of Behçet disease, in whom the left anterior descending coronary artery was found fully open into a giant pseudoaneurysm, with occlusion of the distal segment. Surgical treatment included opening of the pseudoaneurysm with clot and fibrous tissue removal, proximal left anterior descending coronary artery closure, and distal left anterior descending coronary artery grafting. In patients with Behçet disease, it is advisable to perform computed tomography coronary angiography to rule out the presence of coronary artery disease and the occurrence of a rare but potentially life-threatening complication. PMID:25742859

  19. Deep venous thrombosis and inferior vena cava agenesis causing double crush sciatic neuropathy in Behçet's disease.

    PubMed

    Kara, Murat; Ozçakar, Levent; Eken, Güneş; Ozen, Gülsen; Kiraz, Sedat

    2008-12-01

    We report here the case of a 18-year-old young man with Behçet's disease who had suffered deep venous thrombosis of the right femoral and popliteal veins. Consequently, right sciatic nerve injury, drop foot and tightness of the achilles tendon also ensued. The clinical scenario was further challenged by demonstration of the agenetic inferior vena cava and epidural vein dilatations compressing the lumbar nerve roots. To the best notice of the authors, this is the first patient encompassing all these complications in the literature concerning Behçet's disease. PMID:18848486

  20. Association of anti-cardiolipin antibodies with vascular thrombosis and neurological manifestation of Behçets disease.

    PubMed

    al-Dalaan, A N; al-Ballaa, S R; al-Janadi, M A; Bohlega, S; Bahabri, S

    1993-03-01

    We have studied 44 patients with Behçet's Disease (BD) to look for any correlation of arterial and venous thrombosis or central nervous system (CNS) manifestations with anti-cardiolipin antibodies (ACLA). Twenty patients were positive for ACLA by MELISA method. Ten patients had IgG antibody, four had IgM and six had both IgG and IgM. Of these patients, 11 had a history of vascular thrombosis and thrombophlebitis and nine had CNS manifestations. The association of ACLA with vascular thrombosis or CNS manifestation of Behçet's disease was statistically not significant. PMID:8467608

  1. [Neurologic appearence of Behçet disease in 14-year old boy treated with adalimumab with good result].

    PubMed

    Iwańczak, Barbara; Reich, Adam; Kofla-Dłubacz, Anna; Kazanowska, Bernarda; Ruczka, Małgorzata

    2016-02-01

    Behçet disease is a multiorgan inflammatory vessel disorder of unknown etiology which only occasionally occurs in children. Here, we demonstrate a 14-year-old boy with Behçet disease diagnosed based on recurrent aphthous stomatitis, acneiform facial lesions, subpreputial erosions and extensive thrombosis involving sigmoid sinus, transverse sinus and right internal cervical vein. Treatment with low molecular weight heparins, systemic corticosteroids, and azathioprine only resulted in partial remission of clinical symptoms. Addition of adalimumab led to complete resolution of clinical and biochemical abnormalities and disappearance of thrombosis in central nervous system. PMID:27000816

  2. Successful Treatment and Secondary Prevention of Venous Thrombosis Secondary to Behçet Disease with Rivaroxaban

    PubMed Central

    Lambert, Catherine; Hermans, Cedric

    2016-01-01

    We here present the successful initial treatment and secondary prophylaxis of superficial venous thrombosis secondary to Behçet's disease by a novel anticoagulant drug, rivaroxaban (Xarelto®). To our knowledge, this is the first case of using an oral direct inhibitor of FXa in this setting. Our findings are promising; the outcome was favourable without any adverse effect noted. We propose that the patients with Behçet's disease and venous thrombosis might benefit from the advantages of the new anticoagulant drug. PMID:27437154

  3. Acute Monocytic Leukemia Masquerading Behçet's Disease-Like Illness at Onset in an Elderly Female

    PubMed Central

    Koba, Shigeru; Sekioka, Toshio; Takeda, Sorou; Miyagawa-Hayashino, Aya; Nishimura, Keisuke

    2016-01-01

    A previously healthy 74-year-old Japanese female was hospitalized with fever and high C-reactive protein. She developed palatal herpangina-like aphthous ulcers, localized intestinal wall thickening, terminal ileum ulcers, and an erythematous acneiform rash; thus Behçet's disease-like illness was suspected. Significant peripheral blood acute monocytosis developed during her hospitalization and acute monocytic leukemia (FAB M5b) with normal karyotype was diagnosed. By immunostaining, the infiltrating cells in the skin and the terminal ileum were identified as monocytic leukemic cells. This case exhibited a unique initial presentation of Behçet's disease-like illness associated with acute monocytic leukemia. PMID:27610252

  4. Acute Monocytic Leukemia Masquerading Behçet's Disease-Like Illness at Onset in an Elderly Female.

    PubMed

    Koba, Shigeru; Sekioka, Toshio; Takeda, Sorou; Miyagawa-Hayashino, Aya; Nishimura, Keisuke; Imashuku, Shinsaku

    2016-01-01

    A previously healthy 74-year-old Japanese female was hospitalized with fever and high C-reactive protein. She developed palatal herpangina-like aphthous ulcers, localized intestinal wall thickening, terminal ileum ulcers, and an erythematous acneiform rash; thus Behçet's disease-like illness was suspected. Significant peripheral blood acute monocytosis developed during her hospitalization and acute monocytic leukemia (FAB M5b) with normal karyotype was diagnosed. By immunostaining, the infiltrating cells in the skin and the terminal ileum were identified as monocytic leukemic cells. This case exhibited a unique initial presentation of Behçet's disease-like illness associated with acute monocytic leukemia. PMID:27610252

  5. CMV retinitis after intravitreal triamcinolone acetonide injection in a patient with Behçet's uveitis.

    PubMed

    Tugal-Tutkun, Ilknur; Araz, Bilge; Cagatay, Atahan

    2010-10-01

    We report the case of a patient with Behçet's uveitis who developed cytomegalovirus (CMV) retinitis after intravitreal triamcinolone acetonide (IVTA) injection. We reviewed the patient's chart for the purpose of this report. An IVTA injection was performed for treatment of severe panuveitis in the left eye of a 30-year-old male patient with Behçet's disease. Systemic treatment included high dose corticosteroid and azathioprine. Fourteen weeks after IVTA, extensive areas of necrotizing retinitis developed in the left eye. Polymerase chain reaction of serum and vitreous samples was positive for CMV DNA. Serum anti-CMV IgG was positive, IgM was negative, anti-HIV antibody was negative, complete blood count was normal, and CD4 count was 1,060 cells/μl. The patient responded well to intravitreal ganciclovir injection performed twice and intravenous ganciclovir treatment administered for five weeks. Local immunosuppression with IVTA may cause CMV retinitis. Awareness of this serious complication is important for correct diagnosis and treatment. PMID:20033756

  6. Unusual Late Onset of Parenchymal Neuro-Behçet Disease

    PubMed Central

    2016-01-01

    Neuro-Behçet disease (NBD) is a multisystem inflammatory disorder characterized by oral lesions, genital lesions, uveitis, and neurological deficits. If left untreated, it may lead to worsening neurological function and can be fatal. Here we present a case of a 52-year-old woman who was diagnosed with Behçet disease (BD) as a teenager and had a relatively mild disease course. Decades later after her initial DB diagnosis, she presented to our hospital with a chief complaint of headache. She did not have focal neurological deficits or any active mucosal lesions. Upon further investigation, the patient was found to have multiple inflammatory changes on neuroimaging and abnormal cerebrospinal fluid (CSF), consistent with the diagnosis of NBD. She was treated with intravenous corticosteroid therapy and her symptoms resolved. Although our patient presented with minimal symptoms decades after her initial diagnosis, any neurological complaint warranted a thorough investigation for a proper diagnosis and treatment given the multisystem involvement of BD. PMID:27529041

  7. Periodontal Health Status among Patients with Behçet's Disease

    PubMed Central

    Habibagahi, Zahra; Khorshidi, Hooman; Hekmati, Shahrzad

    2016-01-01

    We aimed to evaluate the relationship of individual periodontal parameters with the severity of Behçet's disease (BD) and attempt to find the correlation between chronic periodontitis and BD. In this study, 74 registered subjects attending Behçet's clinic with BD symptoms were recruited. The diagnosis was based on the criteria presented by the international study group for BD (ISG) and the total clinical severity score was determined for each patient. All individuals underwent clinical examination to assess oral and periodontal status and presence of oral ulcers. Periodontal clinical parameters of bleeding on probing (BOP), probing depth (PD), and clinical attachment level (CAL) and also hygiene index (HI) and decayed, missing, and filled (DMF) teeth were noted and analyzed to assess the correlation with severity of BD. There was no significant correlation between DMF and severity of BD. The strong association was found between periodontal parameters (BOP, PD, and CAL) and the severity of BD (P < 0.001). It seems that relation of BD to oral health is higher up in severe forms of BD and periodontal diseases. Clinical association between the diseases might be due to a common underlying etiopathogenesis of periodontitis and BD. PMID:27034903

  8. Atypical manifestations in Brazilian patients with neuro-Behçet's disease.

    PubMed

    Dutra, Lívia Almeida; Gonçalves, Célio Roberto; Braga-Neto, Pedro; Pedroso, José Luiz; Gabbai, Alberto Alain; Barsottini, Orlando Graziani Povoas; de Souza, Alexandre Wagner Silva

    2012-06-01

    Type and frequency of systemic and neurologic manifestations of Behçet's disease (BD) vary with ethnicity. In Brazil, BD occurs as sporadic cases. We describe clinical and radiological features of 36 Brazilian patients of mixed ethnicity with neuro-Behçet's disease (NBD). Medical records of 178 BD patients were reviewed and 36 (20%) NBD patients were identified. Twenty-one NBD patients (58.3%) were female and 27 (75%) presented with parenchymal manifestations. Brainstem involvement was the most common neurologic syndrome (41.7%). Seizures (27.8%), isolated aseptic meningitis (16.7%), optic neuropathy (ON) (16.7%), cerebral venous thrombosis (CVT) (8.3%), peripheral neuropathy (2.8%), and spinal cord involvement (5.6%) were other neurologic manifestations observed among Brazilian NBD patients. Eighteen (50%) had at least one relapse, and isolated aseptic meningitis was the most common relapsing manifestation. No significant differences concerning the number of relapses between parenchymal and non-parenchymal groups were found. A multivariate model including disease duration, cell count in spinal fluid, cyclosporine use, immunosuppressive use at disease onset, age at NBD onset, and ON did not reveal any significant associations with NBD relapse. There was a low frequency of CVT and an unexpected higher number of isolated aseptic meningitis. Brazilian NBD patients present more parenchymal and atypical manifestations, and relapse more often than NBD patients from other populations. PMID:22169955

  9. Annexin A2 as a target endothelial cell membrane autoantigen in Behçet's disease

    PubMed Central

    Chen, Peng; Yan, Hai; Tian, Yaping; Xun, Yiping; Shi, Lili; Bao, Ran; Zhang, Huai; Chen, Guangyu; Yang, Chunhe; Sun, Shutao; Wang, Yajie; Liu, Li; Zhou, Yabin; Zhang, Chunyan; Wang, Xiaoxu; Wen, Yongqiang; Bian, Yongzhong; Du, Hongwu

    2015-01-01

    Cell membrane proteins are believed to play a critical role in the pathogenesis of autoimmune diseases. However, few membrane autoantigens have been linked with Behçet's disease. Here, a cell-chip was performed to identify autoantibody target cells, and the suspected autoantigens were detected using immunoblotting. The amino acid sequences of the detected proteins were determined using LC-MALDI-TOF/TOF. Putative proteins were recombinantly expressed and purified, and a corresponding ELISA was developed and clinically validated using real clinical samples. It was found that a 36-kDa membrane protein - annexin A2 - was detected in approximately one-third of the patients' blood circulation. The immunohistochemistry results showed that annexin A2 was highly expressed in vascular endothelial cells. Moreover, vascular involvement was significantly higher in the anti-annexin A2 antibody-positive group versus the anti-annexin A2 antibody-negative group among all the clinical samples analyzed, indicating that annexin A2 is a novel endothelial cell membrane antigen involved in Behçet's disease. PMID:25641213

  10. [A case of Behçet disease developing recurrent ischemic stroke with fever and scrotal ulcers].

    PubMed

    Koike, Yuka; Sakai, Naoko; Umeda, Yoshitaka; Umeda, Maiko; Oyake, Mutsuo; Fujita, Nobuya

    2015-01-01

    A 30-year-old man, who was diagnosed with Behçet disease at 10 years of age, was hospitalized because of transient right hemiparesis after presenting with high fever and scrotal ulcers. Brain MRI revealed ischemic lesions in the area supplied by the anterior cerebral arteries. Analysis of cerebrospinal fluid (CSF) showed pleocytosis and a high interleukin-6 (IL-6) concentration (668 pg/ml). The patient was diagnosed with acute ischemic stroke associated with exacerbation of Behçet disease. After initiation of corticosteroid therapy, his clinical symptoms improved, and the CSF IL-6 concentration decreased. One year later, the patient developed high fever and scrotal ulcers after the onset of transient left upper limb plegia. Brain MRI showed an acute ischemic lesion in the right putamen, and CSF analysis showed an elevated IL-6 concentration (287 pg/ml). Brain CT angiography revealed stenosis of the left anterior cerebral artery and occlusion of the right anterior cerebral artery, which had been well visualized one year previously. Involvement of the intracranial cerebral arteries in Behçet disease is extremely rare. To the best of our knowledge, this is the first case report of a patient with recurrent symptomatic ischemic stroke associated with high fever and scrotal ulcers, which suggests exacerbation of Behçet disease. PMID:26103818

  11. 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.

  12. The use of hydroxy acids on the skin: characteristics of C8-lipohydroxy acid.

    PubMed

    Saint-Léger, Didier; Lévêque, Jean-Luc; Verschoore, Michèle

    2007-03-01

    The hydroxy acids are widely used in skin creams because of their exfoliating and rejuvenating effect on photoaged skin. As a member of this family, the salicylic acid derivative known in the literature as 2-hydroxy-5-octanoyl benzoic acid or beta-lipohydroxy acid has also been proposed as an exfoliant and as a treatment of photoaged skin and acne. This article reviews the effects of the hydroxy acids and compares them to those of the salicylic acid derivative. We propose the name C(8)-lipohydroxy acid (C8-LHA) for this derivative to differentiate it from other related compounds. The lipophilic nature of C8-LHA and its relatively slow penetration in the skin afford it an exfoliating effect that is efficient at low concentrations. It appears to have antimicrobial, anti-inflammatory, and anticomedogenic properties, which make it effective against acne. Its antifungal and exfoliating properties are also likely to prove useful in combating dandruff. PMID:17348998

  13. 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

  14. Behçet's: A Disease or a Syndrome? Answer from an Expression Profiling Study.

    PubMed

    Oğuz, Ali Kemal; Yılmaz, Seda Taşır; Oygür, Çağdaş Şahap; Çandar, Tuba; Sayın, Irmak; Kılıçoğlu, Sibel Serin; Ergün, İhsan; Ateş, Aşkın; Özdağ, Hilal; Akar, Nejat

    2016-01-01

    Behçet's disease (BD) is a chronic, relapsing, multisystemic inflammatory disorder with unanswered questions regarding its etiology/pathogenesis and classification. Distinct manifestation based subsets, pronounced geographical variations in expression, and discrepant immunological abnormalities raised the question whether Behçet's is "a disease or a syndrome". To answer the preceding question we aimed to display and compare the molecular mechanisms underlying distinct subsets of BD. For this purpose, the expression data of the gene expression profiling and association study on BD by Xavier et al (2013) was retrieved from GEO database and reanalysed by gene expression data analysis/visualization and bioinformatics enrichment tools. There were 15 BD patients (B) and 14 controls (C). Three subsets of BD patients were generated: MB (isolated mucocutaneous manifestations, n = 7), OB (ocular involvement, n = 4), and VB (large vein thrombosis, n = 4). Class comparison analyses yielded the following numbers of differentially expressed genes (DEGs); B vs C: 4, MB vs C: 5, OB vs C: 151, VB vs C: 274, MB vs OB: 215, MB vs VB: 760, OB vs VB: 984. Venn diagram analysis showed that there were no common DEGs in the intersection "MB vs C" ∩ "OB vs C" ∩ "VB vs C". Cluster analyses successfully clustered distinct expressions of BD. During gene ontology term enrichment analyses, categories with relevance to IL-8 production (MB vs C) and immune response to microorganisms (OB vs C) were differentially enriched. Distinct subsets of BD display distinct expression profiles and different disease associated pathways. Based on these clear discrepancies, the designation as "Behçet's syndrome" (BS) should be encouraged and future research should take into consideration the immunogenetic heterogeneity of BS subsets. Four gene groups, namely, negative regulators of inflammation (CD69, CLEC12A, CLEC12B, TNFAIP3), neutrophil granule proteins (LTF, OLFM4, AZU1, MMP8, DEFA4, CAMP), antigen

  15. 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

  16. Behçet's: A Disease or a Syndrome? Answer from an Expression Profiling Study

    PubMed Central

    Oğuz, Ali Kemal; Yılmaz, Seda Taşır; Oygür, Çağdaş Şahap; Çandar, Tuba; Sayın, Irmak; Kılıçoğlu, Sibel Serin; Ergün, İhsan; Ateş, Aşkın; Özdağ, Hilal; Akar, Nejat

    2016-01-01

    Behçet’s disease (BD) is a chronic, relapsing, multisystemic inflammatory disorder with unanswered questions regarding its etiology/pathogenesis and classification. Distinct manifestation based subsets, pronounced geographical variations in expression, and discrepant immunological abnormalities raised the question whether Behçet’s is “a disease or a syndrome”. To answer the preceding question we aimed to display and compare the molecular mechanisms underlying distinct subsets of BD. For this purpose, the expression data of the gene expression profiling and association study on BD by Xavier et al (2013) was retrieved from GEO database and reanalysed by gene expression data analysis/visualization and bioinformatics enrichment tools. There were 15 BD patients (B) and 14 controls (C). Three subsets of BD patients were generated: MB (isolated mucocutaneous manifestations, n = 7), OB (ocular involvement, n = 4), and VB (large vein thrombosis, n = 4). Class comparison analyses yielded the following numbers of differentially expressed genes (DEGs); B vs C: 4, MB vs C: 5, OB vs C: 151, VB vs C: 274, MB vs OB: 215, MB vs VB: 760, OB vs VB: 984. Venn diagram analysis showed that there were no common DEGs in the intersection “MB vs C” ∩ “OB vs C” ∩ “VB vs C”. Cluster analyses successfully clustered distinct expressions of BD. During gene ontology term enrichment analyses, categories with relevance to IL-8 production (MB vs C) and immune response to microorganisms (OB vs C) were differentially enriched. Distinct subsets of BD display distinct expression profiles and different disease associated pathways. Based on these clear discrepancies, the designation as “Behçet’s syndrome” (BS) should be encouraged and future research should take into consideration the immunogenetic heterogeneity of BS subsets. Four gene groups, namely, negative regulators of inflammation (CD69, CLEC12A, CLEC12B, TNFAIP3), neutrophil granule proteins (LTF, OLFM4, AZU1, MMP8

  17. 26 CFR 1.501(c)(8)-1 - Fraternal beneficiary societies.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 26 Internal Revenue 7 2010-04-01 2010-04-01 true Fraternal beneficiary societies. 1.501(c)(8)-1... beneficiary societies. (a) A fraternal beneficiary society is exempt from tax only if operated under the lodge... exempt it is also necessary that the society have an established system for the payment to its members...

  18. Epitope mapping of monoclonal antibody 4C8 recognizing the protein huntingtin.

    PubMed

    Cong, Shu-Yan; Pepers, Barry A; Roos, Raymund A C; Van Ommen, Gert-Jan B; Dorsman, Josephine C

    2005-10-01

    Huntington's disease is a dominantly inherited, devastating neurodegenerative disorder, caused by a polyglutamine expansion (>37) in the N-terminal region of huntingtin, a protein of unknown function. In patients and normal individuals, N-terminal fragments of huntingtin are found, and the N-terminal fragments of mutant huntingtin are cytotoxic. The functions of wild-type huntingtin and the mechanisms underlying the toxic effects of mutant huntingtin are still ill defined. To get more insight into these topics, monoclonal antibodies (MAbs) are indispensable tools. Antibodies raised against the N-terminus are especially important. Among these, the 4C8 mouse MAb has been extensively used in various approaches. In this study, we have mapped the epitope of 4C8 to a 15-amino acid (aa) region spanning from aa 443 to 457 of the human protein, and found that mutation of three consecutive glutamic acids present in this region disrupts the recognition by 4C8. These results allow a more accurate interpretation of the results obtained by usage of the 4C8 antibody and broaden the utility of this antibody. PMID:16225422

  19. 75 FR 8796 - Civil Penalties Under ERISA Section 502(c)(8)

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-02-26

    ...\\ Pursuant to Reorganization Plan No. 4 of 1978, 43 FR 47713 (Oct. 17, 1978), the Department of the Treasury... model notice for plans in critical status. See 73 FR 15688 (Mar. 25, 2008). However, section 102(b)(1)(C... regulation, to be codified at 29 CFR 2560.502c-8, without change. \\6\\ 74 FR 45791. B. Overview of Final...

  20. NQRS Data for C8H9DO (Subst. No. 1091)

    NASA Astrophysics Data System (ADS)

    Chihara, H.; Nakamura, N.

    This document is part of Subvolume A `Substances Containing Ag … C10H15' of Volume 48 `Nuclear Quadrupole Resonance Spectroscopy Data' of Landolt-Börnstein - Group III `Condensed Matter'. It contains an extract of Section `3.2 Data tables' of the Chapter `3 Nuclear quadrupole resonance data' providing the NQRS data for C8H9DO (Subst. No. 1091)

  1. A potential therapeutic effect of CYP2C8 overexpression on anti-TNF-α activity

    PubMed Central

    LIU, WANJUN; WANG, BEI; DING, HU; WANG, DAO WEN; ZENG, HESONG

    2014-01-01

    Epoxyeicosatrienoic acids (EETs) are generated from arachidonic acid catalysed by cytochrome P450 (CYP) epoxygenases. In addition to regulating vascular tone EETs may alleviate inflammation and ROS. The present study was conducted to determine whether CYP2C8 gene overexpression was able to increase the level of EETs, and subsequently prevent TNF-α induced inflammation and reactive oxygen species (ROS) in human umbilical vein endothelial cells (HUVECs) and macrophages. Peroxisome proliferator-activated receptor γ (PPARγ) activation, nuclear factor-κB (NF-κB) activation, endothelial nitric oxide synthase (eNOS) activation, gp-91 activation, and inflammatory cytokine expression were detected by western blot analysis or enzyme-linked immunosorbent assay. Intracellular reactive oxygen species (ROS) was measured by flow cytometry, while the migration of vascular smooth muscle cells (VSMCs) was detected by Transwell assay. pCMV-mediated CYP2C8 overexpression and its metabolites, EETs, markedly suppressed TNF-α induced inflammatory cytokines IL-6 and MCP-1 expression via the activation of NF-κB and degradation of IκBα. Moreover, pretreatment with 11,12-EET significantly blocked TNF-α-induced ROS production. CYP2C8-derived EETs also effectively alleviated the migration of VSMCs and improved the function of endothelial cells through the upregulation of eNOS, which was significantly decreased under the stimulation of TNF-α. Furthermore, these protective effects observed were mediated by PPARγ activation. To the best of our knowledge, the results of the present study demonstrated for the first time that CYP2C8-derived EETs exerted antivascular inflammatory and anti-oxidative effects, at least in part, through the activation of PPARγ. Thus, the CYP2C8 gene may be useful in the prevention and treatment of vascular inflammatory diseases. PMID:25017038

  2. Paradoxical mucocutaneous flare in a case of Behçet's disease treated with tocilizumab.

    PubMed

    Cantarini, Luca; Lopalco, Giuseppe; Vitale, Antonio; Coladonato, Laura; Rigante, Donato; Lucherini, Orso Maria; Lapadula, Giovanni; Iannone, Florenzo

    2015-06-01

    We report on a patient with a long-standing history of recurrent oral aphthosis and pseudofolliculitis, diagnosed with Behçet's disease (BD), previously treated with high-dose prednisone, colchicine, cyclosporine, cyclophosphamide and methotrexate, all of which were partially effective. Treatment with the chimeric mouse-human anti-tumour necrosis factor (TNF)-α monoclonal antibody infliximab brought about the resolution of mucocutaneous lesions for a period of 6 years. After an oral and articular BD relapse, the anti-interleukin-6 agent tocilizumab was started in association with high-dose prednisone. Unexpectedly, the patient experienced a paradoxical mucocutaneous flare following tocilizumab administration, which worsened after the second infusion. Tocilizumab was then discontinued, and total recovery was achieved after the patient was started on the fully human anti-TNF-α monoclonal antibody golimumab in association with colchicine and methylprednisolone. PMID:24733249

  3. Neuro-Behçet's disease mimicking a cerebral tumor: a case report.

    PubMed Central

    Park, Jeong-Ho; Jung, Myung-Keun; Bang, Cha-Ok; Park, Hyung-Kook; Sung, Ki-Bum; Ahn, Moo-Young; Bae, Won-Kyeong; Chi, Je G.

    2002-01-01

    We report a rare case of neuro-Behcet's disease (NBD) presenting as an inflammatory pseudotumor in the brain. A 52-year-old woman was evaluated for subacute dizziness and headache. Brain magnetic resonance (MR) imaging showed a right cerebellar mass, which disappeared 2 weeks later. After a year, recurrent mucocutaneous manifestations of Beh et's disease were observed. Immunosuppressant and steroid maintenance treatment were started. She experienced two more neurologic attacks and brain MR imaging revealed an enhancing mass in the right temporal lobe. The second attack showed a good response to steroid pulse therapy, but the third attack did not respond to steroid and her neurologic signs suggested an impending transtentorial hernia. The right temporal lobectomy was performed for the purpose of life-saving. The pathologic finding of the mass was a chronic inflammatory vasculitis, compatible with NBD. PMID:12378032

  4. Morbus Behçet – a rare disease in Central Europe

    PubMed Central

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

    2015-01-01

    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. PMID:26788079

  5. Aseptic Endocarditis in Behçet's Disease Presenting as Tricuspid Valve Stenosis

    PubMed Central

    Lee, Hyun Sang; Choi, Won Suk; Kim, Kyun Hee; Kang, Jung Kyu; Kim, Na Young; Park, Sun Hee; Park, Youngwhi; Nam, Eon Jeong; Yang, Dong Heon; Cho, Yongkeun; Lee, Jong-Myung; Chae, Shung-Chull

    2011-01-01

    Aseptic endocarditis is an uncommon complication of Behçet's disease (BD). We describe a rare case of a 39-year-old female who had BD with aseptic endocarditis of the tricuspid valve (TV) presenting as tricuspid stenosis. She was diagnosed with BD four years ago. The mucocutaneous lesions were well-controlled with colchicine and short courses of corticosteroids. She remained free of signs and symptoms of BD for one year without any medication. Three months before admission, she gradually developed dyspnea on exertion and peripheral edema. Echocardiography revealed dilated right atrium and markedly thickened TV with severe stenosis. TV replacement was performed. Pathologic examination of the valve showed fibrinoid necrotic material and inflammatory cell infiltration. Blood cultures and cultures of the excised valve were negative for microorganisms. PMID:21860642

  6. Treatment of ocular symptoms of Behçet's disease with interferon α2a: a pilot study

    PubMed Central

    Kotter, I.; Eckstein, A.; Stubiger, N.; Zierhut, M.

    1998-01-01

    AIM—To study long term effects of interferon α2a (IFNα2a) on panuveitis in seven patients with Behçet's disease in a prospective, open clinical trial.
METHODS—Seven patients were treated with IFNα2a for a mean of 23.6 months (14-37 months). They received an initial dose of IFNα2a of 6×106 IU/day, followed by 3×106 IU/day after 1 month and 3×106 IU every other day after 3 months. Two patients received low dose prednisolone (between 0.2 and 0.4 mg/kg/body weight) additionally at the beginning of the therapy. Complete cessation of IFNα2a was possible in three patients (observation period 22, 6, and 4 months).
RESULTS—Marked improvement occurred in six patients who had ocular manifestations of Behçet's disease for the first time or with minor damage during their course of chronic relapsing panuveitis. In one patient with advanced ocular Behçet's disease, new relapses were prevented. Retinal infiltrates resolved within 2 weeks; vasculitis, macular oedema, infiltration of the anterior chamber and vitreous resolved within 4 weeks. Mean posterior uveitis score before treatment (nine affected eyes) was 6.6, 4 weeks after IFN it was reduced to 0.4. The mean observation period is 27.6 months, ranging from 14 to 42 months.
CONCLUSION—Treatment of ocular symptoms of Behçet's disease with IFNα2a alone or in combination with low dose steroids led to complete remission of ocular vasculitis in all patients treated in this open, uncontrolled trial. Treatment with IFNα2a may prevent permanent retinal or optic nerve damage due to vascular occlusion. No severe side effects occurred. Controlled randomised studies are warranted in order to prove the efficacy of IFNα2a in ocular Behçet's disease and to compare it with other, established treatments such as azathioprine or cyclosporin A.

 Keywords: Behçet's disease; uveitis; interferon α2a PMID:9713053

  7. Design, synthesis, and anticancer activity of C8-substituted-4'-thionucleosides as potential HSP90 inhibitors.

    PubMed

    Qu, Shuhao; Mulamoottil, Varughese A; Nayak, Akshata; Ryu, Seungyeon; Hou, Xiyan; Song, Jayoung; Yu, Jinha; Sahu, Pramod K; Zhao, Long Xuan; Choi, Sun; Lee, Sang Kook; Jeong, Lak Shin

    2016-08-15

    A series of C8-substituted-4'-thioadenosine analogs 3a-3g, 15, and 17 and their truncated derivatives 4a-4j, 23-25, and 27 have been successfully synthesized from d-ribose and d-mannose, respectively, employing Pummerer type or Vorbrüggen condensation reactions and the functionalization at the C8-position of nucleobase via Stille coupling or nucleophilic aromatic substitution reactions as key steps. All the synthesized compounds were assayed for their HSP90 inhibitory activity, but they were found to be inactive up to 100μM. However, the 8-iodo derivatives 15, 17, and 27 exhibited potent anticancer activity, indicating that different mechanism of action might be involved in their biological activity. PMID:27283788

  8. Nqrs Data for C8H7ClN2O3 (Subst. No. 1078)

    NASA Astrophysics Data System (ADS)

    Chihara, H.; Nakamura, N.

    This document is part of Subvolume A `Substances Containing Ag … C10H15' of Volume 48 `Nuclear Quadrupole Resonance Spectroscopy Data' of Landolt-Börnstein - Group III `Condensed Matter'. It contains an extract of Section `3.2 Data tables' of the Chapter `3 Nuclear quadrupole resonance data' providing the NQRS data for C8H7ClN2O3 (Subst. No. 1078)

  9. Nqrs Data for C8H6O4 (Subst. No. 1074)

    NASA Astrophysics Data System (ADS)

    Chihara, H.; Nakamura, N.

    This document is part of Subvolume A `Substances Containing Ag … C10H15' of Volume 48 `Nuclear Quadrupole Resonance Spectroscopy Data' of Landolt-Börnstein - Group III `Condensed Matter'. It contains an extract of Section `3.2 Data tables' of the Chapter `3 Nuclear quadrupole resonance data' providing the NQRS data for C8H6O4 (Subst. No. 1074)

  10. NQRS Data for C8H7Cl5NSb (Subst. No. 1082)

    NASA Astrophysics Data System (ADS)

    Chihara, H.; Nakamura, N.

    This document is part of Subvolume A `Substances Containing Ag … C10H15' of Volume 48 `Nuclear Quadrupole Resonance Spectroscopy Data' of Landolt-Börnstein - Group III `Condensed Matter'. It contains an extract of Section `3.2 Data tables' of the Chapter `3 Nuclear quadrupole resonance data' providing the NQRS data for C8H7Cl5NSb (Subst. No. 1082)

  11. NQRS Data for C8H7BrO (Subst. No. 1076)

    NASA Astrophysics Data System (ADS)

    Chihara, H.; Nakamura, N.

    This document is part of Subvolume A `Substances Containing Ag … C10H15' of Volume 48 `Nuclear Quadrupole Resonance Spectroscopy Data' of Landolt-Börnstein - Group III `Condensed Matter'. It contains an extract of Section `3.2 Data tables' of the Chapter `3 Nuclear quadrupole resonance data' providing the NQRS data for C8H7BrO (Subst. No. 1076)

  12. NQRS Data for C8H20Br3GeN (Subst. No. 1129)

    NASA Astrophysics Data System (ADS)

    Chihara, H.; Nakamura, N.

    This document is part of Subvolume A `Substances Containing Ag … C10H15' of Volume 48 `Nuclear Quadrupole Resonance Spectroscopy Data' of Landolt-Börnstein - Group III `Condensed Matter'. It contains an extract of Section `3.2 Data tables' of the Chapter `3 Nuclear quadrupole resonance data' providing the NQRS data for C8H20Br3GeN (Subst. No. 1129)

  13. Stereocontrolled synthesis of the C8-C22 fragment of rhizopodin.

    PubMed

    Kretschmer, Manuel; Menche, Dirk

    2012-01-01

    A convergent synthesis of the central C8-C22 core of the potent macrolide antibiotic rhizopodin is reported. Notable features of the stereocontrolled approach include an asymmetric reverse prenylation of an alcohol using a method of Krische, a thiazolium catalyzed transformation of an epoxyaldehyde as described by Bode, and a late-stage oxazole formation from advanced intermediates. This route demonstrates the applicability of these methodologies in complex natural product synthesis. PMID:22149453

  14. NQRS Data for C8H10BrN (Subst. No. 1096)

    NASA Astrophysics Data System (ADS)

    Chihara, H.; Nakamura, N.

    This document is part of Subvolume A `Substances Containing Ag … C10H15' of Volume 48 `Nuclear Quadrupole Resonance Spectroscopy Data' of Landolt-Börnstein - Group III `Condensed Matter'. It contains an extract of Section `3.2 Data tables' of the Chapter `3 Nuclear quadrupole resonance data' providing the NQRS data for C8H10BrN (Subst. No. 1096)

  15. Nqrs Data for C8H7ClN2O3 (Subst. No. 1079)

    NASA Astrophysics Data System (ADS)

    Chihara, H.; Nakamura, N.

    This document is part of Subvolume A `Substances Containing Ag … C10H15' of Volume 48 `Nuclear Quadrupole Resonance Spectroscopy Data' of Landolt-Börnstein - Group III `Condensed Matter'. It contains an extract of Section `3.2 Data tables' of the Chapter `3 Nuclear quadrupole resonance data' providing the NQRS data for C8H7ClN2O3 (Subst. No. 1079)

  16. Biodegradation of C7 and C8 iso-alkanes under methanogenic conditions.

    PubMed

    Abu Laban, Nidal; Dao, Anh; Semple, Kathleen; Foght, Julia

    2015-12-01

    Iso-alkanes comprise a substantial proportion of petroleum and refined products that impact the environment, but their fate is cryptic under methanogenic conditions. We investigated methanogenic biodegradation of C7 and C8 iso-alkanes found in naphtha, specifically 2-methylhexane, 3-methylhexane, 2-methylheptane, 4-methylheptane and 3-ethylhexane. These were incubated as a mixture or individually with enrichment cultures derived from oil sands tailings ponds that generate methane from naphtha components; substrate depletion and methane production were monitored for up to 663 days. 3-Methylhexane and 4-methylheptane were degraded both singly and in the mixture, whereas 2-methylhexane and 2-methylheptane resisted degradation as single substrates but were depleted in the iso-alkane mixture, suggesting co-metabolism. 3-Ethylhexane was degraded neither singly nor with co-substrates. Putative metabolites consistent with succinylated C7 and C8 were detected, suggesting activation by addition of iso-alkanes to fumarate and corresponding to detection of alkylsuccinate synthase-like genes. 454 pyrotag sequencing, cloning and terminal restriction fragment length polymorphism of 16S rRNA genes revealed predominance of a novel member of the family Peptococcaceae (order Clostridiales) and Archaea affiliated with Methanoregula and Methanosaeta. We report here isomer-specific metabolism of C7 -C8 iso-alkanes under methanogenic conditions and propose their activation by a novel Peptococcaceae via addition to fumarate. PMID:25331365

  17. Effects of Angiotensin II Receptor Blockers on Metabolism of Arachidonic Acid via CYP2C8.

    PubMed

    Senda, Asuna; Mukai, Yuji; Toda, Takaki; Hayakawa, Toru; Yamashita, Miki; Eliasson, Erik; Rane, Anders; Inotsume, Nobuo

    2015-01-01

    Arachidonic acid (AA) is metabolized to epoxyeicosatrienoic acids (EETs) via cytochrome enzymes such as CYP 2C9, 2C8 and 2J2. EETs play a role in cardioprotection and regulation of blood pressure. Recently, adverse reactions such as sudden heart attack and fatal myocardial infarction were reported among patients taking angiotensin II receptor blockers (ARBs). As some ARBs have affinity for these CYP enzymes, metabolic inhibition of AA by ARBs is a possible cause for the increase in cardiovascular events. In this study, we quantitatively investigated the inhibitory effects of ARBs on the formation of EETs and further metabolites, dihydroxyeicosatrienoic acids (DHETs), from AA via CYP2C8. In incubations with recombinant CYP2C8 in vitro, the inhibitory effects were compared by measuring EETs and DHETs by HPLC-MS/MS. Inhibition of AA metabolism by ARBs was detected in a concentration-dependent manner with IC50 values of losartan (42.7 µM), telmisartan (49.5 µM), irbesartan (55.6 µM), olmesartan (66.2 µM), candesartan (108 µM), and valsartan (279 µM). Losartan, telmisartan and irbesartan, which reportedly accumulate in the liver and kidneys, have stronger inhibitory effects than other ARBs. The lower concentration of EETs leads to less protective action on the cardiovascular system and a higher incidence of adverse effects such as sudden heart attack and myocardial infarction in patients taking ARBs. PMID:26632190

  18. Molecular Characterization and Expression Analyses of the Complement Component C8α, C8β and C9 Genes in Yellow Catfish (Pelteobagrus fulvidraco) after the Aeromonas hydrophila Challenge.

    PubMed

    Zheng, Huan; Ji, Wei; Zhang, Gui-Rong; Zhang, Xiao-Ting; Shi, Ze-Chao; Wei, Kai-Jian; Yang, Rui-Bin; Gardner, Jonathan P A

    2016-01-01

    The complement components C8α, C8β and C9 have important roles in the innate immune system against invading microorganisms. Partial cDNA sequences of the Pf_C8α, Pf_C8β and Pf_C9 genes (Pf: abbreviation of Pelteobagrus fulvidraco) were cloned from yellow catfish. The Pf_C8α, Pf_C8β and Pf_C9 genes showed the greatest amino acid similarity to C8α (54%) and C8β (62%) of zebrafish and to C9 (52%) of grass carp, respectively. Ontogenetic expression analyses using real-time quantitative PCR suggested that the three genes may play crucial roles during embryonic and early larval development. The mRNA expressions of the three genes were all at the highest levels in liver tissue, and at lower or much lower levels in 16 other tissues, demonstrating that the liver is the primary site for the protein synthesis of Pf_C8α, Pf_C8β and Pf_C9. Injection of Aeromonas hydrophila led to up-regulation of the three genes in the spleen, head kidney, kidney, liver and blood tissues, indicating that the three genes may contribute to the host's defense against invading pathogenic microbes. An increased understanding of the functions of the Pf_C8α, Pf_C8β and Pf_C9 genes in the innate immunity of yellow catfish will help enhance production of this valuable freshwater species. PMID:27005612

  19. Molecular Characterization and Expression Analyses of the Complement Component C8α, C8β and C9 Genes in Yellow Catfish (Pelteobagrus fulvidraco) after the Aeromonas hydrophila Challenge

    PubMed Central

    Zheng, Huan; Ji, Wei; Zhang, Gui-Rong; Zhang, Xiao-Ting; Shi, Ze-Chao; Wei, Kai-Jian; Yang, Rui-Bin; Gardner, Jonathan P. A.

    2016-01-01

    The complement components C8α, C8β and C9 have important roles in the innate immune system against invading microorganisms. Partial cDNA sequences of the Pf_C8α, Pf_C8β and Pf_C9 genes (Pf: abbreviation of Pelteobagrus fulvidraco) were cloned from yellow catfish. The Pf_C8α, Pf_C8β and Pf_C9 genes showed the greatest amino acid similarity to C8α (54%) and C8β (62%) of zebrafish and to C9 (52%) of grass carp, respectively. Ontogenetic expression analyses using real-time quantitative PCR suggested that the three genes may play crucial roles during embryonic and early larval development. The mRNA expressions of the three genes were all at the highest levels in liver tissue, and at lower or much lower levels in 16 other tissues, demonstrating that the liver is the primary site for the protein synthesis of Pf_C8α, Pf_C8β and Pf_C9. Injection of Aeromonas hydrophila led to up-regulation of the three genes in the spleen, head kidney, kidney, liver and blood tissues, indicating that the three genes may contribute to the host’s defense against invading pathogenic microbes. An increased understanding of the functions of the Pf_C8α, Pf_C8β and Pf_C9 genes in the innate immunity of yellow catfish will help enhance production of this valuable freshwater species. PMID:27005612

  20. [Budd-Chiari syndrome and Behçet's disease. A case treated by mesenterico-atrial prosthesis].

    PubMed

    Le Treut, Y P; Comiti, Y; Bremondy, A; Magnan, P E; Raoult, D; Botta, D; Bricot, R

    1988-03-01

    A 36 year-old North African man, with Behçet's syndrome complicated by an inferior vena caval thrombosis, developed a chronic Budd-Chiari syndrome associated with bleeding esophageal varices. He was treated by an emergency mesoatrial shunt. Results at 2 years were good. Analysis of this case and the 13 other similar cases with associated Budd-Chiari syndrome and Behçet's syndrome found in the literature showed that hepatic veins thrombosis: a) is often due to inferior vena caval thrombosis or membranous obstruction; b) has a high spontaneous mortality rate by acute liver failure; c) remains a potential indication for porto-systemic shunt, as are other causes of Budd-Chiari syndrome. PMID:3286358

  1. Ab-initio study of structural phase transitions and optoelectronic properties in BeH2 at increasing pressure

    NASA Astrophysics Data System (ADS)

    Nayak, Vikas; Verma, Udai Pratap

    2016-06-01

    The structural stability, electronic and optical properties of BeH2 under high pressure have been studied using the density functional theory (DFT) employing full potential-linearized augmented plane wave (FP-LAPW) method. The exchange correlation functional has been solved using the generalized gradient approximation. The calculations show that BeH2 becomes unstable upon application of pressure. At a pressure of 29.40 GPa the ground state α-BeH2 transforms to hypothetical phase β-BeH2 and further at a pressure of 53.77 GPa (with respect to the ground state α-BeH2) β-BeH2 transforms to γ-BeH2. In α-BeH2 phase it remains as an insulator while in β-BeH2 phase its behavior becomes metallic. But upon further increase in pressure it becomes a semiconductor in γ-BeH2 phase. Hence the possibility of obtaining high-pressure phases with superconducting properties cannot be ruled out. There occurs a huge equilibrium volume collapse at α- to β-phase transition and relatively smaller volume changes at β- to γ-phase transition. Our obtained value of dielectric constant (3.0) for α-BeH2 is in excellent agreement with earlier reported value (3.1). Also BeH2 shows anisotropic behavior in all three studied phases.

  2. Chemical and electrochemical oxidation of C8-arylamine adducts of 2′-deoxyguanosine

    PubMed Central

    Stover, James S.; Ciobanu, Madalina; Cliffel, David E.; Rizzo, Carmelo J.

    2008-01-01

    The electrochemical and chemical oxidation of a series of C8-arylamine adducts of 2′-deoxyguanosine has been examined. The oxidations were found to be reversible by cyclic and square-wave voltammetry in both aqueous buffer and aprotic organic solvent. The mechanism of the oxidation in protic media was either one- or two-electron depending on the aryl group. The chemical oxidation resulted in guanidinohydantoin and spiroiminodihydantoin rearrangement products similar to those observed for 8-oxo-7,8-dihydro-2′-deoxyguanosine. PMID:17256856

  3. Synthesis of the C8'-epimeric thymine pyranosyl amino acid core of amipurimycin.

    PubMed

    Markad, Pramod R; Kumbhar, Navanath; Dhavale, Dilip D

    2016-01-01

    The C8'-epimeric pyranosyl amino acid core 2 of amipurimycin was synthesized from D-glucose derived alcohol 3 in 13 steps and 14% overall yield. Thus, the Sharpless asymmetric epoxidation of allyl alcohol 7 followed by trimethyl borate mediated regio-selective oxirane ring opening with azide, afforded azido diol 10. The acid-catalyzed 1,2-acetonide ring opening in 10 concomitantly led to the formation of the pyranose ring skeleton to give 2,7-dioxabicyclo[3.2.1]octane 12. Functional group manipulation in 12 gave 21 that on stereoselective β-glycosylation afforded the pyranosyl thymine nucleoside 2 - a core of amipurimycin. PMID:27559421

  4. Right Ventricular Thrombus and Cerebral Artery Aneurysm in a Patient with Behçet's Disease.

    PubMed

    Sabzi, Feridoun; Mirzaei, Samaneh; Faraji, Reza

    2016-05-01

    We report a 35-year-old woman referred to the Imam Ali Hospital, Kermanshah, Iran, in July 2014 for evaluation of postoperative dyspnoea after neurosurgery performed seven days previously for a ruptured cerebral artery aneurysm. She was known to have Behçet's disease with a history of recurrent oral and genital aphthous ulcers and uveitis. At referral, her symptoms included vertigo, dysarthria, palpitations and chest pain. Transthoracic echocardiography (TTE) revealed a large thrombus in her right ventricle outflow tract and open-heart surgery was performed eight days after the previous surgery to remove the clot. The postoperative period was complicated by transient acute renal failure, which resolved spontaneously. The patient was discharged 13 days after the cardiac surgery on warfarin, prednisolone, azathioprine and cyclophosphamide. Cyclophosphamide and azathioprine were discontinued after three months as the symptoms had completely resolved; however, prednisolone was continued due to recurrent uveitis. A 10-month follow-up TTE scan revealed no thrombus recurrence and treatment with warfarin and prednisolone was continued. PMID:27226921

  5. Behçet's syndrome: a report of 41 patients with emphasis on neurological manifestations

    PubMed Central

    Farah, S; Al-Shubaili, A; Montaser, A; Hussein, J; Malaviya, A; Mukhtar, M; Al-Shayeb, A; Khuraibet, A; Khan, R; Trontelj, J

    1998-01-01

    Forty one patients with the clinical diagnosis of Behçet's syndrome from two teaching hospitals in Kuwait were studied. There were 34 male and seven female patients. Age at presentation ranged from 14 to 48 years. Neurological manifestations were present in 24 patients. Eleven patients showed evidence of increased intracranial pressure, and 10 of these had radiologically confirmed dural sinus thrombosis. Five patients presented with a meningoencephalitic or meningomyelitic picture, three with a stroke-like picture, and three with primarily brain stem signs. One patient developed trigeminal neuritis, and five patients exhibited (along with other features) variable degrees of psychological manifestations. All patients with neurological involvement were treated with steroids, and some also had courses of other immunosuppressant drugs and colchicine. The disease took a relatively benign course, except those patients with meningoencephalitic and meningomyelitic presentation, one of whom died from the disease. Those treated early had a better prognosis. The incidence of dural sinus thrombosis in this series of patients is unusually high. In most patients, the course of the disease was more favourable than reported in the literature. This may be attributed to early and aggressive treatment.

 PMID:9527155

  6. 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. PMID:23156855

  7. Biological Treatments in Behçet's Disease: Beyond Anti-TNF Therapy

    PubMed Central

    Costa, Luisa; Caso, Paolo; Bascherini, Vittoria; Frediani, Bruno; Cimaz, Rolando; Nieves-Martín, Laura; Atteno, Mariangela; Raffaele, Carmela G. L.; Tarantino, Giusyda; Galeazzi, Mauro; Punzi, Leonardo

    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. PMID:25061259

  8. Gamma Delta (γδ) T Cells and Their Involvement in Behçet's Disease

    PubMed Central

    Hasan, Md. Samiul; Bergmeier, Lesley Ann; Petrushkin, Harry; Fortune, Farida

    2015-01-01

    Behçet's disease (BD) is a multisystem inflammatory disorder characterized by orogenital ulcerations, ocular manifestations, arthritis, and vasculitis. The disease follows a relapsing-remitting course and its pathogenesis is unknown. Genetic predisposition and immune-dysregulation involving gamma delta (γδ) T cells are reported to have a role. γδ T cells are atypical T cells, which represent a small proportion of total lymphocytes. They have features of both innate and adaptive immunity and express characteristics of conventional T cells, natural killer cells, and myeloid antigen presenting cells. These unconventional T cells are found in the inflammatory BD lesions and have been suggested to be responsible for inducing and/or maintaining the proinflammatory environment characteristic of the disease. Over the last 20 years there has been much interest in the role of γδ T cells in BD. We review the literature and discuss the roles that γδ T cells may play in BD pathogenesis. PMID:26539557

  9. Mandibular bone mineral density in patients with Behçet’s disease

    PubMed Central

    Asutay, Fatih; Atalay, Yusuf; Acar, Ahmet Hüseyin; Asutay, Hilal; Eroğlu, Selma; Burdurlu, Muammer Çağrı

    2015-01-01

    Objectives Behçet’s disease (BD) is a chronic, recurring vasculitis of unknown etiology. Patients with BD may use a lot of medications associated with the clinical symptoms. Drugs that are used in the treatment of BD may cause bone loss. The aims of the current study were to compare the bone mineral density (BMD) values between BD and healthy volunteers and describe the effect of disease duration on mandibular BMD. Materials and methods The study comprised 30 healthy volunteers (15 males and 15 females, mean age 35.50±6.80 years) and 45 patients with BD (24 males and 21 females, mean age 38.93±8.93 years). The BD group was subdivided according to disease duration (0–5, 6–10, and >10 years). The BMD value of the mandibular body was determined by the dual energy X-ray absorptiometry technique. Results The mean mandibular body BMD values were 1.294±0.21 g/cm2 in the control group and 1.216±0.22 g/cm2 in the BD patients, although there was no statistically significant difference. The BMD was observed to decrease with increased disease duration but not to a statistically significant degree. Conclusion The results of this study showed that although the BMD value decreased as the duration of the disease increased, no statistically significant difference was found between the BD patients and the healthy control group. PMID:26508868

  10. Spontaneous H2 loss through the interaction of squaric acid derivatives and BeH2.

    PubMed

    Montero-Campillo, M Merced; Yáñez, Manuel; Lamsabhi, Al Mokhtar; Mó, Otilia

    2014-04-25

    The most stable complexes between squaric acid and its sulfur- and selenium-containing analogues (C4X4H2 ; X = O, S, Se) with BeY2 (Y = H, F) were studied by means of the Gaussian 04 (G4) composite ab initio theory. Squaric acid derivatives are predicted to be very strong acids in the gas phase; their acidity increases with the size of the chalcogen, with C4Se4H2 being the strongest acid of the series and stronger than sulfuric acid. The relative stability of the C4X4H2⋅BeY2 (X = O, S, Se; Y = H, F) complexes changes with the nature of the chalcogen atom; but more importantly, the formation of the C4X4H2⋅BeF2 complexes results in a substantial acidity enhancement of the squaric moiety owing to the dramatic electron-density redistribution undergone by the system when the beryllium bond is formed. The most significant consequence of this acidity enhancement is that when BeF2 is replaced by BeH2, a spontaneous exergonic loss of H2 is observed regardless of the nature of the chalcogen atom. This is another clear piece of evidence of the important role that closed-shell interactions play in the modulation of physicochemical properties of the Lewis acid and/or the Lewis base. PMID:24665080

  11. Neuro-Behçet’s disease: A report of sixteen patients

    PubMed Central

    Shahien, Radi; Bowirrat, Abdalla

    2010-01-01

    Background Neurologic involvement in Behçet’s disease (BD), also known as neuro-Behcet’s disease (NBD), is one of the most devastating manifestations of the disease. The etiology of BD remains obscure and speculative. NBD usually occurs 1–10 years after the first symptom of BD has occurred, and its incidence is 18% (range of 4%–49%). Objective This study was conducted to describe the clinical and prognostic aspects of neurologic involvement in BD among patients attending a multidisciplinary hospital clinic. Methods Eighty patients with BD were diagnosed according to the International Study Group Criteria for BD at our hospital. Sixteen patients (20%, including 11 men and five women) had evidence of and fulfilled the diagnostic criteria for NBD. These patients underwent laboratory and imaging investigations, including human leukocyte antigen-typing, lumbar puncture, electroencephalographic studies, and computed tomography scanning. Results Fourteen of the 16 patients received high-dose steroids, and four of these 14 patients were treated with a combination of steroids and cytotoxic agents. Relief was observed in 14 of 16 patients (87.5%). The remaining two patients were untreated males who suffered severe brainstem lesions, and later died. Conclusion In contrast with previous reports of a poor prognosis with NBD, our study shows that early aggressive intervention with corticosteroids and cytotoxic agents may ameliorate the prognosis in these patients, and can diminish and stabilize the negative effect of neurologic involvement. PMID:20520785

  12. Behçet's Disease, Associated Large Vessel Thrombosis, and Coexistent Thrombophilia: A Distinct Nosological Entity?

    PubMed Central

    Stoimenis, Dimitrios; Petridis, Nikolaos; Papaioannou, Nikos

    2013-01-01

    Behçet's disease (BD) represents a multisystemic disorder that combines features of immune-mediated diseases and autoinflammatory disorders. Even though it is recognized that every type or size of vessel can be affected in this disease, there is an inability to describe a coherent model that sufficiently explains the predilection of certain patients with BD for manifesting severe large vessel thrombosis. The inconsistent epidemiologic data and the complex genetic background of BD, along with the controversy of multiple international studies regarding the coexistence of thrombophilia in patients with BD and large vessel thrombosis, make us think that a percentage of these patients may actually suffer from a distinct clinical entity. The stimulus for this concept arose from the clinical observation of three male patients who were admitted to our clinic due to extended vena cava thrombosis. On the occasion of those clinically and laboratory resembling cases, we performed a literature review concerning the epidemiology of BD, associated thrombosis, and coexistent thrombophilic factors, in order to present some evidence, which sustains our hypothesis that certain patients with large vessel thrombosis, who share features of BD and coexistent thrombophilia, should actually be further investigated for the possibility of suffering from a distinct nosological entity. PMID:24151511

  13. Pathogenesis of Behçet's disease: autoinflammatory features and beyond.

    PubMed

    Gül, Ahmet

    2015-07-01

    Behçet's disease (BD) is an inflammatory disorder of unknown aetiology characterised by recurrent attacks affecting the mucocutaneous tissues, eyes, joints, blood vessels, brain and gastrointestinal tract. It is a multifactorial disease classified as a variable vessel vasculitis, and several environmental triggers may induce inflammatory episodes in genetically susceptible individuals. BD has several autoinflammatory features including recurrent self-limited clinical manifestations overlapping with monogenic autoinflammatory disorders, significant host predisposition and abnormally increased inflammatory response, with a robust innate component. Human leukocyte antigen (HLA)-B*51 is the strongest susceptibility factor described so far affecting the disease risk and typical phenotype. Non-HLA genetic associations such as endoplasmic reticulum aminopeptidase 1 (ERAP1), interleukin 23 receptor (IL23R) and IL10 variations suggest that BD shares susceptibility genes and inflammatory pathways with spondyloarthritis. Although genomewide association studies revealed an increased risk associated with recessively inherited ERAP1 variations in HLA-B*51 positive patients, it is not clear yet whether certain peptide-HLA allele combinations result in an adaptive response by a self-antigen-directed cytotoxic response or an innate response by modulating an NK cell activity or causing an unfolded protein response. Understanding of major histocompatibility complex (MHC) Class I-driven inflammatory response is expected to provide insights for the development of better treatment and remission-induction options in BD as well as in ankylosing spondylitis (AS) and psoriasis. PMID:26068404

  14. The possible role of HSPs on Behçet's disease: a bioinformatic approach.

    PubMed

    Ghasemi, Younes; Dabbagh, Fatemeh; Rasoul-Amini, Sara; Borhani Haghighi, Afshin; Morowvat, Mohammad Hossein

    2012-11-01

    Current evidence lends increasing support to immunoinflammatory mechanisms as one of the prime pathogenic processes involved in the development and progression of Behçet's disease (BD). It has been observed that most human beings have cellular and humoral reactions against microbial heat shock proteins (HSPs). The observation that eukaryotic and prokaryotic HSPs have high sequence similarity promoted the hypothesis that HSPs might be potential candidates for molecular mimicry and could act as potentially dangerous autoantigens. In this study, using bioinformatics tools, we examined the hypothesis that HSPs (evolutionarily conserved proteins), which are present in pathogenic and commensal organisms and their hosts, provide the stimulus that initiates BD in susceptible individuals. In this regards, the nucleotide and amino acid sequences of the human HSP 60 kDa and bacterial HSP 60 kDa deposited in the NCBI and PDB databases were subjected to analysis using bioinformatics tools, including The CLC Sequence Viewer and MEGA softwares. These data showed that the sequence homology between bacterial and self HSPs (leading to cross-reactivity and molecular mimicry phenomenon) may be associated with the development of the disease; and suggesting that microbial HSPs, which cross-react with host tissues and elicit significant immune responses are possible pathogenetic agents involved in the development and progression of BD. PMID:23036375

  15. Microarray and whole-exome sequencing analysis of familial Behçet’s disease patients

    PubMed Central

    Okuzaki, Daisuke; Yoshizaki, Kazuyuki; Tanaka, Toshio; Hirano, Toru; Fukushima, Kohshiro; Washio, Takanori; Nojima, Hiroshi

    2016-01-01

    Behçet’s disease (BD), a chronic systemic inflammatory disorder, is characterized by recurrent oral and genital mucous ulcers, uveitis, and skin lesions. We performed DNA microarray analysis of peripheral blood mononuclear cell (PBMC) mRNA from 41 Japanese BD patients and revealed elevated levels of interleukin (IL) 23 receptor (IL23R) mRNA in many BD patients. DNA sequencing around a SNV (Rs12119179) tightly linked to BD revealed an elevated frequency of the C genotype, consistent with a previous report that IL23R is a susceptibility locus for BD. Notably, four of these BD patients are members of familial BD; a whole-exome sequencing (WES) of these BD patients identified 19 novel single-nucleotide variations (SNVs) specific to these patients. They include heterozygous SNVs in the genes encoding IL-1 receptor-associated kinase 4 (IRAK4), nucleotide-binding oligomerization domain (NOD)-like receptor family pyrin domain-containing 14 (NRP14) and melanoma antigen-encoding gene E2 (MAGEE2); IRAK4 harbors a missense mutation, whereas NRP14 and MAGEE2 harbor nonsense mutations. These SNVs may serve as genetic markers that characterize BD. PMID:26785681

  16. 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

  17. Successful Discontinuation of Infliximab in a Refractory Case of Vasculo-Behçet Disease

    PubMed Central

    Miyamura, Tomoya; Suematsu, Eiichi

    2016-01-01

    Reports have shown that antitumor necrosis factor alpha (anti-TNF-α) agents including infliximab (IFX) can dramatically suppress the disease activity of refractory vasculo-Behçet disease (vasculo-BD). However, it is completely unknown whether we can discontinue anti-TNF-α agents under clinical remission. A 31-year-old patient with vasculo-BD was initially treated with a high dose of steroid and intravenous cyclophosphamide therapy. Six months later, however, the disease recurred. IFX was administered and immediately the disease activity was reduced. Fortunately, we could discontinue IFX after 18-month remission and no recurrence has been observed. Based on previous reports and our patient, all patients who could discontinue IFX sustained clinical remission for at least one year, continued taking immunosuppressive agents such as methotrexate and azathioprine, and had vascular involvements only in non-life-threatening major vessels such as leg or arm arteries/veins. This is a report suggesting the possibility of discontinuation of IFX in vasculo-BD. PMID:27034879

  18. Treatment of myelitis in Behçet's disease with rituximab

    PubMed Central

    Messina, Maria Josè; Rodegher, Mariaemma; Scotti, Roberta; Martinelli, Vittorio

    2014-01-01

    Behçet's disease (BD) is a chronic inflammatory disorder that involves the parenchymal central nervous system (neuro-BD, NBD) approximately in 5–49% of patients, causing lesions rarely located in the spinal cord (SC). We report the first case of NBD-myelitis treated with intravenous rituximab. A 41-year-old man affected by BD presented with mild paraparesis with a miliary involvement and a ‘net-like’ gadolinium enhancement (Gde) of the SC. After a therapeutic attempt with pulsed cyclophosphamide and intravenous methylprednisolone, the clinical and neuroradiological course worsened. A progressive improvement was observed after rituximab administration associated with low doses of oral prednisone. No disease activity was detected and the patient reported no adverse event. After six rituximab cycles, cervical MRI was normal while thoracic MRI showed a slight T2–weighted hyperintensity of D4–D10 spinal tract without Gde. A combined use of rituximab and oral steroids resulted in a long-term suppression of NBD activity without any safety concern. PMID:24879733

  19. New Evidence-Based Treatment Approach in Behçet's Disease

    PubMed Central

    Alpsoy, Erkan

    2012-01-01

    Behçet's disease (BD) is a chronic, relapsing, and debilitating systemic vasculitis of unknown aetiology with the clinical features of mucocutaneous lesions, ocular, vascular, articular, neurologic, gastrointestinal, urogenital, and pulmonary involvement. The disease is much more frequent along the ancient “Silk Route” extending from Eastern Asia to the Mediterranean basin, compared with Western countries. The disease usually starts around the third or fourth decade of life. Male sex and a younger age of onset are associated with more severe disease. Although the treatment has become much more effective in recent years, BD is still associated with severe morbidity and considerable mortality. The main aim of the treatment should be the prevention of irreversible organ damage. Therefore, close monitoring, early, and appropriate treatment is mandatory to reduce morbidity and mortality. The treatment is mainly based on the suppression of inflammatory attacks of the disease using immunomodulatory and immunosuppressive agents. In this paper, current state of knowledge regarding the therapeutic approaches is outlined. To provide a rational framework for selecting the appropriate therapy along the various treatment choices, a stepwise, symptom-based, evidence-based algorithmic approach was developed. PMID:22007346

  20. Volatile C8 compounds and pseudomonads influence primordium formation of Agaricus bisporus.

    PubMed

    Noble, Ralph; Dobrovin-Pennington, Andreja; Hobbs, Philip J; Pederby, Jemma; Rodger, Alison

    2009-01-01

    Primordium formation of Agaricus bisporus depends on the presence of a casing layer containing stimulatory bacteria and on sufficient air exchange. The influence of specific pseudomonad populations and volatile organic compounds (VOC) on primordium formation of A. bisporus was studied in microcosm cultures. VOC produced by A. bisporus mycelium were predominantly C8 compounds, some of which could inhibit primordium formation, with 1-octen-3-ol being most inhibitory. A VOC produced by the rye grain substrate, 2-ethyl-1-hexanol, on which A. bisporus was grown also inhibited primordium formation. 2-Ethyl-1-hexanol and 1-octen-3-ol were metabolized by pseudomonad populations and adsorbed by activated charcoal, with both modes of removal enabling primordium formation in the casing. Removal of VOC by ventilation also enabled primordium formation to occur under axenic conditions. The presence of 2-ethyl-1-hexanol and 1-octen-3-ol in the microcosms resulted in higher total bacterial and pseudomonad populations in the casing. The stimulatory effects of the casing and its microbiota and air exchange on primordium formation of A. bisporus at least partly are due to the removal of inhibitory C8 compounds produced by the mycelium and its substrate. Monitoring and controlling the levels of these inhibitory VOC in mushroom culture should enable primordium formation of A. bisporus to be more efficiently and precisely controlled. PMID:19750937

  1. Identification and characterization of the carboxy-terminal region of Sip-1, a novel autoantigen in Behçet's disease

    PubMed Central

    Delunardo, Federica; Conti, Fabrizio; Margutti, Paola; Alessandri, Cristiano; Priori, Roberta; Siracusano, Alessandra; Riganò, Rachele; Profumo, Elisabetta; Valesini, Guido; Sorice, Maurizio; Ortona, Elena

    2006-01-01

    Given the lack of a serological test specific for Behçet's disease, its diagnosis rests upon clinical criteria. The clinical diagnosis is nevertheless difficult because the disease manifestations vary widely, especially at the onset of disease. The aim of this study was to identify molecules specifically recognized by serum autoantibodies in patients with Behçet's disease and to evaluate their diagnostic value. We screened a cDNA library from human microvascular endothelial cells with serum IgG from two patients with Behçet's disease and isolated a reactive clone specific to the carboxy-terminal subunit of Sip1 (Sip1 C-ter). Using ELISA, we measured IgG, IgM and IgA specific to Sip1 C-ter in patients with various autoimmune diseases characterized by the presence of serum anti-endothelial cell antibodies, such as Behçet's disease, systemic lupus erythematosus, systemic sclerosis and various forms of primary vasculitis, as well as in patients with diseases that share clinical features with Behçet's disease, such as inflammatory bowel disease and uveitis. IgM immunoreactivity to Sip1 C-ter was significantly higher in patients with Behçet's disease and in patients with primary vasculitis than in the other groups of patients and healthy subjects tested (P < 10-4 by Mann-Whitney test). ELISA detected IgG specific to Sip1 C-ter in sera from 11/56 (20%) patients with Behçet's disease, IgM in 23/56 (41%) and IgA in 9/54 (17%). No sera from patients with systemic lupus erythematosus, systemic sclerosis, inflammatory bowel disease, uveitis or healthy subjects but 45% of sera from patients with primary vasculitis contained IgM specific to Sip1 C-ter. Serum levels of soluble E-selectin, a marker of endothelial activation and inflammation, correlated with levels of serum IgM anti Sip-1 C-ter in patients with Behçet's disease (r = 0.36, P = 0.023). In conclusion, Sip1 C-ter is a novel autoantigen in Behçet's disease. IgM specific to Sip1 C-ter might be useful in clinical

  2. Structure of GaAs(100)- c\\(8×2\\)-Ga

    NASA Astrophysics Data System (ADS)

    Cerdá, J.; Palomares, F. J.; Soria, F.

    1995-07-01

    The crystallography of the GaAs(100)- c\\(8×2\\)-Ga surface, prepared by simultaneous cycles of Ar ion bombardment and annealing at 825 K, has been determined by a low energy electron diffraction I-V analysis. A model consisting of three adjacent dimers and a dimer vacancy yielded the best fit. The main feature of the corresponding structure is the presence of two different types of Ga dimers at the surface. The dimer in the middle is fully dimerized ( dGa -Ga = 2.13 Å), while the dimerization for the Ga atoms in both outer dimers is much more subtle ( dGa -Ga = 3.45 Å).

  3. Test of acoustic tone source and propulsion performance of C8A Buffalo suppressor nozzle

    NASA Technical Reports Server (NTRS)

    Marrs, C. C.; Harkonen, D. L.; Okeefe, J. V.

    1974-01-01

    Results are presented for a static acoustic and propulsion performance ground test conducted at the Boeing hot nozzle facility on the C8A Buffalo noise suppressor nozzle. Various methods to remove a nozzle-associated 2000-Hz tone are evaluated. Results of testing this rectangular-array lobed nozzle for propulsion performance and acoustic directivity are reported. Recommendations for future nozzle modifications and further testing are included. Appendix A contains the test plan. Appendix B presents the test log. Appendix C contains plots of the one-third octave sound pressure levels recorded during the test. Appendix D describes the acoustic data recording and reduction systems. The performance data is tabulated in Appendix E.

  4. Static noise tests on augmentor wing jet STOL research aircraft (C8A Buffalo)

    NASA Technical Reports Server (NTRS)

    Marrs, C. C.; Harkonen, D. L.; Okeefe, J. V.

    1974-01-01

    Results are presented for full scale ground static acoustic tests of over-area conical nozzles and a lobe nozzle installed on the Augmentor Wing Jet STOL Research Aircraft, a modified C8A Buffalo. The noise levels and spectrums of the test nozzles are compared against those of the standard conical nozzle now in use on the aircraft. Acoustic evaluations at 152 m (500 ft), 304 m (1000 ft), and 1216 m (4000 ft) are made at various engine power settings with the emphasis on approach and takeoff power. Appendix A contains the test log and propulsion calculations. Appendix B gives the original test plan, which was closely adhered to during the test. Appendix C describes the acoustic data recording and reduction systems, with calibration details.

  5. Stereoselective Luche reduction of deoxynivalenol and three of its acetylated derivatives at C8.

    PubMed

    Fruhmann, Philipp; Hametner, Christian; Mikula, Hannes; Adam, Gerhard; Krska, Rudolf; Fröhlich, Johannes

    2014-01-01

    The trichothecene mycotoxin deoxynivalenol (DON) is a well known and common contaminant in food and feed. Acetylated derivatives and other biosynthetic precursors can occur together with the main toxin. A key biosynthetic step towards DON involves an oxidation of the 8-OH group of 7,8-dihydroxycalonectrin. Since analytical standards for the intermediates are not available and these intermediates are therefore rarely studied, we aimed for a synthetic method to invert this reaction, making a series of calonectrin-derived precursors accessible. We did this by developing an efficient protocol for stereoselective Luche reduction at C8. This method was used to access 3,7,8,15-tetrahydroxyscirpene, 3-deacetyl-7,8-dihydroxycalonectrin, 15-deacetyl-7,8-dihydroxycalonectrin and 7,8-dihydroxycalonectrin, which were characterized using several NMR techniques. Beside the development of a method which could basically be used for all type B trichothecenes, we opened a synthetic route towards different acetylated calonectrins. PMID:24434906

  6. Synthesis of the C8’-epimeric thymine pyranosyl amino acid core of amipurimycin

    PubMed Central

    Markad, Pramod R; Kumbhar, Navanath

    2016-01-01

    Summary The C8’-epimeric pyranosyl amino acid core 2 of amipurimycin was synthesized from D-glucose derived alcohol 3 in 13 steps and 14% overall yield. Thus, the Sharpless asymmetric epoxidation of allyl alcohol 7 followed by trimethyl borate mediated regio-selective oxirane ring opening with azide, afforded azido diol 10. The acid-catalyzed 1,2-acetonide ring opening in 10 concomitantly led to the formation of the pyranose ring skeleton to give 2,7-dioxabicyclo[3.2.1]octane 12. Functional group manipulation in 12 gave 21 that on stereoselective β-glycosylation afforded the pyranosyl thymine nucleoside 2 – a core of amipurimycin. PMID:27559421

  7. Growth directions of C8-BTBT thin films during drop-casting

    NASA Astrophysics Data System (ADS)

    Iizuka, Naoki; Zanka, Tomohiko; Onishi, Yosuke; Fujieda, Ichiro

    2016-02-01

    Because charge transport in a single crystal is anisotropic, control of its orientation is important for enhancing electrical characteristics and reducing variations among devices. For growing an organic thin film, a solution process such as inkjet printing offers advantages in throughput. We have proposed to apply an external temperature gradient during drop-casting and to control the direction of solvent evaporation. In experiment, a temperature gradient was generated in a bare Si substrate by placing it on a Si plate bridging two heat stages. When a solution containing 2,7-dioctyl [1]benzothieno[3,2-b]benzothiophene (C8-BTBT) was dropped on the substrate, evaporation started at the hotter side of the droplet and proceeded toward the colder side. The front line of the liquid was not pinned and the solution extended toward the colder region. As a result, a thin film was formed in a 7mm-long region. The peripheral region of the film was significantly thicker due to the coffee ring effect. The surface of the rest of the film was mostly smooth and terrace structures with 2.6nm steps were observed. The step roughly corresponds to the length of the C8-BTBT molecule. The film thickness varied from 20nm to 50nm over the distance of 3mm. Another film was grown on a glass substrate under a similar condition. Observation of the film with a polarizing microscope revealed that fan-shaped domains were formed in the film and that their optical axes were mostly along the directions of the solvent evaporation.

  8. Peroxisome proliferator-activated receptor alpha, PPARα, directly regulates transcription of cytochrome P450 CYP2C8

    PubMed Central

    Thomas, Maria; Winter, Stefan; Klumpp, Britta; Turpeinen, Miia; Klein, Kathrin; Schwab, Matthias; Zanger, Ulrich M.

    2015-01-01

    The cytochrome P450, CYP2C8, metabolizes more than 60 clinically used drugs as well as endogenous substances including retinoic acid and arachidonic acid. However, predictive factors for interindividual variability in the efficacy and toxicity of CYP2C8 drug substrates are essentially lacking. Recently we demonstrated that peroxisome proliferator-activated receptor alpha (PPARα), a nuclear receptor primarily involved in control of lipid and energy homeostasis directly regulates the transcription of CYP3A4. Here we investigated the potential regulation of CYP2C8 by PPARα. Two linked intronic SNPs in PPARα (rs4253728, rs4823613) previously associated with hepatic CYP3A4 status showed significant association with CYP2C8 protein level in human liver samples (N = 150). Furthermore, siRNA-mediated knock-down of PPARα in HepaRG human hepatocyte cells resulted in up to ∼60 and ∼50% downregulation of CYP2C8 mRNA and activity, while treatment with the PPARα agonist WY14,643 lead to an induction by >150 and >100%, respectively. Using chromatin immunoprecipitation scanning assay we identified a specific upstream gene region that is occupied in vivo by PPARα. Electromobility shift assay demonstrated direct binding of PPARα to a DR-1 motif located at positions –2762/–2775 bp upstream of the CYP2C8 transcription start site. We further validated the functional activity of this element using luciferase reporter gene assays in HuH7 cells. Moreover, based on our previous studies we demonstrated that WNT/β-catenin acts as a functional inhibitor of PPARα-mediated inducibility of CYP2C8 expression. In conclusion, our data suggest direct involvement of PPARα in both constitutive and inducible regulation of CYP2C8 expression in human liver, which is further modulated by WNT/β-catenin pathway. PPARA gene polymorphism could have a modest influence on CYP2C8 phenotype. PMID:26582990

  9. Development of de novo major involvement during follow-up in Behçet's syndrome.

    PubMed

    Talarico, Rosaria; Cantarini, Luca; d'Ascanio, Anna; Figus, Michele; Favati, Benedetta; Baldini, Chiara; Tani, Chiara; Neri, R; Bombardieri, Stefano; Mosca, Marta

    2016-01-01

    The primary aim of the study was to evaluate the incidence of de novo major involvement during follow-up in a cohort of patients with Behçet's syndrome (BS); the secondary aim was to analyse the epidemiological profile and the long-term outcome of those patients who developed new major involvement. Among our cohort of 120 BS patients, we evaluated all subjects who had no major organ involvement during the early years of their disease; specifically, at disease onset, the 52% of the cohort presented a prevalent mucocutaneous involvement. The primary outcomes were represented by the following: Hatemi et al. (Rheum Dis Clin North Am 39(2):245-61, 2013) the incidence of de novo major involvement during the follow-up and Hatemi et al. (Clin Exp Rheumatol 32(4 Suppl 84):S112-22, 2014) the use of immunosuppressive drugs during the follow-up. We have defined the development of de novo major involvement during the follow-up as the occurrence of severe ocular, vascular or CNS involvement after a latency period from the diagnosis of at least 3 years. Among 62 patients characterized by a mild onset of disease, we observed that after at least 3 years from the diagnosis, 21 BS patients (34%) still developed serious morbidities. Specifically, three patients developed ocular involvement, nine patients developed neurological involvement and nine patients presented vascular involvement. Comparing main epidemiological and clinical findings of the two groups, we observed that patients who developed de novo major involvement were more frequently males and younger; furthermore, 95% of these patients were characterized by a young onset of disease (p < 0.001). Being free of major organ complication in the first years of BS is not necessary a sign of a favourable outcome. Globally, the development of de novo major involvement during the coursfce of BS suggests that a tight control is strongly recommended during the course of the disease. PMID:25750177

  10. Criteria for Behçet's disease with reflections on all disease criteria.

    PubMed

    Yazici, Hasan; Yazici, Yusuf

    2014-01-01

    With no specific histologic, laboratory or imaging features the diagnosis/classification of Behçet's Disease (BD) remains clinical. As such, disease criteria are needed. The International Study Group Criteria set is the most widely used. It has some limitations, especially in telling BD from Crohn's disease. On the other hand the main issue, as it also applies to many of the other criteria sets in rheumatology, is our lack of appreciation of a list of misconceptions--some examples of which are unluckily also found in the 2010 ACR/EULAR RA Criteria set--about diagnostic/classification criteria making and their implementation. 1. The view that classification and diagnostic criteria should be different is ill advised in that the cerebral/arithmetic basis of both are the same. 2. The default promise of diagnostic criteria to come once we formulate a classification criteria set is an extension of the previous misconception. 3.Taking pains to avoid circularity in criteria making is unwarranted since the essence of criteria making is circular. In addition we fail to exploit the utility of the disease criteria in ruling out, rather than ruling in, the diseases we seek. Finally we also fail to appreciate the paramount importance of the Bayesian prior (the pretest) probability in formulating and implementing these disease criteria. To formulate criteria tailored to subspecialties, as well as giving the often forgotten family history more importance in our criteria sets are some ways to improve the prior probability on which our diagnostic/classification decisions will be based. We first have to reconcile with ourselves that probabilities are very important in our practice and research. Moreover that reconciliation must also be shared with the public, which includes our patients. PMID:24461382

  11. Cross-cultural adaptation and validation of Behçet's disease quality of life questionnaire

    PubMed Central

    2011-01-01

    Background Currently, there is one Behçet's disease (BD) specific self reporting questionnaire developed and published in the literature, The Leeds BD-quality of life (QoL). We conducted a cross-cultural adaptation and validation of the Arabic version of the Leeds BD-QoL Methods A cross-sectional study was conducted among 41 consecutive patients attending rheumatology clinics at the American University of Beirut Medical Center between June and December 2007. The BD-QoL questionnaire, the Katz Index of Activities of Daily Living (ADL) and the Lawton Instrumental Activities of Daily Living (IADL) questionnaires were co-administered during the same visit, and severity scores were calculated. Cross-cultural adaptation of BD-QoL was performed using forward and backward translations of the original questionnaire. Internal consistency and test-retest reliability of the final version were determined. Exploratory Factor Analysis (EFA) was used to assess the dimensionality of the scale items. External construct validity was examined by correlating Arabic BD-QoL with the severity score, ADL and IADL. Results The 30 items of the adapted Arabic BD-QoL showed a high internal consistency (KR-20 coefficient 0.89) and test-retest reliability (Spearman's test 0.91). The convergence of all 30 items suggests that the 30-item adapted Arabic BD-QoL scale is unidimensional. BD-QoL did not correlate with any of the patients' demographics. Still, it was positively correlated with patient severity score (r 0.4, p 0.02), and IADL (but not ADL). Conclusions This cross-cultural adaptation has produced an Arabic BD-QoL questionnaire that is now available for use in clinical settings and in research studies, among Arabic speaking patients. PMID:21507231

  12. A 30-year-old female Behçet’s disease patient with recurrent pleural and pericardial effusion and elevated adenosine deaminase levels: case report

    PubMed Central

    Choi, Joon Young; Kim, Sung-Hwan; Kwok, Seung-Ki; Jung, Jung Im; Lee, Kyo-Young; Kim, Tae-Jung

    2016-01-01

    Behçet’s disease is a systemic disease which may involve various organs. We describe a case of a patient diagnosed as pleuropericardial involvement of Behçet’s disease. A 30-year-old woman visited our clinic presented with left pleuritic chest pain for s days. She had been diagnosed as Behçet’s disease and admitted to our clinic due to pericardial and pleural effusion repeatedly in past two years. In the previous studies, effusion analysis revealed to be lympho-dominant exudate with high adenosine deaminase level. Acid-fast bacilli (AFB) culture and polymerase chain reaction (PCR) for mycobacterial tuberculosis (M.TB) were negative in the pericardial tissue, and pathologic finding showed mild endothelitis with micro-thrombi formation in the lumen. The patient had been treated with antituberculous medication for a year. In the current admission, chest computed tomography (CT) again showed left pleural effusion without other significant lesion. Pleural fluid analysis was similar with the previous study. Video-assisted thoracoscopic pleural biopsy was performed to obtain the definite diagnosis. Pathology confirmed the diagnosis as pleuropericardial involvement of Behçet’s disease, and we treated the patient with oral steroid in the out-patient department. Pleuropericardial involvement of Behçet’s disease may mimic TB pleurisy or pericarditis due to high adenosine deaminase (ADA) level in effusion analysis. Clinicians should keep in mind that Behçet’s disease may manifest as pleural or pericardial effusion, and pathologic confirmation could be helpful for the definite diagnosis. PMID:27499994

  13. 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. PMID:25665824

  14. Bonding in Complexes of Bis(pentalene)dititanium, Ti2(C8H6)2

    PubMed Central

    2015-01-01

    Bonding in the bis(pentalene)dititanium “double-sandwich” species Ti2Pn2 (Pn = C8H6) and its interaction with other fragments have been investigated by density functional calculations and fragment analysis. Ti2Pn2 with C2v symmetry has two metal–metal bonds and a low-lying metal-based empty orbital, all three frontier orbitals having a1 symmetry. The latter may be regarded as being derived by symmetric combinations of the classic three frontier orbitals of two bent bis(cyclopentadienyl) metal fragments. Electrochemical studies on Ti2Pn†2 (Pn† = 1,4-{SiiPr3}2C8H4) revealed a one-electron oxidation, and the formally mixed-valence Ti(II)–Ti(III) cationic complex [Ti2Pn†2][B(C6F5)4] has been structurally characterized. Theory indicates an S = 1/2 ground-state electronic configuration for the latter, which was confirmed by EPR spectroscopy and SQUID magnetometry. Carbon dioxide binds symmetrically to Ti2Pn2, preserving the C2v symmetry, as does carbon disulfide. The dominant interaction in Ti2Pn2CO2 is σ donation into the LUMO of bent CO2, and donation from the O atoms to Ti2Pn2 is minimal, whereas in Ti2Pn2CS2 there is significant interaction with the S atoms. The bridging O atom in the mono(oxo) species Ti2Pn2O, however, employs all three O 2p orbitals in binding and competes strongly with Pn, leading to weaker binding of the carbocyclic ligand, and the sulfur analogue Ti2Pn2S behaves similarly. Ti2Pn2 is also capable of binding one, two, or three molecules of carbon monoxide. The bonding demands of a single CO molecule are incompatible with symmetric binding, and an asymmetric structure is found. The dicarbonyl adduct Ti2Pn2(CO)2 has Cs symmetry with the Ti2Pn2 unit acting as two MCp2 fragments. Synthetic studies showed that in the presence of excess CO the tricarbonyl complex Ti2Pn†2(CO)3 is formed, which optimizes to an asymmetric structure with one semibridging and two terminal CO ligands. Low-temperature 13C NMR spectroscopy revealed a rapid

  15. CYP2C8 Is a Novel Target of Peroxisome Proliferator-Activated Receptor α in Human Liver.

    PubMed

    Makia, Ngome L; Goldstein, Joyce A

    2016-01-01

    Human cytochrome P450 (CYP) 2C enzymes metabolize ∼30% of clinically prescribed drugs and various environmental chemicals. CYP2C8, an important member of this subfamily, metabolizes the anticancer drug paclitaxel, certain antidiabetic drugs, and endogenous substrates, including arachidonic acid, to physiologically active epoxyeicosatrienoic acids. Previous studies from our laboratory showed that microRNA 107 (miR107) and microRNA 103 downregulate CYP2C8 post-transcriptionally. miR107 is located in intron 5 of the pantothenate kinase 1 (PANK1) gene. p53 has been reported to coregulate the induction of PANK1 and miR107. Here, we examine the possible downregulation of CYP2C8 by drugs capable of inducing miR107. Hypolipidemic drugs, such as bezafibrate, known activators of the peroxisome proliferator-activated receptor α (PPARα), induce both the PANK1 gene and miR107 (∼2.5-fold) in primary human hepatocytes. Surprisingly, CYP2C8 mRNA and protein levels were induced by bezafibrate. CYP2C8 promoter activity was increased by ectopic expression of PPARα in HepG2 cells, with a further increase after bezafibrate (∼18-fold), 4-chloro-6-(2,3-xylidino)-2-pyrimidinylthio acetic acid (∼10-fold) treatment, or the antidiabetic drug rosiglitazone, all known PPAR activators. Promoter sequence analyses, deletion studies, mutagenesis studies, and electrophoretic mobility shift assays identified a PPARα response element located at position -2109 base pair relative to the translation start site of CYP2C8. Chromatin immunopreciptation assay analysis confirmed recruitment of PPARα to this PPARα response element after bezafibrate treatment of human hepatocytes. Thus, we show for the first time that CYP2C8 is transcriptionally regulated by PPARα, suggesting the potential for drug-drug interactions due to upregulation of CYP2C8 by PPAR activators. PMID:26467040

  16. TspanC8 Tetraspanins and A Disintegrin and Metalloprotease 10 (ADAM10) Interact via Their Extracellular Regions

    PubMed Central

    Noy, Peter J.; Yang, Jing; Reyat, Jasmeet S.; Matthews, Alexandra L.; Charlton, Alice E.; Furmston, Joanna; Rogers, David A.; Rainger, G. Ed; Tomlinson, Michael G.

    2016-01-01

    A disintegrin and metalloprotease 10 (ADAM10) is a ubiquitously expressed transmembrane metalloprotease that cleaves the extracellular regions from its transmembrane substrates. ADAM10 is essential for embryonic development and is implicated in cancer, Alzheimer, and inflammatory diseases. The tetraspanins are a superfamily of 33 four-transmembrane proteins in mammals, of which the TspanC8 subgroup (Tspan5, 10, 14, 15, 17, and 33) promote ADAM10 intracellular trafficking and enzymatic maturation. However, the interaction between TspanC8s and ADAM10 has only been demonstrated in overexpression systems and the interaction mechanism remains undefined. To address these issues, an antibody was developed to Tspan14, which was used to show co-immunoprecipitation of Tspan14 with ADAM10 in primary human cells. Chimeric Tspan14 constructs demonstrated that the large extracellular loop of Tspan14 mediated its co-immunoprecipitation with ADAM10, and promoted ADAM10 maturation and trafficking to the cell surface. Chimeric ADAM10 constructs showed that membrane-proximal stalk, cysteine-rich, and disintegrin domains of ADAM10 mediated its co-immunoprecipitation with Tspan14 and other TspanC8s. This TspanC8-interacting region was required for ADAM10 exit from the endoplasmic reticulum. Truncated ADAM10 constructs revealed differential TspanC8 binding requirements for the stalk, cysteine-rich, and disintegrin domains. Moreover, Tspan15was the only TspanC8 to promote cleavage of the ADAM10 substrate N-cadherin, whereas Tspan14 was unique in reducing cleavage of the platelet collagen receptor GPVI. These findings suggest that ADAM10 may adopt distinct conformations in complex with different TspanC8s, which could impact on substrate selectivity. Furthermore, this study identifies regions of TspanC8s and ADAM10 for potential interaction-disrupting therapeutic targeting. PMID:26668317

  17. CYP2C8 Is a Novel Target of Peroxisome Proliferator-Activated Receptor α in Human Liver

    PubMed Central

    Makia, Ngome L.

    2016-01-01

    Human cytochrome P450 (CYP) 2C enzymes metabolize ∼30% of clinically prescribed drugs and various environmental chemicals. CYP2C8, an important member of this subfamily, metabolizes the anticancer drug paclitaxel, certain antidiabetic drugs, and endogenous substrates, including arachidonic acid, to physiologically active epoxyeicosatrienoic acids. Previous studies from our laboratory showed that microRNA 107 (miR107) and microRNA 103 downregulate CYP2C8 post-transcriptionally. miR107 is located in intron 5 of the pantothenate kinase 1 (PANK1) gene. p53 has been reported to coregulate the induction of PANK1 and miR107. Here, we examine the possible downregulation of CYP2C8 by drugs capable of inducing miR107. Hypolipidemic drugs, such as bezafibrate, known activators of the peroxisome proliferator-activated receptor α (PPARα), induce both the PANK1 gene and miR107 (∼2.5-fold) in primary human hepatocytes. Surprisingly, CYP2C8 mRNA and protein levels were induced by bezafibrate. CYP2C8 promoter activity was increased by ectopic expression of PPARα in HepG2 cells, with a further increase after bezafibrate (∼18-fold), 4-chloro-6-(2,3-xylidino)-2-pyrimidinylthio acetic acid (∼10-fold) treatment, or the antidiabetic drug rosiglitazone, all known PPAR activators. Promoter sequence analyses, deletion studies, mutagenesis studies, and electrophoretic mobility shift assays identified a PPARα response element located at position −2109 base pair relative to the translation start site of CYP2C8. Chromatin immunopreciptation assay analysis confirmed recruitment of PPARα to this PPARα response element after bezafibrate treatment of human hepatocytes. Thus, we show for the first time that CYP2C8 is transcriptionally regulated by PPARα, suggesting the potential for drug-drug interactions due to upregulation of CYP2C8 by PPAR activators. PMID:26467040

  18. 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.

  19. Linear, planar, and tubular molecular structures constructed by double planar tetracoordinate carbon D2hC2(BeH)4 species via hydrogen-bridged -BeH2Be- bonds.

    PubMed

    Zhao, Xue-Feng; Li, Haixia; Yuan, Cai-Xia; Li, Yan-Qin; Wu, Yan-Bo; Wang, Zhi-Xiang

    2016-01-15

    This computational study identifies the rhombic D2hC2 (BeH)4 (2a) to be a species featuring double planar tetracoordinate carbons (ptCs). Aromaticity and the peripheral BeBeBeBe bonding around CC core contribute to the stabilization of the ptC structure. Although the ptC structure is not a global minimum, its high kinetic stability and its distinct feature of having a bonded C2 core from having two separated carbon atoms in the global minimum and other low-lying minima could make the ptC structure to be preferred if the carbon source is dominated by C2 species. The electron deficiency of the BeH group allows the ptC species to serve as building blocks to construct large/nanostructures, such as linear chains, planar sheets, and tubes, via intermolecular hydrogen-bridged bonds (HBBs). Formation of one HBB bond releases more than 30.0 kcal/mol of energy, implying the highly exothermic formation processes and the possibility to synthesize these nano-size structures. PMID:26202851

  20. Application of Empore C-8 extraction disks for screening urine in systematic toxicological analysis.

    PubMed

    Ensing, K; Franke, J P; Temmink, A; Chen, X H; de Zeeuw, R A

    1992-03-01

    Solid-phase extraction (SPE) by means of disposable columns has become a widely accepted technique for sample pretreatment in toxicology, both for directed analyses and for screening analyses. However, the sample capacity in SPE is usually limited to a few millilitres. Therefore, we have investigated to what extent these problems can be overcome by using Empore extraction disks, consisting of chemically modified C-8 reversed-phase silica, embedded in an inert polytetrafluoroethylene (PTFE) matrix. Human urine was selected as the matrix and dexetimide and mepyramine were initially used as test drugs because these drugs were available in tritiated form. Additional drugs investigated included codeine, hexobarbital, imipramine, methamphetamine, and nitrazepam. In these investigations, the sample capacity for untreated urine was at least 25 mL, and analyte quantities up to 250 micrograms could be retained by these filters. Washing with water/methanol mixtures was successful in removing substantial amounts of endogenous interferences, and methanol proved to be an acceptable eluent. Thus, these disks seem to have interesting potential for toxicological analysis in that sample concentration and cleanup can be achieved at the same time. PMID:1354247

  1. Lipophilicity of porphyrins and their retention in IAM, C8-C18 and HILIC chromatographic systems.

    PubMed

    Essaid, D; Chaminade, P; Maillard, Ph; Kasselouri, A

    2015-10-10

    Porphyrins are a class of photosensitizers used in photodynamic therapy (PDT). Understanding the interaction of porphyrins with membrane cells components is important in order to improve this therapy. Many analytical methods can be used for this aim. High performance liquid chromatography (HPLC) was used for the separation of porphyrins on RP and HILIC stationary phases as well as on a biomimetic membrane IAM phase. Twenty-six tetraphenyl porphyrins (TPP) were successfully separated on an IAM column, a C18 Gravity RP column, a C8 Gravity RP column, a PolarTec RP column and a HILIC column. Stationary phases were chosen as the most appropriate to cover the study of different types of interactions. Elution was performed with a 45 min linear gradient. Obtained gradient retention times were converted to gradient chromatography hydrophobicity index (CHI) and to an apparent retention factor (kapp). The partition coefficients (logP) of the 26 compounds were measured in a 2-octanol/PBS system and estimated in silico. Correlation between kapp values was studied. Moreover, a multivariate analysis was performed to explain columns relationships. Obtained results show that porphyrins are separated mainly according to hydrophobic interactions that are relative to their structure (sugar number and the disposition around the porphyrin macrocycle). PMID:26099259

  2. Perfluorocarbons and Gilbert syndrome (phenotype) in the C8 Health Study Population

    SciTech Connect

    Fan, Hongmin; Ducatman, Alan; Zhang, Jianjun

    2014-11-15

    Background: Gilbert syndrome (GS) is an inherited defect of bilirubin conjugation, most commonly caused by a gene mutation for the enzyme UGT1A. GS is known to affect the metabolism and excretion of drugs and xenobiotics. Perfluorocarbon compounds (PFCs) are bio-persistent environmental contaminants that affect metabolic regulation. In this study, we examined the associations of GS phenotype and serum PFCs in the C8 Health Study Population. Materials and methods: Using 2005–2006 data from a large PFC-exposure population survey, we compared serum PFCs concentrations between GS and non GS clinical phenotypes, in a cross sectional design, adjusting for standard risk factors, including age, BMI, smoking status, socioeconomic status and gender. Results: Among 10 PFC compounds considered, only perfluorohexanoic acid (PFHxA) was seen at a significantly higher concentration in GS men and women. Conclusion: PFHxA exposure may be associated with GS. Our findings do not support increased exposure in GS for other PFCs. - Highlights: • Most serum PFCs are not associated with clinically evident Gilbert syndrome. • However, serum perfluorohexanoic acid is positively associated. • The investigation addresses the clinical presentation, not the genetic mutation.

  3. Synthesis, High-Resolution Infrared Spectroscopy, and Vibrational Structure of Cubane, C8H8.

    PubMed

    Boudon, V; Lamy, M; Dugue-Boyé, F; Pirali, O; Gruet, S; D'Accolti, L; Fusco, C; Annese, C; Alikhani, M E

    2016-06-30

    Carbon-cage molecules have generated a considerable interest from both experimental and theoretical points of view. We recently performed a high-resolution study of adamantane (C10H16), the smallest hydrocarbon cage belonging to the diamandoid family ( Pirali , O. ; et al. J. Chem. Phys. 2012 , 136 , 024310 ). There exist another family of hydrocarbon cages with additional interesting chemical properties: the so-called platonic hydrocarbons that comprise dodecahedrane (C20H20) and cubane (C8H8). Both possess C-C bond angles that deviate from the tetrahedral angle (109.8°) of the sp(3) hybridized form of carbon. This generates a considerable strain in the molecule. We report a new wide-range high-resolution study of the infrared spectrum of cubane. The sample was synthesized in Bari upon decarboxylation of 1,4-cubanedicarboxylic acid thanks to the improved synthesis of literature. Several spectra have been recorded at the AILES beamline of the SOLEIL synchrotron facility. They cover the 600-3200 cm(-1) region. Besides the three infrared-active fundamentals (ν10, ν11, and ν12), we could record many combination bands, all of them displaying a well-resolved octahedral rotational structure. We present here a preliminary analysis of some of the recorded bands, performed thanks the SPVIEW and XTDS software, based on the tensorial formalism developed in the Dijon group. A comparison with ab initio calculations, allowing to identify some combination bands, is also presented. PMID:27267150

  4. Cytokines Modulate the “Immune-Metabolism” Interactions during Behçet Disease: Effect on Arginine Metabolism

    PubMed Central

    Lahmar-Belguendouz, Karima; Messaoudene, Djamel; Djeraba, Zineb; Otmani, Fifi; Hakem, Djennat; Lahlou-Boukoffa, Ouided S.; Youinou, Pierre; Touil-Boukoffa, Chafia

    2015-01-01

    Aim and Methods. In this study, we evaluated NOS and arginase activities and their regulation during Behçet disease, a systemic chronic inflammatory disorder with uncertain etiology. The peripheral blood mononuclear cells of 36 patients and 15 control samples (PBMC) were cultured in either RPMI 1640, MEM, or DMEM complemented with 10% of FBS and antibiotics. Cultures were performed with or without the control or patients plasma. Subsequent treatment contained anticytokines (IL-6, TGF-β), a mitogenic effector (PHA), or NOS modulators (L-NMMA, BH4). Culture supernatants were harvested after 24 h of incubation. NO and urea measurements were, respectively, performed by modified Griess and Berthelot methods. Results. Higher urea levels were found in patients' plasma compared to the control's (P < 0.05). NOS modulators induced inverted production profiles for NO and urea (P < 0.05). Their results differed depending on the clinical findings (P < 0.05). It was also found that cytokine neutralization induced different response profiles in patients as opposed to control cultures (P < 0.05). Conclusion. Our results suggest that arginases can compete with NOS2 for L-arginine during Behçet disease. Both enzymes are regulated by environmental cytokines and substrate availability. Furthermore, it seems that NOS/arginase balance is dependent on clinical expression. PMID:25692069

  5. Cytokines Modulate the "Immune-Metabolism" Interactions during Behçet Disease: Effect on Arginine Metabolism.

    PubMed

    Belguendouz, Houda; Lahmar-Belguendouz, Karima; Messaoudene, Djamel; Djeraba, Zineb; Otmani, Fifi; Hakem, Djennat; Lahlou-Boukoffa, Ouided S; Youinou, Pierre; Touil-Boukoffa, Chafia

    2015-01-01

    Aim and Methods. In this study, we evaluated NOS and arginase activities and their regulation during Behçet disease, a systemic chronic inflammatory disorder with uncertain etiology. The peripheral blood mononuclear cells of 36 patients and 15 control samples (PBMC) were cultured in either RPMI 1640, MEM, or DMEM complemented with 10% of FBS and antibiotics. Cultures were performed with or without the control or patients plasma. Subsequent treatment contained anticytokines (IL-6, TGF-β), a mitogenic effector (PHA), or NOS modulators (L-NMMA, BH4). Culture supernatants were harvested after 24 h of incubation. NO and urea measurements were, respectively, performed by modified Griess and Berthelot methods. Results. Higher urea levels were found in patients' plasma compared to the control's (P < 0.05). NOS modulators induced inverted production profiles for NO and urea (P < 0.05). Their results differed depending on the clinical findings (P < 0.05). It was also found that cytokine neutralization induced different response profiles in patients as opposed to control cultures (P < 0.05). Conclusion. Our results suggest that arginases can compete with NOS2 for L-arginine during Behçet disease. Both enzymes are regulated by environmental cytokines and substrate availability. Furthermore, it seems that NOS/arginase balance is dependent on clinical expression. PMID:25692069

  6. Bilateral optic neuritis in a patient with Behçet's disease who respond to therapeutic plasma exchange.

    PubMed

    Erdoğan, Seyda; Sorgun, Mine Hayriye; Yalçındağ, Nilüfer; Atilla, Huban; Yücesan, Canan

    2015-01-01

    Bilateral optic neuritis has been reported very rarely as a manifestation of neuro-Behçet's disease. We present a 50 year old woman who had 20-year history of Behçet's disease presented with acutely blurred vision associated with orbital pain in both eyes. Visual acuity was 0.4 in the right eye and light perception in the left eye; afferent pupillary defect was detected in the left eye. Bilateral swelling of the optic disk was found. The cerebrospinal fluid sample tests were within normal limits. Brain magnetic resonance imaging, magnetic resonance venography and fundus fluorescein angiography were normal. She was diagnosed with bilateral optic neuritis and treated with intravenous methyl prednisolone for 10 days. As there was no response to the treatment, therapeutic plasma exchange was started and the patient's visual acuities improved moderately. We suggest that when high dose steroid is failed to treat ON in BD, treatment with TPE may be considered. PMID:26586983

  7. Interferon-γ and nitric oxide production during Behçet uveitis: immunomodulatory effect of interleukin-10.

    PubMed

    Belguendouz, Houda; Messaoudène, Djamel; Lahmar, Karima; Ahmedi, Laid; Medjeber, Osama; Hartani, Dahbia; Lahlou-Boukoffa, Ouidad; Touil-Boukoffa, Chafia

    2011-09-01

    Uveitis is one of the major manifestations of Behçet Disease, a systemic inflammatory vasculitis. Our aim is to investigate in vivo and in vitro production of interferon (IFN)-γ and nitric oxide (NO) during Behçet uveitis (BU). Moreover, we evaluated the implication of IFN-γ and interleukin (IL)-10 in the regulation of NO production in vitro. Cytokines' concentrations were measured by ELISA, and NO levels were assessed by modified Griess's method. Our results showed that patients with active disease had significant elevation of IFN-γ and NO concentrations in both plasma and peripheral blood mononuclear cell culture supernatants compared with controls (P<0.01) or to patients with inactive disease (P<0.05). Further, IFN-γ induced significantly higher production of NO in cell culture supernatants, whereas IL-10 significantly reduced it (P<0.05). In conclusion, the elevated levels of IFN-γ in vivo and in vitro in patients with BU reflect the implication of this cytokine in the disease physiopathology. These results suggest that IFN-γ, through the induction of NO synthase 2 and the production of NO, is implicated in the genesis of the inflammatory process during active BU; whereas IL-10 seems to have protective properties. PMID:21510811

  8. High-dose short-term chlorambucil for intractable sympathetic ophthalmia and Behçet's disease.

    PubMed Central

    Tessler, H H; Jennings, T

    1990-01-01

    We treated five patients with intractable sympathetic ophthalmia and six patients with severe Behçet's disease by high-dose, short-term chlorambucil therapy. We used a total dose ranging from 306 mg to 4.2 g and a duration of therapy no longer than 36 weeks and in most cases less than 24 weeks. After termination of therapy all 11 patients had a sustained remission of their eye disease. Unless subretinal neovascularisation was present, all had a final visual acuity of 20/50 or better. Malignancy has not developed in any of our cases, with a follow-up ranging from 6 months to 12 years (mean, 4.5 years). Although 30- and 40-year follow-ups and larger numbers of patients may be necessary fully to realise the risks of chlorambucil, we believe that our high-dose, short-term regimen (Behçet's disease: average duration, 23 weeks; average total dose 2.2 g; sympathetic ophthalmia: average duration, 11 weeks; total average dose, 0.9 g) may be safer than previously reported chlorambucil regimens of one to two years or longer. In addition we fulfilled our aim of discontinuing all concomitant systemic corticosteroids within a relatively short time (usually six to eight weeks). PMID:2378842

  9. Recurrent headaches: a case of neurological Behçet's disease.

    PubMed

    Ismail, Alaa M; Dubrey, Simon W; Patel, Maneesh C

    2013-10-01

    A 48-year-old black male, of Nigerian heritage, presented with a 24-hour history of frontal headache of gradual onset. The headache characteristic was migranous, being described as throbbing in nature and located to the right frontal area with associated blurring of vision. Although similar to prior frequent headaches, there was now increasing unsteadiness on walking. Diagnosed 10 years earlier with Behçet's disease, the initial presentation was with oral and genital ulceration. Recurrent episodes of headache caused by neurological flare-ups resulted in a stroke at the age of 46 years. This previous stroke was ischaemic in character with involvement of the brainstem, pons, midbrain and right cerebral peduncle with extension into the right internal capsule. Surveillance brain imaging (computed tomographic and magnetic resonance imaging with venography) 10 months earlier showed brainstem disease activity (Figure 1a) with disease quiescence a month later (Figure 1b) following an escalation of immunosuppressant therapy. Regular medications comprised prednisolone 10 mg (however, regular recurrences had resulted in him taking doses of between 20 and 30 mg/day of prednisolone for most of the past 24 months) and azathioprine 150 mg daily, aspirin 75 mg daily, one adcal D3 twice daily with weekly alendronic acid, and omeprazole 20 mg daily. For headache he took topiramate 25 mg daily and for depression mirtazepine 15 mg daily. The patient was also addicted to a high level of cannabis use which he was reluctant to stop as he felt it helped his symptoms. On examination he was apyrexial and cardiovascularly stable. Neurological examination revealed a residual horizontal nystagmus to the right on lateral gaze, mild left hemiparesis with moderate spasticity, in addition to dysarthria and dysphonia from his prior stroke. A new feature was an exacerbation of gait unsteadiness. Blood tests were unremarkable and specifically the erythrocyte sedimentation rate was normal at 2 mm

  10. Design and Characterization of a Multifunctional pH-Triggered Peptide C8 for Selective Anticancer Activity.

    PubMed

    Lu, Sheng; Bennett, W F Drew; Ding, Yong; Zhang, Lei; Fan, Helen Y; Zhao, Danyang; Zheng, Tao; Ouyang, Ping-Kai; Li, Jason; Wu, Yan; Xu, Wen; Chu, Dafeng; Yuan, Yongfang; Heerklotz, Heiko; Karttunen, Mikko; Chen, P

    2015-12-01

    Most drug delivery systems have been developed for efficient delivery to tumor sites via targeting and on-demand strategies, but the carriers rarely execute synergistic therapeutic actions. In this work, C8, a cationic, pH-triggered anticancer peptide, is developed by incorporating histidine-mediated pH-sensitivity, amphipathic helix, and amino acid pairing self-assembly design. We designed C8 to function as a pH-responsive nanostructure whose cytotoxicity can be switched on and off by its self-assembly: Noncytotoxic β-sheet fibers at high pH with neutral histidines, and positively charged monomers with membrane lytic activity at low pH. The selective activity of C8, tested for three different cancer cell lines and two noncancerous cell lines, is shown. Based on liposome leakage assays and multiscale computer simulations, its physical mechanisms of pore-forming action and selectivity are proposed, which originate from differences in the lipid composition of the cellular membrane and changes in hydrogen bonding. C8 is then investigated for its potential as a drug carrier. C8 forms a nanocomplex with ellipticine, a nonselective model anticancer drug. It selectively targets cancer cells in a pH-responsive manner, demonstrating enhanced efficacy and selectivity. This study provides a novel powerful strategy for the design and development of multifunctional self-assembling peptides for therapeutic and drug delivery applications. PMID:26474414

  11. A comparative MRD-CI study of the electronic spectrum of linear and cyclic C 8+ clusters

    NASA Astrophysics Data System (ADS)

    Haubrich, Jan; Mühlhäuser, Max; Peyerimhoff, Sigrid D.

    2004-11-01

    Multi-reference configuration interaction MRD-CI calculations are performed to compute the vertical electronic spectrum of linear and cyclic C 8+ clusters. The electronic spectrum of the linear C 8+ isomer is dominated by the transition 2Πu←X 2Πg computed at 5.45 eV. The first dipole-allowed transition of linear C 8+ ( 2Δu←X 2Πg) is calculated at 1.69 eV, whereas several transitions are calculated with medium oscillator strengths between 2.30 and 5.14 eV. For the cyclic C 8+ form we computed important transitions at 1.83 and 4.20 eV. In addition, the first dipole-allowed transition of cyclic isomer is computed at 0.77 eV ( 1 2B g←X 2B u). This transition should help to identify the cyclic C 8+ species since there are no dipole-allowed transitions of the linear isomer in this energy region.

  12. Probes for narcotic receptor mediated phenomena. 48. C7- and C8-substituted 5-phenylmorphan opioids from diastereoselective alkylation.

    PubMed

    Lim, Hwan Jung; Dersch, Christina M; Rothman, Richard B; Deschamps, Jeffrey R; Jacobson, Arthur E; Rice, Kenner C

    2013-09-01

    The exploration of the effect of substituents at C7 and C8 of the 5-phenylmorphans on their affinity for opioid receptors was enabled by our recently introduced "one pot" diastereoselective synthesis that provided C7-oxo, hydroxy and alkyl substituents, C8-alkyl substituted 5-phenylmorphans, and compounds that had a new cyclohexane ring that includes the C7 and C8 carbon atoms of the 5-phenylmorphan. The affinity of the 5-phenylmorphans for opioid receptors is increased by a C8-methyl substituent, compared with its C7 analog. The affinity of the newly synthesized compounds is generally for the μ-opioid receptor, rather than the δ- or κ-receptors. Addition of a new cyclohexane ring to the C7 and C8 positions on the cyclohexane ring of the 5-phenylmorphans enhances μ-receptor affinity, bringing the Ki to the subnanomolar level. Unexpectedly, the N-methyl substituted compounds generally had higher affinity than comparable N-phenethyl-substituted relatives. The configurations of two compounds were determined by single-crystal X-ray crystallographic analyses. PMID:23880358

  13. Nqrs Data for C8H5Li2O4.5 [C8H4Li2O4·1/2(H2O)] (Subst. No. 1059)

    NASA Astrophysics Data System (ADS)

    Chihara, H.; Nakamura, N.

    This document is part of Subvolume A `Substances Containing Ag … C10H15' of Volume 48 `Nuclear Quadrupole Resonance Spectroscopy Data' of Landolt-Börnstein - Group III `Condensed Matter'. It contains an extract of Section `3.2 Data tables' of the Chapter `3 Nuclear quadrupole resonance data' providing the NQRS data for C8H5Li2O4.5 [C8H4Li2O4·1/2(H2O)] (Subst. No. 1059)

  14. High-Resolution Infrared Spectroscopy of Cubane, C_8H_8

    NASA Astrophysics Data System (ADS)

    Boudon, Vincent; Pirali, Olivier; Gruet, Sébastien; D'accolti, Lucia; Fusco, Caterina; Annese, Cosimo

    2014-06-01

    Carbon-cage molecules have generated a considerable interest from both experimental and theoretical point of views. We recently performed a high-resolution study of adamantane (C10H16), the smallest hydrocarbon cage belonging to the diamandoid family. There exist another family of hydrocarbon cages with additional interesting chemical properties: the so-called Platonic hydrocarbons that comprise dodecahedrane (C20H20) and cubane (C_8H_8). Both possess C-C bond angles that deviate from the tetrahedral angle (109.8°) of the sp^3 hybridized form of carbon. This generates a considerable strain in the molecule. Cubane itself has the highest density of all hydrocarbons (1.29 g/cm^3). This makes it able to store larges amounts of energy, although the molecule is fully stable. Up to now, only one high-resolution study of cubane has been performed on a few bands [2]. We report here a new wide-range high-resolution study of the infrared spectrum of cubane. The sample was synthesized in Bari upon decarboxylation of 1,4-cubanedicarboxylic acid thanks to the improved synthesis of literature [3]; its {}1H and 13C NMR, FTIR, and mass spectrometry agreed with reported data [4]. Several spectra have been recorded at the AILES beamline of the SOLEIL French synchrotron facility. They cover the 800 to 3100 cm-1 region. Besides the three infrared-active fundamentals (ν10, ν11 and ν12), we could record many combination bands, all of them displaying a well-resolved octahedral rotational structure. We present here a preliminary analysis of some of the recorded bands, performed thanks the SPVIEW and XTDS software, based on the tensrorial formalism developed in the Dijon group [5]. [1] O. Pirali, V. Boudon, J. Oomens, M. Vervloet, J. Chem. Phys., 136, 024310 (2012). [2] A. S. Pine, A. G. Maki, A. G. Robiette, B. J. Krohn, J. K. G. Watson, Th. Urbanek, J. Am. Chem. Soc., 106, 891-897 (1984). [3] P. E. Eaton, N. Nordari, J. Tsanaktsidis, P. S. Upadhyaya, Synthesis, 1, 501, (1995). [4] E

  15. Direct Imaging of the InSb(001)-c(8×2) Surface: Evidence for Large Anisotropy of the Reconstruction

    NASA Astrophysics Data System (ADS)

    Mishima, T. D.; Naruse, N.; Cho, S. P.; Kadohira, T.; Osaka, T.

    2002-12-01

    We have observed the InSb(001)-c(8×2) surface by using high-resolution transmission electron microscopy in the profile-imaging geometry. All images observed at temperatures up to 420 °C agree well with the c(8×2) model reported by Kumpf et al. [

    Phys. Rev. Lett.PRLTAO0031-9007 86, 3586 (2001)
    ]. 1/30 sec real-time observations at 420 °C evidence that a part of the subsurface and surface layers (called a gull-type segment) undergo switching to and from a bulk configuration. The finding is suggestive of large anisotropy in the mean square displacement of the c(8×2) surface.

  16. Successful treatment with adalimumab in a patient with coexisting Behçet's disease and ankylosing spondylitis.

    PubMed

    Yildiz, Necmettin; Alkan, Hakan; Ardic, Fusun; Topuz, Oya

    2010-09-01

    The objective is to report a patient with concomitant ankylosing spondylitis (AS) and Behçet's disease (BD) successfully treated with adalimumab. A 44-year-old male diagnosed as AS applied to our outpatient clinic with complaints of morning stiffness, pain and limitation of motion at spine, concurrence of oral and genital ulcerated lesions. He was on sulfasalazine together with different NSAIDs for the past 1 year. According to the criteria of International Study Group, he was diagnosed as BD. The patient was considered as refractory to current treatment and adalimumab treatment was started. During follow-up, not only AS was in remission, but also no new oral and genital ulcerations appeared. There were no complications related to the use of anti-TNFalpha therapy. In our case it was observed that anti-TNFalpha therapy, specifically adalimumab, was effective for symptoms of both AS and BD. PMID:19705123

  17. Mucocutaneous Involvement in Behçet's Disease: How Systemic Treatment Has Changed in the Last Decades and Future Perspectives

    PubMed Central

    Rotondo, Cinzia; Lopalco, Giuseppe; Iannone, Florenzo; Vitale, Antonio; Talarico, Rosaria; Galeazzi, Mauro; Lapadula, Giovanni; Cantarini, Luca

    2015-01-01

    Behçet's disease (BD) is a multisystemic disorder of unknown etiology characterized by the “triple symptom complex” consisting of recurrent oral aphthosis, genital ulcers, and chronic relapsing bilateral uveitis. Recurrent mucocutaneous lesions are generally considered the hallmark of the disease, being the most common symptoms presenting at the onset of disease. Although the improvement of knowledge about the pathogenetic mechanism added important changes in the treatment management of BD clinical manifestations, thus avoiding the appearance of serious life-threatening complications which are disease related, the mucocutaneous lesions are still the most nagging clinical manifestations to be treated. In this work we reviewed the current state of knowledge regarding the therapeutic approaches for mucocutaneous lesions of BD mainly based on controlled studies to provide a rational framework for selecting the appropriate therapy for treating these troublesome features of the disease. PMID:26185360

  18. Mucocutaneous Involvement in Behçet's Disease: How Systemic Treatment Has Changed in the Last Decades and Future Perspectives.

    PubMed

    Rotondo, Cinzia; Lopalco, Giuseppe; Iannone, Florenzo; Vitale, Antonio; Talarico, Rosaria; Galeazzi, Mauro; Lapadula, Giovanni; Cantarini, Luca

    2015-01-01

    Behçet's disease (BD) is a multisystemic disorder of unknown etiology characterized by the "triple symptom complex" consisting of recurrent oral aphthosis, genital ulcers, and chronic relapsing bilateral uveitis. Recurrent mucocutaneous lesions are generally considered the hallmark of the disease, being the most common symptoms presenting at the onset of disease. Although the improvement of knowledge about the pathogenetic mechanism added important changes in the treatment management of BD clinical manifestations, thus avoiding the appearance of serious life-threatening complications which are disease related, the mucocutaneous lesions are still the most nagging clinical manifestations to be treated. In this work we reviewed the current state of knowledge regarding the therapeutic approaches for mucocutaneous lesions of BD mainly based on controlled studies to provide a rational framework for selecting the appropriate therapy for treating these troublesome features of the disease. PMID:26185360

  19. Behçet's pulmonary artery aneurysms treated with infliximab and monitored with the 6-min walk test.

    PubMed

    Kotecha, Jalpa; Kamath, Ajay V; Mukhtyar, Chetan

    2016-04-01

    Pulmonary involvement in Behçet's disease (BD) is uncommon; however, it is potentially fatal due to the risk of massive haemoptysis. We describe the case of a 36-year-old male presenting with a 2-month history of worsening dyspnoea, weight loss, haemoptysis, oral ulceration, erythema nodosum and superficial thrombophlebitis. He was diagnosed with pulmonary vasculitis secondary to BD; however, his symptoms were refractory to initial treatment with cyclophosphamide, azathioprine and prednisolone. We therefore trialled infliximab alongside methotrexate, which led to a remarkable improvement in his condition, enabling eventual discontinuation of prednisolone. Whilst not being one of the treatments currently recommended for managing pulmonary involvement in BD, infliximab has previously been successfully used in cases refractory to conventional therapy. We used the 6-min walk test (distance covered and lowest oxygen saturations) to monitor his progress, which correlated with his symptoms. This may represent a useful adjunct in monitoring the activity of pulmonary vasculitis. PMID:27123312

  20. Behçet's pulmonary artery aneurysms treated with infliximab and monitored with the 6-min walk test

    PubMed Central

    Kotecha, Jalpa; Kamath, Ajay V.; Mukhtyar, Chetan

    2016-01-01

    Pulmonary involvement in Behçet's disease (BD) is uncommon; however, it is potentially fatal due to the risk of massive haemoptysis. We describe the case of a 36-year-old male presenting with a 2-month history of worsening dyspnoea, weight loss, haemoptysis, oral ulceration, erythema nodosum and superficial thrombophlebitis. He was diagnosed with pulmonary vasculitis secondary to BD; however, his symptoms were refractory to initial treatment with cyclophosphamide, azathioprine and prednisolone. We therefore trialled infliximab alongside methotrexate, which led to a remarkable improvement in his condition, enabling eventual discontinuation of prednisolone. Whilst not being one of the treatments currently recommended for managing pulmonary involvement in BD, infliximab has previously been successfully used in cases refractory to conventional therapy. We used the 6-min walk test (distance covered and lowest oxygen saturations) to monitor his progress, which correlated with his symptoms. This may represent a useful adjunct in monitoring the activity of pulmonary vasculitis. PMID:27123312

  1. Investigation of Behçet’s Disease and Recurrent Aphthous Stomatitis Frequency: The Highest Prevalence in Turkey

    PubMed Central

    Baş, Yalçın; Seçkin, Havva Yıldız; Kalkan, Göknur; Takcı, Zennure; Önder, Yalçın; Çıtıl, Rıza; Demir, Selim; Şahin, Şafak

    2016-01-01

    Background: The Recurrent Aphthous Stomatitis (RAS) is the most frequently observed painful pathology of the oral mucosa in the society. It appears mostly in idiopathic form; however, it may also be related with systemic diseases like Behçet’s Disease (BD). Aims: Determining the prevalence of RAS and BD in the Northern Anatolian Region, which is one of the important routes on the Antique Silk Road. Study Design: Cross-sectional study. Methods: Overall, 85 separate exemplification groups were formed to reflect the population density, and the demographic data of the region they represent. In the first stage, the individuals, who were selected in random order, were invited to a Family Physician Unit at a certain date and time. The dermatological examinations of the volunteering individuals were performed by only 3 dermatology specialists. In the second stage, those individuals who had symptoms of BD were invited to our hospital, and the Pathergy Test and eye examinations were performed. Results: The annual prevalence of RAS was determined as 10.84%. The annual prevalence was determined to be higher in women than in men (p=0.000). It was observed that the prevalence was at the peak level in the 3rd decade, and then decreased proportionally in the following decades (p=0.000). It was also observed that the aphtha recurrence decreased in the following decades (p=0.048). The Behçet’s prevalence was found to be 0.60%. The prevalence in women was found to be higher than in men (0.86% female, 0.14% male; p=0.022). Conclusion: While the RAS prevalence ratio was at an average value when compared with the other societies; the BD prevalence was found as the highest ratio in the world according to the literature. PMID:27606133

  2. Inhibitory effect of six herbal extracts on CYP2C8 enzyme activity in human liver microsomes.

    PubMed

    Albassam, Ahmed A; Mohamed, Mohamed-Eslam F; Frye, Reginald F

    2015-05-01

    1. Herbal supplements widely used in the US were screened for the potential to inhibit CYP2C8 activity in human liver microsomes. The herbal extracts screened were garlic, echinacea, saw palmetto, valerian, black cohosh and cranberry. N-desethylamodiaquine (DEAQ) and hydroxypioglitazone metabolite formation were used as indices of CYP2C8 activity. 2. All herbal extracts showed inhibition of CYP2C8 activity for at least one of three concentrations tested. A volume per dose index (VDI) was calculated to determine the volume in which a dose should be diluted to obtain IC50 equivalent concentration. Cranberry and saw palmetto had a VDI value > 5.0 l per dose unit, suggesting a potential for interaction. 3. Inhibition curves were constructed and the IC50 (mean ± SE) values were 24.7 ± 2.7 μg/ml for cranberry and 15.4 ± 1.7 μg/ml for saw palmetto. 4. The results suggest a potential for cranberry or saw palmetto extracts to inhibit CYP2C8 activity. Clinical studies are needed to evaluate the significance of this interaction. PMID:25430798

  3. The development of an augmentor wing jet STOL research airplane (modified C-8A). Volume 1: Summary

    NASA Technical Reports Server (NTRS)

    Ashleman, R. H.; Kavdahl, H.

    1972-01-01

    A project to develop an experimental aircraft for use as an inflight demonstrator of the augmentor wing, short takeoff concept is discussed. The required modifications were made on a de Havilland C-8A aircraft. The modifications to the aircraft are explained and the performance of the modified aircraft is reported.

  4. Cytochrome P450 2C8*2 allele in Botswana: Human genetic diversity and public health implications.

    PubMed

    Motshoge, Thato; Tawe, Leabaneng; Muthoga, Charles Waithaka; Allotey, Joel; Romano, Rita; Quaye, Isaac; Paganotti, Giacomo Maria

    2016-05-01

    Human cytochrome P450 2C8 is a highly polymorphic gene and shows variation according to ethnicity. The CYP2C8*2 is a slow drug metabolism allele and shows 10-24% frequency in Black populations. The objective of this study was to assess the prevalence of CYP2C8*2 allele in Botswana among the San (or Bushmen) and the Bantu ethnic groups. For that purpose we recruited 544 children of the two ethnicities in three districts of Botswana from primary schools, collected blood samples, extracted DNA and genotyped them through PCR-based restriction fragment length polymorphism analysis. The results demonstrated that in the San the prevalence of the CYP2C8*2 allele is significantly higher than among the Bantu-related ethnic groups (17.5% and 8.5% for San and Bantu, respectively; P=0.00002). These findings support the evidence of a different genetic background of the San with respect to Bantu-related populations, and highlight a possible higher risk of longer drug clearance or poor level of activation of pro-drugs among the San group. PMID:26836270

  5. Investigations into the separation behaviour of perfluorinated C8 and undecanoic acid modified silica hydride stationary phases.

    PubMed

    Kulsing, Chadin; Yang, Yuanzhong; Sepehrifar, Roshanak; Lim, Michael; Toppete, Joshua; Matyska, Maria T; Pesek, Joseph J; Boysen, Reinhard I; Hearn, Milton T W

    2016-04-15

    In this study, the surface charge properties of perfluorinated C8 (PerfluoroC8) and undecanoic acid (UDA) modified silica hydride stationary phases have been investigated. The zeta potential values of these stationary phases were measured in aqueous/acetonitrile mobile phases of different pH, buffer concentrations and acetonitrile contents. The retention behaviour of several basic, acidic and neutral compounds were then examined with these two stationary phases, with U-shaped retention dependencies evident with regard to the organic solvent content of the mobile phase. Plots of the logarithmic retention factor versus buffer concentration revealed slopes ≥ -0.41 for both stationary phases, indicating the involvement of mixed mode retention mechanisms with contributions from both ionic and non-ionic interactions. Using a linear solvation energy relationship approach, the origins of these interactions under different mobile phase conditions were differentiated and quantified. The PerfluoroC8 stationary phase exhibited stronger retention for basic compounds under high acetonitrile content mobile phase conditions, whilst stronger retention was observed for all compounds with the UDA stationary phase under high aqueous content mobile phase conditions. The more negative zeta potentials of the UDA stationary phase correlated with higher total charge density, surface charge density and charge density at the beta plane (the outer plane of the double layer) compared to the PerfluoroC8 stationary phase. With mobile phases of low buffer concentrations, more negative zeta potential values were unexpectedly observed for the PerfluoroC8 stationary phase with slight increases in the C descriptor value, reflecting also the greater accessibility of the analytes to the stationary phase surface. Comparison of the retention behaviours on these phases with other types of silica hydride stationary phases has revealed different patterns of selectivity. PMID:27016444

  6. Revisiting the metabolism and physiological functions of caprylic acid (C8:0) with special focus on ghrelin octanoylation.

    PubMed

    Lemarié, Fanny; Beauchamp, Erwan; Legrand, Philippe; Rioux, Vincent

    2016-01-01

    Caprylic acid (octanoic acid, C8:0) belongs to the class of medium-chain saturated fatty acids (MCFAs). Dairy products and specific oils like coconut oil are natural sources of dietary C8:0 but higher intakes of this fatty acid can be provided with MCT (Medium-Chain Triglycerides) oil that consists in 75% of C8:0. MCFAs have physical and metabolic properties that are distinct from those of long-chain saturated fatty acids (LCFAs ≥ 12 carbons). Beneficial physiological effects of dietary C8:0 have been studied for a long time and MCT oil has been used as a special energy source for patients suffering from pancreatic insufficiency, impaired lymphatic chylomicron transport and fat malabsorption. More recently, caprylic acid was also shown to acylate ghrelin, the only known peptide hormone with an orexigenic effect. Through its covalent binding to the ghrelin peptide, caprylic acid exhibits an emerging and specific role in modulating physiological functions themselves regulated by octanoylated ghrelin. Dietary caprylic acid is therefore now suspected to provide the ghrelin O-acyltransferase (GOAT) enzyme with octanoyl-CoA co-substrates necessary for the acyl modification of ghrelin. This review tries to highlight the discrepancy between the formerly described beneficial effects of dietary MCFAs on body weight loss and the C8:0 newly reported effect on appetite stimulation via ghrelin octanoylation. The subsequent aim of this review is to demonstrate the relevance of carrying out further studies to better understand the physiological functions of this particular fatty acid. PMID:26253695

  7. Emissions of C6-C8 aromatic compounds in the United States: Constraints from tall tower and aircraft measurements

    NASA Astrophysics Data System (ADS)

    Hu, Lu; Millet, Dylan B.; Baasandorj, Munkhbayar; Griffis, Timothy J.; Travis, Katherine R.; Tessum, Christopher W.; Marshall, Julian D.; Reinhart, Wesley F.; Mikoviny, Tomas; Müller, Markus; Wisthaler, Armin; Graus, Martin; Warneke, Carsten; Gouw, Joost

    2015-01-01

    present two full years of continuous C6-C8 aromatic compound measurements by PTR-MS at the KCMP tall tower (Minnesota, US) and employ GEOS-Chem nested grid simulations in a Bayesian inversion to interpret the data in terms of new constraints on US aromatic emissions. Based on the tall tower data, we find that the RETRO inventory (year-2000) overestimates US C6-C8 aromatic emissions by factors of 2.0-4.5 during 2010-2011, likely due in part to post-2000 reductions. Likewise, our implementation of the US EPA's NEI08 overestimates the toluene flux by threefold, reflecting an inventory bias in non-road emissions plus uncertainties associated with species lumping. Our annual top-down emission estimates for benzene and C8 aromatics agree with the NEI08 bottom-up values, as does the inferred contribution from non-road sources. However, the NEI08 appears to underestimate on-road emissions of these compounds by twofold during the warm season. The implied aromatic sources upwind of North America are more than double the prior estimates, suggesting a substantial underestimate of East Asian emissions, or large increases there since 2000. Long-range transport exerts an important influence on ambient benzene over the US: on average 43% of its wintertime abundance in the US Upper Midwest is due to sources outside North America. Independent aircraft measurements show that the inventory biases found here for C6-C8 aromatics also apply to other parts of the US, with notable exceptions for toluene in California and Houston, Texas. Our best estimates of year-2011 contiguous US emissions are 206 (benzene), 408 (toluene), and 822 (C8 aromatics) GgC.

  8. Ultrastructure of lymphocyte-mediated fat-cell lysis in erythema nodosum-like lesions of Behçet's syndrome.

    PubMed

    Honma, T; Bang, D; Saito, T; Nakagawa, S; Ueki, H; Lee, S

    1987-12-01

    In this study, biopsy specimens from 18 patients with Behçet's syndrome were examined by electron microscopy with particular attention to the appearance of the lymphocyte-macrophage infiltrate into the interlobules of subcutaneous fat in erythema nodosum-like lesions. Electron microscopic evaluation revealed vacuolization changes of fat cells with detachment of their cell membrane from the basal lamina that permitted lymphocytes and macrophages to enter into this developed space. We believe that the detachment of fat cells from the basal lamina precedes invasion by lymphocytes which, in turn, attracts macrophages into the space. This eventually leads to fat-cell lysis accompanied by activation of macrophages, which causes further inflammation, completing the picture of panniculitis in the erythema nodosum-like lesions in Behçet's syndrome. PMID:3688905

  9. C6 –C8 Bridged Epothilones: Consequences of Installing a Conformational Lock at the Edge of the Macrocycle

    PubMed Central

    Jiang, Yi; Banerjee, Abhijit; Brodie, Peggy J.; Bane, Susan; Kingston, David G. I.; Liotta, Dennis C.

    2011-01-01

    A series of conformationally restrained epothilone analogs with a short bridge between the methyl groups at C6 and C8 was designed to mimic the binding pose assigned to our recently reported EpoA-microtubule binding model. A versatile synthetic route to these bridged epothilone analogs has been successfully devised and implemented. Biological evaluation of the compounds against A2780 human ovarian cancer and PC3 prostate cancer cell lines suggested that the introduction of a bridge between C6-C8 reduced potency by 25–1000 fold in comparison with natural epothilone D. Tubulin assembly measurements indicate these bridged epothilone analogs to be mildly active, but without significant microtubule stabilization capacity. Molecular mechanics and DFT energy evaluations suggest the mild activity of the bridged epo-analogs may be due to internal conformational strain. PMID:22127984

  10. Interior and exterior fuselage noise measured on NASA's C-8a augmentor wing jet-STOL research aircraft

    NASA Technical Reports Server (NTRS)

    Shovlin, M. D.

    1977-01-01

    Interior and exterior fuselage noise levels were measured on NASA's C-8A Augmentor Wing Jet-STOL Research Aircraft in order to provide design information for the Quiet Short-Haul Research Aircraft (QSRA), which will use a modified C-8A fuselage. The noise field was mapped by 11 microphones located internally and externally in three areas: mid-fuselage, aft fuselage, and on the flight deck. Noise levels were recorded at four power settings varying from takeoff to flight idle and were plotted in one-third octave band spectra. The overall sound pressure levels of the external noise field were compared to previous tests and found to correlate well with engine primary thrust levels. Fuselage values were 145 + or - 3 dB over the aircraft's normal STOL operating range.

  11. A Remarkable Oxidative Cascade That Replaces the Riboflavin C8 Methyl with an Amino Group during Roseoflavin Biosynthesis.

    PubMed

    Jhulki, Isita; Chanani, Prem K; Abdelwahed, Sameh H; Begley, Tadhg P

    2016-07-13

    Roseoflavin is a naturally occurring riboflavin analogue with antibiotic properties. It is biosynthesized from riboflavin in a reaction involving replacement of the C8 methyl with a dimethylamino group. Herein we report the identification of a flavin-dependent enzyme that converts flavin mononucleotide (FMN) and glutamate to 8-amino-FMN via the intermediacy of 8-formyl-FMN. A mechanistic proposal for this remarkable transformation is proposed. PMID:27331868

  12. Nqrs Data for C8H8Cl3N3O4S2 (Subst. No. 1087)

    NASA Astrophysics Data System (ADS)

    Chihara, H.; Nakamura, N.

    This document is part of Subvolume A `Substances Containing Ag … C10H15' of Volume 48 `Nuclear Quadrupole Resonance Spectroscopy Data' of Landolt-Börnstein - Group III `Condensed Matter'. It contains an extract of Section `3.2 Data tables' of the Chapter `3 Nuclear quadrupole resonance data' providing the NQRS data for C8H8Cl3N3O4S2 (Subst. No. 1087)

  13. Epigenetic regulation of cyclooxygenase-2 by methylation of c8orf4 in pulmonary fibrosis

    PubMed Central

    Evans, Iona C.; Barnes, Josephine L.; Garner, Ian M.; Pearce, David R.; Maher, Toby M.; Shiwen, Xu; Renzoni, Elisabetta A.; Wells, Athol U.; Denton, Christopher P.; Laurent, Geoffrey J.; Abraham, David J.

    2016-01-01

    Fibroblasts derived from the lungs of patients with idiopathic pulmonary fibrosis (IPF) and systemic sclerosis (SSc) produce low levels of prostaglandin (PG) E2, due to a limited capacity to up-regulate cyclooxygenase-2 (COX-2). This deficiency contributes functionally to the fibroproliferative state, however the mechanisms responsible are incompletely understood. In the present study, we examined whether the reduced level of COX-2 mRNA expression observed in fibrotic lung fibroblasts is regulated epigenetically. The DNA methylation inhibitor, 5-aza-2′-deoxycytidine (5AZA) restored COX-2 mRNA expression by fibrotic lung fibroblasts dose dependently. Functionally, this resulted in normalization of fibroblast phenotype in terms of PGE2 production, collagen mRNA expression and sensitivity to apoptosis. COX-2 methylation assessed by bisulfite sequencing and methylation microarrays was not different in fibrotic fibroblasts compared with controls. However, further analysis of the methylation array data identified a transcriptional regulator, chromosome 8 open reading frame 4 (thyroid cancer protein 1, TC-1) (c8orf4), which is hypermethylated and down-regulated in fibrotic fibroblasts compared with controls. siRNA knockdown of c8orf4 in control fibroblasts down-regulated COX-2 and PGE2 production generating a phenotype similar to that observed in fibrotic lung fibroblasts. Chromatin immunoprecipitation demonstrated that c8orf4 regulates COX-2 expression in lung fibroblasts through binding of the proximal promoter. We conclude that the decreased capacity of fibrotic lung fibroblasts to up-regulate COX-2 expression and COX-2-derived PGE2 synthesis is due to an indirect epigenetic mechanism involving hypermethylation of the transcriptional regulator, c8orf4. PMID:26744410

  14. Endovascular Treatment of a Ruptured Pulmonary Artery Aneurysm in a Patient with Behçet's Disease Using the Amplatzer Vascular Plug 4

    PubMed Central

    Carrafiello, Gianpaolo; Nicotera, Paolo; Vaghi, Adriano; Cazzulani, Alberto

    2013-01-01

    A pulmonary artery aneurysm is a common manifestation and the leading cause of mortality in Behçet's disease. We describe a case of spontaneous rupture of a pulmonary artery aneurysm that, due to the inadequacy of medical therapy and the disadvantages of surgery, became the ideal candidate for endovascular management and was successfully performed by using the Amplatzer Vascular Plug 4. PMID:23482415

  15. Angio-Behçet thoracique - régression totale sous traitement immuno-suppresseur (à propos d'un cas)

    PubMed Central

    Berrady, Rhizlane; Khammar, Zineb; Lahlou, Mariam; Boukhrissa, Amal; Bono, Wafaa

    2014-01-01

    La maladie de Behçet est une Vascularite multisystémique d’étiologie obscure. L'angio-Behçet thoracique est en rapport avec le tropisme vasculaire bien connu de la maladie, et les anévrysmes des artères pulmonaires constituent une des complications majeures de cette maladie. Nous rapportons le cas d'un patient qui s'est présenté en consultation pour douleur thoracique avec toux et crachats hémoptoïques. Le diagnostic d'une maladie de Behçet est retenu sur des arguments cliniques et confirmé par un angioscanner thoracique qui a objectivé des dilatations anévrysmales des bronches lobaires et segmentaires des deux artères pulmonaires. Devant l'urgence thérapeutique, un bolus de solumédrol sur trois jours est réalisé relayé par un bolus de cyclophosphamide. Après 12 mois de suivi, le patient rapporte une nette amélioration clinique. L'angio-scanner de contrôle note une disparition totale des anévrysmes des artères pulmonaires. L'atteinte thoracique de l'angio-Behçet est grave et met en jeu le pronostic vital, le traitement médical de ces anévrysmes à base d'immunosuppresseur permet une évolution favorable. PMID:25404976

  16. 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

  17. C8-structured carbon quantum dots: Synthesis, blue and green double luminescence, and origins of surface defects

    NASA Astrophysics Data System (ADS)

    Xifang, Chen; Wenxia, Zhang; Qianjin, Wang; Jiyang, Fan

    Carbon quantum dots (CQDs) have attracted great attention in the past few years due to their low cytotoxicity, exploited various synthesis methods, unexampled abundance of raw materials on earth, and robust near-infrared to near-UV luminescence. Carbon nanoparticles have applications in biological labeling, delivery of drugs and biological molecules into cells, and light emitting diodes and lasing. CQDs generally exist as nanodiamonds or graphite quantum dots according to previous research reports. In this study, we report the first synthesis of the third-allotrope CQDs through carbonization of sucrose and study their luminescence properties. These CQDs have a body-centered cubic structure and each lattice point is composed of eight atoms which form a sub-cube (so called C8 crystal structure). High-resolution transmission electron microscopy and X-ray diffraction confirm the C8 structure of the synthesized carbon nanocrystallites with an average size of 2 nm. The C8 CQDs exhibit double-band luminescence with two peaks centered at around 432 and 520 nm. The study based on the photoluminescence, UV-Vis absorption, Fourier-transform infrared, and X-ray photoelectron spectroscopies reveals that the green emission originates from the C=O related surface defect.

  18. The Cologne Carbon Cluster Experiment: ro-vibrational spectroscopy on C 8 and other small carbon clusters

    NASA Astrophysics Data System (ADS)

    Neubauer-Guenther, P.; Giesen, T. F.; Berndt, U.; Fuchs, G.; Winnewisser, G.

    2003-02-01

    We report on our ongoing efforts in obtaining the IR-spectra of the linear carbon cluster molecules C n with n=8-13. So far C 8, C 9, C 10, and C 13 have been recorded at Cologne. With the exception of C 8 all assignments have been secured. For C 8 a tentative assignment could be derived with the bandcenter of the σu antisymmetric stretching mode located at ν0=2067.9779 cm -1 and a preliminary rotational constant in the vibrational ground state of B″=0.02068 cm -1. The measured signal to noise ratio of the ro-vibrational band is fairly weak and thus the lower J ro-vibrational transitions can not be assigned with certainty. As a consequence the band center remains uncertain by 4 J or 0.17 cm -1. For a more reliable assignment the sensitivity of the system has to be increased by at least one order of magnitude. The envisaged sensitivity increase of our experiment will be discussed along with the intention to perform terahertz observations of the low energetic bending ro-vibrational spectra. These sub-mm wave measurements will be carried out simultaneously with the IR measurements.

  19. Drug metabolism by CYP2C8.3 is determined by substrate dependent interactions with cytochrome P450 reductase and cytochrome b5.

    PubMed

    Kaspera, Rüdiger; Naraharisetti, Suresh B; Evangelista, Eric A; Marciante, Kristin D; Psaty, Bruce M; Totah, Rheem A

    2011-09-15

    Genetic polymorphisms in CYP2C8 can influence the metabolism of important therapeutic agents and cause interindividual variation in drug response and toxicity. The significance of the variant CYP2C8*3 has been controversial with reports of higher in vivo but lower in vitro activity compared to CYP2C8*1. In this study, the contribution of the redox partners cytochrome P450 reductase (CPR) and cytochrome b5 to the substrate dependent activity of CYP2C8.3 (R139K, K399R) was investigated in human liver microsomes (HLMs) and Escherichia coli expressed recombinant CYP2C8 proteins using amodiaquine, paclitaxel, rosiglitazone and cerivastatin as probe substrates. For recombinant CYP2C8.3, clearance values were two- to five-fold higher compared to CYP2C8.1. CYP2C8.3's higher k(cat) seems to be dominated by a higher, but substrate specific affinity, towards cytochrome b5 and CPR (K(D) and K(m,red)) which resulted in increased reaction coupling. A stronger binding affinity of ligands to CYP2C8.3, based on a two site binding model, in conjunction with a five fold increase in amplitude of heme spin change during binding of ligands and redox partners could potentially contribute to a higher k(cat). In HLMs, carriers of the CYP2C8*1/*3 genotype were as active as CYP2C8*1/*1 towards the CYP2C8 specific reaction amodiaquine N-deethylation. Large excess of cytochrome b5 compared to CYP2C8 in recombinant systems and HLMs inhibited metabolic clearance, diminishing the difference in k(cat) between the two enzymes, and may provide an explanation for the discrepancy to in vivo data. In silico studies illustrate the genetic differences between wild type and variant on the molecular level. PMID:21726541

  20. 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. PMID:25630753

  1. Determination of ν2 fundamental band origin for BeH2 and BeD2 from deperturbation analysis of hot bands.

    PubMed

    Motallebipour, Maryam S; Shayesteh, Alireza

    2016-08-21

    New vibration-rotation hot bands, i.e., 031 → 030 and 041 → 040, have been assigned and rotationally analyzed for the gaseous BeH2 molecule. The 03(1)0 (Πu), 03(1)1 (Πg), 04(2)0 (Δg), and 04(2)1 (Δu) states are locally perturbed by the nearby 001 (Σu (+)), 002 (Σg (+)), 01(1)1 (Πg), and 01(1)2 (Πu) states, respectively [A. Shayesteh et al., J. Chem. Phys. 118, 3622 (2003)]. Appropriate Hamiltonian matrices have been constructed to take the effects of rotational ℓ-type doubling, ℓ-type resonance, and third order Coriolis interactions into account, and used in deperturbation analyses. From nonlinear least squares fits of all the data, relative energies and unperturbed rotational constants have been determined for the 030, 031, 040, and 041 vibrational levels of BeH2. Similar deperturbation fits were performed for the 001 → 000 and 011 → 010 bands of the BeD2 isotopologue, while the 030 and 040 vibrational levels were treated as dark states. From relative vibrational energies of the 030 and 040 levels, the ν2 fundamental band origins were determined to be 711.48 ± 0.05 cm(-1) and 548.21 ± 0.1 cm(-1) for BeH2 and BeD2, respectively. PMID:27544108

  2. The eighth Frederick H. Verhoeff Lecture. presented by saiichi mishima, MD Behçet's disease in Japan: ophthalmologic aspects.

    PubMed Central

    Mishima, S; Masuda, K; Izawa, Y; Mochizuki, M; Namba, K

    1979-01-01

    The problems of Behçet's disease in Japan have been reviewed with particular emphasis on the ophthalmologic aspects: the historical background for the Japanese works, diagnostic critieria, epidemiology, some statistics, ocular symptomatology, ocular histopathology, etiology, pathophysiology, and treatment. Behçet's disease is the most frequent entity in endogenous uveitis in Japan. Patients are found throughout the country, and the prevalence rate averages seven to eight per 100,000 population: the rate is higher in the northern than in the southern districts. The diagnosis is made on the basis of a combination of clinical symptoms that are divided into the major and minor criteria symptoms. The major criteria comprise the ocular involvement, aphthous ulcers of the oral mucous membrane, genital ulcers, and skin lesions. These symptoms recur often as attacks and the disease follows a chronic course. The ocular involvement is found in 83% to 95% in males and 67% to 73% in females; the male to female ratio in the number of patients is 1.78. Both into the anterior segment type and the fundus and panophthalmic types. The anterior segment type shows serous iridocyclitis with the classic type of hypopyon appearing in about 12% of the attacks. This type is found in about 20%, more often in females than in males, and the visual prognosis is more favorable than in the fundus and panophthalmic types. In the latter two types, attacks of retinal angitis resulting in intensive retinal edema, yellowish-white exudate, and hemorrhages recur particularly in the macular region, and the visual prognosis is poor. More than 50% of male patients lose visual acuity to less than 0.1 in five years, but this is the case in only 10% of female patients. Consequently, Behçet's disease is the cause of blindness in about 12% of acquired blindness in adults. The ocular histopathology during the attack is characterized by severe angitis with intensive infiltration of neutrophil leucocytes

  3. Preliminary Study of High Resolution HPLC Analytical Method for Sedimentary Pigments Based on Coupled C8 Columns

    NASA Astrophysics Data System (ADS)

    Yao, P.; Yu, Z.; Deng, C.; Liu, S.; Zhao, J.

    2008-05-01

    The pigments in marine water columns can provide accurate estimates of community composition and abundance of phytoplankton. In addition, the sedimentary pigments, especially the derivatives of chlorophyll such as pyrophaeophytins, pyrophaeophorbides and steryl chlorin esters (SCEs) formed during early diagenesis can also provide information on the primary producer community and the changes in paleoproductivity. Accordingly, analysis of pigments and their derivatives is of great importance for oceanography, limnology and geochemistry. Many methods have been developed for the separation of chlorophylls, carotenoids and their derivatives derived from phytoplankton and water column samples using high-performance liquid chromatography (HPLC). Methods widely cited in the literatures include those developed by Wright et al. (1991) and Zapata et al. (2000). Both methods use reversed-phase columns, but C18 column was employed in Wright et al. (1991) and C8 column in Zapata et al. (2000). However, evident coelutions are observed in published works. This will particularly cause problematic identification and quantification in dealing with sedimentary pigments which are highly complex and often display a broad range in polarity. Clearly, it is necessary to improve the separation of the complex pigments if the information carried by the pigments is to be used fully. Coupled C18 columns were used in the HPLC method developed by Airs et al. (2001) for the analysis of complex pigment distributions. Improved chromatographic resolution, more pigment components and novel bacteriochlorophyll derivatives were obtained by this method. It indicates a new road for HPLC method development. C8 column has shorter carbon chains than that of C18 column and can provide less retention of apolar compounds which is of particular advantaged to hydrophobic chlorophyll a, b and their derivatives. That is one of the reasons why the C8 method developed by Zapata et al. (2000) is admittedly better than

  4. Electrodiagnostic values through the thoracic outlet using C8 root needle studies, F-waves, and cervical somatosensory evoked potentials.

    PubMed

    Livingstone, E F; DeLisa, J A; Halar, E M

    1984-11-01

    Mid-humerus cadaver determinations of ulnar F-wave, C7 spinal somatosensory evoked potential (SEP), and modified C8 root stimulation (RS) were performed bilaterally on 20 normal subjects to standardize technique and obtain normal values for the segment from mid-humerus to cervical spine. Our cadaver study shows that the best position for upper extremity measurement of mid-humerus-cervical spine distance is at 60 degrees of shoulder abduction, 45 degrees of internal rotation, and at the distance of 35cm, measured by caliper. Using this position and distance the following normal values were obtained: 1) Mid-humerus F-wave minimal, maximal, and mean latencies, and minimal nerve conduction velocity (NCV) were 21.8 +/- 1.2msec, 22.3 +/- 1.2msec, 22.3 +/- 1.1msec, and 59.7 +/- 2.4m/sec, respectively. Latency difference between minimal and maximal F-wave was 1.4 +/- 0.4msec. 2) Cervical spine SEP was 5.1 +/- 0.4msec, with left to right difference of less than 0.9msec. 3) C8 RS and mid-humerus ulnar nerve (UN) pick-up latency and NCV were 4.9 +/- 0.2msec and 71.4 +/- 2.2m/sec, whereas C8 root pick-up and mid-humerus UN stimulation latency and NCV were 5.2 +/- 0.4msec and 66.9 +/- 5.2m/sec, respectively. To evaluate proximal nerve conductivity through the thoracic outlet, the sequential use of the three modified techniques for 35cm mid-humerus-cervical spine distance is recommended. PMID:6497620

  5. MRI in neuro-Behçet's syndrome: comparison of conventional spin-echo and FLAIR pulse sequences.

    PubMed

    Jäger, H R; Albrecht, T; Curati-Alasonatti, W L; Williams, E J; Haskard, D O

    1999-10-01

    We compared the sensitivity of a fluid-attenuated inversion-recovery (FLAIR) sequence with that of a conventional dual-echo spin-echo (SE) sequence) to brain lesions in 20 patients with Behçet's syndrome. They underwent 25 MRI examinations. The images were independently analysed for the number, type and anatomical location of lesions shown. There were 18 abnormal studies (13 initial and 5 follow-up). The FLAIR sequence detected significantly more lesions than the SE TE 80 (P < 0.05) and SE TE 20 (P < 0.01) sequences. It was particularly useful for demonstrating lesions in the juxtacortical white matter, which accounted for over half the lesions detected on the FLAIR images. Of patients presenting with nonspecific symptoms such as headache, seven had normal and five had abnormal studies. All patients presenting with focal neurological signs had abnormal imaging. We found supratentorial and, in particular, juxtacortical lesions to be more frequent than previously described. PMID:10552026

  6. Recurrent Interstitial Pneumonitis in a Patient with Entero-Behçet's Disease Initially Treated with Mesalazine

    PubMed Central

    Miyamura, Tomoya; Wu, Brian; Suematsu, Eiichi

    2016-01-01

    A 65-year-old man with entero-Behçet's disease (BD) being treated with mesalazine was presented to our hospital complaining of dyspnea. Computed tomography (CT) of the chest showed ground-glass opacities and he was initially diagnosed with mesalazine-induced interstitial pneumonitis (IP). Besides the discontinuation of mesalazine, a high dose of oral prednisolone was administered and the patient seemed to recover. However, four months later, dyspnea recurred and repeated CT revealed more extensive pulmonary infiltration despite steroid therapy. After the exclusion of infections, we suspected either a recurrence of mesalazine-induced IP or BD-related IP as a clinical manifestation of BD. The patient was treated with intravenous methylprednisolone and cyclophosphamide, followed by orally administered azathioprine, based on the assumption of underlying vasculitis. Thereafter, his condition improved. BD-related IP is an extremely rare condition with limited reports in the literature. Mesalazine-induced IP is also uncommon but the prognosis is generally good after discontinuation of mesalazine with or without steroid therapy. We discuss an extremely rare case, especially focusing on BD-related IP and mesalazine-induced IP as a potential cause of recurrent IP in a patient with entero-BD. PMID:27429824

  7. HnRNP A1 is Involved in Deep Vein Thrombosis Patients with Behçet's Disease

    PubMed Central

    Chen, Peng; Zhang, Chunyan; Liu, Chen; Zhang, Liyun; Yang, Chunhe; Chen, Guangyu; Ma, Dan; Tian, Yaping; Du, Hongwu

    2016-01-01

    Objective The aim of this study was to verify the hypothesis originated from bioinformatics and literature reviews that hnNRP A1 may be a new immune target of Behçet's disease (BD). Methods First, bioinformatics was used to show the correlation between hnRNP A1 and A2/B1 in amino acid sequences and three dimensional structures. Second, hnRNP A1 was expressed, purified, and immunologically confirmed by systematic immunology methods including: Western blotting, immunoprecipitation and Dot-ELISA. Then, ELISA was used to screen the anti-hnRNP A1 autoantibodies in newly confirmed clinical samples and the clinical significance was compared between anti-hnRNP A1 antibody positive and negative groups. Finally, the endothelial cells antigen profile of one anti-hnRNP A1 antibody positive BD patient was detected using immunoprecipitation with liquid chromatography tandem mass spectrometry (LC–TMS). Results In total 720 subjects enrolled and tested in this study. Our results demonstrated hnRNP A1 as a new immune target of BD. The reactivity of BD serum IgG antibodies against hnRNP A1 was significantly higher than healthy controls (P < 0.0001), and deep vein thrombosis (DVT) showed a significant higher in the anti-hnRNP A1 antibodies positive group (P < 0.05). PMID:27211563

  8. Intima-media thickness and arterial stiffness of carotid artery in Korean patients with Behçet's disease.

    PubMed

    Rhee, Moo-Yong; Chang, Hyun Kyu; Kim, Seong-Kyu

    2007-06-01

    Behçet's disease (BD) is a systemic vasculitis involving diverse sizes of arteries and veins. We performed this study to evaluate the vascular changes by assessment of the arterial stiffness and intima-media thickness (IMT) of carotid artery in Korean patients with BD. Forty-one patients with BD and age-, and sex-matched 53 healthy subjects were recruited in this study. Carotid arterial stiffness and IMT were assessed by using high-resolution B-mode ultrasonography. Arterial stiffness parameters such as carotid arterial distensibility coefficient, stiffness index, and incremental elastic modulus (E(inc)) were significantly increased in BD patients compared with those in healthy subjects, but not in IMT. Positive relationship was noted between age and IMT, whereas age of onset was significantly associated with arterial stiffness in BD. This finding suggests impaired endothelial function before visible structural changes of arterial wall in BD. Age and age of onset may be an independent risk factor for carotid IMT and arterial stiffness, respectively. Further studies in more large populations are required to confirm our results. PMID:17596642

  9. Sequencing of 16S rRNA reveals a distinct salivary microbiome signature in Behçet's disease.

    PubMed

    Coit, Patrick; Mumcu, Gonca; Ture-Ozdemir, Filiz; Unal, Ali Ugur; Alpar, Ugur; Bostanci, Nagihan; Ergun, Tulin; Direskeneli, Haner; Sawalha, Amr H

    2016-08-01

    Behçet's disease (BD) is characterized by recurrent oro-genital ulcers, mucocutaneous lesions, and serious organ involvement. We investigated the salivary microbiome in BD using high-throughput sequencing of the 16S rRNA V4 region. Stimulated saliva samples were collected from 31 BD patients and 15 healthy controls, and in 9 BD patients, a second saliva sample was collected following dental and periodontal treatment. Sequence analysis identified a total of 908 operational taxonomic units (OTUs) present across all samples. Patients had a microbial community structure that is significantly less diverse than healthy controls. The most overabundant species in BD was Haemophilus parainfluenzae, while the most depleted included Alloprevotella rava and species in the genus Leptotrichia. Periodontal treatment improved oral health indices in BD but had no short-term effect on bacterial community structure. Neither the BD-associated genetic risk locus within the HLA-B/MICA region nor being on immunosuppressive medications explained the differences between patients and controls. PMID:27283393

  10. Right Ventricular Thrombus and Cerebral Artery Aneurysm in a Patient with Behçet’s Disease

    PubMed Central

    Sabzi, Feridoun; Mirzaei, Samaneh; Faraji, Reza

    2016-01-01

    We report a 35-year-old woman referred to the Imam Ali Hospital, Kermanshah, Iran, in July 2014 for evaluation of postoperative dyspnoea after neurosurgery performed seven days previously for a ruptured cerebral artery aneurysm. She was known to have Behçet’s disease with a history of recurrent oral and genital aphthous ulcers and uveitis. At referral, her symptoms included vertigo, dysarthria, palpitations and chest pain. Transthoracic echocardiography (TTE) revealed a large thrombus in her right ventricle outflow tract and open-heart surgery was performed eight days after the previous surgery to remove the clot. The postoperative period was complicated by transient acute renal failure, which resolved spontaneously. The patient was discharged 13 days after the cardiac surgery on warfarin, prednisolone, azathioprine and cyclophosphamide. Cyclophosphamide and azathioprine were discontinued after three months as the symptoms had completely resolved; however, prednisolone was continued due to recurrent uveitis. A 10-month follow-up TTE scan revealed no thrombus recurrence and treatment with warfarin and prednisolone was continued. PMID:27226921

  11. Intestinal Behçet's Disease: A True Inflammatory Bowel Disease or Merely an Intestinal Complication of Systemic Vasculitis?

    PubMed Central

    Kim, Duk Hwan

    2016-01-01

    Behçet's disease (BD) is a multi-systemic inflammatory disorder of an unknown etiology and shows a chronic recurrent clinical course. When the disease involves the alimentary tract, it is called intestinal BD because of its clinical importance. Intestinal BD is more frequently reported in East Asian countries than in Western or Middle Eastern countries. While any part of the gastrointestinal tract can be involved, the most common location of intestinal BD is the ileocecal area. A few, large, deep ulcerations with discrete border are characteristic endoscopic findings of intestinal BD. Currently, there is no single gold standard test or pathognomonic finding of intestinal BD. However, recently developed novel diagnostic criteria and a disease activity index have helped in assessing intestinal BD. As intestinal BD shares a lot of characteristics with inflammatory bowel disease, including genetic background, clinical manifestations, and therapeutic strategies, distinguishing between the two diseases in clinical practice is quite difficult. However, biologic agents such as anti-tumor necrosis factor α antibody shows a considerable efficacy similar to inflammatory bowel disease cases. It is important to distinguish and treat those two disease entities separately from the standpoint of precise medicine. Clinicians should require comprehensive knowledge regarding the similarities and differences between intestinal BD and inflammatory bowel disease for making an accurate clinical decision. PMID:26632379

  12. Streptococcal infection in the pathogenesis of Behçet's disease and clinical effects of minocycline on the disease symptoms.

    PubMed

    Kaneko, F; Oyama, N; Nishibu, A

    1997-12-01

    Although the precise pathoetiology of Behçet's disease (BD) remains obscure, patients with BD have a high incidence of chronic infectious foci, indicating an enhanced susceptibility to chronic tonsillitis, and dental caries. Sometimes, clinical symptoms appear after treatment of these foci in BD patients. It is believed that BD might be related to an allergic reaction to a bacterial infection in view of the many clinical symptoms, especially the presence of aphthous and genital ulcerations. An attempt to obtain cutaneous responses to bacterial antigens has been carried out using various vaccines developed from bacteria isolated from the ulcerative lesions and oral cavities of BD patients. BD patients often show intense hypersensitivity to various strains of streptococci, not only by their cutaneous reactions but also by in vitro testing. In this report, we describe our previous studies on the correlation between streptococcal antigens and the pathogenesis of BD and also discuss the recent reports of other authors. The intense hypersensitivity to streptococcal antigens acquired after streptococcal infection is thought to play an important role in the appearance of symptoms in BD patients since the production of pro-inflammatory cytokines by peripheral blood mononuclear cells (PBMC) was enhanced when stimulated with streptococcal antigen in a culture system. Minocycline, an antibiotic to which certain strains of streptococci are sensitive, reduced the frequency of clinical symptoms in BD patients as well as the production of pro-inflammatory cytokines by BD-PBMC stimulated with streptococcal antigen. PMID:9509915

  13. C-8 Modifications of 3-alkyl-1,8-dibenzylxanthines as Inhibitors of Human Cytosolic Phosphoenolpyruvate Carboxykinase

    SciTech Connect

    Pietranico,S.; Foley, L.; Huby, N.; Yun, W.; Dunten, P.; Vermeulen, J.; Wang, P.; Toth, K.; Ramsey, G.; et al.

    2007-01-01

    New modifications on the C-8 4-aminobenzyl unit of the previously reported 3-alkyl-1,8-dibenzylxanthine inhibitors of cPEPCK are presented. The most active compound reported here is the 5-chloro-1,3-dimethyl-1H-pyrazole-4-sulfonic acid amide derivative 2 with an IC{sub 50} of 0.29 {+-} 0.08 {mu}M. An X-ray analysis of a heteroaromatic sulfonamide is presented showing a new {pi}-{pi} interaction.

  14. Theoretical vibrations of carbon chains C3, C4, C5, C6, C7, C8, and C9

    NASA Technical Reports Server (NTRS)

    Kurtz, Joe; Adamowicz, Ludwik

    1991-01-01

    The MBPT (2) procedure with the 6-31g (asterisk) basis set was used to study nearly linear carbon chains. The theoretical vibrational frequencies of the molecules C3 through C9 are presented and, for C3 through C6, compared to experimental stretching frequencies and their (C-13)/(C-12) isotopomers. Predictions for C7, C8, and C9 stretching frequencies are calculated by directly scaling the theoretical frequencies with factors derived from experimental-to-theoretical ratios known for the smaller molecules.

  15. The effect of the cytochrome P450 CYP2C8 polymorphism on the disposition of (R)-ibuprofen enantiomer in healthy subjects

    PubMed Central

    Martínez, Carmen; García-Martín, Elena; Blanco, Gerardo; Gamito, Francisco J G; Ladero, José M; Agúndez, José A G

    2005-01-01

    Aims To study the effect of CYP2C8*3, the most common CYP2C8 variant allele on the dis-position of (R)-ibuprofen and the association of CYP2C8*3 with variant CYP2C9 alleles. Methods Three hundred and fifty-five randomly selected Spanish Caucasians were screened for the common CYP2C8 and CYP2C9 mutations. The pharmacokinetics of (R)-ibuprofen were studied in 25 individuals grouped into different CYP2C8 genotypes. Results The allele frequency of CYP2C8*3 (0.17) was found to be higher than that reported for other Caucasian populations (P = 0.0001). The frequencies of CYP2C9*2 and CYP2C9*3 were 0.19 (0.16–0.21) and 0.10 (0.08–0.12), respectively. An association between CYP2C8*3 and CYP2C9*2 alleles was observed, occurring together at a frequency 2.4-fold higher than expected for a random association of alleles (P = 0.0001). The presence of the CYP2C8*3 allele was found to influence the pharmacokinetics of (R)-ibuprofen in a gene–dose effect manner. Thus, after administration of 400 mg ibuprofen, the plasma half-life (95% confidence intervals) for individuals with genotypes CYP2C8*1/*1, CYP2C8*1/*3 and CYP2C8*3/*3, was 2.0 h (1.8–2.2), 4.2 h (1.9–6.5; P < 0.05) and 9.0 h (7.8–10.2; P < 0.002), respectively. A statistically significant trend with respect to the number of variant CYP2C8*3 alleles was also observed for the area under the concentration-time curve (P < 0.025), and drug clearance (P < 0.03). Conclusion Polymorphism of the CYP2C8 gene was found to be common, with nearly 30% of the population studied carrying the variant CYP2C8*3 allele. The presence of the latter caused a significant effect on the disposition of (R)-ibuprofen. This suggests that a substantial proportion of Caucasian subjects may show alterations in the disposition of drugs that are CYP2C8 substrates. PMID:15606441

  16. TspanC8 tetraspanins differentially regulate the cleavage of ADAM10 substrates, Notch activation and ADAM10 membrane compartmentalization.

    PubMed

    Jouannet, Stéphanie; Saint-Pol, Julien; Fernandez, Laurent; Nguyen, Viet; Charrin, Stéphanie; Boucheix, Claude; Brou, Christel; Milhiet, Pierre-Emmanuel; Rubinstein, Eric

    2016-05-01

    The metalloprotease ADAM10 mediates the shedding of the ectodomain of various cell membrane proteins, including APP, the precursor of the amyloid peptide Aβ, and Notch receptors following ligand binding. ADAM10 associates with the members of an evolutionary conserved subgroup of tetraspanins, referred to as TspanC8, which regulate its exit from the endoplasmic reticulum. Here we show that 4 of these TspanC8 (Tspan5, Tspan14, Tspan15 and Tspan33) which positively regulate ADAM10 surface expression levels differentially impact ADAM10-dependent Notch activation and the cleavage of several ADAM10 substrates, including APP, N-cadherin and CD44. Sucrose gradient fractionation, single molecule tracking and quantitative mass-spectrometry analysis of the repertoire of molecules co-immunoprecipitated with Tspan5, Tspan15 and ADAM10 show that these two tetraspanins differentially regulate ADAM10 membrane compartmentalization. These data represent a unique example where several tetraspanins differentially regulate the function of a common partner protein through a distinct membrane compartmentalization. PMID:26686862

  17. 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

    ... TOLERANCES AND EXEMPTIONS FOR PESTICIDE CHEMICAL RESIDUES IN FOOD Exemptions From Tolerances § 180.1250 C8... a tolerance. The C8, C10, and C12 straight-chain fatty acid monoesters of glycerol (glycerol... of a tolerance in or on all food commodities when used in accordance with approved label rates...

  18. 40 CFR 180.1250 - C8, C10, and C12 fatty acid monoesters of glycerol and propylene glycol; exemption from the...

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... TOLERANCES AND EXEMPTIONS FOR PESTICIDE CHEMICAL RESIDUES IN FOOD Exemptions From Tolerances § 180.1250 C8... a tolerance. The C8, C10, and C12 straight-chain fatty acid monoesters of glycerol (glycerol... of a tolerance in or on all food commodities when used in accordance with approved label rates...

  19. 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

    ... TOLERANCES AND EXEMPTIONS FOR PESTICIDE CHEMICAL RESIDUES IN FOOD Exemptions From Tolerances § 180.1250 C8... a tolerance. The C8, C10, and C12 straight-chain fatty acid monoesters of glycerol (glycerol... of a tolerance in or on all food commodities when used in accordance with approved label rates...

  20. 40 CFR 180.1250 - C8, C10, and C12 fatty acid monoesters of glycerol and propylene glycol; exemption from the...

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... TOLERANCES AND EXEMPTIONS FOR PESTICIDE CHEMICAL RESIDUES IN FOOD Exemptions From Tolerances § 180.1250 C8... a tolerance. The C8, C10, and C12 straight-chain fatty acid monoesters of glycerol (glycerol... of a tolerance in or on all food commodities when used in accordance with approved label rates...

  1. CYP2J2 and CYP2C8 polymorphisms and coronary heart disease risk: the Atherosclerosis Risk in Communities (ARIC) study

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The cytochromes P450 epoxygenases CYP2J2 and CYP2C8 synthesize epoxyeicosatrienoic acids, which regulate endothelial function. We sought to determine if genetic variation in CYP2J2 and CYP2C8 was associated with coronary heart disease risk. We genotyped 2065 Atherosclerosis Risk in Communities stud...

  2. 26 CFR 31.3306(c)(8)-1 - Services in employ of religious, charitable, educational, or certain other organizations exempt...

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... performed by an employee in the employ of an organization described in section 3306(c)(8) as in effect... of which is carrying on propaganda, or otherwise attempting, to influence legislation, are excepted... section 3306(c)(8) as in effect before 1962. An organization which would be an organization of a...

  3. Analysis of the Functional Polymorphism in the Cytochrome P450 CYP2C8 Gene rs11572080 with Regard to Colorectal Cancer Risk

    PubMed Central

    Ladero, José M.; Agúndez, José A. G.; Martínez, Carmen; Amo, Gemma; Ayuso, Pedro; García-Martín, Elena

    2012-01-01

    In addition to the known effects on drug metabolism and response, functional polymorphisms of genes coding for xenobiotic-metabolizing enzymes (XME) play a role in cancer. Genes coding for XME act as low-penetrance genes and confer modest but consistent and significant risks for a variety of cancers related to the interaction of environmental and genetic factors. Consistent evidence supports a role for polymorphisms of the cytochrome P450 CYP2C9 gene as a protecting factor for colorectal cancer susceptibility. It has been shown that CYP2C8 and CYP2C9 overlap in substrate specificity. Because CYP2C8 has the common functional polymorphisms rs11572080 and rs10509681 (CYP2C8*3), it could be speculated that part of the findings attributed to CYP2C9 polymorphisms may actually be related to the presence of polymorphisms in the CYP2C8 gene. Nevertheless, little attention has been paid to the role of the CYP2C8 polymorphism in colorectal cancer. We analyzed the influence of the CYP2C8*3 allele in the risk of developing colorectal cancer in genomic DNA from 153 individuals suffering colorectal cancer and from 298 age- and gender-matched control subjects. Our findings do not support any effect of the CYP2C8*3 allele (OR for carriers of functional CYP2C8 alleles = 0.50 (95% CI = 0.16–1.59; p = 0.233). The absence of a relative risk related to CYP2C8*3 did not vary depending on the tumor site. We conclude that the risk of developing colorectal cancer does not seem to be related to the commonest functional genetic variation in the CYP2C8 gene. PMID:23420707

  4. Design of a powered elevator control system. [powered elevator system for modified C-8A aircraft for STOL operation

    NASA Technical Reports Server (NTRS)

    Glende, W. L. B.

    1974-01-01

    The design, fabrication and flight testing of a powered elevator system for the Augmentor Wing Jet STOL Research Aircraft (AWJSRA or Mod C-8A) are discussed. The system replaces a manual spring tab elevator control system that was unsatisfactory in the STOL flight regime. Pitch control in the AWJSRA is by means of a single elevator control surface. The elevator is used for both maneuver and trim control as the stabilizer is fixed. A fully powered, irreversible flight control system powered by dual hydraulic sources was designed. The existing control columns and single mechanical cable system of the AWJSRA have been retained as has been the basic elevator surface, except that the elevator spring tab is modified into a geared balance tab. The control surface is directly actuated by a dual tandem moving body actuator. Control signals are transmitted from the elevator aft quadrant to the actuator by a linkage system that includes a limited authority series servo actuator.

  5. Desorption of dimethylformamide from Zn4O(C8H4O4)3 framework

    NASA Astrophysics Data System (ADS)

    Zhang, Lei; Hu, Yun Hang

    2011-02-01

    Both dimethylformamide (DMF) and diethylformamide (DEF) are important solvents for the synthesis of Zn4O(C8H4O4)3 framework (MOF-5). It is generally recognized that DMF molecules can be completely displaced by CH2Cl2 during the synthesis of MOF-5. Herein, however, it was found that the DMF molecules inside the pores of the MOF-5 framework cannot be displaced by CH2Cl2. The desorption of the DMF molecules from the pores, which requires a temperature of 100 °C or above, is the first order with activation energy of 56.38 kJ/mol. In contrast, DEF molecules can be completely displaced by CH2Cl2 during the synthesis of MOF-5, because DEF molecules cannot penetrate into the pores of the MOF-5 paste.

  6. The oral mucosal and salivary microbial community of Behçet's syndrome and recurrent aphthous stomatitis

    PubMed Central

    Seoudi, Noha; Bergmeier, Lesley A.; Drobniewski, Francis; Paster, Bruce; Fortune, Farida

    2015-01-01

    Background Behçet's syndrome (BS) is a multisystem immune-related disease of unknown etiology. Recurrent aphthous stomatitis (RAS) is characterized by the presence of idiopathic oral ulceration without extraoral manifestation. The interplay between the oral microbial communities and the immune response could play an important role in the etiology and pathogenesis of both BS and RAS. Objective To investigate the salivary and oral mucosal microbial communities in BS and RAS. Methods Purified microbial DNA isolated from saliva samples (54 BS, 25 healthy controls [HC], and 8 RAS) were examined by the human oral microbe identification microarray. Cultivable salivary and oral mucosal microbial communities from ulcer and non-ulcer sites were identified by matrix-assisted laser desorption/ionization time-of-flight analysis. Mycobacterium spp. were detected in saliva and in ulcer and non-ulcer oral mucosal brush biopsies following culture on Lowenstein-Jensen slopes and Mycobacterial Growth Indicator Tubes. Results There was increased colonization with Rothia denticariosa of the non-ulcer sites of BS and RAS patients (p<0.05). Ulcer sites in BS were highly colonized with Streptococcus salivarius compared to those of RAS (p<0.05), and with Streptococcus sanguinis compared to HC (p<0.0001). Oral mucosa of HC were more highly colonized with Neisseria and Veillonella compared to all studied groups (p<0.0001). Conclusions Despite the uncertainty whether the reported differences in the oral mucosal microbial community of BS and RAS are of causative or reactive nature, it is envisaged that restoring the balance of the oral microbial community of the ulcer sites may be used in the future as a new treatment modality for oral ulceration. PMID:26037240

  7. Comparison of the Clinical Manifestations, Brain MRI and Prognosis between NeuroBehçet's Disease and Neuropsychiatric Lupus

    PubMed Central

    Cho, Byung-Sik; Kim, Hyun-Sook; Oh, Su-Jin; Ko, Hyeok-Jae; Yoon, Chong-Hyun; Jung, So-Lyung; Min, Do-June

    2007-01-01

    Background Neuropsychiatric systemic lupus erythematosus (NPSLE) shows some similarities to neuroBehçet's disease (NBD) in that both conditions have some analogous clinical features and they are both pathologically associated cerebral vasculopathy. This study compared the clinical manifestations, brain MRI findings and prognosis of NPSLE and NBD patients. Methods Forty three patients with NPSLE (n = 25) or NBD (n = 18), who were monitored at a single center, were enrolled in this study. We retrospectively analyzed the clinical and brain MRI data. The neuropsychiatric manifestations were classified in both groups according to the new American College of Rheumatology nomenclature for NPSLE. Results The diffuse symptoms that included mood disorders, psychosis, confusion, cognitive dysfunctions, generalized seizures and headaches other than migraine or cluster headaches were more commonly observed in the NPSLE patients, while the frequency of focal diseases such as cranial neuropathy tended to be higher in the NBD patients. The brain MRI revealed that the NBD patients had more abnormalities in the brain stem than did the NPSLE patients. Most of the patients improved, at least partially, after being treated with glucocorticoid and/or immune suppressants. However, the disease course differed significantly between the two groups. There were more episodic cases in the NPSLE group of patients, while there were more remittent cases in the NBD group of patients. Conclusion NPSLE had a tendency to cause diffuse neuropsychiatric manifestations, and it has a different predilection of brain lesions compared with NBD. The NBD patients showed a poorer outcome than did the NPSLE patients, suggesting that different therapeutic strategies for the two diseases need to be considered. PMID:17616022

  8. Current Status, Goals, and Research Agenda for Outcome Measures Development in Behçet Syndrome: Report from OMERACT 2014

    PubMed Central

    Hatemi, Gulen; Ozguler, Yesim; Direskeneli, Haner; Mahr, Alfred; Gul, Ahmet; Levi, Virna; Aydin, Sibel Z.; Mumcu, Gonca; Sertel-Berk, Ozlem; Stevens, Randall M.; Yazici, Hasan; Merkel, Peter A.

    2016-01-01

    Objective There is an unmet need for reliable, validated, and widely accepted outcomes and outcome measures for use in clinical trials in Behçet syndrome (BS). Our report summarizes initial steps taken by the Outcome Measures in Rheumatology (OMERACT) vasculitis working group toward developing a core set of outcome measures for BS according to the OMERACT methodology, including the OMERACT Filter 2.0, and discussions during the first meeting of the BS working group held during OMERACT 12 (2014). Methods During OMERACT 12, some of the important challenges in developing outcomes for BS were outlined and discussed, and a research agenda was drafted. Results Among topics discussed were the advantages and disadvantages of a composite measure for BS that evaluates several organs/organ systems; bringing patients and physicians together for discussions about how to assess disease activity; use of organ-specific measures developed for other diseases; and the inclusion of generic, disease-specific, or organ-specific measures. The importance of incorporating patients’ perspectives, concerns, and ideas into outcome measure development was emphasized. Conclusion The planned research agenda includes conducting a Delphi exercise among physicians from different specialties that are involved in the care of patients with BS and among patients with BS, with the aim of identifying candidate domains and subdomains to be assessed in randomized clinical trials of BS, and candidate items for a composite measure. The ultimate goal of the group is to develop a validated and widely accepted core set of outcomes and outcome measures for use in clinical trials in BS. PMID:26373563

  9. Molecular Dynamics Simulation Reveals the Selective Binding of Human Leukocyte Antigen Alleles Associated with Behçet's Disease

    PubMed Central

    Kongkaew, Sirilak; Yotmanee, Pathumwadee; Rungrotmongkol, Thanyada; Kaiyawet, Nopporn; Meeprasert, Arthitaya; Kaburaki, Toshikatsu; Noguchi, Hiroshi; Takeuchi, Fujio; Kungwan, Nawee; Hannongbua, Supot

    2015-01-01

    Behçet’s disease (BD), a multi-organ inflammatory disorder, is associated with the presence of the human leukocyte antigen (HLA) HLA-B*51 allele in many ethnic groups. The possible antigen involvement of the major histocompatibility complex class I chain related gene A transmembrane (MICA-TM) nonapeptide (AAAAAIFVI) has been reported in BD symptomatic patients. This peptide has also been detected in HLA-A*26:01 positive patients. To investigate the link of BD with these two specific HLA alleles, molecular dynamics (MD) simulations were applied on the MICA-TM nonapeptide binding to the two BD-associated HLA alleles in comparison with the two non-BD-associated HLA alleles (B*35:01 and A*11:01). The MD simulations were applied on the four HLA/MICA-TM peptide complexes in aqueous solution. As a result, stabilization for the incoming MICA-TM was found to be predominantly contributed from van der Waals interactions. The P2/P3 residue close to the N-terminal and the P9 residue at the C-terminal of the MICA-TM nonapeptide served as the anchor for the peptide accommodated at the binding groove of the BD associated HLAs. The MM/PBSA free energy calculation predicted a stronger binding of the HLA/peptide complexes for the BD-associated HLA alleles than for the non-BD-associated ones, with a ranked binding strength of B*51:01 > B*35:01 and A*26:01 > A*11:01. Thus, the HLAs associated with BD pathogenesis expose the binding efficiency with the MICA-TM nonapeptide tighter than the non-associated HLA alleles. In addition, the residues 70, 73, 99, 146, 147 and 159 of the two BD-associated HLAs provided the conserved interaction for the MICA-TM peptide binding. PMID:26331842

  10. Behçet's disease departs the 'Silk Road': a case report and brief review of literature with geographical comparison.

    PubMed

    Ahmed, Zohair; Rossi, Maria L; Yong, Sherri; Martin, Daniel K; Walayat, Saqib; Cashman, Michael; Tsoraides, Steven; Dhillon, Sonu

    2016-01-01

    Behçet's disease (BD) is a chronic multisystem inflammatory disease most prevalent in Eastern Asia and along the Mediterranean basin, an area referred to as the 'Silk Road'. The diagnosis of BD is largely based on the International Study Group (ISG) criteria, which are more specific than sensitive. ISG criteria do not include intestinal manifestations, a feature more commonly seen in the West. Intestinal BD is one of several findings that are not typically seen along the 'Silk Road'. Herein we report a rare case of intestinal BD and compare Western versus traditional BD. A 25-year-old male with a history of painful oral aphthous ulcers, pericarditis, and diffuse papulopustular rash presented to the emergency department with two terminal ileal perforations. Pathology demonstrated mucosal necrosis with active inflammation and no chronic inflammatory changes. Post-surgical laboratory studies showed an elevated c-reactive protein of 35.57 mg/dL, erythrocyte sedimentation rate of 82 mm/h, and a positive anti-Saccharomyces cerevisiae antibody. Rheumatological workup including ANA, RF, PR3 antibody, MPO antibody, ANCA, SSA and SSB, Smith antibody, SCL-70, and anti-Jo-1 antibodies were all negative. His pericarditis symptoms improved with colchicine and prednisone prior to discharge. Our patient did not meet the current ISG criteria for traditional BD; however, he clearly showed findings typically seen in Western patients with BD, which include intestinal manifestations, cardiac involvement, and lack of pathergy reaction and ocular changes. Our investigation demonstrates that the clinical manifestations common to this disorder vary among geographic and ethnic populations. Commonly used criteria for the diagnosis of BD may not be sensitive for some populations, such as Western BD, potentially leading to underdiagnoses and mismanagement. Recognition and select inclusion of these differences may be one way to assist with diagnosing Western BD in the future. As our knowledge

  11. The seroprevalence and salivary shedding of herpesviruses in Behçet's syndrome and recurrent aphthous stomatitis

    PubMed Central

    Seoudi, Noha; Bergmeier, Lesley A.; Hagi-Pavli, Eleni; Bibby, David; Fortune, Farida

    2015-01-01

    Background Behçet's syndrome (BS) is one of the multisystemic diseases that presents with oral ulceration and several other systemic manifestations including genital ulceration, folliculitis, erythema nodosum-like lesions, uveitis, and arthropathy. Ocular manifestation, central nervous system involvement, and gastrointestinal manifestation account for most of the complications of this disease, whereas orogenital ulceration and dermatological involvement affects the quality of life. The cause of the disease is not fully elucidated; however, herpesviruses have long been thought to play a pivotal role in the disease pathogenesis. Objective To investigate the seroprevalence and salivary shedding of herpesviruses in BS. Method The levels of specific immunoglobulin G in six different herpesviruses in serum samples collected from 54 BS, 28 healthy controls (HC), and 7 recurrent aphthous stomatitis (RAS) patients were investigated. Salivary viral load was also quantified for these viruses in matched saliva samples using quantitative real-time polymerase chain reaction. Results The BS had lower cytomegalovirus (CMV) IgG level in comparison to HC (p=0.0226) and RAS (p=0.0450). There was statistically significant higher salivary shedding of Epstein-Barr virus (EBV) in BS in comparison to HC (p=0.0052), but not RAS (p=0.3318). Conclusions A high EBV shedding was observed in both BS and RAS and a lower level of CMV IgG was observed in BS only. The reason for the observed lower level of CMV IgG in BS is not clear. However, one explanation might be a defect in the cross-talk between innate and adaptive immune responses which was suggested by a previously described defect in the toll-like receptor 1 and 2 heterodimer formation and function, this being the initial receptor sensing of CMV. PMID:26051327

  12. The IL-8 Gene Polymorphisms in Behçet's Disease Observed in Denizli Province of Turkey.

    PubMed

    Atalay, Ayfer; Arıkan, Sanem; Ozturk, Onur; Öncü, Mustafa; Tasli, Mehmet Levent; Duygulu, Seniz; Atalay, Erol Omer

    2016-05-01

    Behçet's disease is a multisystemic inflammatory disorder as a triad of symptoms including recurrent oral and genital aphthous ulceration and uveitis with unknown pathogenesis. IL-8, a proinflammatory cytokine, has been found increased in the active stage of BD. DNA samples were obtained from 88 patients with BD and 112 healthy control subjects in Denizli province of Turkey. All genotyping experiments of SNPs in IL-8 gene were performed using polymerase chain reaction-restriction fragment polymorphism. We found that IL-8 -845 T > C and -738 T > A sites are non-polymorphic. There were no differences in the polymorphisms of IL-8 +396 G/T, +781 C/T, and +1633 C/T sites except IL-8 -251 T > A in between patients and healthy controls. Analysis of IL-8 polymorphisms indicates that the distribution of frequencies seems to be associated with -251 T > A and gender, -251 T > A and erythema nodosum, -251 T > A and ocular involvement, +781 C > T and erythema nodosum, +396 G > T and pathergy positivity, and +1633 C > T and papulopustular lesion. We demonstrated that the frequencies of IL-8 haplotypes were significantly different with BD patients than control group. We found that the distribution of IL-8 haplotypes was significantly different with genital ulcers, ocular involvement, positive pathergy test, erythema nodosum, papulopustular lesions, and arthritis with BD patients than healthy control individuals. Our study suggests that IL-8 gene polymorphisms may affect susceptibility to BD and increase the risk of developing disease. In order to confirm and assess the association of IL-8 and other cytokine gene polymorphisms in the pathophysiology of BD, large cohort studies are needed. PMID:27101127

  13. Efficacy and safety profile of anti-interleukin-1 treatment in Behçet's disease: a multicenter retrospective study.

    PubMed

    Emmi, Giacomo; Talarico, Rosaria; Lopalco, Giuseppe; Cimaz, Rolando; Cantini, Fabrizio; Viapiana, Ombretta; Olivieri, Ignazio; Goldoni, Matteo; Vitale, Antonio; Silvestri, Elena; Prisco, Domenico; Lapadula, Giovanni; Galeazzi, Mauro; Iannone, Florenzo; Cantarini, Luca

    2016-05-01

    Growing data have provided encouraging results on the use of interleukin (IL)-1 inhibitors in Behçet's disease (BD). This study was aimed at reporting the largest experience with anti-IL-1 agents in BD patients. We evaluated 30 BD patients receiving treatment with anti-IL-1 agents. The primary aims of the study were to evaluate the efficacy of anakinra (ANA) and canakinumab (CAN) in a cohort of BD. The secondary aims were to evaluate the overall safety profile of the treatments, explore the timing of response to therapy and any adjustment of dosage and frequency of drugs studied, and investigate predictive factors of response to therapy. The frequency of first line therapy was 90 % with ANA and 10 % with CAN. The overall number of subjects in complete remission after 12 months of therapy with anti-IL-1 drugs was 13: 6 maintained the initial therapy regimen, 1 maintained the same initial anti-IL-1 drug with further therapeutic adjustments, and the remaining 6 shifted from ANA to CAN. Among them, 3 used CAN for at least 12 months without therapeutic adjustments, 1 had therapeutic adjustments, and 3 had an overall history of a 12-month complete remission. Adverse events (AEs) were reported in 15 % patients who received ANA, represented in all cases by local cutaneous reactions, while no AE were observed in patients who received CAN; we did not observe any serious AEs (SAEs) during the follow-up period. Our data have confirmed that the use of anti-IL-1β drugs is efficacious and safe with an overall acceptable retention on treatment. PMID:26156661

  14. Retrospective Exposure Estimation and Predicted versus Observed Serum Perfluorooctanoic Acid Concentrations for Participants in the C8 Health Project

    PubMed Central

    Vieira, Verónica M.; Ryan, P. Barry; Steenland, Kyle; Bartell, Scott M.

    2011-01-01

    Background: People living or working in eastern Ohio and western West Virginia have been exposed to perfluorooctanoic acid (PFOA) released by DuPont Washington Works facilities. Objectives: Our objective was to estimate historical PFOA exposures and serum concentrations experienced by 45,276 non-occupationally exposed participants in the C8 Health Project who consented to share their residential histories and a 2005–2006 serum PFOA measurement. Methods: We estimated annual PFOA exposure rates for each individual based on predicted calibrated water concentrations and predicted air concentrations using an environmental fate and transport model, individual residential histories, and maps of public water supply networks. We coupled individual exposure estimates with a one-compartment absorption, distribution, metabolism, and excretion (ADME) model to estimate time-dependent serum concentrations. Results: For all participants (n = 45,276), predicted and observed median serum concentrations in 2005–2006 are 14.2 and 24.3 ppb, respectively [Spearman’s rank correlation coefficient (rs) = 0.67]. For participants who provided daily public well water consumption rate and who had the same residence and workplace in one of six municipal water districts for 5 years before the serum sample (n = 1,074), predicted and observed median serum concentrations in 2005–2006 are 32.2 and 40.0 ppb, respectively (rs = 0.82). Conclusions: Serum PFOA concentrations predicted by linked exposure and ADME models correlated well with observed 2005–2006 human serum concentrations for C8 Health Project participants. These individualized retrospective exposure and serum estimates are being used in a variety of epidemiologic studies being conducted in this region. PMID:21813367

  15. Investigation of the in vitro toxicological properties of the synthetic cannabimimetic drug CP-47,497-C8.

    PubMed

    Koller, Verena J; Auwärter, Volker; Grummt, Tamara; Moosmann, Bjoern; Mišík, Miroslav; Knasmüller, Siegfried

    2014-06-01

    Cannabicyclohexanol (CP-47,497-C8) is a representative of a group of cannabimimetic cyclohexylphenols which is added to herbal mixtures as a cannabis substitute since 2008. Although in the beginning CP-47,497-C8 was the main ingredient of "Spice" and similar products, it was partly replaced by aminoalkylindole-type cannabinoid receptor agonists like JWH-018, JWH-073 or JWH-250, but never completely disappeared from the market. Since information on its toxicological properties is scarce, we investigated the effects of the drug in human derived cell lines. The cytotoxic effects were studied in a panel of assays (SRB, XTT, LDHe and NR tests) in a buccal derived (TR146) and a liver derived (HepG2) cell line. The strongest effects were seen in the two former assays at levels ≥ 7.5 μM indicating that the compound interferes with protein synthesis and causes membrane damage. In additional comet assays, DNA damage was detected at levels ≥10 μM. Experiments with lesion specific enzymes showed that these effects are not due to oxidative damage of DNA bases. The negative findings obtained in Salmonella/microsome assays and the positive results of micronucleus tests with the cell lines indicate that the compound does not cause gene mutations but acts on the chromosomal level. In contrast to other synthetic cannabinoids, no indication for estrogenic/antiestrogenic properties was seen in a luciferase assay with bone marrow derived U2-OS cells. In conclusion, our findings show that the drug has only weak cytotoxic properties. However, the induction of chromosomal damage indicates that it may cause adverse effects in users due to its impact on the stability of the genetic material. PMID:24686252

  16. Impact of Exposure Uncertainty on the Association between Perfluorooctanoate and Preeclampsia in the C8 Health Project Population

    PubMed Central

    Avanasi, Raghavendhran; Shin, Hyeong-Moo; Vieira, Verónica M.; Savitz, David A.; Bartell, Scott M.

    2015-01-01

    Background Uncertainty in exposure estimates from models can result in exposure measurement error and can potentially affect the validity of epidemiological studies. We recently used a suite of environmental models and an integrated exposure and pharmacokinetic model to estimate individual perfluorooctanoate (PFOA) serum concentrations and assess the association with preeclampsia from 1990 through 2006 for the C8 Health Project participants. Objectives The aims of the current study are to evaluate impact of uncertainty in estimated PFOA drinking-water concentrations on estimated serum concentrations and their reported epidemiological association with preeclampsia. Methods For each individual public water district, we used Monte Carlo simulations to vary the year-by-year PFOA drinking-water concentration by randomly sampling from lognormal distributions for random error in the yearly public water district PFOA concentrations, systematic error specific to each water district, and global systematic error in the release assessment (using the estimated concentrations from the original fate and transport model as medians and a range of 2-, 5-, and 10-fold uncertainty). Results Uncertainty in PFOA water concentrations could cause major changes in estimated serum PFOA concentrations among participants. However, there is relatively little impact on the resulting epidemiological association in our simulations. The contribution of exposure uncertainty to the total uncertainty (including regression parameter variance) ranged from 5% to 31%, and bias was negligible. Conclusions We found that correlated exposure uncertainty can substantially change estimated PFOA serum concentrations, but results in only minor impacts on the epidemiological association between PFOA and preeclampsia. Citation Avanasi R, Shin HM, Vieira VM, Savitz DA, Bartell SM. 2016. Impact of exposure uncertainty on the association between perfluorooctanoate and preeclampsia in the C8 Health Project population

  17. Pulmonary aneurysms and intracardiac thrombi due to Behçet's disease in an African-American adolescent with oculocutaneous albinism.

    PubMed

    Endo, Lois M; Rowe, Steven M; Romp, Robb L; Buckmaster, Mark A; Atkinson, T Prescott

    2007-09-01

    Behçet's disease (BD) is a systemic vasculitis that may involve a variety of organs. We describe a girl with oculocutaneous albinism (OCA) who, on initial evaluation for popliteal artery occlusion, was noted to have multiple cardiac thrombi. She later developed hemoptysis, which was the result of bilateral pulmonary artery aneurysms. Her clinical picture was consistent with BD. She was initially treated with prednisone and cyclophosphamide, followed by maintenance therapy with infliximab. This case describes a unique patient with OCA who developed BD with large pulmonary aneurysms and has remained stable for over 1 year while receiving infliximab. PMID:17047893

  18. Mutations in the gene encoding C8orf38 block complex I assembly by inhibiting production of the mitochondria-encoded subunit ND1.

    PubMed

    McKenzie, Matthew; Tucker, Elena J; Compton, Alison G; Lazarou, Michael; George, Christa; Thorburn, David R; Ryan, Michael T

    2011-12-01

    The assembly of complex I (NADH-ubiquinone oxidoreductase) is a complicated process, requiring the integration of 45 subunits encoded by both nuclear and mitochondrial DNAs into a structure of approximately 1 MDa. A number of "assembly factors" that aid complex I biogenesis have recently been described, including C8orf38. This protein was identified as an assembly factor by its evolutionary conservation in organisms containing complex I and by a C8orf38 mutation in a patient presenting with Leigh syndrome and isolated complex I deficiency. In this report, we have undertaken the characterization of C8orf38 and its role in complex I assembly. Analysis of mitochondria from fibroblasts of a patient harboring a C8orf38 mutation showed almost undetectable levels of steady-state complex I and defective biogenesis of the mtDNA-encoded subunit ND1. Complementation with wild-type C8orf38 restored the levels of both ND1 and complex I, confirming the C8orf38 mutation as the cause of the complex I defect in the patient. In the absence of ND1 in patient cells, early- and mid-stage intermediate complexes were still formed; however, assembly of late-stage intermediates was impaired, indicating a convergence point in the assembly process. While C8orf38 appears to behave at a step in complex I biogenesis similar to that of the assembly factor C20orf7, complementation studies showed that both proteins are required for ND1 synthesis/stabilization. We conclude that C8orf38 is a crucial factor required for the translation and/or integration of ND1 into an early-stage assembly intermediate and that mutation of C8orf38 disrupts the initial stages of complex I biogenesis. PMID:22019594

  19. Effect of preduodenal lipase inhibition in suckling rats on dietary octanoic acid (C8:0) gastric absorption and plasma octanoylated ghrelin concentration.

    PubMed

    Lemarié, F; Cavalier, J-F; Garcia, C; Boissel, F; Point, V; Catheline, D; Legrand, P; Carrière, F; Rioux, V

    2016-09-01

    Part of medium chain fatty acids (MCFAs) coming from dietary triglycerides (TGs) can be directly absorbed through the gastric mucosa after the action of preduodenal lipase (lingual lipase in the rat). MCFA gastric absorption, particularly that of octanoic acid (C8:0), may have a physiological importance in the octanoylation of ghrelin, the orexigenic gastric peptide acting as an endogenous ligand of the hypothalamic growth hormone secretagogue receptor 1a (GHSR-1a). However, the amount of C8:0 absorbed in the stomach and its metabolic fate still haven't been clearly characterized. The purpose of the present study was to further characterize and quantify the importance of preduodenal lipase activity on the release and gastric absorption of dietary C8:0 and on the subsequent ghrelin octanoylation in the stomach mucosa. Fifteen days old rats received fat emulsions containing triolein or [1,1,1-(13)C]-Tri-C8:0 and a specific inhibitor of preduodenal lipase, 5-(2-(benzyloxy)ethoxy)-3-(3-phenoxyphenyl)-1,3,4-oxadiazol-2(3H)-one or BemPPOX. The fate of the (13)C-C8:0 was followed in rat tissues after 30 and 120min of digestion and octanoylated ghrelin was measured in the plasma. This work (1) demonstrates that part of C8:0 coming from Tri-C8:0 is directly absorbed at the gastric level, (2) allows the estimation of C8:0 gastric absorption level (1.3% of the (13)C-C8:0 in sn-3 position after 30min of digestion), as well as (3) the contribution of rat lingual lipase to total lipolysis and to duodenal absorption of dietary FAs (at least 30%), (4) shows no short-term effect of dietary Tri-C8:0 consumption and subsequent increase of C8:0 gastric tissue content on plasma octanoylated ghrelin concentration. PMID:27317984

  20. Investigation of the in vitro toxicological properties of the synthetic cannabimimetic drug CP-47,497-C8

    SciTech Connect

    Koller, Verena J.; Auwärter, Volker; Grummt, Tamara; Moosmann, Bjoern; Mišík, Miroslav; Knasmüller, Siegfried

    2014-06-01

    Cannabicyclohexanol (CP-47,497-C8) is a representative of a group of cannabimimetic cyclohexylphenols which is added to herbal mixtures as a cannabis substitute since 2008. Although in the beginning CP-47,497-C8 was the main ingredient of “Spice” and similar products, it was partly replaced by aminoalkylindole-type cannabinoid receptor agonists like JWH-018, JWH-073 or JWH-250, but never completely disappeared from the market. Since information on its toxicological properties is scarce, we investigated the effects of the drug in human derived cell lines. The cytotoxic effects were studied in a panel of assays (SRB, XTT, LDHe and NR tests) in a buccal derived (TR146) and a liver derived (HepG2) cell line. The strongest effects were seen in the two former assays at levels ≥ 7.5 μM indicating that the compound interferes with protein synthesis and causes membrane damage. In additional comet assays, DNA damage was detected at levels ≥ 10 μM. Experiments with lesion specific enzymes showed that these effects are not due to oxidative damage of DNA bases. The negative findings obtained in Salmonella/microsome assays and the positive results of micronucleus tests with the cell lines indicate that the compound does not cause gene mutations but acts on the chromosomal level. In contrast to other synthetic cannabinoids, no indication for estrogenic/antiestrogenic properties was seen in a luciferase assay with bone marrow derived U2-OS cells. In conclusion, our findings show that the drug has only weak cytotoxic properties. However, the induction of chromosomal damage indicates that it may cause adverse effects in users due to its impact on the stability of the genetic material. - Highlights: • We tested the toxic properties of a synthetic cannabinoid. • Acute cytotoxic effects were detected with doses ≥ 7 μM. • No hormonal effects were found. • DNA damage was detected at levels ≥ 10 μM in comet assay and micronucleus tests. • Effects in directly

  1. A novel pentiptycene bis(crown ether)-based [2](2)rotaxane whose two DB24C8 rings act as flapping wings of a butterfly.

    PubMed

    Ma, Ying-Xian; Meng, Zheng; Chen, Chuan-Feng

    2014-04-01

    A novel [2](2)rotaxane based on pentiptycene-derived bis(crown ether) can be efficiently synthesized via a "click chemistry" method and the subsequent N-methylation. Due to the different affinities of DB24C8 with the ammonium and triazolium stations, the wing-flapping movement of the DB24C8 "wings" in the [2](2)rotaxane can be easily achieved by acid/base stimulus. PMID:24635015

  2. Association of VDR ApaI and TaqI Gene Polymorphisms with the Risk of Scleroderma and Behçet's Disease.

    PubMed

    Kamal, Asmaa; Gamal, Sherif M; Elgengehy, Fatema T; Alkemary, Alkhateeb K; Siam, Ibrahem

    2016-08-01

    Vitamin D deficiency and vitamin D receptor (VDR) gene polymorphisms have been reported in autoimmune diseases. However, their role in Behçet's disease (BD) and scleroderma remains inconclusive. Our aim was to evaluate vitamin D receptor (ApaI, TaqI) gene polymorphisms in relation to Behçet's disease and scleroderma in Egyptians. The study was conducted on 54 patients with BD, 30 scleroderma patients, and 60 healthy control subjects. VDR (ApaI, TaqI) gene polymorphisms were investigated using polymerase chain reaction-restriction fragment length polymorphism technique. The "a" allele of ApaI (A/a) polymorphism was significantly associated with increased BD risk (OR = 2.09, 95% CI = 1.18-3.71, p = 0.011), while the TaqI "tt" genotype was significantly lower in BD patients as compared to control subjects (OR = 0.35, 95% CI = 0.13-0.9, p = 0.026). Carriage of "aT" VDR haplotype was significantly associated with higher BD risk (OR = 2.28, 95% = 1.14-4.56, p = 0.022). In conclusion, our findings suggest that VDR gene polymorphisms have a significant association with BD in Egyptian patients. PMID:27409400

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

    PubMed Central

    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. PMID:26722585

  4. Ulcère de jambe récidivant et surinfecté au cours de la maladie de Behçet

    PubMed Central

    Salem, Bouomrani; Ichrak, Kilani; Hanène, Nouma; Safouane, Chebbi; Maher, Béji

    2013-01-01

    Parmi les manifestations cutanées de la maladie de Behçet, les ulcères de jambes sont exceptionnels mais gardent une implication pronostique fonctionnelle importante surtout dans les formes récidivantes et surinfectées. Nous rapportons l'observation d'un patient âgé de 42 ans porteur de maladie de Behçet depuis l’âge de 27 ans qui fût exploré pour ulcères de jambes bilatéraux, récidivants et invalidants nécessitant l'hospitalisation à plusieurs reprises. A chaque fois les récidives de l'ulcère s'associaient à une poussée cutanéo-muqueuse de la maladie avec notion d'arrêt intempestif de traitement. Il a présenté plusieurs épisodes de surinfection nécessitant le recours aux antibiotiques. Le doppler veineux et artériel ne montraient ni signes d'insuffisance veineuse ni d'artériopathie sous-jacentes. Sous antibiothérapie, en plus des soins locaux et la reprise de la colchicine et des corticostéroïdes, l’évolution se faisait vers la cicatrisation complète des ulcérations mais les récidives étaient fréquentes. PMID:23785544

  5. Glucuronidation converts clopidogrel to a strong time-dependent inhibitor of CYP2C8: a phase II metabolite as a perpetrator of drug-drug interactions.

    PubMed

    Tornio, A; Filppula, A M; Kailari, O; Neuvonen, M; Nyrönen, T H; Tapaninen, T; Neuvonen, P J; Niemi, M; Backman, J T

    2014-10-01

    Cerivastatin and repaglinide are substrates of cytochrome P450 (CYP)2C8, CYP3A4, and organic anion-transporting polypeptide (OATP)1B1. A recent study revealed an increased risk of rhabdomyolysis in patients using cerivastatin with clopidogrel, warranting further studies on clopidogrel interactions. In healthy volunteers, repaglinide area under the concentration-time curve (AUC(0-∞)) was increased 5.1-fold by a 300-mg loading dose of clopidogrel and 3.9-fold by continued administration of 75 mg clopidogrel daily. In vitro, we identified clopidogrel acyl-β-D-glucuronide as a potent time-dependent inhibitor of CYP2C8. A physiologically based pharmacokinetic model indicated that inactivation of CYP2C8 by clopidogrel acyl-β-D-glucuronide leads to uninterrupted 60-85% inhibition of CYP2C8 during daily clopidogrel treatment. Computational modeling resulted in docking of clopidogrel acyl-β-D-glucuronide at the CYP2C8 active site with its thiophene moiety close to heme. The results indicate that clopidogrel is a strong CYP2C8 inhibitor via its acyl-β-D-glucuronide and imply that glucuronide metabolites should be considered potential inhibitors of CYP enzymes. PMID:24971633

  6. Estimated pKa values for the environmentally relevant C1 through C8 perfluorinated sulfonic acid isomers.

    PubMed

    Rayne, Sierra; Forest, Kaya

    2016-10-14

    In order to estimate isomer-specific acidity constants (pKa) for the perfluorinated sulfonic acid (PFSA) environmental contaminants, the parameterization method 6 (PM6) pKa prediction method was extensively validated against a wide range of carbon oxyacids and related sulfonic/sulfinic acids. Excellent pKa prediction performance was observed for the carbon oxyacids using the PM6 method, but this approach was found to have a severe positive bias for sulfonic/sulfinic acids. To overcome this obstacle, a correlation was developed between non-adjusted PM6 pKa values and the corresponding experimentally obtained/estimated acidity constants for a range of representative alkyl, aryl and halogen-substituted sulfonic acids. Application of this correction to the PM6 values allows for extension of this computational method to a new acid functional group. When used to estimate isomer-specific pKa values for the C1 through C8 PFSAs, the modified PM6 approach suggests an adjusted pKa range from -5.3 to -9.0, indicating that all members of this class of well-known environmental contaminants will be effectively completely dissociated in aquatic systems. PMID:27389973

  7. Al2O3-Phosphated Green Catalysts with High Selectivity to Ecological Gasoline C8= by Dimerization of Isobutene.

    PubMed

    Mantilla, Angeles; Tzompantzi, Francisco; Morales-Mendoza, Getsemaní; Jácome-Acatitla, Gabriela; Gómez, Ricardo

    2015-09-01

    In this paper, phosphated-alumina prepared from boehmite and phosphoric acid (1, 4, and 6 mmol of PO4(3-)) is proposed as a good alternative catalyst to obtain ecological gasoline by the reaction of dimerization of butenes in gas phase using a flow reactor and mild conditions (60 degrees C and a C4/C4= molar ratio = 1). XRD spectra of the samples showed the formation of the gamma-alumina phase in the solids. BET specific surface area values of the bare alumina were not notably modified when these materials were phosphate, from 180-m2/g to 170 m2/g. All the solids are mesoporous structured materials. FTIR pyridine-adsorption spectra showed the formation of strong Lewis acid sites, which remains stable even at desorption temperatures above 300 degrees C. Brönsted acid sites were not observed on the materials. The phosphated-alumina catalysts were active for the dimerization of isobutene in mild conditions and 100% selectivitiy to C8= olefins was reached without the presence of olefinic compounds with higher molecular weight (trimers, tetramers). PMID:26716319

  8. The metabolism and distribution of sup 14 C-8N sup 6 -benzyladenine in lettuce seeds and seedlings

    SciTech Connect

    Seeber, R.G. Jr.

    1989-01-01

    This investigation sought to follow the uptake of the cytokinin, {sup 14}C-8N{sup 6}-benzyladenine (BAP), by lettuce seeds through time, trace the movement of the metabolites through several areas of the seedling, and identify the BAP metabolites. Lettuce seeds (Lactuca sativa L. cv. Grand Rapids) were exposed to a two hour pulse of the radioactive BAP. These seeds were harvested at 4 hour intervals from 2-48 hours. Seedlings incubated from 36-48 hours were cut in two; root, stem, shoot tip and seed coats. Each of these groups were extracted in 70% methanol and their radioactive isolated by high performance liquid chromatography. Radioactive fractions were pooled and reduced for further analysis by thin layer chromatography. The major compound identified throughout the time periods was BAP, exclusively found from 2-20 hours. BAP riboside was found in addition to BAP from 24-32 hours. The 40 and 44 hour extracts contained BAP and its riboside in the shoot and BAP in the seed coat. The 48 hours extract contained BAP and its riboside in both the shoot tip and the seed coat. This study produced information on the following points. A cytokinin exposure of 2 hours or less is needed to break dormancy in these seeds.

  9. Novel myokine: irisin may be an independent predictor for subclinic atherosclerosis in Behçet's disease

    PubMed Central

    Icli, Abdullah; Cure, Erkan; Cumhur Cure, Medine; Uslu, Ali Ugur; Balta, Sevket; Arslan, Sevket; Sakiz, Davut; Kucuk, Adem

    2016-01-01

    Behçet's disease (BD) is a vasculitic and inflammatory disease causing endothelial dysfunction. Irisin is a metabolic hormone related to insulin resistance and endothelial functions. In this study, we investigated the relationship between irisin and carotid intima-media thickness (cIMT), which is a marker of atherosclerosis in patients with BD. 48 patients with BD and 50 healthy individuals were enrolled in the study. Disease severity was evaluated by BD current activity form. Irisin, glucose, insulin, C reactive protein, erythrocyte sedimentation rate and lipid panel were examined in all patients. Homeostasis Model Assessment of Insulin Resistance (HOMA-IR) was used to calculate insulin resistance. A simple and inexpensive cIMT test was used as indicator of atherosclerosis. cIMT was 0.62 (0.45–1.05) mm in the patients, while it was 0.38 (0.25–0.65) mm in the control group (p<0.001). Irisin value was found to be 197.3 (24.8–834.2) ng/mL in the control group, while it was 85.4 (4.7–471.1) ng/mL in the patient group (p=0.007). There was a negative correlation between irisin level and cIMT (r=−0.511, p<0.001) and HOMA-IR (r=−0.371, p=0.009). Decreased irisin levels (OR 0.996, 95% CI 0.992 to 1.000, p=0.041), male gender (OR 7.634, 95% CI 1.415 to 41.191, p=0.018), and HOMA-IR (OR 2.596, 95% CI 1.451 to 4.643, p=0.001) are independent risk factors for cIMT in patients with BD. We detected a very strong relationship between cIMT, which is an indicator of subclinical atherosclerosis, and decreased irisin levels in patients with BD. BD is characterized by chronic inflammation, and low serum irisin levels in BD may be related to atherosclerosis. PMID:26941246

  10. VUV and soft x-ray ionization of a plant volatile: Vanillin (C8H8O3).

    PubMed

    Betancourt, A Moreno; Coutinho, L H; Bernini, R B; de Moura, C E V; Rocha, A B; de Souza, G G B

    2016-03-21

    Plant volatiles are emitted by plants in response to several forms of stress, including interaction with energetic photons. In the present work, we discuss the interaction of extreme UV and soft X-ray photons with a plant volatile, vanillin. The single and double (multiple) ionization of the vanillin molecule have been studied for the first time using time-of-flight mass spectrometry and VUV and soft X-ray photons (synchrotron radiation, at 12.0 eV, 21.2 eV, 130 eV, 310 eV, 531 eV, and 550 eV). At 12.0 and 21.2 eV, only singly charged species are observed and the parent ion, C8H8O3 (+), is the dominant species. Energy differences for some selected fragments were calculated theoretically in this energy region. At 130 eV, direct double and triple ionization of the valence electrons may occur. The fragmentation increases and CHO(+) becomes one of the main cations in the mass spectrum. The molecular ion is still the dominant species, but other fragments, such as C6H5O(+), begin to present similar intensities. At 310 eV, C 1s electrons may be ionized and Auger processes give rise to dissociative doubly ionized cations. Ionization around the O 1s edge has been studied both at the 531 eV resonance and above the ionization edge. Resonant and normal Auger processes play a significant role in each case and a large fragmentation of the molecule is observed at both photon energies, with intense fragments such as CHO(+) and CH3 (+) being clearly observed. A near edge X-ray absorption fine structure spectrum of the vanillin molecule was obtained around the O 1s ionization threshold. In addition, the fragmentation of vanillin has also been studied using a fast beam of electrons (800 eV), for the sake of comparison. PMID:27004874

  11. VUV and soft x-ray ionization of a plant volatile: Vanillin (C8H8O3)

    NASA Astrophysics Data System (ADS)

    Betancourt, A. Moreno; Coutinho, L. H.; Bernini, R. B.; de Moura, C. E. V.; Rocha, A. B.; de Souza, G. G. B.

    2016-03-01

    Plant volatiles are emitted by plants in response to several forms of stress, including interaction with energetic photons. In the present work, we discuss the interaction of extreme UV and soft X-ray photons with a plant volatile, vanillin. The single and double (multiple) ionization of the vanillin molecule have been studied for the first time using time-of-flight mass spectrometry and VUV and soft X-ray photons (synchrotron radiation, at 12.0 eV, 21.2 eV, 130 eV, 310 eV, 531 eV, and 550 eV). At 12.0 and 21.2 eV, only singly charged species are observed and the parent ion, C8H8O3+, is the dominant species. Energy differences for some selected fragments were calculated theoretically in this energy region. At 130 eV, direct double and triple ionization of the valence electrons may occur. The fragmentation increases and CHO+ becomes one of the main cations in the mass spectrum. The molecular ion is still the dominant species, but other fragments, such as C6H5O+, begin to present similar intensities. At 310 eV, C 1s electrons may be ionized and Auger processes give rise to dissociative doubly ionized cations. Ionization around the O 1s edge has been studied both at the 531 eV resonance and above the ionization edge. Resonant and normal Auger processes play a significant role in each case and a large fragmentation of the molecule is observed at both photon energies, with intense fragments such as CHO+ and CH3+ being clearly observed. A near edge X-ray absorption fine structure spectrum of the vanillin molecule was obtained around the O 1s ionization threshold. In addition, the fragmentation of vanillin has also been studied using a fast beam of electrons (800 eV), for the sake of comparison.

  12. Perfluorooctanoic acid, perfluorooctanesulfonate, and serum lipids in children and adolescents: results from the C8 Health Project

    PubMed Central

    Frisbee, Stephanie J.; Shankar, Anoop; Knox, Sarah S.; Steenland, Kyle; Savitz, David A.; Fletcher, Tony; Ducatman, Alan M.

    2011-01-01

    Objective Perfluorooctanoic acid (PFOA) and perfluorooctanesulfonate (PFOS) are man-made compounds with widespread presence in human sera. In previous occupational and adult studies, PFOA and PFOS have been positively associated with serum lipids. Our objective is to interrogate the association between PFOA and PFOS and serum lipids in children. Design Cross-sectional community-based study. Setting Mid-Ohio river valley. Participants 12,476 children included in the C8 Health Project, resultant from the pre-trial settlement of a class action lawsuit pursuant to PFOA contamination of the drinking water supply. Main Outcome Measures Serum lipids (total, HDL, and LDL cholesterol, and fasting triglycerides). Results Mean serum PFOA and PFOS concentrations were 69.2±111.9 ng/mL and 22.7±12.6 ng/mL. In linear regression after adjustment for covariables, PFOA was significantly associated with increased total and LDL cholesterol, and PFOS was significantly associated with increased total, HDL, and LDL cholesterol. In GLM ANCOVA analysis, between the 1st—5th quintiles of PFOA there was a 4.6 mg/dL and 3.8 mg/dL increase in the adjusted mean of total and LDL cholesterol, and an 8.5 mg/dL and 5.8 mg/dL increase in the adjusted mean for total and LDL cholesterol between the 1st—5th quintiles of PFOS. Increases were 10 mg/dL for some age- and gender-group strata. Observed effects were non-linear, with larger increases in total and LDL cholesterol occurring the lowest range of particularly PFOA. Conclusions While the epidemiologic and cross-sectional nature of the current study limit causal inferences, the consistent observed associations between increasing PFOA and PFOS and elevated total and LDL cholesterol warrant further study. PMID:20819969

  13. Dietary Caprylic Acid (C8:0) Does Not Increase Plasma Acylated Ghrelin but Decreases Plasma Unacylated Ghrelin in the Rat

    PubMed Central

    Lemarié, Fanny; Beauchamp, Erwan; Dayot, Stéphanie; Duby, Cécile; Legrand, Philippe; Rioux, Vincent

    2015-01-01

    Focusing on the caprylic acid (C8:0), this study aimed at investigating the discrepancy between the formerly described beneficial effects of dietary medium chain fatty acids on body weight loss and the C8:0 newly reported effect on food intake via ghrelin octanoylation. During 6 weeks, Sprague-Dawley male rats were fed with three dietary C8:0 levels (0, 8 and 21% of fatty acids) in three experimental conditions (moderate fat, caloric restriction and high fat). A specific dose-response enrichment of the stomach tissue C8:0 was observed as a function of dietary C8:0, supporting the hypothesis of an early preduodenal hydrolysis of medium chain triglycerides and a direct absorption at the gastric level. However, the octanoylated ghrelin concentration in the plasma was unchanged in spite of the increased C8:0 availability. A reproducible decrease in the plasma concentration of unacylated ghrelin was observed, which was consistent with a decrease in the stomach preproghrelin mRNA and stomach ghrelin expression. The concomitant decrease of the plasma unacylated ghrelin and the stability of its acylated form resulted in a significant increase in the acylated/total ghrelin ratio which had no effect on body weight gain or total dietary consumption. This enhanced ratio measured in rats consuming C8:0 was however suspected to increase (i) growth hormone (GH) secretion as an increase in the GH-dependent mRNA expression of the insulin like growth Factor 1 (IGF-1) was measured (ii) adipocyte diameters in subcutaneous adipose tissue without an increase in the fat pad mass. Altogether, these results show that daily feeding with diets containing C8:0 increased the C8:0 level in the stomach more than all the other tissues, affecting the acylated/total ghrelin plasma ratio by decreasing the concentration of circulating unacylated ghrelin. However, these modifications were not associated with increased body weight or food consumption. PMID:26196391

  14. 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. PMID:26551762

  15. Identification of putative substrates for cynomolgus monkey cytochrome P450 2C8 by substrate depletion assays with 22 human P450 substrates and inhibitors.

    PubMed

    Hosaka, Shinya; Murayama, Norie; Satsukawa, Masahiro; Uehara, Shotaro; Shimizu, Makiko; Iwasaki, Kazuhide; Iwano, Shunsuke; Uno, Yasuhiro; Yamazaki, Hiroshi

    2016-07-01

    Cynomolgus monkeys are widely used in drug developmental stages as non-human primate models. Previous studies used 89 compounds to investigate species differences associated with cytochrome P450 (P450 or CYP) function that reported monkey specific CYP2C76 cleared 19 chemicals, and homologous CYP2C9 and CYP2C19 metabolized 17 and 30 human CYP2C9 and/or CYP2C19 substrates/inhibitors, respectively. In the present study, 22 compounds selected from viewpoints of global drug interaction guidances and guidelines were further evaluated to seek potential substrates for monkey CYP2C8, which is highly homologous to human CYP2C8 (92%). Amodiaquine, montelukast, quercetin and rosiglitazone, known as substrates or competitive inhibitors of human CYP2C8, were metabolically depleted by recombinant monkey CYP2C8 at relatively high rates. Taken together with our reported findings of the slow eliminations of amodiaquine and montelukast by monkey CYP2C9, CYP2C19 and CYP2C76, the present results suggest that these at least four chemicals may be good marker substrates for monkey CYP2C8. Copyright © 2016 John Wiley & Sons, Ltd. PMID:26581561

  16. Evaluation of the acute behavioral effects and abuse potential of a C8-C9 isoparaffin solvent.

    PubMed

    Balster, R L; Bowen, S E; Evans, E B; Tokarz, M E

    1997-07-01

    We hypothesized that the abuse potential of certain types of inhalants could be evaluated in animals by determining the overlap in their profile of behavioral effects with that of CNS depressant drugs and other depressant-like abused inhalants. For our first attempt in evaluating a solvent with an unknown abuse potential we tested ISOPAR-E. ISOPAR-E is a mixture of predominantly C8-C9 isoparaffinic hydrocarbons that is being used more and more frequently as a solvent in industrial and consumer products, including, but not limited to, typewriter correction fluids. Presently, nothing is known about the potential for abuse of products containing this solvent. In the present studies, we compared the volatility of ISOPAR-E and the abused solvent 1,1,1-trichloroethane (TCE) in our exposure systems. Additionally, five behavioral procedures were conducted in mice to compare the effects of the two compounds. The results demonstrate that: (1) ISOPAR-E was less volatile than TCE; (2) ISOPAR-E produced a somewhat different profile of effects than did TCE as assessed with a functional observational battery; (3) unlike TCE, ISOPAR-E did not affect performance on tests of motor coordination; (4) TCE and ISOPAR-E produced concentration-related decreases in schedule-controlled operant performance with recovery from TCE being somewhat more rapid; (5) ISOPAR-E produced cross dependence in TCE-dependent mice; and (6) both TCE and ISOPAR-E produced substantial levels of ethanol-lever responding in a drug discrimination procedure, although the ethanol-like effects of ISOPAR-E only occurred at response rate decreasing concentrations. Overall, there was a poorer separation of behavioral and lethal concentrations for ISOPAR-E than for TCE. Although a somewhat different profile of behavioral effects was obtained with ISOPAR-E and TCE, we cannot say with certainty if enough similarities exist with abused inhalants to predict that ISOPAR-E would be subject to depressant-like abuse

  17. Cytochrome P450 2C8 ω3-Long-Chain Polyunsaturated Fatty Acid Metabolites Increase Mouse Retinal Pathologic Neovascularization—Brief Report

    PubMed Central

    Shao, Zhuo; Fu, Zhongjie; Stahl, Andreas; Joyal, Jean-Sébastien; Hatton, Colman; Juan, Aimee; Hurst, Christian; Evans, Lucy; Cui, Zhenghao; Pei, Dorothy; Gong, Yan; Xu, Dan; Tian, Katherine; Bogardus, Hannah; Edin, Matthew L.; Lih, Fred; Sapieha, Przemyslaw; Chen, Jing; Panigrahy, Dipak; Hellstrom, Ann; Zeldin, Darryl C.; Smith, Lois E.H.

    2014-01-01

    Objective Regulation of angiogenesis is critical for many diseases. Specifically, pathological retinal neovascularization, a major cause of blindness, is suppressed with dietary ω3-long-chain polyunsaturated fatty acids (ω3LCPUFAs) through antiangiogenic metabolites of cyclooxygenase and lipoxygenase. Cytochrome P450 epoxygenases (CYP2C8) also metabolize LCPUFAs, producing bioactive epoxides, which are inactivated by soluble epoxide hydrolase (sEH) to transdihydrodiols. The effect of these enzymes and their metabolites on neovascularization is unknown. Approach and Results The mouse model of oxygen-induced retinopathy was used to investigate retinal neovascularization. We found that CYP2C (localized in wild-type monocytes/macrophages) is upregulated in oxygen-induced retinopathy, whereas sEH is suppressed, resulting in an increased retinal epoxide:diol ratio. With a ω3LCPUFA-enriched diet, retinal neovascularization increases in Tie2-driven human-CYP2C8–overexpressing mice (Tie2-CYP2C8-Tg), associated with increased plasma 19,20-epoxydocosapentaenoic acid and retinal epoxide:diol ratio. 19,20-Epoxydocosapentaenoic acids and the epoxide:diol ratio are decreased with overexpression of sEH (Tie2-sEH-Tg). Overexpression of CYP2C8 or sEH in mice does not change normal retinal vascular development compared with their wild-type littermate controls. The proangiogenic role in retina of CYP2C8 with both ω3LCPUFA and ω6LCPUFA and antiangiogenic role of sEH in ω3LCPUFA metabolism were corroborated in aortic ring assays. Conclusions Our results suggest that CYP2C ω3LCPUFA metabolites promote retinal pathological angiogenesis. CYP2C8 is part of a novel lipid metabolic pathway influencing retinal neovascularization. PMID:24458713

  18. Cometabolism of Methyl tertiary Butyl Ether and Gaseous n-Alkanes by Pseudomonas mendocina KR-1 Grown on C5 to C8 n-Alkanes

    PubMed Central

    Smith, Christy A.; O'Reilly, Kirk T.; Hyman, Michael R.

    2003-01-01

    Pseudomonas mendocina KR-1 grew well on toluene, n-alkanes (C5 to C8), and 1° alcohols (C2 to C8) but not on other aromatics, gaseous n-alkanes (C1 to C4), isoalkanes (C4 to C6), 2° alcohols (C3 to C8), methyl tertiary butyl ether (MTBE), or tertiary butyl alcohol (TBA). Cells grown under carbon-limited conditions on n-alkanes in the presence of MTBE (42 μmol) oxidized up to 94% of the added MTBE to TBA. Less than 3% of the added MTBE was oxidized to TBA when cells were grown on either 1° alcohols, toluene, or dextrose in the presence of MTBE. Concentrated n-pentane-grown cells oxidized MTBE to TBA without a lag phase and without generating tertiary butyl formate (TBF) as an intermediate. Neither TBF nor TBA was consumed by n-pentane-grown cells, while formaldehyde, the expected C1 product of MTBE dealkylation, was rapidly consumed. Similar Ks values for MTBE were observed for cells grown on C5 to C8 n-alkanes (12.95 ± 2.04 mM), suggesting that the same enzyme oxidizes MTBE in cells grown on each n-alkane. All growth-supporting n-alkanes (C5 to C8) inhibited MTBE oxidation by resting n-pentane-grown cells. Propane (Ki = 53 μM) and n-butane (Ki = 16 μM) also inhibited MTBE oxidation, and both gases were also consumed by cells during growth on n-pentane. Cultures grown on C5 to C8 n-alkanes also exhibited up to twofold-higher levels of growth in the presence of propane or n-butane, whereas no growth stimulation was observed with methane, ethane, MTBE, TBA, or formaldehyde. The results are discussed in terms of their impacts on our understanding of MTBE biodegradation and cometabolism. PMID:14660389

  19. DNA polymerases κ and ζ cooperatively perform mutagenic translesion synthesis of the C8–2′-deoxyguanosine adduct of the dietary mutagen IQ in human cells

    PubMed Central

    Bose, Arindam; Pande, Paritosh; Jasti, Vijay P.; Millsap, Amy D.; Hawkins, Edward K.; Rizzo, Carmelo J.; Basu, Ashis K.

    2015-01-01

    The roles of translesion synthesis (TLS) DNA polymerases in bypassing the C8–2′-deoxyguanosine adduct (dG-C8-IQ) formed by 2-amino-3-methylimidazo[4,5-f]quinoline (IQ), a highly mutagenic and carcinogenic heterocyclic amine found in cooked meats, were investigated. Three plasmid vectors containing the dG-C8-IQ adduct at the G1-, G2- or G3-positions of the NarI site (5′-G1G2CG3CC-3′) were replicated in HEK293T cells. Fifty percent of the progeny from the G3 construct were mutants, largely G→T, compared to 18% and 24% from the G1 and G2 constructs, respectively. Mutation frequency (MF) of dG-C8-IQ was reduced by 38–67% upon siRNA knockdown of pol κ, whereas it was increased by 10–24% in pol η knockdown cells. When pol κ and pol ζ were simultaneously knocked down, MF of the G1 and G3 constructs was reduced from 18% and 50%, respectively, to <3%, whereas it was reduced from 24% to <1% in the G2 construct. In vitro TLS using yeast pol ζ showed that it can extend G3*:A pair more efficiently than G3*:C pair, but it is inefficient at nucleotide incorporation opposite dG-C8-IQ. We conclude that pol κ and pol ζ cooperatively carry out the majority of the error-prone TLS of dG-C8-IQ, whereas pol η is involved primarily in its error-free bypass. PMID:26220181

  20. DNA polymerases κ and ζ cooperatively perform mutagenic translesion synthesis of the C8-2'-deoxyguanosine adduct of the dietary mutagen IQ in human cells.

    PubMed

    Bose, Arindam; Pande, Paritosh; Jasti, Vijay P; Millsap, Amy D; Hawkins, Edward K; Rizzo, Carmelo J; Basu, Ashis K

    2015-09-30

    The roles of translesion synthesis (TLS) DNA polymerases in bypassing the C8-2'-deoxyguanosine adduct (dG-C8-IQ) formed by 2-amino-3-methylimidazo[4,5-f]quinoline (IQ), a highly mutagenic and carcinogenic heterocyclic amine found in cooked meats, were investigated. Three plasmid vectors containing the dG-C8-IQ adduct at the G1-, G2- or G3-positions of the NarI site (5'-G1G2CG3CC-3') were replicated in HEK293T cells. Fifty percent of the progeny from the G3 construct were mutants, largely G→T, compared to 18% and 24% from the G1 and G2 constructs, respectively. Mutation frequency (MF) of dG-C8-IQ was reduced by 38-67% upon siRNA knockdown of pol κ, whereas it was increased by 10-24% in pol η knockdown cells. When pol κ and pol ζ were simultaneously knocked down, MF of the G1 and G3 constructs was reduced from 18% and 50%, respectively, to <3%, whereas it was reduced from 24% to <1% in the G2 construct. In vitro TLS using yeast pol ζ showed that it can extend G3*:A pair more efficiently than G3*:C pair, but it is inefficient at nucleotide incorporation opposite dG-C8-IQ. We conclude that pol κ and pol ζ cooperatively carry out the majority of the error-prone TLS of dG-C8-IQ, whereas pol η is involved primarily in its error-free bypass. PMID:26220181

  1. Pharmacological Inactivation of Src Family Kinases Inhibits LPS-Induced TNF-α Production in PBMC of Patients with Behçet's Disease

    PubMed Central

    Pektanc, Gulsum; Akkurt, Zeynep M.; Bozkurt, Mehtap; Turkcu, Fatih M.; Kalkanli-Tas, Sevgi

    2016-01-01

    Behçet's disease (BD) is a multisystemic chronic inflammatory disease characterized by relapsing oral and genital ulcers, uveitis, and skin lesions. The pathogenesis of BD is still unknown. Aberrant production of some cytokines/chemokines plays an important role in the pathogenesis of various inflammatory diseases. Revealing a key signaling regulatory mechanism involved in proinflammatory cytokines/chemokines production is critical for understanding of the pathogenesis of BD. The aim of this study was to determine the role of Src family kinases (SFKs) in production of some LPS-induced proinflammatory cytokines/chemokines in peripheral blood mononuclear cells (PBMC) of active BD patients. Chemical inhibition of SFKs activity impaired LPS-induced TNF-α production in PBMC of active BD patients, suggesting that modulating SFKs activity may be a potential target for BD treatment. PMID:27445436

  2. 18F-FDG PET/CT Findings in Two Cases With Myelodysplastic Syndrome Accompanied by Behçet's Disease.

    PubMed

    Ito, Kimiteru; Kubota, Kazuo

    2016-08-01

    Recently, the co-occurrence of myelodysplastic syndrome (MDS) and Behçet's disease (BD) has been reported in association with trisomy 8 and HLA 51, with the pathology varying from vasculitis to acute neutrophilic inflammation. We report for the first time about imaging findings of F-fluorodeoxyglucose (FDG) positron emission/computed tomography (PET/CT) in 2 cases having MDS accompanied by BD. In these cases, 18 F-FDG PET/CT images clearly revealed high uptake by bone marrow in MDS and by genital aphthous or ileocecal ulcers in BD. F-FDG PET/CT may be the ideal modality for the detection of comorbidity of MDS and BD. PMID:26909715

  3. Development of an analytical method to quantify PBDEs, OH-BDEs, HBCDs, 2,4,6-TBP, EH-TBB, and BEH-TEBP in human serum.

    PubMed

    Butt, Craig M; Miranda, Marie Lynn; Stapleton, Heather M

    2016-04-01

    Polybrominated diphenyl ethers (PBDEs) flame retardants (FRs) were phased-out in the mid-2000s (penta- and octaBDE) and 2013 (decaBDE); however, their hydroxylated metabolites (OH-BDEs) are still commonly detected in human serum. Today, novel FRs such as Firemaster® 550, a mixture that contains two brominated compounds, EH-TBB and BEH-TEBP are used as replacements for PBDEs in some applications, and there is a need to develop a comprehensive analytical method to assess exposure to both legacy PBDEs and novel FRs. This study developed a solid-phase extraction (SPE)-based method to analyze PBDEs, OH-BDEs, 2,4,6-tribromophenol (TBP), hexabromocylcododecane isomers (HBCDs), EH-TBB, and BEH-TEBP in human serum. Briefly, serum proteins were first denatured with formic acid, and then the target analytes were isolated using a SPE column. Finally, the extract was cleaned and fractioned using a silica SPE column. Method performance was assessed by spiking fetal bovine serum with 1-2 ng of the target analytes, and method accuracy was quantified by comparison to a serum Standard Reference Material (SRM). The developed method showed good recovery and accuracy for all target analytes with the exception of the very low and very high molecular weight PBDE congeners. Using this method, 43 serum samples collected from the Healthy Pregnancy, Healthy Baby Study (HPHB) cohort in Durham, NC, USA were analyzed for FRs. A novel finding was the ubiquitous detection of 2,4,6-TBP, at levels greater than the individual PBDE congeners. Furthermore, 2,4,6-TBP was positively correlated with PBDEs, suggesting that they may have a similar source of exposure, or that 2,4,6-TBP may result from metabolism of PBDEs in vivo. PMID:26864867

  4. Triplet repeat polymorphism in the transmembrane region of the MICA gene: A strong association of six GCT repetitions with Behçet disease

    PubMed Central

    Mizuki, Nobuhisa; Ota, Masao; Kimura, Minoru; Ohno, Shigeaki; Ando, Hitoshi; Katsuyama, Yoshihiko; Yamazaki, Masaaki; Watanabe, Koji; Goto, Kaori; Nakamura, Satoshi; Bahram, Seiamak; Inoko, Hidetoshi

    1997-01-01

    A member of a novel family of the human major histocompatibility complex (MHC) class I genes termed MIC (MHC class I chain-related genes), MICA, has been recently identified near the HLA-B gene on the short arm of human chromosome 6. The predicted amino acid sequence of the MICA chain suggests that it folds similarly to typical class I chains and may have the capacity to bind peptides or other short ligands. Therefore, MICA is predicted to have a specialized function in antigen presentation or T cell recognition. During nucleotide sequence analyses of the MICA genomic clone, we found a triplet repeat microsatellite polymorphism of (GCT/AGC)n in the transmembrane (TM) region of the MICA gene. In 68 HLA homozygous B cell lines, 5 distinct alleles of this microsatellite sequence were detected. One of them contained an additional one base insertion that created a frameshift mutation resulting in a premature termination codon in the TM region. This particular allele may encode a soluble, secreted form of the MICA molecule. In addition, we have investigated this microsatellite polymorphism in 77 Japanese patients with Behçet disease, which is known to be associated with HLA-B51. The microsatellite allele consisting of 6 repetitions of GCT/AGC was present at significantly higher frequency in the patient group (Pc = 0.00055) than in a control population. Furthermore, the (GCT/AGC)6 allele was present in all B51 positive patients and in an additional 13 B51 negative patients. These results suggest the possibility of a primary association of Behçet disease with MICA rather than HLA-B. PMID:9037047

  5. C8-Selective Acylation of Quinoline N-Oxides with α-Oxocarboxylic Acids via Palladium-Catalyzed Regioselective C-H Bond Activation.

    PubMed

    Chen, Xiaopei; Cui, Xiuling; Wu, Yangjie

    2016-08-01

    A facile and efficient protocol for palladium-catalyzed C8-selective acylation of quinoline N-oxides with α-oxocarboxylic acids has been developed. In this approach, N-oxide was utilized as a stepping stone for the remote C-H functionalization. The reactions proceeded efficiently under mild reaction conditions with excellent regioselectivity and broad functional group tolerance. PMID:27441527

  6. C8orf37 is mutated in Bardet-Biedl syndrome and constitutes a locus allelic to non-syndromic retinal dystrophies.

    PubMed

    Khan, Arif O; Decker, Eva; Bachmann, Nadine; Bolz, Hanno J; Bergmann, Carsten

    2016-09-01

    Bardet-Biedl syndrome (BBS) is a pleiotropic and clinically and genetically heterogeneous ciliopathy. Primary features are early-onset retinal dystrophy that is typically rod-cone, obesity, polydactyly, renal abnormalities, hypogonadism, and learning difficulties, but most patients do not present with the full clinical picture. In a BBS patient from a consanguineous marriage we performed next-generation sequencing targeting all known BBS genes and other genes known or hypothesized to cause ciliopathies. While no mutation was present in any of the recognized genes for BBS, we were able to identify the homozygous non-conservative mutation c.529C>T (p.Arg177Trp) in C8orf37 that segregated with the phenotype, affects an evolutionarily highly conserved residue, and is bioinformatically predicted to be pathogenic. The same mutation has been described in unrelated patients with non-syndromic cone-rod dystrophy and other C8orf37 changes were found in individuals with retinitis pigmentosa. We conclude that C8orf37 should be added to BBS screening panels as a probable rare cause of the disease and that individuals with C8orf37-related retinal dystrophy should be screened for BBS features. PMID:26854863

  7. Synthesis of Key Points from the OSEP Early Childhood Transition FAQ (SPP/APR Indicators C-8, B-11 and B-12)

    ERIC Educational Resources Information Center

    Diefendorf, M.; Henson, J.; Lucas, A.; Whaley, K.

    2010-01-01

    This document is a synthesis of the key points provided in the Office of Special Education Programs (OSEP) Early Childhood Transition FAQs: SPP/APR indicators C-8 and B-12 released on December 1, 2009. It was developed to assist states with the implementation of effective transition policies and practices. The following is included: (1) Transition…

  8. 40 CFR 180.1250 - C8, C10, and C12 fatty acid monoesters of glycerol and propylene glycol; exemption from the...

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 40 Protection of Environment 24 2014-07-01 2014-07-01 false C8, C10, and C12 fatty acid monoesters of glycerol and propylene glycol; exemption from the requirement of a tolerance. 180.1250 Section 180.1250 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) PESTICIDE PROGRAMS TOLERANCES AND EXEMPTIONS FOR PESTICIDE...

  9. CP47,497-C8 and JWH073, commonly found in 'Spice' herbal blends, are potent and efficacious CB(1) cannabinoid receptor agonists.

    PubMed

    Atwood, Brady K; Lee, Donghoon; Straiker, Alex; Widlanski, Theodore S; Mackie, Ken

    2011-06-01

    'Spice' is an herbal blend that has been reported to produce cannabis-like effects when smoked and is marketed as an alternative to marijuana. Synthetic additives have been identified in numerous 'Spice' preparations from different sources. Common among many of the preparations were the compounds JWH018 and a dimethyloctyl variant of CP47,497 (CP47,497-C8) and, more recently JWH073. The synaptic effects of each of these compounds were uncharacterized. We previously reported that JWH018 is a potent and efficacious CB(1) cannabinoid receptor agonist. In this study we have examined the abilities of CP47,497-C8 and JWH073 to inhibit neurotransmission in cultured autaptic hippocampal neurons. Each inhibited EPSCs with an efficacy and potency similar to JWH018. We also analyzed these compounds' effects on promoting internalization of CB(1) receptors in HEK293 cells stably expressing CB(1) receptors. Similar to our neurotransmission data, CP47,497-C8 internalized CB(1) in a fashion indistinguishable from JWH018. However, JWH073 was less potent and produced slower internalization than JWH018 and CP47,497-C8. It appears that 'Spice' contains a number of cannabinoid receptor agonists that activate CB(1) receptors to inhibit synaptic transmission with similar potencies and efficacies. It is highly probable that the cannabis-like effects of 'Spice' are due to the presence of these and analogous synthetic additives acting on CB(1) receptors. PMID:21333643

  10. Synthesis of C4 and C8 Chemicals from Ethanol on MgO-Incorporated Faujasite Catalysts with Balanced Confinement Effects and Basicity.

    PubMed

    Zhang, Lu; Pham, Tu N; Faria, Jimmy; Santhanaraj, Daniel; Sooknoi, Tawan; Tan, Qiaohua; Zhao, Zheng; Resasco, Daniel E

    2016-04-01

    A new type of catalyst has been designed to adjust the basicity and level of molecular confinement of KNaX faujasites by controlled incorporation of Mg through ion exchange and precipitation of extraframework MgO clusters at varying loadings. The catalytic performance of these catalysts was compared in the conversion of C2 and C4 aldehydes to value-added products. The product distribution depends on both the level of acetaldehyde conversion and the fraction of magnesium as extraframework species. These species form rather uniform and highly dispersed nanostructures that resemble nanopetals. Specifically, the sample containing Mg only in the form of exchangeable Mg(2+) ions has much lower activity than those in which a significant fraction of Mg exists as extraframework MgO. Both the (C6 +C8 )/C4 and C8 /C6 ratios increase with additional extraframework Mg at high acetaldehyde conversion levels. These differences in product distribution can be attributed to 1) higher basicity density on the samples with extraframework species, and 2) enhanced confinement inside the zeolite cages in the presence of these species. Additionally, the formation of linear or aromatic C8 aldehyde compounds depends on the position on the crotonaldehyde molecule from which abstraction of a proton occurs. In addition, catalysts with different confinement effects result in different C8 products. PMID:26938793

  11. Evacetrapib: in vitro and clinical disposition, metabolism, excretion, and assessment of drug interaction potential with strong CYP3A and CYP2C8 inhibitors.

    PubMed

    Cannady, Ellen A; Wang, Ming-Dauh; Friedrich, Stuart; Rehmel, Jessica L F; Yi, Ping; Small, David S; Zhang, Wei; Suico, Jeffrey G

    2015-10-01

    Evacetrapib is an investigational cholesteryl ester transfer protein inhibitor (CETPi) for reduction of risk of major adverse cardiovascular events in patients with high-risk vascular disease. Understanding evacetrapib disposition, metabolism, and the potential for drug-drug interactions (DDI) may help guide prescribing recommendations. In vitro, evacetrapib metabolism was investigated with a panel of human recombinant cytochromes P450 (CYP). The disposition, metabolism, and excretion of evacetrapib following a single 100-mg oral dose of (14)C-evacetrapib were determined in healthy subjects, and the pharmacokinetics of evacetrapib were evaluated in the presence of strong CYP3A or CYP2C8 inhibitors. In vitro, CYP3A was responsible for about 90% of evacetrapib's CYP-associated clearance, while CYP2C8 accounted for about 10%. In the clinical disposition study, only evacetrapib and two minor metabolites circulated in plasma. Evacetrapib metabolism was extensive. A mean of 93.1% and 2.30% of the dose was excreted in feces and urine, respectively. In clinical DDI studies, the ratios of geometric least squares means for evacetrapib with/without the CYP3A inhibitor ketoconazole were 2.37 for area under the curve (AUC)(0-∞) and 1.94 for C max. There was no significant difference in evacetrapib AUC(0-τ) or C max with/without the CYP2C8 inhibitor gemfibrozil, with ratios of 0.996 and 1.02, respectively. Although in vitro results indicated that both CYP3A and CYP2C8 metabolized evacetrapib, clinical studies confirmed that evacetrapib is primarily metabolized by CYP3A. However, given the modest increase in evacetrapib exposure and robust clinical safety profile to date, there is a low likelihood of clinically relevant DDI with concomitant use of strong CYP3A or CYP2C8 inhibitors. PMID:26516590

  12. Evacetrapib: in vitro and clinical disposition, metabolism, excretion, and assessment of drug interaction potential with strong CYP3A and CYP2C8 inhibitors

    PubMed Central

    Cannady, Ellen A; Wang, Ming-Dauh; Friedrich, Stuart; Rehmel, Jessica L F; Yi, Ping; Small, David S; Zhang, Wei; Suico, Jeffrey G

    2015-01-01

    Evacetrapib is an investigational cholesteryl ester transfer protein inhibitor (CETPi) for reduction of risk of major adverse cardiovascular events in patients with high-risk vascular disease. Understanding evacetrapib disposition, metabolism, and the potential for drug–drug interactions (DDI) may help guide prescribing recommendations. In vitro, evacetrapib metabolism was investigated with a panel of human recombinant cytochromes P450 (CYP). The disposition, metabolism, and excretion of evacetrapib following a single 100-mg oral dose of 14C-evacetrapib were determined in healthy subjects, and the pharmacokinetics of evacetrapib were evaluated in the presence of strong CYP3A or CYP2C8 inhibitors. In vitro, CYP3A was responsible for about 90% of evacetrapib's CYP-associated clearance, while CYP2C8 accounted for about 10%. In the clinical disposition study, only evacetrapib and two minor metabolites circulated in plasma. Evacetrapib metabolism was extensive. A mean of 93.1% and 2.30% of the dose was excreted in feces and urine, respectively. In clinical DDI studies, the ratios of geometric least squares means for evacetrapib with/without the CYP3A inhibitor ketoconazole were 2.37 for area under the curve (AUC)(0–∞) and 1.94 for Cmax. There was no significant difference in evacetrapib AUC(0–τ) or Cmax with/without the CYP2C8 inhibitor gemfibrozil, with ratios of 0.996 and 1.02, respectively. Although in vitro results indicated that both CYP3A and CYP2C8 metabolized evacetrapib, clinical studies confirmed that evacetrapib is primarily metabolized by CYP3A. However, given the modest increase in evacetrapib exposure and robust clinical safety profile to date, there is a low likelihood of clinically relevant DDI with concomitant use of strong CYP3A or CYP2C8 inhibitors. PMID:26516590

  13. 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

  14. Orientation-dependent energy level alignment and film growth of 2,7-diocty[1]benzothieno[3,2-b]benzothiophene (C8-BTBT) on HOPG

    NASA Astrophysics Data System (ADS)

    Lyu, Lu; Niu, Dongmei; Xie, Haipeng; Cao, Ningtong; Zhang, Hong; Zhang, Yuhe; Liu, Peng; Gao, Yongli

    2016-01-01

    Combining ultraviolet photoemission spectroscopy, X-ray photoemission spectroscopy, atomic force microscopy, and X-ray diffraction measurements, we performed a systematic investigation on the correlation of energy level alignment, film growth, and molecular orientation of 2,7-diocty[1]benzothieno[3,2-b]benzothiophene (C8-BTBT) on highly oriented pyrolytic graphite. The molecules lie down in the first layer and then stand up from the second layer. The ionization potential shows a sharp decrease from the lying down region to the standing up region. When C8-BTBT molecules start standing up, unconventional energy level band-bending-like shifts are observed as the film thickness increases. These shifts are ascribed to gradual decreasing of the molecular tilt angle about the substrate normal with the increasing film thickness.

  15. Tenuous dose-response correlations for common disease states: case study of cholesterol and perfluorooctanoate/sulfonate (PFOA/PFOS) in the C8 Health Project.

    PubMed

    Kerger, Brent D; Copeland, Teri L; DeCaprio, Anthony P

    2011-10-01

    Persistent organic chemicals, such as perfluorooctanoic acid (PFOA), perfluorooctanesulfonate (PFOS), dioxins, and polychlorinated biphenyls, pose investigative challenges because they are found in virtually everyone (there is no unexposed control group). To overcome this problem, outcome data in some studies are sorted by chemical dose level and findings in low-end dose groups are compared to sequential higher dose groups. An example is the C8 Health Project that evaluated serum PFOA/PFOS (C8) and total cholesterol among 46,294 West Virginia residents who lived, worked, or went to school for at least 1 year in a C8 contaminated drinking-water district and were over age 18 in 2005-2006. The risk for high total cholesterol (>240 mg/dL) measured via odds ratios (ORs) in logistic regression models showed sequential OR increases with PFOA quartile, in comparison to the lowest quartile (OR = 1.00), that were each significantly elevated (OR = 1.21, 1.33, and 1.40, respectively), but age, sex, and body mass index were stronger correlates. Importantly, the magnitude of cholesterol increase was small (12 mg/dL from lowest to highest exposure deciles) and comparison to similar statistics for the general U.S. population showed the C8 cohort had lower rates of high cholesterol. This suggests that inadvertent selection bias may have affected the lowest exposure quartile (control group), making tenuous the dose-response relationship between PFOA/PFOS and risk of high cholesterol. This case illustrates the substantial difficulties in assigning toxicological importance to statistical comparisons for common disease states that utilize subgroups with low exposures as an effective control group. PMID:21770727

  16. Adsorption behaviors of neutral and ionizable compounds on hybrid stationary phases in the absence (BEH-C18) and the presence (CSH-C18) of immobile surface charges.

    PubMed

    Gritti, Fabrice; Guiochon, Georges

    2013-03-22

    The adsorption behaviors of a neutral (caffeine) and a positively charged compound (nortriptylinium) are investigated on two RPLC/hybrid stationary phases, eluted with a low ionic strength buffer (phosphate buffer, W(S)pH 2.63, I=10mM). The first phase, bridge ethylene hybrid (BEH), is neutral at all pHs whereas the second, charged surface hybrid (CSH), contains a protonated ligand at W(W)pH <7. The band profiles of these two compounds eluted by mixture of acetonitrile and water were recorded under overloaded conditions. The adsorption isotherms of the neutral compound on both columns were well accounted for by a heterogeneous Linear-Langmuir (LL) model, which has an adsorption-desorption equilibrium constants about twice larger for caffeine on the CSH than on the BEH, due to charge-dipole interactions. In contrast, at low loadings (0.3 and 1.2μL, C=30g/L), the adsorption isotherm of the charged compound can be accounted for by a homogeneous electrostatically modified Langmuir (EML) or by a heterogeneous bi-EML implicit isotherms onto the CSH and BEH adsorbent, respectively. Electrostatic repulsions definitely account the lesser retention of the ionizable compound on CSH than on BEH. This is explained by the surface potential of CSH-C18 at 20mV and by the subsequent decrease of the equilibrium constant of weak adsorption sites (C18 environment) and removal of the strong adsorption sites (accessible silanols). At the highest sample loadings (5 and 20μL, C=30g/L), the EML and the bi-EML isotherms failed because some adsorbate-adsorbate interactions take place when bulk concentrations exceed 0.2g/L. The experimental data were then successively fitted to an empirical heterogeneous Langmuir-Moreau (LM) explicit isotherm. The best saturation capacities of the empirical heterogeneous LM isotherm is consistent with the manufacturer's estimate of the surface concentration of residual silanols onto the BEH- and CSH-C18 endcapped adsorbent (<0.1μmol/m(2)). PMID:23422897

  17. Atmospheric histories and growth trends of C4F10, C5F12, C6F14, C7F16 and C8F18

    NASA Astrophysics Data System (ADS)

    Ivy, D. J.; Arnold, T.; Harth, C. M.; Steele, L. P.; Mühle, J.; Rigby, M.; Salameh, P. K.; Leist, M.; Krummel, P. B.; Fraser, P. J.; Weiss, R. F.; Prinn, R. G.

    2012-02-01

    The first atmospheric observations and trends are presented for the high molecular weight perfluorocarbons (PFCs): decafluorobutane (C4F10), dodecafluoropentane (C5F12), tetradecafluorohexane (C6F14), hexadecafluoroheptane (C7F16) and octadecafluorooctane (C8F18). Their atmospheric histories are based on measurements of 38 Northern Hemisphere and 46 Southern Hemisphere archived air samples collected between 1973 to 2011 using the Advanced Global Atmospheric Gases Experiment (AGAGE) "Medusa" preconcentration gas chromatography-mass spectrometry systems. A new calibration scale was prepared for each PFC, with estimated accuracies of 6.8% for C4F10, 7.8% for C5F12, 4.0% for C6F14, 6.6% for C7F16 and 7.9% for C8F18. Based on our observations the 2011 globally averaged dry air mole fractions of these heavy PFCs are: 0.18 parts-per-trillion (ppt, i.e., parts per 1012) for C4F10, 0.12 ppt for C5F12, 0.28 ppt for C6F14, 0.12 ppt for C7F16 and 0.09 ppt for C8F18. These atmospheric mole fractions combine to contribute to a global average radiative forcing of 0.35 mW m-2, which is 3.6% of the total PFC radiative forcing. The globally averaged mean atmospheric growth rates of these PFCs during 1973-2011 are 4.58 parts per quadrillion (ppq, i.e., parts per 1015) per year (yr) for C4F10, 3.29 ppq yr-1 for C5F12, 7.50 ppq yr-1 for C6F14, 3.19 ppq yr-1 for C7F16 and 2.51 ppq yr-1 for C8F18. The growth rates of the heavy perfluorocarbons were largest in the early 1990s for C4F10 and C5F12 and in the mid-to-late 1990s for C6F14, C7F16 and C8F18. The more recent slow down in the growth rates of the high molecular weight PFCs suggests that emissions are declining as compared to the 1980s and 1990s. Nevertheless continued monitoring of these potent, extremely long-lived greenhouse gases is necessary to verify that global PFC emissions continue to decline.

  18. Atmospheric histories and growth trends of C4F10, C5F12, C6F14, C7F16 and C8F18

    NASA Astrophysics Data System (ADS)

    Ivy, D. J.; Arnold, T.; Harth, C. M.; Steele, L. P.; Mühle, J.; Rigby, M.; Salameh, P. K.; Leist, M.; Krummel, P. B.; Fraser, P. J.; Weiss, R. F.; Prinn, R. G.

    2012-05-01

    Atmospheric observations and trends are presented for the high molecular weight perfluorocarbons (PFCs): decafluorobutane (C4F10), dodecafluoropentane (C5F12), tetradecafluorohexane (C6F14), hexadecafluoroheptane (C7F16) and octadecafluorooctane (C8F18). Their atmospheric histories are based on measurements of 36 Northern Hemisphere and 46 Southern Hemisphere archived air samples collected between 1973 to 2011 using the Advanced Global Atmospheric Gases Experiment (AGAGE) "Medusa" preconcentration gas chromatography-mass spectrometry systems. A new calibration scale was prepared for each PFC, with estimated accuracies of 6.8% for C4F10, 7.8% for C5F12, 4.0% for C6F14, 6.6% for C7F16 and 7.9% for C8F18. Based on our observations the 2011 globally averaged dry air mole fractions of these heavy PFCs are: 0.17 parts-per-trillion (ppt, i.e., parts per 1012) for C4F10, 0.12 ppt for C5F12, 0.27 ppt for C6F14, 0.12 ppt for C7F16 and 0.09 ppt for C8F18. These atmospheric mole fractions combine to contribute to a global average radiative forcing of 0.35 mW m-2, which is 6% of the total anthropogenic PFC radiative forcing (Montzka and Reimann, 2011; Oram et al., 2012). The growth rates of the heavy perfluorocarbons were largest in the late 1990s peaking at 6.2 parts per quadrillion (ppq, i.e., parts per 1015) per year (yr) for C4F10, at 5.0 ppq yr-1 for C5F12 and 16.6 ppq yr-1 for C6F14 and in the early 1990s for C7F16 at 4.7 ppq yr-1 and in the mid 1990s for C8F18 at 4.8 ppq yr-1. The 2011 globally averaged mean atmospheric growth rates of these PFCs are subsequently lower at 2.2 ppq yr-1 for C4F10, 1.4 ppq yr-1 for C5F12, 5.0 ppq yr-1 for C6F14, 3.4 ppq yr-1 for C7F16 and 0.9 ppq yr-1 for C8F18. The more recent slowdown in the growth rates suggests that emissions are declining as compared to the 1980s and 1990s.

  19. 40 CFR 721.10004 - 2-Butenoic acid, 4,4′-[(dibutylstannylene)bis(oxy)]bis[4-oxo-, (2Z,2′Z)-, di-C8-10-isoalkyl...

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ...-, (2Z,2â²Z)-, di-C8-10-isoalkyl esters, C9-rich. 721.10004 Section 721.10004 Protection of Environment...-, (2Z,2′Z)-, di-C8-10-isoalkyl esters, C9-rich. (a) Chemical substance and significant new uses subject...)-, di-C8-10-isoalkyl esters, C9-rich (PMN P-98-1181; CAS No. 247041-56-1) is subject to reporting...

  20. 40 CFR 721.10004 - 2-Butenoic acid, 4,4′-[(dibutylstannylene)bis(oxy)]bis[4-oxo-, (2Z,2′Z)-, di-C8-10-isoalkyl...

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ...-, (2Z,2â²Z)-, di-C8-10-isoalkyl esters, C9-rich. 721.10004 Section 721.10004 Protection of Environment...-, (2Z,2′Z)-, di-C8-10-isoalkyl esters, C9-rich. (a) Chemical substance and significant new uses subject...)-, di-C8-10-isoalkyl esters, C9-rich (PMN P-98-1181; CAS No. 247041-56-1) is subject to reporting...

  1. Inhibition of SA Node at Supine Position in Right Atrial Thrombus Complicating Behçet’s Disease – From Cardiac Surgical Point of View

    PubMed Central

    Hijazi, Emad Mohamed; Ibdah, Rasheed Khaled; Rawashdeh, Sukina Ismael; Saadeh, Abdullah Mahmoud; Al-Balas, Hamzeh Ibrahim

    2016-01-01

    Patient: Female, 27 Final Diagnosis: Right atrial thrombus compressing the sinoatrial node Symptoms: Dyspnea • cough and hemoptysis with supine bradycardia reaching 36/min and dizziness Medication: — Clinical Procedure: Cardiac surgical intervention removing the mechanical cause if conservative management failed can be done safely Specialty: Surgery Objective: Rare disease Background: Behçet’s disease (BD) is a chronic multi-systemic disease of unknown cause. Intra-cardiac thrombus (ICT) complicating BD is extremely rare. In general, cardiac manifestations in BD are associated with poor prognosis. Chest computed tomography (CT) scan and echocardiogram are excellent modalities for diagnosis and patient assessment. Cardiac surgical intervention can be done safely using an on-pump technique when medical management has failed. Case Report: We report on a case of a 27-year-old Jordanian woman diagnosed with BD who presented with dyspnea, cough, and hemoptysis, with supine bradycardia reaching 36 beats/minute and dizziness which disappear on sitting or standing position, and with heart rate reaching 76 beats/minute. Right atrial thrombus was identified using transthoracic echocardiogram and chest CT scan. After medical management failed, cardiac surgical intervention became an option and targeted extraction of the right atrial thrombus compressing the sinoatrial node (SA node). Conclusions: In BD, right atrial thrombus compressing the SA node is rare. If conservative management has failed, cardiac surgical intervention removing the mechanical cause can be done safely, either using on-pump with cross clamp or on-pump with beating heart technique. PMID:27311379

  2. Effectiveness and tuberculosis-related safety profile of interleukin-1 blocking agents in the management of Behçet's disease.

    PubMed

    Cantarini, Luca; Lopalco, Giuseppe; Caso, Francesco; Costa, Luisa; Iannone, Florenzo; Lapadula, Giovanni; Anelli, Maria Grazia; Franceschini, Rossella; Menicacci, Cristina; Galeazzi, Mauro; Selmi, Carlo; Rigante, Donato

    2015-01-01

    Behçet's disease (BD) is a multi-systemic disorder of unknown etiology characterized by relapsing oral-genital ulcers, uveitis, and involvement of the articular, gastrointestinal, neurologic, and vascular systems. Although the primum movens of this condition remains unknown, a tangled plot combining autoimmune and autoinflammatory pathways has been hypothesized to explain its start and recurrence. In-depth analysis of BD pathogenetic mechanisms, involving dysfunction of multiple proinflammatory molecules, has opened new modalities of treatment: different agents targeting interleukin-1 have been studied in recent years to manage the most difficult and multi-resistant cases of BD. Growing experience with anakinra, canakinumab and gevokizumab is discussed in this review, highlighting the relative efficacy of each drug upon the protean BD clinical manifestations. Safety and tolerability of interleukin-1 antagonists in different doses have been confirmed by numerous observational studies on both large and small cohorts of patients with BD. In particular, the potential for Mycobacterium tuberculosis reactivation and tuberculosis development appears to be significantly lower with interleukin-1 blockers compared to tumor necrosis factor-α inhibitors, thus increasing the beneficial profile of this approach. PMID:25151975

  3. Case of Behçet's disease complicated by oculomotor nerve palsy associated with internal carotid artery-posterior communicating artery aneurysm.

    PubMed

    Yamaoka, Toshifumi; Murota, Hiroyuki; Katayama, Ichiro

    2015-03-01

    Behçet's disease (BD) is a relapsing systemic inflammatory disorder of unknown etiology involving systemic vasculitis. Vasculitis in BD results from the involvement of arteries, veins and blood vessels of all sizes, which leads to the three major manifestations of this condition: venous occlusion, arterial occlusion and aneurysm formation. Therefore, whole-body vascular involvement should always be considered in BD patients. Here, we describe the first appearance of an internal carotid-posterior communicating artery aneurysm, resulting in complete oculomotor nerve palsy in a BD patient. A 44-year-old Japanese man suffered from recurrent episodes of erythema nodosum that had presented on the lower extremities for the past 2 years. His condition was diagnosed as an incomplete type of BD based on relapsing oral and genital ulcers, skin eruptions, such as erythema nodosum and folliculitis, a positive pathergy test and systemic arthralgia. Ten years after his initial clinical presentation, he had manifestations of right-sided ptosis and cyclic dull pain in his right temporal region. Magnetic resonance imaging and angiography revealed a right internal carotid artery-posterior communicating artery aneurysm. Although oculomotor nerve palsy associated with internal carotid artery-posterior communicating artery aneurysm in a BD patient has not been reported previously, our report highlights the fact that this abnormal manifestation should be considered in those with vasculo-BD. PMID:25573207

  4. Sigmoid sinus thrombosis presenting with posterior alexia in a patient with Behçet's disease and polycythaemia: a case report

    PubMed Central

    Thomas, P; Keightley, A; Kamble, R; Gunasekera, N; Johnson, MR

    2008-01-01

    Introduction A 59-year-old Caucasian woman presented with an acute onset of alexia, noticed whilst driving. She described how while she could read car number plates, she had lost the ability to read and understand words on roadside advertisements and car window stickers. Case presentation Neurological examination was unremarkable apart from the inability to read full words or sentences. Imaging of the brain, initially computed tomography, followed by magnetic resonance venography, confirmed a diagnosis of sigmoid sinus thrombosis with associated venous infarction. The patient's past medical history revealed that she had suffered an ischemic stroke and following investigation for this, had undergone a nephrectomy for renal cell carcinoma. This was complicated by postoperative deep venous thrombosis. She had a persistent polycythaemia that was managed with venesection, and recently she had been diagnosed with Behçet's disease. Prior to this presentation, she had recently stopped her prophylactic antiplatelet medication as she was due to undergo a total knee replacement for osteoarthritis. She was managed with weight-adjusted, low molecular weight heparin followed by oral anticoagulation, and made a good recovery from her symptoms. Conclusion This case illustrates a classical neurological syndrome, highlights the importance of cerebral venous and sinus thrombosis as a cause of stroke, and the importance of remaining vigilant to a person's changing risk of venous thrombosis with evolving comorbidity. PMID:18500981

  5. Association of a NOS3 gene polymorphism with Behçet’s disease but not with Vogt-Koyanagi-Harada syndrome in Han Chinese

    PubMed Central

    Zhou, Yan; Yu, Hongsong; Hou, Shengping; Fang, Jing; Qin, Jieying; Yuan, Gangxiang; Kijlstra, Aize

    2016-01-01

    Purpose Previous studies have identified that nitric oxide synthase (NOS) genes are associated with several immune-mediated diseases. This study aimed to investigate whether NOS2 and NOS3 gene polymorphisms are associated with Behçet’s disease (BD) and Vogt-Koyanagi-Harada (VKH) syndrome in a Han Chinese population. Methods An association analysis of NOS2/rs4795067, NOS3/rs1799983 and NOS3/rs1800779 was performed in 733 patients with BD, 800 patients with VKH syndrome, and 1,359 controls using PCR restriction fragment length polymorphism (PCR-RFLP) assay. Statistical analysis was performed with the chi-square test followed by the Bonferroni correction. Results The result showed a decreased frequency of the NOS3/rs1799983 GG genotype and an increased frequency of NOS3/rs1799983 GT genotype in the patients with BD (Bonferroni correction test [Pc]=0.02, odds ratio [OR]=0.74; Pc=2.1×10−3, OR=1.57, respectively). No significant association was found between rs1799983 and VKH syndrome. NOS2/ rs4795067 and NOS3/rs1800779 were not associated with either BD or VKH syndrome. Conclusions Our findings suggest that a NOS3/rs1799983polymorphism is associated with susceptibility to BD in Han Chinese. PMID:27114698

  6. Inhibition of SA Node at Supine Position in Right Atrial Thrombus Complicating Behçet's Disease - From Cardiac Surgical Point of View.

    PubMed

    Hijazi, Emad Mohamed; Ibdah, Rasheed Khaled; Rawashdeh, Sukina Ismael; Saadeh, Abdullah Mahmoud; Al-Balas, Hamzeh Ibrahim

    2016-01-01

    BACKGROUND Behçet's disease (BD) is a chronic multi-systemic disease of unknown cause. Intra-cardiac thrombus (ICT) complicating BD is extremely rare. In general, cardiac manifestations in BD are associated with poor prognosis. Chest computed tomography (CT) scan and echocardiogram are excellent modalities for diagnosis and patient assessment. Cardiac surgical intervention can be done safely using an on-pump technique when medical management has failed. CASE REPORT We report on a case of a 27-year-old Jordanian woman diagnosed with BD who presented with dyspnea, cough, and hemoptysis, with supine bradycardia reaching 36 beats/minute and dizziness which disappear on sitting or standing position, and with heart rate reaching 76 beats/minute. Right atrial thrombus was identified using transthoracic echocardiogram and chest CT scan. After medical management failed, cardiac surgical intervention became an option and targeted extraction of the right atrial thrombus compressing the sinoatrial node (SA node). CONCLUSIONS In BD, right atrial thrombus compressing the SA node is rare. If conservative management has failed, cardiac surgical intervention removing the mechanical cause can be done safely, either using on-pump with cross clamp or on-pump with beating heart technique. PMID:27311379

  7. The Role of T Cell Immunoglobulin Mucin Domains 1 and 4 in a Herpes Simplex Virus-Induced Behçet's Disease Mouse Model

    PubMed Central

    Shim, Ju A.

    2013-01-01

    The T cell immunoglobulin mucin (TIM) proteins regulate T cell activation and tolerance. TIM-1 plays an important role in the regulation of immune responses and the development of autoimmune diseases. TIM-4 is a natural ligand of TIM-1, and the interaction of TIM-1 and TIM-4 is involved in the regulation of T helper (Th) cell responses and modulation of the Th1/Th2 cytokine balance. Behçet's disease (BD) is a chronic, multisystemic inflammatory disorder with arthritic, intestinal, mucocutaneous, ocular, vascular, and central nervous system involvement. Tim-1 expression was lower in a herpes simplex virus-induced BD mouse model compared to that in asymptomatic BD normal (BDN) mice. Tim-4 expression was higher in BD mice than that in BDN mice. In this study, we investigated the Tim expression in a BD mouse model with BD-like symptoms. Tim-1 and Tim-4 expression was regulated by an expression vector or siRNA injected into the BD mouse model. The Tim-1 vector injected into BD mice resulted in changes in BD-like symptoms and decreased the severity score. Treatment with Tim-4 siRNA also improved BD-like symptoms and decreased the severity score accompanied by upregulation of regulatory T cells. We showed that regulating Tim-1 or Tim-4 affected BD-like symptoms in mice. PMID:24453431

  8. In vitro evaluation of γδ T cells regulatory function in Behçet's disease patients and healthy controls.

    PubMed

    Clemente Ximenis, Antonio; Crespí Bestard, Catalina; Cambra Conejero, Ana; Pallarés Ferreres, Lucio; Juan Mas, Antonio; Olea Vallejo, José Luis; Julià Benique, Maria Rosa

    2016-01-01

    CD8-positive γδ T lymphocytes (GDCD8(+)) are specifically increased in peripheral blood of Behçet's disease (BD) patients. GDCD8(+) have shown a T regulatory (Treg) function in autoimmune experimental models, human tumor infiltrates and intestinal intraepithelial lymphocytes from celiac patients. The aim of this study was to evaluate the Treg function of GDCD8(+) and GDCD8(-), freshly isolated from peripheral blood, in comparison to CD4(+)CD25(high) naturally occurring Treg cells (nTreg) in BD and healthy controls (HC). We tested their suppressive activity on CD4(+)CD25(-) T effector cells (Teff) proliferation by a CFSE dilution protocol, after suboptimal activation with anti-CD3, in the absence or presence of IL-2. Furthermore, secreted cytokines and suppressive latency associated peptide (LAP)-TGFβ surface upregulation were determined after GD activation. We found that Vδ1 chains contribution to GDCD8(+) was higher in BD than in HC, but neither GDCD8(+) nor GDCD8(-); (i) suppressed Teff proliferation, (ii) expressed LAP-TGFβ (iii) nor secreted IL-10, in either group. Moreover, GD presented a proinflammatory cytokine profile, mainly producing IFNγ and TNFα, in contrast to nTregs. In conclusion, peripheral GD could contribute more to the dysregulation of TH1 type of cytokines than to exerting a Treg function in BD. PMID:26439770

  9. Global emission estimates and radiative impact of C4F10, C5F12, C6F14, C7F16 and C8F18

    NASA Astrophysics Data System (ADS)

    Ivy, D. J.; Rigby, M.; Baasandorj, M.; Burkholder, J. B.; Prinn, R. G.

    2012-05-01

    Global emission estimates based on new atmospheric observations are presented for the acylic high molecular weight perfluorocarbons (PFCs): decafluorobutane (C4F10), dodecafluoropentane (C5F12), tetradecafluorohexane (C6F14), hexadecafluoroheptane (C7F16) and octadecafluorooctane (C8F18). Emissions are estimated using a 3-dimensional chemical transport model and an inverse method that includes a growth constraint on emissions. The observations used in the inversion are based on newly measured archived air samples that cover a 39-yr period, from 1973 to 2011, and include 36 Northern Hemispheric and 46 Southern Hemispheric samples (Ivy et al., 2012). The derived emission estimates show that global emission rates were largest in the 1980s and 1990s for C4F10 and C5F12, and in the 1990s for C6F14,C7F16 and C8F18. After a subsequent decline, emissions have remained relatively stable, within 20%, for the last 5 yr. Bottom-up emission estimates are available from the Emission Database for Global Atmospheric Research version 4.2 (EDGARv4.2) for C4F10, C5F12, C6F14 and C7F16, and inventories of C4F10, C5F12 andC6F14 are reported to the United Nations' Framework Convention on Climate Change (UNFCCC) by Annex 1 countries that have ratified the Kyoto Protocol. The atmospheric measurement based emission estimates are 20 times larger than EDGARv4.2 for C4F10 and over three orders of magnitude for C5F12. The derived emission estimates for C6F14 largely agree with the bottom-up estimates from EDGARv4.2. Moreover, the C7F16 emission estimates are comparable to those of EDGARv4.2 at their peak in the 1990s, albeit significant underestimation for the other time periods. There are no bottom-up emission estimates for C8F18, thus the emission rates reported here are the first for C8F18. The reported inventories for C4F10, C5F12 and C6F14 to UNFCCC are five to ten times lower than those estimated in this study. In addition, we present measured infrared absorption spectra for C7F16 and C8

  10. Global emission estimates and radiative impact of C4F10, C5F12, C6F14, C7F16 and C8F18

    NASA Astrophysics Data System (ADS)

    Ivy, D. J.; Rigby, M.; Baasandorj, M.; Burkholder, J. B.; Prinn, R. G.

    2012-08-01

    Global emission estimates based on new atmospheric observations are presented for the acylic high molecular weight perfluorocarbons (PFCs): decafluorobutane (C4F10), dodecafluoropentane (C5F12), tetradecafluorohexane (C6F14), hexadecafluoroheptane (C7F16) and octadecafluorooctane (C8F18). Emissions are estimated using a 3-dimensional chemical transport model and an inverse method that includes a growth constraint on emissions. The observations used in the inversion are based on newly measured archived air samples that cover a 39-yr period, from 1973 to 2011, and include 36 Northern Hemispheric and 46 Southern Hemispheric samples. The derived emission estimates show that global emission rates were largest in the 1980s and 1990s for C4F10 and C5F12, and in the 1990s for C6F14, C7F16 and C8F18. After a subsequent decline, emissions have remained relatively stable, within 20%, for the last 5 yr. Bottom-up emission estimates are available from the Emission Database for Global Atmospheric Research version 4.2 (EDGARv4.2) for C4F10, C5F12, C6F14 and C7F16, and inventories of C4F10, C5F12 and C6F14 are reported to the United Nations' Framework Convention on Climate Change (UNFCCC) by Annex 1 countries that have ratified the Kyoto Protocol. The atmospheric measurement-based emission estimates are 20 times larger than EDGARv4.2 for C4F10 and over three orders of magnitude larger for C5F12 (with 2008 EDGARv4.2 estimates for C5F12 at 9.6 kg yr-1, as compared to 67±53 t yr-1 as derived in this study). The derived emission estimates for C6F14 largely agree with the bottom-up estimates from EDGARv4.2. Moreover, the C7F16 emission estimates are comparable to those of EDGARv4.2 at their peak in the 1990s, albeit significant underestimation for the other time periods. There are no bottom-up emission estimates for C8F18, thus the emission rates reported here are the first for C8F18. The reported inventories for C4F10, C5F12 and C6F14 to UNFCCC are five to ten times lower than those

  11. Determinants of Cytochrome P450 2C8 Substrate Binding: Structures of Complexes With Montelukast, Troglitazone, Felodipine And 9-CIS-Retinoic Acid

    SciTech Connect

    Schoch, G.A.; Yano, J.K.; Dansette, P.M.; Stout, C.D.; Johnson, E.F.

    2009-05-27

    Although a crystal structure and a pharmacophore model are available for cytochrome P450 2C8, the role of protein flexibility and specific ligand-protein interactions that govern substrate binding are poorly understood. X-ray crystal structures of P450 2C8 complexed with montelukast (2.8 {angstrom}), troglitazone (2.7 {angstrom}), felodipine (2.3 {angstrom}), and 9-cis-retinoic acid (2.6 {angstrom}) were determined to examine ligand-protein interactions for these chemically diverse compounds. Montelukast is a relatively large anionic inhibitor that exhibits a tripartite structure and complements the size and shape of the active-site cavity. The inhibitor troglitazone occupies the upper portion of the active-site cavity, leaving a substantial part of the cavity unoccupied. The smaller neutral felodipine molecule is sequestered with its dichlorophenyl group positioned close to the heme iron, and water molecules fill the distal portion of the cavity. The structure of the 9-cis-retinoic acid complex reveals that two substrate molecules bind simultaneously in the active site of P450 2C8. A second molecule of 9-cis-retinoic acid is located above the proximal molecule and can restrain the position of the latter for more efficient oxygenation. Solution binding studies do not discriminate between cooperative and noncooperative models for multiple substrate binding. The complexes with structurally distinct ligands further demonstrate the conformational adaptability of active site-constituting residues, especially Arg-241, that can reorient in the active-site cavity to stabilize a negatively charged functional group and define two spatially distinct binding sites for anionic moieties of substrates.

  12. Landing performance of an air cushion landing system installed on a 1/10-scale dynamic model on the C-8 Buffalo airplane

    NASA Technical Reports Server (NTRS)

    Thompson, W. C.

    1973-01-01

    An experimental study was conducted to evaluate the landing behavior of a 1/10-scale dynamic model of the C-8 Buffalo airplane equipped with an air-cushion landing system (ACLS) on a variety of surfaces including both calm and rough water and a smooth hard surface. Taxi runs were made on the hard surface over several obstacles. Landings were made with the model at various pitch and roll attitudes and vertical velocities and at one nominal horizontal velocity. Data from the landings include time histories of the trunk and air-cushion pressures and accelerations at selected locations on the model.

  13. Volumetric Properties of the Mixture Propenenitrile C3H3N + C8H18O Octan-1-ol (VMSD1211, LB4554_V)

    NASA Astrophysics Data System (ADS)

    Cibulka, I.; Fontaine, J.-C.; Sosnkowska-Kehiaian, K.; Kehiaian, H. V.

    This document is part of Subvolume C 'Binary Liquid Systems of Nonelectrolytes III' of Volume 26 'Heats of Mixing, Vapor-Liquid Equilibrium, and Volumetric Properties of Mixtures and Solutions' of Landolt-Börnstein Group IV 'Physical Chemistry'. It contains the Chapter 'Volumetric Properties of the Mixture Propenenitrile C3H3N + C8H18O Octan-1-ol (VMSD1211, LB4554_V)' providing data from direct low-pressure dilatometric measurement of molar excess volume at variable mole fraction and constant temperature.

  14. C-C Bond Formation: Synthesis of C5 Substituted Pyrimidine and C8 Substituted Purine Nucleosides Using Water Soluble Pd-imidate Complex.

    PubMed

    Gayakhe, Vijay; Ardhapure, Ajaykumar V; Kapdi, Anant R; Sanghvi, Yogesh S; Serrano, Jose Luis; Schulzke, Carola

    2016-01-01

    The synthesis of a highly efficient, water soluble [Pd(Sacc)2 (TPA)2 ] complex for C-C bond formation is described. Additionally, application of the [Pd(Sacc)2 (TPA)2 ] complex for Suzuki-Miyaura arylation of all four nucleosides (5-iodo-2'-deoxyuridine [5-IdU], 5-iodo-2'-deoxycytidine [5-IdC], 8-bromo-2'-deoxyadenosine, and 8-bromo-2'-deoxyguanosine) with various aryl/heteroaryl boronic acids in plain water under milder conditions is demonstrated. © 2016 by John Wiley & Sons, Inc. PMID:27248782

  15. In-Rich Reconstructions of the InSb(100) Surface and Chemisorption of Lithium on the c (8x2) Surface - An Ab Initio Study.*

    NASA Astrophysics Data System (ADS)

    Ganapathy, Sridevi L.

    2005-03-01

    The local density approximation to density functional theory (LDA-DFT) has been used to study the different possible relaxations and reconstructions of the In-rich InSb (100) surface. The surfaces are modeled by a three-layer surface with alternating In and Sb atoms and In atoms in the first layer. Hydrogen atoms are used to saturate the dangling bonds of In atoms in the bottom layer to simulate the semi-infinite effect of the surface. Periodic boundary conditions with pseudo-potentials have been used and all simulations have been carried out with the Gaussian 03 suite of programs.^1 We will report on various electronic and geometric structure properties of the possible (1x2), (2x1), (4x2) and c (8x2) reconstructed surfaces. We will also report our studies on adsorption of Li in the most symmetric sites of c (8x2) surface. Details of the chemisorption process, such as the adsorption energies, adatom separation distances, charge distributions, density of states, will be presented and compared with available results in the literature. Possible changes in the InSb surface due to Li adsorption will also be discussed in detail. ^*Work supported, in part, by the Welch Foundation, Houston, Texas (Grant No. Y-1525). ^1 Gaussian03, M. J. Frisch et al., Gaussian Inc., Pittsburgh, PA.

  16. Repression of Hox genes by LMP1 in nasopharyngeal carcinoma and modulation of glycolytic pathway genes by HoxC8.

    PubMed

    Jiang, Y; Yan, B; Lai, W; Shi, Y; Xiao, D; Jia, J; Liu, S; Li, H; Lu, J; Li, Z; Chen, L; Chen, X; Sun, L; Muegge, K; Cao, Y; Tao, Y

    2015-12-10

    Epstein-Barr virus (EBV) causes human lymphoid malignancies, and the EBV product latent membrane protein 1 (LMP1) has been identified as an oncogene in epithelial carcinomas such as nasopharyngeal carcinoma (NPC). EBV can epigenetically reprogram lymphocyte-specific processes and induce cell immortalization. However, the interplay between LMP1 and the NPC host cell remains largely unknown. Here, we report that LMP1 is important to establish the Hox gene expression signature in NPC cell lines and tumor biopsies. LMP1 induces repression of several Hox genes in part via stalling of RNA polymerase II (RNA Pol II). Pol II stalling can be overcome by irradiation involving the epigenetic regulator TET3. Furthermore, we report that HoxC8, one of the genes silenced by LMP1, has a role in tumor growth. Ectopic expression of HoxC8 inhibits NPC cell growth in vitro and in vivo, modulates glycolysis and regulates the expression of tricarboxylic acid (TCA) cycle-related genes. We propose that viral latency products may repress via stalling key mediators that in turn modulate glycolysis. PMID:25745994

  17. Repression of Hox genes by LMP1 in nasopharyngeal carcinoma and modulation of glycolytic pathway genes by HoxC8

    PubMed Central

    Jiang, Yiqun; Yan, Bin; Lai, Weiwei; Shi, Ying; Xiao, Desheng; Jia, Jiantao; Liu, Shuang; Li, Hongde; Lu, Jinchen; Li, Zhi; Chen, Ling; Chen, Xue; Sun, Lunqun; Muegge, Kathrin; Cao, Ya; Tao, Yongguang

    2015-01-01

    Epstein-Barr virus (EBV) causes human lymphoid malignancies, and the EBV product latent membrane protein 1 (LMP1) has been identified as an oncogene in epithelial carcinomas such as nasopharyngeal carcinoma (NPC). EBV can epigenetically reprogram lymphocyte specific processes and induce cell immortalization. However, the interplay between LMP1 and the NPC host cell remains largely unknown. Here, we report that LMP1 is important to establish the Hox gene expression signature in NPC cell lines and tumor biopsies. LMP1 induces repression of several Hox genes in part via stalling of RNA Pol II. Pol II stalling can be overcome by irradiation involving the epigenetic regulator TET3. Furthermore, we report that HoxC8, one of the genes silenced by LMP1, plays a role in tumor growth. Ectopic expression of HoxC8 inhibits NPC cell growth in vitro and in vivo, modulates glycolysis and regulates the expression of TCA-cycle related genes. We propose that viral latency products may repress via stalling key mediators that in turn modulate glycolysis. PMID:25745994

  18. Phosphorylation of 20S proteasome alpha subunit C8 (alpha7) stabilizes the 26S proteasome and plays a role in the regulation of proteasome complexes by gamma-interferon.

    PubMed Central

    Bose, Suchira; Stratford, Fiona L L; Broadfoot, Kerry I; Mason, Grant G F; Rivett, A Jennifer

    2004-01-01

    In animal cells there are several regulatory complexes which interact with 20S proteasomes and give rise to functionally distinct proteasome complexes. gamma-Interferon upregulates three immuno beta catalytic subunits of the 20S proteasome and the PA28 regulator, and decreases the level of 26S proteasomes. It also decreases the level of phosphorylation of two proteasome alpha subunits, C8 (alpha7) and C9 (alpha3). In the present study we have investigated the role of phosphorylation of C8 by protein kinase CK2 in the formation and stability of 26S proteasomes. An epitope-tagged C8 subunit expressed in mammalian cells was efficiently incorporated into both 20S proteasomes and 26S proteasomes. Investigation of mutants of C8 at the two known CK2 phosphorylation sites demonstrated that these are the two phosphorylation sites of C8 in animal cells. Although phosphorylation of C8 was not absolutely essential for the formation of 26S proteasomes, it did have a substantial effect on their stability. Also, when cells were treated with gamma-interferon, there was a marked decrease in phosphorylation of C8, a decrease in the level of 26S proteasomes, and an increase in immunoproteasomes and PA28 complexes. These results suggest that the down-regulation of 26S proteasomes after gamma-interferon treatment results from the destabilization that occurs after dephosphorylation of the C8 subunit. PMID:14583091

  19. Novel markers of endothelial dysfunction and inflammation in Behçet's disease patients with ocular involvement: epicardial fat thickness, carotid intima media thickness, serum ADMA level, and neutrophil-to-lymphocyte ratio.

    PubMed

    Yuksel, Murat; Yildiz, Abdulkadir; Oylumlu, Mustafa; Turkcu, Fatih Mehmet; Bilik, Mehmet Zihni; Ekinci, Aysun; Elbey, Bilal; Tekbas, Ebru; Alan, Sait

    2016-03-01

    The etiology of Behçet's disease (BD) has not been fully elucidated. However, immunological and environmental factors, endothelial dysfunction (ED), and genetic susceptibility have been proposed to play a role. In this study, we aimed to evaluate epicardial fat thickness (EFT) together with serum asymmetric dimethylarginine (ADMA), carotid intima media thickness (CIMT), and neutrophil-to-lymphocyte ratio (NLR) in BD patients with ocular involvement. Thirty-six ocular BD patients (17 active and 19 inactive ocular involvement), and 35 age and sex-matched healthy controls were enrolled to this cross-sectional study. All patients underwent examinations with transthoracic echocardiography and carotid Doppler ultrasound. Serum ADMA levels, CIMT, EFT, and NLR were compared between groups, and their association with disease activity was evaluated. Behçet's disease patients had higher WBC counts, neutrophil counts, NLR, CIMT, EFT values, and serum ADMA levels than do healthy controls. The other biochemical, hematological, and echocardiographic parameters were comparable between the two groups. Behçet's disease duration was positively correlated with EFT and CIMT. Multivariate logistic regression analysis revealed that increased serum ADMA concentration and CIMT are independently associated with BD. Neutrophil counts, NLR, and serum ADMA level were higher, and lymphocyte count was lower in patients with active ocular BD compared to those of inactive ocular BD group. Carotid intima media thickness, serum ADMA level, EFT, and NLR were increased in ocular BD patients compared to healthy subjects. In addition, both serum ADMA level and NLR were associated with disease activity of ocular involvement. Increase in disease duration was associated with increase in CIMT and EFT which suggests that anatomical changes occur in time during the disease course. Increased CIMT, serum ADMA level, EFT, and NLR may provide new clues about the role of ED and inflammation in the

  20. Behçet's disease: A comprehensive review with a focus on epidemiology, etiology and clinical features, and management of mucocutaneous lesions.

    PubMed

    Alpsoy, Erkan

    2016-06-01

    Behçet's disease (BD) is a chronic, relapsing, inflammatory multisystem disease of unknown etiology. Oral ulcers, genital ulcers, cutaneous lesions, and ocular and articular involvement are the most frequent features of the disease. Mucocutaneous lesions are considered hallmarks of the disease, and often precede other manifestations. Therefore, their recognition may permit earlier diagnosis and treatment with beneficial results for prognosis. BD is particularly prevalent in "Silk Route" populations but has a global distribution. The disease usually starts around the third or fourth decade of life. Sex distribution is roughly equal. The diagnosis is based on clinical criteria, as there is no pathognomonic test. Genetic factors have been investigated extensively, and association with human leukocyte antigen (HLA)-B51 is still known as the strongest genetic susceptibility factor. The T-helper 17 and interleukin (IL)-17 pathways are active, and play an important role, particularly in acute attacks of BD. Neutrophil activity is increased in BD, and the affected organs show a significant neutrophil and lymphocyte infiltration. HLA-B51 association and increased IL-17 response are thought to play a role in neutrophil activation. Treatment is mainly based on the suppression of inflammatory attacks of the disease using immunomodulatory and immunosuppressive agents. Although treatment has become much more effective in recent years with the introduction of newer drugs, BD is still associated with considerable morbidity and increased mortality. Male sex, younger age of onset and increased number of organs involved at the diagnosis are associated with a more severe disease and, therefore, require more aggressive treatment. PMID:27075942

  1. Novel heterozygous C243Y A20/TNFAIP3 gene mutation is responsible for chronic inflammation in autosomal-dominant Behçet's disease

    PubMed Central

    Shigemura, Tomonari; Kaneko, Naoe; Kobayashi, Norimoto; Kobayashi, Keiko; Takeuchi, Yusuke; Nakano, Naoko; Masumoto, Junya; Agematsu, Kazunaga

    2016-01-01

    Objective Although Behçet's disease (BD) is a chronic inflammatory disorder of uncertain aetiology, the existence of familial BD with autosomal-dominant traits suggests that a responsibility gene (or genes) exists. We investigated a Japanese family with a history of BD to search for pathogenic mutations underlying the biological mechanisms of BD. Methods 6 patients over 4 generations who had suffered from frequent oral ulcers, genital ulcers and erythaema nodosum-like lesions in the skin were assessed. Whole-exome sequencing was performed on genomic DNA, and cytokine production was determined from stimulated mononuclear cells. Inflammatory cytokine secretion and Nod2-mediated NF-κB activation were analysed using the transfected cells. Results By whole-exome sequencing, we identified a common heterozygous missense mutation in A20/TNFAIP3, a gene known to regulate NF-κB signalling, for which all affected family members carried a heterozygous C243Y mutation in the ovarian tumour domain. Mononuclear cells obtained from the proband and his mother produced large amounts of interleukin 1β, IL-6 and tumour necrosis factor α (TNF-a) on stimulation as compared with those from normal controls. Although inflammatory cytokine secretion was suppressed by wild-type transfected cells, it was suppressed to a much lesser extent by mutated C243Y A20/TNFAIP3-transfected cells. In addition, impaired suppression of Nod2-mediated NF-κB activation by C243Y A20/TNFAIP3 was observed. Conclusions A C243Y mutation in A20/TNFAIP3 was likely responsible for increased production of human inflammatory cytokines by reduced suppression of NF-κB activation, and may have accounted for the autosomal-dominant Mendelian mode of BD transmission in this family. PMID:27175295

  2. Procoagulant microparticles are increased in patients with Behçet's disease but do not define a specific subset of clinical manifestations.

    PubMed

    Mejía, Juan Carlos; Ortiz, Thaia; Tàssies, Dolors; Solanich, Xavier; Vidaller, Antonio; Cervera, Ricard; Reverter, Joan-Carles; Espinosa, Gerard

    2016-03-01

    Microparticles (MP) are considered a key component in the haemostatic response. Beyond their in vitro procoagulant properties, a number of pieces of evidence points to procoagulant MP as efficient effectors in the haemostatic response and as pathogenic markers of thrombotic disorders and vascular damage. The aim of the present study was to analyze the procoagulant activity of MP and its correlation with clinical manifestations focusing on vascular involvement in patients with Behçet's disease (BD). We analyzed 55 BD patients in inactive phase of the disease (26 men; mean age, 35 ± 15 years) of which 19 had previously suffered from thrombosis (deep venous thrombosis in 17 and ischemic stroke in 2), and 73 healthy controls matched for age and sex. Procoagulant MP were assessed by a functional assay. BD patients showed higher procoagulant MP values than controls (22.89 ± 15.74 nM versus 14.47 ± 7.34 nM; p < 0.0001). Conversely, we did not find differences in the levels of procoagulant MP according to the gender of patients (22.22 ± 16.23 nM for men versus 21.46 ± 16.47 for women; p = 0.846) or to previous and current treatments. Moreover, the plasmatic concentration of MP does not define any clinical phenotype and it was not related to the time of evolution of the disease. Although inactive BD patients had high values of procoagulant MP, they did not differentiate between BD patients with or without thrombosis. PMID:25711877

  3. Epistatic interaction of ERAP1 and HLA-B in Behçet disease: a replication study in the Spanish population.

    PubMed

    Conde-Jaldón, Marta; Montes-Cano, Marco Antonio; García-Lozano, José Raul; Ortiz-Fernández, Lourdes; Ortego-Centeno, Norberto; González-León, Rocío; Espinosa, Gerard; Graña-Gil, Genaro; Sánchez-Bursón, Juan; González-Gay, Miguel Angel; Barnosi-Marín, Ana Celia; Solans, Roser; Fanlo, Patricia; Carballeira, Mónica Rodríguez; Camps, Teresa; Castañeda, Santos; Martín, Javier; González-Escribano, María Francisca

    2014-01-01

    Behçet's disease (BD) is a multifactorial disorder associated with the HLA region. Recently, the ERAP1 gene has been proposed as a susceptibility locus with a recessive model and with epistatic interaction with HLA-B51. ERAP1 trims peptides in the endoplasmic reticulum to optimize their length for MHC-I binding. Polymorphisms in this gene have been related with the susceptibility to other immune-mediated diseases associated to HLA class I. Our aim was, the replication in the Spanish population of the association described in the Turkish population between ERAP1 (rs17482078) and BD. Additionally, in order to improve the understanding of this association we analyzed four additional SNPs (rs27044, rs10050860, rs30187 and rs2287987) associated with other diseases related to HLA class I and the haplotype blocks in this gene region. According to our results, frequencies of the homozygous genotypes for the minor alleles of all the SNPs were increased among patients and the OR values were higher in the subgroup of patients with the HLA-B risk factors, although differences were not statistically significant. Moreover, the presence of the same mutation in both chromosomes increased the OR values from 4.51 to 10.72 in individuals carrying the HLA-B risk factors. Therefore, although they were not statistically significant, our data were consistent with an association between ERAP1 and BD as well as with an epistatic interaction between ERAP1 and HLA-B in the Spanish population. PMID:25019531

  4. Association between MEFV Mutations M694V and M680I and Behçet’s Disease: A Meta-Analysis

    PubMed Central

    Chen, Si; Li, Ping; Sun, Fei; Wen, Xiaoting; Zheng, Wenjie; Zhang, Fengchun; Li, Yongzhe

    2015-01-01

    Objective Several studies have identified an association between Behçet’s disease (BD) and mutations in the Mediterranean fever (MEFV) gene, which was originally linked to the autosomal recessive disease, Familial Mediterranean fever. However, no consensus has been reached. Here, a meta-analysis was conducted on published data to comprehensively evaluate this relationship. Methods Literature searches were performed in Pubmed, Embase, the Web of Science, and HuGE Navigator databases, in order to identify studies pertaining to the association between MEFV mutations and BD. Two investigators independently extracted and evaluated the data from eligible studies. The association between MEFV mutations (M694V, M680I, and E148Q) and BD was estimated overall by the odds ratio (OR) and 95% confidence intervals (95% CI). Further analysis was conducted with STATA 12.0 software (Stata Corp.; College Station, TX). Results Eligible studies (n=8) included genotyping data obtained from 2538 BD patients and 2792 healthy controls. Of the three mutations, M694V (pooled OR: 2.60, 95% CI: 2.02-3.34) and M680I (pooled OR: 1.74, 95% CI: 1.23-2.46) were found to be associated with BD in the overall analysis. The third mutation, E148Q, however, was not found to be linked with BD (pooled OR: 1.26, 95% CI: 0.69-2.31). Subgroup analysis furthermore revealed that M694V and M680I were risk loci for BD specifically in Turkish patients. Conclusions The meta-analysis confirmed that MEFV mutations M694V and M680I were associated with BD. Additional studies from other ethnic populations and functional experiments are necessary to determine the extent to which the MEFV gene underlies the development of BD. PMID:26176758

  5. Targeted resequencing implicates the familial Mediterranean fever gene MEFV and the toll-like receptor 4 gene TLR4 in Behçet disease.

    PubMed

    Kirino, Yohei; Zhou, Qing; Ishigatsubo, Yoshiaki; Mizuki, Nobuhisa; Tugal-Tutkun, Ilknur; Seyahi, Emire; Özyazgan, Yilmaz; Ugurlu, Serdal; Erer, Burak; Abaci, Neslihan; Ustek, Duran; Meguro, Akira; Ueda, Atsuhisa; Takeno, Mitsuhiro; Inoko, Hidetoshi; Ombrello, Michael J; Satorius, Colleen L; Maskeri, Baishali; Mullikin, James C; Sun, Hong-Wei; Gutierrez-Cruz, Gustavo; Kim, Yoonhee; Wilson, Alexander F; Kastner, Daniel L; Gül, Ahmet; Remmers, Elaine F

    2013-05-14

    Genome-wide association studies (GWAS) are a powerful means of identifying genes with disease-associated common variants, but they are not well-suited to detecting genes with disease-associated rare and low-frequency variants. In the current study of Behçet disease (BD), nonsynonymous variants (NSVs) identified by deep exonic resequencing of 10 genes found by GWAS (IL10, IL23R, CCR1, STAT4, KLRK1, KLRC1, KLRC2, KLRC3, KLRC4, and ERAP1) and 11 genes selected for their role in innate immunity (IL1B, IL1R1, IL1RN, NLRP3, MEFV, TNFRSF1A, PSTPIP1, CASP1, PYCARD, NOD2, and TLR4) were evaluated for BD association. A differential distribution of the rare and low-frequency NSVs of a gene in 2,461 BD cases compared with 2,458 controls indicated their collective association with disease. By stringent criteria requiring at least a single burden test with study-wide significance and a corroborating test with at least nominal significance, rare and low-frequency NSVs in one GWAS-identified gene, IL23R (P = 6.9 × 10(-5)), and one gene involved in innate immunity, TLR4 (P = 8.0 × 10(-4)), were associated with BD. In addition, damaging or rare damaging NOD2 variants were nominally significant across all three burden tests applied (P = 0.0063-0.045). Furthermore, carriage of the familial Mediterranean fever gene (MEFV) mutation Met694Val, which is known to cause recessively inherited familial Mediterranean fever, conferred BD risk in the Turkish population (OR, 2.65; P = 1.8 × 10(-12)). The disease-associated NSVs in MEFV and TLR4 implicate innate immune and bacterial sensing mechanisms in BD pathogenesis. PMID:23633568

  6. [Influence of steroid hormones on the production of two inflammatory markers, IL-12 and nitric oxide, in Behçet's disease].

    PubMed

    Ahmedi, M L; Belguendouz, H; Messaoudene, D; Mesbah-Amroun, H; Terahi, M; Lahlou-Boukoffa, O S; Touil-Boukoffa, C

    2016-04-01

    Uveitis is one of the major diagnostic criteria of Behçet's disease (BD), a chronic systemic inflammatory pathology with an uncertain etiology. Since uveitis is more frequent in male patients, we assessed the level and the effect of sex hormones on inflammatory responses during BD. Peripheral blood was taken from 19 patients with BD and 20 healthy subjects. Estradiol, testosterone and cortisol were measured in plasma by ELISA. Circulating mononuclear cells (PBMC) were obtained on gradient density and cultured with or without the three hormones for 24h at 37 ̊C. IL-12 and nitric oxide (NO) were measured in vivo and ex vivo by ELISA and a modified Griess method, respectively. We confirmed the significantly higher in vivo and in vitro levels of NO and IL-12 in BD in comparison to controls (P<0.05). We also found that circulating cortisol was lower in BD while sex hormones did not show any significant difference between the groups (P>0.05). In vitro, NO was reduced by estradiol and cortisol and increased by testosterone in both sexes. In contrast, while IL-12 production showed the same production profile as NO in women, estradiol and cortisol failed to reduce IL-12 levels in men. Our results may explain in part the differences observed between men and women in disease clinical expression. In fact, male patients seem to have defective IL-12 down-regulation by estradiol and cortisol that increases Th1 immune responses. This may be implicated in the severe expression of BD in men. PMID:27021132

  7. Ex vivo immunomodulatory effect of all-trans-retinoic acid during Behçet's disease: a study in Algerian patients.

    PubMed

    Djeraba, Zineb; Boumedine, Karim; Arroul-Lammali, Amina; Otmani, Fifi; Belguendouz, Houda; Touil-Boukoffa, Chafia

    2014-02-01

    Uveitis, recurrent oral and genital ulcerations associated with skin lesions are the major symptoms of a chronic multisystemic inflammatory disorder known as Behçet's disease (BD). High prevalence of this dreaded disease has been observed in the Mediterranean basin, including Algeria and along the Silk Road. Although the etiologic agent of this disease remains uncertain, many hypotheses have been advanced in its pathogenesis. Our team has previously reported high levels of nitric oxide (NO) in sera of BD patients, suggesting its deleterious effect during chronic inflammation. In our current study, the aim is to investigate the ex vivo immunomodulatory effect of all-trans-retinoic acid (ATRA) on NO pathway in Algerian BD patients. First, peripheral blood mononuclear cells isolated from active and inactive BD patients and healthy controls were cultured with different concentrations of ATRA. NO production was estimated with the Griess method. To elucidate the underlying mechanisms of ATRA effect on NO production, we analyze inducible nitric oxide synthase expression and nuclear factor-κB (NF-κB) activity by immunofluorescence test. Our results revealed a higher production of NO in active BD compared with the inactive stage and healthy controls. We observed that ATRA inhibits NO production in BD both in active and inactive stages and inhibits NF-κB translocation. In conclusion, we report a relationship between NO production and the disease activity. ATRA down-regulates NO production in BD patients. This immunomodulatory effect seems to be mediated through NF-κB pathway. All these findings suggest that ATRA could be considered as a promising therapy for BD. PMID:24369064

  8. Analysis of receptor tyrosine kinase genetics identifies two novel risk loci in GAS6 and PROS1 in Behçet’s disease

    PubMed Central

    Qin, Jieying; Li, Lin; Zhang, Donglei; Yu, Hongsong; Tan, Handan; Zhang, Jun; Deng, Bolin; Kijlstra, Aize; Yang, Peizeng

    2016-01-01

    The TAM kinase (Tyro3, Axl, Mer) and its two ligands (Gas6 and protein S) have been shown to play an important regulatory role in the innate immune response. The present study aimed to investigate whether the tag single-nucleotide polymorphisms (tag SNPs) of these 5 protein-coding genes are associated with Behçet’s disease (BD). A two-stage association study was performed in a total of 907 BD patients and 1780 healthy controls. Altogether 32 polymorphisms were tested, using a Sequenom MassARRAY genotyping method in the first stage and a PCR-restriction fragment length polymorphism (PCR-RFLP) assay in the replication phase. Real-time PCR was performed to test the relative mRNA expression level of GAS6 and PROS1 from different SNP genotyped healthy individuals. The frequency of the C allele and CC genotype of rs9577873 in GAS6 (Pc = 4.92 × 10−5, Pc = 1.91 × 10−5, respectively) and A allele and AA genotype of rs4857037 in PROS1 (Pc = 1.85 × 10−6, Pc = 4.52 × 10−7, respectively) were significantly increased in BD. GAS6 expression in CC carriers of rs9577873 was significantly lower than that in CT/TT individuals (P = 0.001). Decreased expression of GAS6 and increased pro-inflammatory cytokines (IL-6 and IFN-γ: P = 4.23 × 10−4, P = 0.011, respectively) in individuals carrying the CC genotype suggest that the TAM-GAS6/PROS1 signal pathway may be involved in the pathogenesis of BD. PMID:27222359

  9. Analysis of receptor tyrosine kinase genetics identifies two novel risk loci in GAS6 and PROS1 in Behçet's disease.

    PubMed

    Qin, Jieying; Li, Lin; Zhang, Donglei; Yu, Hongsong; Tan, Handan; Zhang, Jun; Deng, Bolin; Kijlstra, Aize; Yang, Peizeng

    2016-01-01

    The TAM kinase (Tyro3, Axl, Mer) and its two ligands (Gas6 and protein S) have been shown to play an important regulatory role in the innate immune response. The present study aimed to investigate whether the tag single-nucleotide polymorphisms (tag SNPs) of these 5 protein-coding genes are associated with Behçet's disease (BD). A two-stage association study was performed in a total of 907 BD patients and 1780 healthy controls. Altogether 32 polymorphisms were tested, using a Sequenom MassARRAY genotyping method in the first stage and a PCR-restriction fragment length polymorphism (PCR-RFLP) assay in the replication phase. Real-time PCR was performed to test the relative mRNA expression level of GAS6 and PROS1 from different SNP genotyped healthy individuals. The frequency of the C allele and CC genotype of rs9577873 in GAS6 (Pc = 4.92 × 10(-5), Pc = 1.91 × 10(-5), respectively) and A allele and AA genotype of rs4857037 in PROS1 (Pc = 1.85 × 10(-6), Pc = 4.52 × 10(-7), respectively) were significantly increased in BD. GAS6 expression in CC carriers of rs9577873 was significantly lower than that in CT/TT individuals (P = 0.001). Decreased expression of GAS6 and increased pro-inflammatory cytokines (IL-6 and IFN-γ: P = 4.23 × 10(-4), P = 0.011, respectively) in individuals carrying the CC genotype suggest that the TAM-GAS6/PROS1 signal pathway may be involved in the pathogenesis of BD. PMID:27222359

  10. The exaggerated inflammatory response in Behçet's syndrome: identification of dysfunctional post-transcriptional regulation of the IFN-γ/CXCL10 IP-10 pathway.

    PubMed

    Ambrose, N; Khan, E; Ravindran, R; Lightstone, L; Abraham, S; Botto, M; Johns, M; Haskard, D O

    2015-09-01

    The mechanisms underlying the exaggerated inflammatory response in Behçet's syndrome (BS) remain poorly understood. We investigated the response of CD14(+) blood monocytes to interferon (IFN)-γ, focusing on the chemokine CXCL10. Chemokine synthesis and release were analysed at a protein and mRNA level following stimulation with IFN-γ. Findings in BS patients were compared with 25 healthy controls (HC), 15 rheumatoid arthritis (RA) and 15 systemic lupus erythematosus (SLE) disease control patients. BS monocytes produced significantly more CXCL10 protein than HC monocytes from 2 h following IFN-γ stimulation, despite equivalent quantities of mRNA, suggesting more efficient translation. This was significantly more pronounced in BS with high disease activity and in those with ocular and neurological clinical manifestations. The imbalance between CXCL10 protein and mRNA expression was not observed in either RA or SLE patients, and was not seen with other chemokines studied (CXCL9, CXCL11 and CCL2). Furthermore, BS monocytes treated with an alternative stimulant (LPS) did not show abnormal tumour necrosis factor (TNF)-α release. Sucrose density gradients to segregate monocyte CXCL10 mRNA into free RNA or polysome-associated RNA showed equal proportions in BS and HC samples, suggesting that the difference between BS and HC may be due to reduced negative control of CXCL10 translation in BS at a post-initiation level. We conclude that BS monocytes have dysfunctional post-transcriptional regulation of CXCL10 mRNA, resulting in over-expression of CXCL10 protein upon IFN-γ stimulation. As CXCL10 is a chemokine that recruits mononuclear cells, this abnormality may contribute to the exaggerated inflammatory responses that characterizes BS. PMID:25982097

  11. Conformational study of C8 diazocine turn mimics using {sup 3}J{sub CH} coupling constants with {sup 13}C in natural abundance

    SciTech Connect

    Bean, J.W.; Briand, J.; Burgess, J.L.; Callahan, J.F.

    1994-12-01

    The conformations of two diazocine turn mimics, which were later incorporated into GPIIb/IIIa peptide antagonists, were investigated using nuclear magnetic resonance techniques. The two compounds, methyl (2,5-dioxo-3-(S)-(3-{omega}-tosylguanidino-propyl)-4-methyl-octahydro-1,4-dazocin-1-yl)acetate (1) and methyl (2,5-dioxo-3-(S)-(3-{omega}-tosyl-guanidino-propyl)-octahydro-1,5-diazocin-1-yl)acetate (2), differ only in their substituent at the diazocine position 4 nitrogen, yet this substitution results in a marked difference in the affinity of the resulting analogs for the GPIIb/IIIa receptor. It was of interest to determine if the difference observed in the antagonistic potency between these analogs was related to constitutional or, perhaps, conformational differences. The backbone conformations of these two molecules can be determined by measuring vicinal coupling constants along the trimethylene portion of the C8 ring backbone and by measuring interproton NOE intensities between the diazocine methine proton and the protons of the trimethylene group. For compound 1, {sup 3}J{sub HH} values measured from a P.E.COSY spectrum and interproton distances calculated from ROESY buildup curves indicated the presence of a single C8 ring backbone conformation where the trimethylene bridge adopted a staggered conformation and the H{alpha}1 and H{gamma}1 protons of the trimethylene group were 2.2 A from the methine proton. For compound 2, however, partial overlap of the central H{beta}1 and H{beta}2 protons made it impossible to measure {sup 3}J{sub HH} values from the P.E.COSY spectrum. We therefore used a {sup 13}C-filtered TOCSY experiment to measure the {sup 3}J{sub CH} values in both compounds 1 and 2. These heteronuclear vicinal coupling constants measured with {sup 13}C in natural abundance in conjunction with measured interproton NOE intensities indicate that these compounds share a common C8 ring backbone conformation.

  12. Oligonucleotides, part 5+: synthesis and fluorescence studies of DNA oligomers d(AT)5 containing adenines covalently linked at C-8 with dansyl fluorophore.

    PubMed Central

    Singh, D; Kumar, V; Ganesh, K N

    1990-01-01

    The synthesis of oligodeoxynucleotides d(AT)5 in which specific adenines are linked at C-8 position with dansyl fluorophores via a variable polymethylene spacer chain are reported. This was achieved by a strategy involving prelabelling at the monomeric stage followed by solid phase assembly of oligonucleotides to obtain regiospecifically labeled oligonucleotides. Several mono and polydansyl d(AT)5 derivatives in which the fluorophore is linked via ethylene, tetramethylene and hexamethylene spacer arms were synthesised for a systematic study of their fluorescence characteristics. It was observed that (i) enhancements in fluorescence intensity and emission quantum yields are seen due to multiple labelling, (ii) the magnitude of enhancements are related to labelling configuration and (iii) quenching efficiency is minimal with shorter and rigid spacer arms. The results may aid rational design of multiple fluorescent DNA probes for nonradioactive detection of nucleic acids. PMID:2356124

  13. Carrier recombination spatial transfer by reduced potential barrier causes blue/red switchable luminescence in C8 carbon quantum dots/organic hybrid light-emitting devices

    NASA Astrophysics Data System (ADS)

    Chen, Xifang; Yan, Ruolin; Zhang, Wenxia; Fan, Jiyang

    2016-04-01

    The underlying mechanism behind the blue/red color-switchable luminescence in the C8 carbon quantum dots (CQDs)/organic hybrid light-emitting devices (LEDs) is investigated. The study shows that the increasing bias alters the energy-level spatial distribution and reduces the carrier potential barrier at the CQDs/organic layer interface, resulting in transition of the carrier transport mechanism from quantum tunneling to direct injection. This causes spatial shift of carrier recombination from the organic layer to the CQDs layer with resultant transition of electroluminescence from blue to red. By contrast, the pure CQDs-based LED exhibits green-red electroluminescence stemming from recombination of injected carriers in the CQDs.

  14. Two Cytotoxic Stereoisomers of Malyngamide C, 8-Epi-Malyngamide C and 8-O-Acetyl-8-epi-Malyngamide C, from the Marine Cyanobacterium Lyngbya majuscula

    PubMed Central

    Gross, Harald; McPhail, Kerry L.; Goeger, Douglas E.; Valeriote, Frederick A.; Gerwick, William H.

    2010-01-01

    Two new epimers of malyngamide C, 8-O-acetyl-8-epi-malyngamide C (1) and 8-epi-malyngamide C (3) have been isolated along with known compounds 6-O-acetylmalyngamide F (5), H (6), J (7) K (8), and characterized from a Grenada field collection of the marine cyanobacterium Lyngbya majuscula. The planar structures of these compounds were deduced by 1D- and 2D-NMR and mass spectral data interpretation. The absolute configurations were determined by a combination of CD-spectroscopy, chemical degradation and the variable temperature Mosher’s method. Compounds 1–5, 7 and 8 displayed moderate cytotoxicity to NCI-H460 human lung tumor and neuro-2a cancer cell lines, with IC50 values ranging between 0.5 and 20 μg/mL. PMID:20701935

  15. Theoretical Investigation on the Substituent Effect of Halogen Atoms at the C8 Position of Adenine: Relative Stability, Vibrational Frequencies, and Raman Spectra of Tautomers.

    PubMed

    Chen, Yan-Li; Wu, De-Yin; Tian, Zhong-Qun

    2016-06-16

    We have theoretically investigated the substituent effect of adenine at the C8 position with a substituent X = H, F, Cl, and Br by using the density functional theory (DFT) at the B3LYP/6-311+G(d, p) level. The aim is to study the substituent effect of halogen atoms on the relative stability, vibrational frequencies, and solvation effect of tautomers. Our calculated results show that for substituted adenine molecules the N9H8X tautomer to be the most stable structure in gas phase at the present theoretical level. Here N9H8X denotes the hydrogen atom binds to the N9 position of imidazole ring and X denotes H, F, Cl, and Br atoms. The influence of the induced attraction of the fluorine substituent is significantly larger than chlorine and bromine ones. The halogen substituent effect has a significant influence on changes of vibrational frequencies and Raman intensities. PMID:27243104

  16. The development of an augmentor wing jet STOL research aircraft (modified C-8A). Volume 2: Analysis of contractor's flight test

    NASA Technical Reports Server (NTRS)

    Skavdahl, H.; Patterson, D. H.

    1972-01-01

    The initial flight test phase of the modified C-8A airplane was conducted. The primary objective of the testing was to establish the basic airworthiness of the research vehicle. This included verification of the structural design and evaluation of the aircraft's systems. Only a minimum amount of performance testing was scheduled; this has been used to provide a preliminary indication of the airplane's performance and flight characteristics for future flight planning. The testing included flutter and loads investigations up to the maximum design speed. The operational characteristics of all systems were assessed including hydraulics, environmental control system, air ducts, the vectoring conical nozzles, and the stability augmentation system (SAS). Approaches to stall were made at three primary flap settings: up, 30 deg and 65 deg, but full stalls were not scheduled. Minimum control speeds and maneuver margins were checked. All takeoffs and landings were conventional, and STOL performance was not scheduled during this phase of the evaluation.

  17. AC conductivity and dielectric relaxation of tris(N,N-dimethylanilinium) hexabromidostannate(IV) bromide: (C8H12N)3SnBr6.Br

    NASA Astrophysics Data System (ADS)

    Chouaib, H.; Kamoun, S.

    2015-10-01

    The X-ray powder analysis, thermogravimetric analysis, differential scanning calorimetry analysis and complex impedance spectroscopic data have been carried out on (C8H12N)3SnBr6.Br compound. The results show that this compound exhibits a phase transition at (T=365±2 K) which has been characterized by differential scanning calorimetry (DSC), AC conductivity and dielectric measurements. The AC conductivity, the modulus analysis, the dielectric constants and the polarizability have been studied using impedance in the temperature range from 334 K to 383 K and in the frequency range between 20 Hz and 2 MHz. The temperature dependence of DC conductivity follows the Arrhenius law. Moreover, the frequency dependence of conductivity follows Jonscher's dynamical law with the relation: σ(ω , T) =σDC + B(T)ω s(T) . Relaxation peaks can be observed in the complex modulus analysis and after a transformation of the complex permittivity ε* to the complex polarizability α*.

  18. GENERAL: Low-temperature heat capacities and standard molar enthalpy of formation of 4-(2-aminoethyl)-phenol (C8H11NO)

    NASA Astrophysics Data System (ADS)

    Di, You-Ying; Kong, Yu-Xia; Yang, Wei-Wei; Tan, Zhi-Cheng

    2008-09-01

    This paper reports that low-temperature heat capacities of 4-(2-aminoethyl)-phenol (C8H11NO) are measured by a precision automated adiabatic calorimeter over the temperature range from 78 to 400 K. A polynomial equation of heat capacities as a function of the temperature was fitted by the least square method. Based on the fitted polynomial, the smoothed heat capacities and thermodynamic functions of the compound relative to the standard reference temperature 298.15 K were calculated and tabulated at the interval of 5 K. The energy equivalent, ɛcalor, of the oxygen-bomb combustion calorimeter has been determined from 0.68 g of NIST 39i benzoic acid to be ɛcalor = (14674.69±17.49)J.K-1. The constant-volume energy of combustion of the compound at T = 298.15 K was measured by a precision oxygen-bomb combustion calorimeter to be ΔcU = -(32374.25±12.93)J.g-1. The standard molar enthalpy of combustion for the compound was calculated to be ΔcHmominus = -(4445.47 ± 1.77) k. J · mol-1 according to the definition of enthalpy of combustion and other thermodynamic principles. Finally, the standard molar enthalpy of formation of the compound was derived to be ΔfHmominus(C8H11NO, s) = -(274.68 ± 2.06) kJ · mol-1, in accordance with Hess law.

  19. High-resolution in situ hybridization analysis on the chromosomal interval 61C7-61C8 of Drosophila melanogaster reveals interbands as open chromatin domains.

    PubMed

    Zielke, Thomas; Glotov, Alexander; Saumweber, Harald

    2016-06-01

    Eukaryotic chromatin is organized in contiguous domains that differ in protein binding, histone modifications, transcriptional activity, and in their degree of compaction. Genome-wide comparisons suggest that, overall, the chromatin organization is similar in different cells within an organism. Here, we compare the structure and activity of the 61C7-61C8 interval in polytene and diploid cells of Drosophila. By in situ hybridization on polytene chromosomes combined with high-resolution microscopy, we mapped the boundaries of the 61C7-8 interband and of the 61C7 and C8 band regions, respectively. Our results demonstrate that the 61C7-8 interband is significantly larger than estimated previously. This interband extends over 20 kbp and is in the range of the flanking band domains. It contains several active genes and therefore can be considered as an open chromatin domain. Comparing the 61C7-8 structure of Drosophila S2 cells and polytene salivary gland cells by ChIP for chromatin protein binding and histone modifications, we observe a highly consistent domain structure for the proximal 13 kbp of the domain in both cell types. However, the distal 7 kbp of the open domain differs in protein binding and histone modification between both tissues. The domain contains four protein-coding genes in the proximal part and two noncoding transcripts in the distal part. The differential transcriptional activity of one of the noncoding transcripts correlates with the observed differences in the chromatin structure between both tissues. The significance of our findings for the organization and structure of open chromatin domains will be discussed. PMID:26520107

  20. Uptake, distribution, and formation of hemoglobin and DNA adducts after inhalation of C2-C8 1-alkenes (olefins) in the rat.

    PubMed

    Eide, I; Hagemann, R; Zahlsen, K; Tareke, E; Törnqvist, M; Kumar, R; Vodicka, P; Hemminki, K

    1995-07-01

    Absorption, distribution, elimination and hemoglobin and DNA adduct formation were studied in the rat after inhalation of individual C2-C8 1-alkenes (olefins) at 300 p.p.m., 12 h a day for 3 consecutive days. The concentrations of olefins were measured in blood, lung, brain, liver, kidney and perirenal fat immediately after each exposure and 12 h after the third exposure. DNA adducts were determined by 32P-postlabeling in liver, and lymphocytes sampled immediately after the last exposure. Hemoglobin adducts were determined by GC/MS and GC/MS/MS in erythrocytes sampled immediately after the last exposure. Concentrations of 1-alkenes in blood and organs reached a steady-state level after the first 12 h exposure, and the concentrations 12 h after the last exposure were generally low, except in fat tissue. Concentrations of 1-alkenes in blood and the different tissues increased with increasing number of carbon atoms. In contrast, levels of hemoglobin and DNA adducts decreased with increasing number of carbon atoms. The decrease was most pronounced from C2 to C3. The decrease through the whole homologous series from ethene to 1-octene was most pronounced for hemoglobin adducts followed by the DNA adducts in the lymphocytes. All 1-alkenes caused formation of detectable levels of hemoglobin and DNA adducts, although the levels of hemoglobin adducts after C4-C8 exposure were low. The project illustrates important aspects of the use of biomarkers. The structure-activity approach gives possibilities for extrapolation within the homologous series. PMID:7614695

  1. Ex vivo effects of flavonoïds extracted from Artemisia herba alba on cytokines and nitric oxide production in Algerian patients with Adamantiades-Behçet's disease

    PubMed Central

    2011-01-01

    Background Adamantiades-Behçet's disease (ABD) is a chronic multisystemic inflammation with unknown pathophysiology. This disorder is associated with a dysregulation of the cytokine network that hyperactivates neutrophils and macrophages. In this study, we investigate the modulatory effects of flavonoïd compounds extracted from Algerian medicinal plant Artemisia herba alba on Th1 and Th2 cytokines and nitric oxide production. Methods The modulatory effects of flavonoïds extracted from Artemisia herba alba on cytokines and nitric oxide production by peripheral blood mononuclear cells isolated from Algerian ABD patients and healthy controls were respectively measured by means of ELISA assays and Griess modified method. Results Our results show that flavonoïds significantly reduce the production of interleukin-12, the key effector of T helper 1 (Th1) cells and nitric oxide in a dose-dependent manner in Adamantiades-Behçet's disease. In contrast, the production of IL-4, the key marker of Th2 cells was increased. Conclusion This study suggests that in vitro supplementation with flavonoïds extracted from Artemisia herba alba could have potential immuno-modulatory effects characterised by a down-regulation and up-regulation of Th1 and Th2 cytokines, respectively. Moreover, flavonoïds may prevent nitric oxide induced damages. PMID:22104639

  2. Behçet's disease departs the ‘Silk Road’: a case report and brief review of literature with geographical comparison

    PubMed Central

    Ahmed, Zohair; Rossi, Maria L.; Yong, Sherri; Martin, Daniel K.; Walayat, Saqib; Cashman, Michael; Tsoraides, Steven; Dhillon, Sonu

    2016-01-01

    Behçet's disease (BD) is a chronic multisystem inflammatory disease most prevalent in Eastern Asia and along the Mediterranean basin, an area referred to as the ‘Silk Road’. The diagnosis of BD is largely based on the International Study Group (ISG) criteria, which are more specific than sensitive. ISG criteria do not include intestinal manifestations, a feature more commonly seen in the West. Intestinal BD is one of several findings that are not typically seen along the ‘Silk Road’. Herein we report a rare case of intestinal BD and compare Western versus traditional BD. A 25-year-old male with a history of painful oral aphthous ulcers, pericarditis, and diffuse papulopustular rash presented to the emergency department with two terminal ileal perforations. Pathology demonstrated mucosal necrosis with active inflammation and no chronic inflammatory changes. Post-surgical laboratory studies showed an elevated c-reactive protein of 35.57 mg/dL, erythrocyte sedimentation rate of 82 mm/h, and a positive anti-Saccharomyces cerevisiae antibody. Rheumatological workup including ANA, RF, PR3 antibody, MPO antibody, ANCA, SSA and SSB, Smith antibody, SCL-70, and anti-Jo-1 antibodies were all negative. His pericarditis symptoms improved with colchicine and prednisone prior to discharge. Our patient did not meet the current ISG criteria for traditional BD; however, he clearly showed findings typically seen in Western patients with BD, which include intestinal manifestations, cardiac involvement, and lack of pathergy reaction and ocular changes. Our investigation demonstrates that the clinical manifestations common to this disorder vary among geographic and ethnic populations. Commonly used criteria for the diagnosis of BD may not be sensitive for some populations, such as Western BD, potentially leading to underdiagnoses and mismanagement. Recognition and select inclusion of these differences may be one way to assist with diagnosing Western BD in the future. As our

  3. Serum Lipid, Lipoprotein and Oxidatively Modified Low Density Lipoprotein Levels in Active or Inactive Patients with Behçet's Disease

    PubMed Central

    Cimen, Fuat; Yildirmak, Sembol Turken; Ergen, Andac; Cakmak, Mustafa; Dogan, Serkan; Yenice, Necati; Sezgin, Funda

    2012-01-01

    Aim: To determine serum lipid, lipoproteins and oxidized low density lipoprotein (oxLDL) levels in Behçet's disease (BD) and to evaluate the relationship of these parameters with the clinical activity of the disease. Materials and Methods: Sixty-two patients (25 active, 37 inactive) and —26 healthy controls were included in the study. We measured serum oxLDL levels using the enzyme-linked immunosorbent assay method, and serum total cholesterol (TC), triglyceride (TG) and high density lipoprotein-cholesterol (HDL-C) levels by spectrophotometric method. Results: Serum TG (108±70 mg/dL and 79±40 mg/dL, respectively; P<0.05), LDL-C (124±35 mg/dL and 108±26 mg/dL, respectively; P<0.05) and oxLDL (65±19 U/L and 53±10 U/L, respectively; P<0.01) levels were significantly higher in patients than in controls, but HDL-C levels were significantly lower in patients than in controls (39±11 mg/dL and 50±13 mg/dL, respectively; P<0.05). The levels of oxLDL in patients were found to correlate with those of TC and LDL-C. Neither the lipid parameters nor the oxLDL levels in the patients with active disease (n=25) were different than those in the patients who were in inactive stage (n=37). Serum levels of oxLDL in the patients with active and inactive disease were significantly higher than those in controls (66±19 U/L, 65±19 U/L, and 53±10 U/L, respectively; P<0.05). Conclusions: We conclude that the increase of TG, LDL-C and oxLDL levels and the decrease of HDL-levels may indicate that there is a tendency to atherothrombotic process in patients with BD. Inflammation and immunologic reactions in BD may be caused by a response to elevated oxLDL. TG, LDL-C and oxLDL are not useful markers for the severity of the disease activity. PMID:22615503

  4. The natural course and factors affecting severity of Behçet's disease: a single-center cohort of 368 patients.

    PubMed

    Ugurlu, Nilay; Bozkurt, Selen; Bacanli, Ali; Akman-Karakas, Ayse; Uzun, Soner; Alpsoy, Erkan

    2015-12-01

    Our goal was to determine, retrospectively, the occurrence of the symptoms of Behçet's disease in chronological order and the course of the disease. Additionally, probable factors affecting the clinical severity were investigated. A total of 368 patients (171 females and 197 males; aged 41.11 ± 10.9 years) were included in this retrospective cohort study. The chronological order of the clinical manifestations was recorded. Patients were also assessed for clinical severity score. Oral ulcer was the most common manifestation (100 %) followed by genital ulcer (89.4 %), papulopustular lesions (75 %) and articular involvement (60.1 %). Oral ulcer was the most common onset manifestation (66.8 %) followed by genital ulcer (4.9 %), erythema nodosum (3.3 %) and ocular involvement (1.4 %). The duration between the onset symptom and the fulfillment of the diagnostic criteria was 4.67 ± 5.9 years. The duration between the time point of fulfillment of diagnostic criteria and the diagnosis (2.5 ± 2.1 years) was longer in patients having only mucocutaneous lesions (2.8 ± 2.2 years) than in patients having serious organ involvements (1.9 ± 1.6 years; p < 0.01). Serious involvements such as neurological involvement and large vessel involvement had their onsets later. Mean clinical severity score was higher in male patients (5.3 ± 2.1 vs 4.8 ± 1.7; p < 0.05). In logistic regression analysis, male gender (p = 0.03) and increased number of symptoms at diagnosis (p < 0.001, R (2) = 0.73) were found to be significant risk factors for severity. Mucocutaneous lesions, especially oral and/or genital ulcers, usually precede possible serious involvements; therefore, careful follow-up is mandatory. Males with increased number of organ involvements at the diagnosis are associated with more severe disease. PMID:26084503

  5. Comparative optical study of the two-dimensional donor-type intercalation compounds graphite-KHx and their binary counterparts C8K and C24K

    NASA Astrophysics Data System (ADS)

    Doll, G. L.; Yang, M. H.; Eklund, P. C.

    1987-06-01

    We report the results of optical reflectivity studies of the stage-1 and -2 graphite-KHx intercalation compounds prepared by direct reaction of highly ordered pyrolytic graphite and KH powder. The stage-1 and -2 binary graphite-K compounds are studied for comparison. The optical data are analyzed in terms of a model involving two-dimensional (2D) graphitic π electrons and three-dimensional (3D) nearly free K(4s) electrons. The model is used to interpret the observed values of the free-carrier unscreened plasma frequencies and the position of the interband absorption threshold to determine experimental values for the Fermi level (EF) in the carbon π band(s) and the fractional occupation of the K(4s) band. For the hydrides, we find quantitative evidence that the hydrogen states lie below EF. Thus, hydrogen is present as H-, acting as an acceptor, thereby compensating the electron donation to the π bands from the K(4s) states. This assumption and the optical data for the stage-1 and -2 hydrides results in a [H]/[K] ratio of 0.8, in excellent agreement with chemical analyses reported by Guérard and co-workers, and leads to very small values for the fractional K(4s) band occupation fK<0.03 electrons per K atom. Within the framework of a superimposed 2D (π) and 3D [K(4s)] rigid-band model, our experimental results support an empty K(4s) band (i.e., fK=0) in stage-2 C24K. In stage-1 C8K, the rigid-band model yields large values for fK (fK>0.5 electrons per K atom), unless the value of the optical mass of the electrons in the K(4s) states is larger than ~2. The C8K results are also discussed in terms of more sophisticated energy-band calculations.

  6. CYP2C8-mediated interaction between repaglinide and steviol acyl glucuronide: In vitro investigations using rat and human matrices and in vivo pharmacokinetic evaluation in rats.

    PubMed

    Xu, Yunting; Zhou, Dandan; Wang, Yedong; Li, Jiajun; Wang, Meiyu; Lu, Jia; Zhang, Hongjian

    2016-08-01

    CYP2C8 is involved in the metabolic clearance of several important drugs and recent reports have shown that acyl glucuronides of gemfibrozil and clopidogrel are potent time-dependent inhibitors of CYP2C8 activity. In the present study, the inhibitory effect of steviol acyl glucuronide (SVAG), a circulating metabolite formed after the ingestion of rebaudioside A, was investigated using in vitro and in vivo systems. Results indicated that SVAG was a reversible but not a time-dependent inhibitor of CYP2C8-mediated paclitaxel 6α-hydroxylation. SVAG was also capable of inhibiting CYP2C8-mediated repaglinide 3'-hydroxylation in human liver microsomes and recombinant human CYP2C8, with Ki values of 15.8 μM and 11.6 μM, respectively. In contrast, SVAG did not exhibit inhibitory effect on CYP2C8 activity in rat liver microsomes. In addition, co-administration of rebaudioside A with repaglinide in rats did not lead to AUC and Cmax changes of repaglinide. Although mathematic prediction using a simplified mechanistic model revealed a moderate interaction potential between repaglinide and SVAG, cautions should be given to patients with hypoglycemia if repaglinide and rebaudioside A are used in combination for the blood sugar control. PMID:27259818

  7. Observed trends in ambient concentrations of C 2-C 8 hydrocarbons in the United Kingdom over the period from 1993 to 2004

    NASA Astrophysics Data System (ADS)

    Dollard, G. J.; Dumitrean, P.; Telling, S.; Dixon, J.; Derwent, R. G.

    Hourly measurements of up to 26 C 2-C 8 hydrocarbons have been made at eight urban background sites, three urban-industrial sites, a kerbside and a rural site in the UK from 1993 onwards up until the end of December 2004. Average annual mean benzene and 1,3-butadiene concentrations at urban background locations have declined at about -20% per year and the observed declines have exactly mimicked the inferred declines in benzene and 1,3-butadiene emissions over the same period. Ninety-day rolling mean concentrations of ethylene, propylene, n- and i-butane, n- and i-pentane, isoprene and propane at urban and rural sites have also declined steadily by between -10% and -30% per year. Rolling mean concentrations of acetylene, 2- and 3-methylpentane, n-hexane, n-heptane, cis- and trans-but-2-ene, cis- and trans-pent-2-ene, toluene, ethylbenzene and o-, m- and p-xylene at a roadside location in London have all declined at between -14% and -21% per year. These declines demonstrate that motor vehicle exhaust catalysts and evaporative canisters have effectively and efficiently controlled vehicular emissions of hydrocarbons in the UK. Urban ethane concentrations arising largely from natural gas leakage have remained largely unchanged over this same period.

  8. Aquasoluble iron(III)-arylhydrazone-β-diketone complexes: structure and catalytic activity for the peroxidative oxidation of C5-C8 cycloalkanes.

    PubMed

    Kopylovich, Maximilian N; Mac Leod, Tatiana C O; Haukka, Matti; Amanullayeva, Gunel I; Mahmudov, Kamran T; Pombeiro, Armando J L

    2012-10-01

    The aquasoluble Fe(III) complexes [Fe(H(2)O)(3)(L(1))]∙4H(2)O (3) and [Fe(H(2)O)(3)(L(2))]∙3H(2)O (4), bearing the basic forms of 5-chloro-3-(2-(4,4-dimethyl-2,6-dioxocyclohexylidene)hydrazinyl)-2-hydroxy-benzenesulfonic acid (H(3)L(1), 1) and 3-(2-(2,4-dioxopentan-3-ylidene)hydrazinyl)-2-hydroxy-5-nitrobenzenesulfonic acid (H(3)L(2), 2), were synthesized and fully characterized including by X-ray crystal structural analysis. In the channels of the water-soluble 3D networks of 3 and 4, the uncoordinated water molecules are held by oxygen atoms of the carbonyl and sulfonyl groups, and by the water ligands. The Fe(III) coordination environment resembles that in the active sites of some mononuclear non-heme iron-containing enzymes. The complexes show a high catalytic activity for the peroxidative oxidation (with aqueous H(2)O(2)) of C(5)-C(8) cycloalkanes to the corresponding alcohols and ketones under mild conditions. The effects of various factors, such as amounts of oxidant, catalyst and HNO(3) additive, were investigated allowing to reach overall yields of ca. 25% and turnover numbers (TONs) up to 290. The catalytic reactions proceed via both oxygen- and carbon-radicals as shown by radical trap experiments. PMID:22926026

  9. Study on the biodegradation of alternatives (four species including C8H8F9KO3S) for perfluorooctane sulfonate

    PubMed Central

    Choi, Bong-In; Na, Suk-Hyun; Kwak, Yeong-Don; Ryu, Byung-Taek; Chung, Seon-Yong

    2015-01-01

    Objectives The objective of this study was to evaluate the biodegradation potential of four perfluorooctane sulfonic acid (PFOS) alternatives that were developed at Changwon National University. While PFOS has been used widely in industrial and consumer products, it is known to be a persistent organic pollutant. Therefore, greener alternatives are highly desirable. Methods Biodegradation tests were run for 28 days using standard test protocols. The biochemical oxygen demand was measured daily throughout the experimental period, and the data were used to calculate the biodegradation rates. Microorganisms were isolated from the some of the tests that showed evidence of biodegradation. Results C8H8F9KO3S, which has the same number of carbons as the parent compound PFOS but a reduced number of fluorines, showed the highest biodegradation rate followed by C10H8F13KO3S. Chemical alternatives with lower number of carbons did not biodegrade readily in the experiments. Conclusions Together, these results suggest that it may be advantageous to develop PFOS alternatives with 8 carbons, the same as PFOS, but a reduced number of fluorines; as such, chemicals are more susceptible to biodegradation than the parent compound. PMID:26206369

  10. Three-layer structure graphene/mesoporous silica composites incorporated with C8-modified interior pore-walls for residue analysis of glucocorticoids in milk by liquid chromatography-tandem mass spectrometry.

    PubMed

    Liu, Xiaodan; Feng, Jianan; Sun, Xueni; Li, Yan; Duan, Gengli

    2015-07-16

    Three-layer structure graphene/mesoporous silica composites incorporated with C8-modified interior pore-walls (graphene@mSiO2-C8) were prepared and applied for efficient extraction of glucocorticoid residuals in milk followed by liquid chromatography-tandem mass spectrometry (LC-MS/MS) analysis. The graphene@mSiO2-C8 nanocomposites were synthesized by coating C8-modified mesoporous silica onto hydrophilic graphene nanosheets through a simple surfactant-mediated co-condensation sol-gel process. The obtained nanosheets possess unique properties of large surface area (632 m(2)/g), extended plate-like morphology in the exterior surface, highly open pore structure with uniform pore size (2.8 nm), numerous C8-modified interior pore-walls, as well as good water dispersibility. The performance of the prepared graphene@mSiO2-C8 materials for extracting small hydrophobic molecules directly from complex protein-rich samples was evaluated by analysis of glucocorticoids in milk. Extraction conditions such as sorbents amount, type and volume of eluting solvent, time of adsorption and desorption were investigated and optimized to achieve the best efficiency. Method validations including linearity, recovery, repeatability, and limit of detection (LOD) were also studied. The results indicated that this methodology provided low LOD (S/N=3, 0.0075-0.03 ng mL(-1)) and good linearity (0.03-60 ng mL(-1), R(2)>0.996) for glucocorticoids. Satisfactory reusability and stability were also obtained during the extraction. Finally, the graphene@mSiO2-C8 composites were successfully applied to the extraction and residue analysis of glucocorticoids in real milk samples. The experimental results showed that this novel approach offered an attractive choice for convenient, efficient and rapid solid-phase extraction of targeted hydrophobic compounds in biological samples. PMID:26073810

  11. Importance of the C2, N7, and C8 positions to the mutagenic potential of 8-Oxo-2'-deoxyguanosine with two A family polymerases.

    PubMed

    Hamm, Michelle L; Crowley, Kelly A; Ghio, Michael; Del Giorno, Laura; Gustafson, Margaret A; Kindler, Kevin E; Ligon, Claire W; Lindell, Maria A M; McFadden, Emily J; Siekavizza-Robles, Carlos; Summers, Matthew R

    2011-12-13

    8-Oxo-2'-deoxyguanosine (OdG) is a prominent DNA lesion produced from the reaction of 2'-deoxyguanosine (dG) with reactive oxygen species. While dG directs the insertion of only dCTP during replication, OdG can direct the insertion of either dCTP or dATP, allowing for the production of dG → dT transversions. When replicated by Klenow fragment-exo (KF-exo), OdG preferentially directs the incorporation of dCTP over dATP, thus decreasing its mutagenic potential. However, when replicated by a highly related polymerase, the large fragment of polymerase I from Bacillus stearothermophilus (BF), dATP incorporation is preferred, and a higher mutagenic potential results. To gain insight into the reasons for this opposite preference and the effects of the C2, N7, and C8 positions on OdG mutagenicity, single-nucleotide insertions of dCTP and/or dATP opposite dG, OdG, and seven of their analogues were examined by steady state kinetics with both KF-exo and BF. Results from these studies suggest that the two enzymes behave similarly and are both sensitive not only to steric and electronic changes within the imidazole ring during both dCTP and dATP incorporation but also to the presence of the C2-exocyclic amine during dATP incorporation. The difference in incorporation preference opposite OdG appears to be due to a somewhat increased sensitivity to structural perturbations during dCTP incorporation with BF. Single-nucleotide extensions past the resulting base pairs were also studied and were not only similar between the two enzymes but also consistent with published ternary crystallographic studies with BF. These results are analyzed in the context of previous biochemical and structural studies, as well as stability studies with the resulting base pairs. PMID:22081979

  12. Explicitly correlated benchmark calculations on C8H8 isomer energy separations: how accurate are DFT, double-hybrid, and composite ab initio procedures?

    NASA Astrophysics Data System (ADS)

    Karton, Amir; Martin, Jan M. L.

    2012-10-01

    Accurate isomerization energies are obtained for a set of 45 C8H8 isomers by means of the high-level, ab initio W1-F12 thermochemical protocol. The 45 isomers involve a range of hydrocarbon functional groups, including (linear and cyclic) polyacetylene, polyyne, and cumulene moieties, as well as aromatic, anti-aromatic, and highly-strained rings. Performance of a variety of DFT functionals for the isomerization energies is evaluated. This proves to be a challenging test: only six of the 56 tested functionals attain root mean square deviations (RMSDs) below 3 kcal mol-1 (the performance of MP2), namely: 2.9 (B972-D), 2.8 (PW6B95), 2.7 (B3PW91-D), 2.2 (PWPB95-D3), 2.1 (ωB97X-D), and 1.2 (DSD-PBEP86) kcal mol-1. Isomers involving highly-strained fused rings or long cumulenic chains provide a 'torture test' for most functionals. Finally, we evaluate the performance of composite procedures (e.g. G4, G4(MP2), CBS-QB3, and CBS-APNO), as well as that of standard ab initio procedures (e.g. MP2, SCS-MP2, MP4, CCSD, and SCS-CCSD). Both connected triples and post-MP4 singles and doubles are important for accurate results. SCS-MP2 actually outperforms MP4(SDQ) for this problem, while SCS-MP3 yields similar performance as CCSD and slightly bests MP4. All the tested empirical composite procedures show excellent performance with RMSDs below 1 kcal mol-1.

  13. Translesion synthesis past guanine(C8)-thymine(N3) intrastrand cross-links catalyzed by selected A- and Y-family polymerases.

    PubMed

    Lee, Young-Ae; Lee, Yuan-Cho; Geacintov, Nicholas E; Shafirovich, Vladimir

    2016-05-24

    Oxidatively generated guanine radicals in DNA can undergo various nucleophilic reactions including the formation of C8-guanine cross-links with adjacent or nearby N3-thymines in DNA in the presence of O2. These G[8-3]T lesions have been identified in the DNA of human cells exposed to oxidative stress, and are most likely genotoxic if not removed by cellular defence mechanisms. The abilities of several representative polymerases to bypass the G[8-3]T lesions in two different sequence contexts, G*T* and G*CT*, were assessed in vitro. The polymerase BF (bacillus fragment) from Bacillus stearothermophilus, the Y-family archaeal polymerases Dpo4 from Sulfolobus sulfataricus P2, and human DNA pol κ and pol η were selected for the study. The A-family polymerase BF was strongly blocked, while relatively weak translesion synthesis was observed in the case of Y-family polymerases Dpo4 and pol κ. Primer extension catalyzed by pol η was also partially stalled at various positions at or near the G[8-3]T cross-linked bases, but a significant and distributive primer extension was observed beyond the sites of the lesions with the efficiency being consistently greater in the case of G*CT* than in the case of G*T* lesions. The results obtained with pol η are compared with translesion synthesis past other intrastrand cross-linked lesions with previously published results of others that include the isomeric G[8-5m]T lesions generated by ionizing radiation, the cis-syn cyclobutane pyrimidine dimer and the 6-4 photoproduct generated by UV irradiation, and the Pt-G*G* lesions derived from the reactions of the chemotherapeutic agent cisplatin with DNA. PMID:27102383

  14. Impact of a synthetic cannabinoid (CP-47,497-C8) on protein expression in human cells: evidence for induction of inflammation and DNA damage.

    PubMed

    Bileck, Andrea; Ferk, Franziska; Al-Serori, Halh; Koller, Verena J; Muqaku, Besnik; Haslberger, Alexander; Auwärter, Volker; Gerner, Christopher; Knasmüller, Siegfried

    2016-06-01

    Synthetic cannabinoids (SCs) are marketed worldwide as legal surrogates for marihuana. In order to predict potential health effects in consumers and to elucidate the underlying mechanisms of action, we investigated the impact of a representative of the cyclohexylphenols, CP47,497-C8, which binds to both cannabinoid receptors, on protein expression patterns, genomic stability and on induction of inflammatory cytokines in human lymphocytes. After treatment of the cells with the drug, we found pronounced up-regulation of a variety of enzymes in nuclear extracts which are involved in lipid metabolism and inflammatory signaling; some of the identified proteins are also involved in the endogenous synthesis of endocannabinoids. The assumption that the drug causes inflammation is further supported by results obtained in additional experiments with cytosols of LPS-stimulated lymphocytes which showed that the SC induces pro-inflammatory cytokines (IL12p40 and IL-6) as well as TNF-α. Furthermore, the proteome analyses revealed that the drug causes down-regulation of proteins which are involved in DNA repair. This observation provides an explanation for the formation of comets which was seen in single-cell gel electrophoresis assays and for the induction of micronuclei (which reflect structural and numerical chromosomal aberrations) by the drug. These effects were seen in experiments with human lymphocytes which were conducted under identical conditions as the proteome analysis. Taken together, the present findings indicate that the drug (and possibly other structurally related SCs) may cause DNA damage and inflammation in directly exposed cells of consumers. PMID:26194647

  15. Selective synthesis of the [Ni36Co8C8(CO)48]6- octa-carbide carbonyl cluster by thermal decomposition of the [H2Ni22Co6C6(CO)36]4- hexa-carbide.

    PubMed

    Ciabatti, Iacopo; Fabrizi de Biani, Fabrizia; Femoni, Cristina; Iapalucci, Maria Carmela; Longoni, Giuliano; Zacchini, Stefano

    2013-07-14

    The thermal decomposition in thf solution of [H2Ni22Co6C6(CO)36](4-) results in the new [HNi36Co8C8(CO)48](5-) bimetallic Ni-Co octa-carbide, which can be converted into the closely related [H6-nNi36Co8C8(CO)48](n-) (n = 3-6) polyhydrides by means of acid-base reactions. The structure of the [Ni36Co8C8(CO)48](6-) hexa-anion has been established via X-ray crystallography, showing that the eight interstitial carbide atoms are lodged within different metal cages. Thus, two C-atoms are enclosed within regular square anti-prismatic Ni8C cages, four within irregular Ni8C square anti-prismatic cages, and the last two within mono-capped trigonal prismatic Ni5Co2C cages. The structure of [Ni36Co8C8(CO)48](6-) is non-compact and closely related to [Ni32C6(CO)38](6-) and [HNi38C6(CO)44](5-). [Ni36Co8C8(CO)48](6-) approaches the nanosize regime and the whole molecular ion has a diameter (measured from the outer oxygen atoms) of ca. 1.61 nm. PMID:23676989

  16. Cooperativity and bond breakage in model X-⋯H3P⋯YZ (X = F, Cl; YZ = HF, ClF, LiF, BeH2) complexes

    NASA Astrophysics Data System (ADS)

    McDowell, Sean A. C.

    2016-08-01

    A computational study of hydrogen-, halogen-, lithium- and beryllium-bonded interactions in model H3P⋯YZ (YZ = HF, ClF, LiF, BeH2) complexes involving the Lewis base phosphine (H3P) was undertaken. A subsequent investigation of the interplay between the F-/Cl-⋯Hsbnd P and P⋯YZ interactions in model F-/Cl-⋯H3P⋯YZ complexes revealed strong cooperative effects, leading to bond breakage of the Hsbnd P and/or Clsbnd F bonds in some cases. These results were rationalized using natural bond orbital (NBO) and quantum atoms in molecules (QTAIM) analyses of the electron density, as well as a consideration of the relative electronegativities of the P and Y atoms.

  17. Synchrotron-Based Highest Resolution FTIR Spectroscopy of Azulene, Naphthalene (C_{10}H_8), Indole (C_{8}H_6N) and Biphenyl (C_{12}H_{10})

    NASA Astrophysics Data System (ADS)

    Albert, S.; Quack, M.; Lerch, Ph.

    2013-06-01

    Great progress has been made in resolution (Δν≤ 20 MHz) and sensitivity in the field of high resolution Fourier transform infrared (FTIR) spectroscopy over the last decade. In particular, the use of synchrotron sources such as the Swiss Light Source (SLS) have overcome one of the disadvantages of high resolution FTIR spectroscopy, the problem of noise related to modest signal strength with broad band coverage from weak light sources. FTIR spectroscopy with synchrotron sources now makes it possible to investigate scientific questions of fundamental physics and astrophysics. One of the great challenges of astronomical infrared spectroscopy is the identification of the Unidentified Infrared Bands (UIBs) found in several interstellar objects. Polycyclic Aromatic Hydrocarbons (PAHs) have been proposed to be the carrier of the UIBs For that reason we have started to investigate with our ETH-SLS interferometer the rotationally resolved FTIR spectra of the bicyclic molecules naphthalene (C_{10}H_8)^d and azulene (C_{10}H_8) as a simple prototypical spectrum for a PAH infrared spectrum and of indole (C_{8}H_6N) as a prototype of a bicyclic heteroaromatic system. We have analysed in high resolution the ν_{46} band of naphthalene, the ν_{35} and 2ν_{40} bands of indole as well as the ν_{44} band of azulene. We have found a coincidence between the ν_{46} fundamental of naphthalene and the UIB at 12.78 μm. A comparison of the biphenyl FTIR spectrum with the UIBs in the range 13 to 15 μm illustrates a coincidence between the UIBs at 13.6 μm and 14.2 μm with the major biphenyl bands. S. Albert, K. Keppler Albert and M. Quack, Trend in Optics and Photonics 2003, 84, 177-180. S. Albert and M. Quack, ChemPhysChem, 2007, 8, 1271-1281. S. Albert, K. Keppler Albert and M. Quack, High Resolution Fourier Transform Infrared Spectroscopy in Handbook of High Resolution Spectroscopy, Vol. 2 (Eds. M. Quack and F. Merkt), Wiley, Chicester 2011, 965-1021. S. Albert, K.K. Albert, Ph

  18. Variability and epistemic uncertainty in water ingestion rates and pharmacokinetic parameters, and impact on the association between perfluorooctanoate and preeclampsia in the C8 Health Project population.

    PubMed

    Avanasi, Raghavendhran; Shin, Hyeong-Moo; Vieira, Veronica M; Bartell, Scott M

    2016-04-01

    We recently utilized a suite of environmental fate and transport models and an integrated exposure and pharmacokinetic model to estimate individual perfluorooctanoate (PFOA) serum concentrations, and also assessed the association of those concentrations with preeclampsia for participants in the C8 Health Project (a cross-sectional study of over 69,000 people who were environmentally exposed to PFOA near a major U.S. fluoropolymer production facility located in West Virginia). However, the exposure estimates from this integrated model relied on default values for key independent exposure parameters including water ingestion rates, the serum PFOA half-life, and the volume of distribution for PFOA. The aim of the present study is to assess the impact of inter-individual variability and epistemic uncertainty in these parameters on the exposure estimates and subsequently, the epidemiological association between PFOA exposure and preeclampsia. We used Monte Carlo simulation to propagate inter-individual variability/epistemic uncertainty in the exposure assessment and reanalyzed the epidemiological association. Inter-individual variability in these parameters mildly impacted the serum PFOA concentration predictions (the lowest mean rank correlation between the estimated serum concentrations in our study and the original predicted serum concentrations was 0.95) and there was a negligible impact on the epidemiological association with preeclampsia (no change in the mean adjusted odds ratio (AOR) and the contribution of exposure uncertainty to the total uncertainty including sampling variability was 7%). However, when epistemic uncertainty was added along with the inter-individual variability, serum PFOA concentration predictions and their association with preeclampsia were moderately impacted (the mean AOR of preeclampsia occurrence was reduced from 1.12 to 1.09, and the contribution of exposure uncertainty to the total uncertainty was increased up to 33%). In conclusion

  19. Synthesis, crystal structure, and properties of Mg(x)B50C8 or Mg(x)(B12)4(CBC)2(C2)2 (x = 2.4-4).

    PubMed

    Adasch, Volker; Schroeder, Melanie; Kotzott, Dominik; Ludwig, Thilo; Vojteer, Natascha; Hillebrecht, Harald

    2010-10-01

    Single crystals of a new magnesium boride carbide Mg(x)B(50)C(8) (x = 2.4-4) were synthesized from the elements in a metallic melt using tantalum ampules. Crystals were characterized by single crystal X-ray diffraction and electron microprobe analysis. The variation of the Mg content results from different reaction conditions. The composition Mg(∼3)B(50)C(8) is by far the most favored. It fulfills the electron counting rules of Wade and Longuet-Higgins and thus explains the light-green to yellow transparent color. The structure of Mg(∼3)B(50)C(8) (C2/m, Z = 1, a = 8.9384(12) Å, b = 5.6514(9) Å, c = 9.6021(13) Å, β = 105.86(1)°) consists of B(12) icosahedra. The icosahedra are interconnected by four exohedral B-B bonds to layers. The layers are connected to a three-dimensional covalent network by C(2) and CBC units and further exohedral B-B bonds. The Mg sites are partially occupied. Different site occupation factors cause the various compositions and colors (Mg(2.4)B(50)C(8), brown; Mg(4)B(50)C(8), black). The vibrational spectra show the modes of B(12) icosahedra and C(2) and CBC units as well. Measurements of the microhardness according to Vickers and Knoop revealed remarkably high values of H(V) = 3286 (32.0 GPa) and H(K) = 3165 (31.5 GPa), which exceed the values of B(4)C. Optical spectra reveal a band gap of 2.7 eV for Mg(∼3)B(50)C(8), in agreement to the observed color. This justifies an ionic description, and the formula can be written as (Mg(2+))(3)(B(12)(2-))(4)(CBC(+))(2)(C(2))(2). PMID:20839790

  20. Room temperature dehydrogenation of ethane, propane, linear alkanes C4-C8, and some cyclic alkanes by titanium-carbon multiple bonds.

    PubMed

    Crestani, Marco G; Hickey, Anne K; Gao, Xinfeng; Pinter, Balazs; Cavaliere, Vincent N; Ito, Jun-Ichi; Chen, Chun-Hsing; Mindiola, Daniel J

    2013-10-01

    The transient titanium neopentylidyne, [(PNP)Ti≡C(t)Bu] (A; PNP(-)≡N[2-P(i)Pr2-4-methylphenyl]2(-)), dehydrogenates ethane to ethylene at room temperature over 24 h, by sequential 1,2-CH bond addition and β-hydrogen abstraction to afford [(PNP)Ti(η(2)-H2C═CH2)(CH2(t)Bu)] (1). Intermediate A can also dehydrogenate propane to propene, albeit not cleanly, as well as linear and volatile alkanes C4-C6 to form isolable α-olefin complexes of the type, [(PNP)Ti(η(2)-H2C═CHR)(CH2(t)Bu)] (R = CH3 (2), CH2CH3 (3), (n)Pr (4), and (n)Bu (5)). Complexes 1-5 can be independently prepared from [(PNP)Ti═CH(t)Bu(OTf)] and the corresponding alkylating reagents, LiCH2CHR (R = H, CH3(unstable), CH2CH3, (n)Pr, and (n)Bu). Olefin complexes 1 and 3-5 have all been characterized by a diverse array of multinuclear NMR spectroscopic experiments including (1)H-(31)P HOESY, and in the case of the α-olefin adducts 2-5, formation of mixtures of two diastereomers (each with their corresponding pair of enantiomers) has been unequivocally established. The latter has been spectroscopically elucidated by NMR via C-H coupled and decoupled (1)H-(13)C multiplicity edited gHSQC, (1)H-(31)P HMBC, and dqfCOSY experiments. Heavier linear alkanes (C7 and C8) are also dehydrogenated by A to form [(PNP)Ti(η(2)-H2C═CH(n)Pentyl)(CH2(t)Bu)] (6) and [(PNP)Ti(η(2)-H2C═CH(n)Hexyl)(CH2(t)Bu)] (7), respectively, but these species are unstable but can exchange with ethylene (1 atm) to form 1 and the free α-olefin. Complex 1 exchanges with D2C═CD2 with concomitant release of H2C═CH2. In addition, deuterium incorporation is observed in the neopentyl ligand as a result of this process. Cyclohexane and methylcyclohexane can be also dehydrogenated by transient A, and in the case of cyclohexane, ethylene (1 atm) can trap the [(PNP)Ti(CH2(t)Bu)] fragment to form 1. Dehydrogenation of the alkane is not rate-determining since pentane and pentane-d12 can be dehydrogenated to 4 and 4-d12 with comparable

  1. 40 CFR 721.10004 - 2-Butenoic acid, 4,4′-[(dibutylstannylene)bis(oxy)]bis[4-oxo-, (2Z,2′Z)-, di-C8-10-isoalkyl...

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ...-, (2Z,2′Z)-, di-C8-10-isoalkyl esters, C9-rich. (a) Chemical substance and significant new uses subject to reporting. (1) The chemical substance identified as 2-butenoic acid, 4,4′- bis[4-oxo-,...

  2. 40 CFR 721.10004 - 2-Butenoic acid, 4,4′-[(dibutylstannylene)bis(oxy)]bis[4-oxo-, (2Z,2′Z)-, di-C8-10-isoalkyl...

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ...-, (2Z,2′Z)-, di-C8-10-isoalkyl esters, C9-rich. (a) Chemical substance and significant new uses subject to reporting. (1) The chemical substance identified as 2-butenoic acid, 4,4′- bis[4-oxo-,...

  3. 40 CFR 721.10004 - 2-Butenoic acid, 4,4′-[(dibutylstannylene)bis(oxy)]bis[4-oxo-, (2Z,2′Z)-, di-C8-10-isoalkyl...

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ...-, (2Z,2′Z)-, di-C8-10-isoalkyl esters, C9-rich. (a) Chemical substance and significant new uses subject to reporting. (1) The chemical substance identified as 2-butenoic acid, 4,4′- bis[4-oxo-,...

  4. A long-standing mystery solved: the formation of 3-hydroxydesloratadine is catalyzed by CYP2C8 but prior glucuronidation of desloratadine by UDP-glucuronosyltransferase 2B10 is an obligatory requirement.

    PubMed

    Kazmi, Faraz; Barbara, Joanna E; Yerino, Phyllis; Parkinson, Andrew

    2015-04-01

    Desloratadine (Clarinex), the major active metabolite of loratadine (Claritin), is a nonsedating long-lasting antihistamine that is widely used for the treatment of allergic rhinitis and chronic idiopathic urticaria. For over 20 years, it has remained a mystery as to which enzymes are responsible for the formation of 3-hydroxydesloratadine, the major active human metabolite, largely due to the inability of any in vitro system tested thus far to generate this metabolite. In this study, we demonstrated that cryopreserved human hepatocytes (CHHs) form 3-hydroxydesloratadine and its corresponding O-glucuronide. CHHs catalyzed the formation of 3-hydroxydesloratadine with a Km of 1.6 μM and a Vmax of 1.3 pmol/min per million cells. Chemical inhibition of cytochrome P450 (P450) enzymes in CHHs demonstrated that gemfibrozil glucuronide (CYP2C8 inhibitor) and 1-aminobenzotriazole (general P450 inhibitor) inhibited 3-hydroxydesloratadine formation by 91% and 98%, respectively. Other inhibitors of CYP2C8 (gemfibrozil, montelukast, clopidogrel glucuronide, repaglinide, and cerivastatin) also caused extensive inhibition of 3-hydroxydesloratadine formation (73%-100%). Assessment of desloratadine, amodiaquine, and paclitaxel metabolism by a panel of individual CHHs demonstrated that CYP2C8 marker activity robustly correlated with 3-hydroxydesloratadine formation (r(2) of 0.70-0.90). Detailed mechanistic studies with sonicated or saponin-treated CHHs, human liver microsomes, and S9 fractions showed that both NADPH and UDP-glucuronic acid are required for 3-hydroxydesloratadine formation, and studies with recombinant UDP-glucuronosyltransferase (UGT) and P450 enzymes implicated the specific involvement of UGT2B10 in addition to CYP2C8. Overall, our results demonstrate for the first time that desloratadine glucuronidation by UGT2B10 followed by CYP2C8 oxidation and a deconjugation event are responsible for the formation of 3-hydroxydesloratadine. PMID:25595597

  5. Palladium-Catalyzed C8-Selective C–H Arylation of Quinoline N-Oxides: Insights into the Electronic, Steric, and Solvation Effects on the Site Selectivity by Mechanistic and DFT Computational Studies

    PubMed Central

    2015-01-01

    We report herein a palladium-catalyzed C–H arylation of quinoline N-oxides that proceeds with high selectivity in favor of the C8 isomer. This site selectivity is unusual for palladium, since all of the hitherto described methods of palladium-catalyzed C–H functionalization of quinoline N-oxides are highly C2 selective. The reaction exhibits a broad synthetic scope with respect to quinoline N-oxides and iodoarenes and can be significantly accelerated to subhour reaction times under microwave irradiation. The C8-arylation method can be carried out on a gram scale and has excellent functional group tolerance. Mechanistic and density functional theory (DFT) computational studies provide evidence for the cyclopalladation pathway and describe key parameters influencing the site selectivity. PMID:25580364

  6. A new monohydrogendecavanadate (V)-dihydrogendecavanadate (V) with dibutylammonium cations [C8NH20]9[H2V10O28][HV10O28].2.13H2O: Synthesis, crystal structure, vibrational and optical properties

    NASA Astrophysics Data System (ADS)

    Omri, Issam; Mhiri, Tahar; Graia, Mohsen

    2016-03-01

    A new decavanadate, [C8NH20]9[H2V10O28][HV10O28].2.13H2O, was synthesized by slow evaporation from aqueous solution and characterized by IR, Raman and UV-Vis spectroscopies. The crystal structure was solved by single-crystal X-ray diffraction. [C8NH20]9[H2V10O28][HV10O28].2.13H2O consists of dihydrogendecavanadate [H2V10O28]4-, monohydrogendecavanadate [HV10O28]5-, dibutylammonium cations and water molecules. The decavanadate units are assembled in tetramers arrays by interanionic hydrogen bonds O-H···O and cation-anion N-H···O interactions. The dibutylammonium [C8NH20]+ cations and water molecules connect the tetramers into a three-dimensional network. The presence of the two types of units, [HnV10O28](6-n)- with n = 1 and n = 2, in one compound was not yet observed and is herein reported for the first time. The IR and Raman spectra exhibit characteristic bands of all groups present in the structure. The optical analysis shows that this compound is a semiconductor material with an optical band gap of 2.59 eV.

  7. Un anévrysme sacciforme de l'aorte abdominale révélant une maladie de Behçet: quand faut-il opérer?

    PubMed Central

    Ajili, Faida; Tounsi, Haifa; Aouini, Fatma; Bousetta, Najeh; Ben Abdelhafidh, Nadia; Louzir, Bassem; Laabidi, Janet; Othmani, Salah

    2014-01-01

    L'atteinte vasculaire est fréquente au cours de la maladie de Behçet. Elle est essentiellement représentée par les thromboses veineuses alors que l'atteinte artérielle est plus rare. Elle peut être isolée ou multifocale et peut toucher tous les territoires avec prédilection pour l'aorte abdominale, les artères pulmonaires et les artères des membres inférieurs. L'atteinte anévrysmale de l'aorte abdominale est trompeuse se manifestant par une symptomatologie atypique responsable d'un retard diagnostique favorisant la rupture. Dans notre cas, des douleurs abdominales paroxystiques ont incité le patient à consulter rapidement. L'enquête étiologique a conclue à un angio Behcet. Rarement, l'anévrysme de l'aorte abdominale est révélé par une complication telle que la rupture dans le rétro péritoine ou le tube digestif. Les indications chirurgicales des anévrysmes de l'aorte sont discutées ici. Un traitement immunosuppresseur au long cours s'impose en post opératoire pour limiter le risque de récidive. PMID:25852795

  8. Translesion Synthesis Past the C8- and N2-Deoxyguanosine Adducts of the Dietary Mutagen 2-Amino-3-methylimidazo[4,5-f]quinoline in the NarI Recognition Sequence by Prokaryotic DNA Polymerases

    PubMed Central

    Stover, James S.; Chowdhury, Goutam; Zang, Hong; Guengerich, F. Peter; Rizzo, Carmelo J.

    2011-01-01

    2-Amino-3-methylimidazo[4,5-f]quinoline (IQ) is found in cooked meats and forms DNA adducts at the C8- and N2-positions of dGuo after appropriate activation. IQ is a potent inducer of frameshift mutations in bacteria and is carcinogenic in laboratory animals. We have incorporated both IQ-adducts into the G1-and G3-positions of the NarI recognition sequence (5′-G1G2CG3CC-3′), which is a hotspot for arylamine modification. The in vitro replication of the oligonucleotides was examined with Escherichia coli pol I Klenow fragment exo−, E. coli pol II exo−, and Sulfolobus solfataricus P2 DNA polymerase IV (Dpo4), and the extension products were sequenced by tandem mass spectrometry. Replication of the C8-adduct at the G3-position resulted in two-base deletions with all three polymerases, whereas error-free bypass and extension was observed at the G1-position. The N2-adduct was bypassed and extended by all three polymerases when positioned at the G1-position, and the error-free product was observed. The N2-adduct at the G3-position was more blocking and was bypassed and extended only by Dpo4 to produce an error-free product. These results indicate that the replication of the IQ-adducts of dGuo is strongly influenced by the local sequence and the regioisomer of the adduct. These results also suggest a possible role for pol II and IV in the error-prone bypass of the C8-IQ-adduct leading to frameshift mutations in reiterated sequences, whereas noniterated sequences result in error-free bypass. PMID:17112239

  9. Stress Degradation Behavior of Abacavir Sulfate and Development of a Suitable Stability-Indicating UHPLC Method for the Determination of Abacavir, its Related Substances, and Degradation Products.

    PubMed

    Vukkum, Pallavi; Deshpande, Girish R; Babu, J Moses; Muralikrishna, R; Jagu, Pavani

    2012-12-01

    A novel, stability-indicating UHPLC method was developed for the quantitative determination of Abacavir sulfate, its related substances, and forced degradation impurities in bulk drugs. The chromatographic separation was achieved on a Waters Acquity BEH C(8), 50 mm × 2.1 mm, 1.7 μm particle size column with a mobile containing a gradient mixture of solution A (0.10 % v/v o-phosphoric acid in water) and solution B (0.10% v/v o-phosphoric acid in methanol). The flow rate was set at 0.40 mL/min and the run time was 6.0 min. The drug substance was subjected to the stress studies of hydrolysis, oxidation, photolysis, and thermal degradation. Abacavir sulfate was found to degrade significantly under acidic hydrolysis and oxidative stress conditions. The formed degradation products were reported and were well-resolved from Abacavir and its related substances. The mass balance was found to be satisfactory in all of the stress conditions, thus proving the stability-indicating capability of the method. The developed UHPLC method was validated to be in agreement with ICH requirements and found to be rapid, accurate, precise, linear, specific, and suitable for the quantitative determination of related substances and degradants in the bulk drug samples of Abacavir sulfate. PMID:23264939

  10. Heat of Mixing and Solution of N,N,N',N'-Tetramethylbutane-1,4-diamine C8H20N2 + C16H34 Hexadecane (HMSD1111, LB3848_H)

    NASA Astrophysics Data System (ADS)

    Cibulka, I.; Fontaine, J.-C.; Sosnkowska-Kehiaian, K.; Kehiaian, H. V.

    This document is part of Subvolume B 'Binary Liquid Systems of Nonelectrolytes II' of Volume 26 'Heats of Mixing, Vapor-Liquid Equilibrium, and Volumetric Properties of Mixtures and Solutions' of Landolt-Börnstein Group IV 'Physical Chemistry'. It contains the Chapter 'Heat of Mixing and Solution of N,N,N',N'-Tetramethylbutane-1,4-diamine C8H20N2 + C16H34 Hexadecane (HMSD1111, LB3848_H)' providing data from direct low-pressure calorimetric measurement of molar excess enthalpy at variable mole fraction and constant temperature.

  11. 77 FR 72747 - Alkyl(C8

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-12-06

    ... . II. Petition for Exemption In the Federal Register of May 2, 2012 (77 FR 25957) (FRL-9346-1), EPA... Order 12866, entitled ``Regulatory Planning and Review'' (58 FR 51735, October 4, 1993). Because this..., Distribution, or Use'' (66 FR 28355, May 22, 2001) or Executive Order 13045, entitled ``Protection of...

  12. Uniaxially oriented polycrystalline thin films and air-stable n-type transistors based on donor-acceptor semiconductor (diC8BTBT)(FnTCNQ) [n = 0, 2, 4

    NASA Astrophysics Data System (ADS)

    Shibata, Yosei; Tsutsumi, Jun'ya; Matsuoka, Satoshi; Matsubara, Koji; Yoshida, Yuji; Chikamatsu, Masayuki; Hasegawa, Tatsuo

    2015-04-01

    We report the fabrication of high quality thin films for semiconducting organic donor-acceptor charge-transfer (CT) compounds, (diC8BTBT)(FnTCNQ) (diC8BTBT = 2,7-dioctyl[1]benzothieno[3,2-b][1]benzothiophene and FnTCNQ [n = 0,2,4] = fluorinated derivatives of 7,7,8,8,-tetracyanoquinodimethane), which have a high degree of layered crystallinity. Single-phase and uniaxially oriented polycrystalline thin films of the compounds were obtained by co-evaporation of the component donor and acceptor molecules. Organic thin-film transistors (OTFTs) fabricated with the compound films exhibited n-type field-effect characteristics, showing a mobility of 6.9 × 10-2 cm2/V s, an on/off ratio of 106, a sub-threshold swing of 0.8 V/dec, and an excellent stability in air. We discuss the suitability of strong intermolecular donor-acceptor interaction and the narrow CT gap nature in compounds for stable n-type OTFT operation.

  13. Development of a high-performance liquid chromatography-tandem mass spectrometry method for the identification and quantification of CP-47,497, CP-47,497-C8 and JWH-250 in mouse brain.

    PubMed

    Samano, Kimberly L; Poklis, Justin L; Lichtman, Aron H; Poklis, Alphonse

    2014-01-01

    While Marijuana continues to be the most widely used illicit drug, abuse of synthetic cannabinoid (SCB) compounds in 'Spice' or 'K2' herbal incense products has emerged as a significant public health concern in many European countries and in the USA. Several of these SCBs have been declared Schedule I controlled substances but detection and quantification in biological samples remain a challenge. Therefore, we present a liquid chromatography-tandem mass spectrometry method after liquid-liquid extraction for the quantitation of CP-47,497, CP-47,497-C8 and JWH-250 in mouse brain. We report data for linearity, limit of quantification, accuracy/bias, precision, recovery, selectivity, carryover, matrix effects and stability experiments which were developed and fully validated based on Scientific Working Group for Forensic Toxicology guidelines for forensic toxicology method validation. Acceptable coefficients of variation for accuracy/bias, within- and between-run precision and selectivity were determined, with all values within ±15% of the target concentration. Validation experiments revealed degradation of CP-47, 497 and CP-47,497-C8 at different temperatures, and significant ion suppression was produced in brain for all compounds tested. The method was successfully applied to detect and quantify CP-47,497 in brains from mice demonstrating significant cannabimimetic behavioral effects as assessed by the classical tetrad paradigm. PMID:24816398

  14. Effect of buffer conditions on CYP2C8-mediated paclitaxel 6α-hydroxylation and CYP3A4-mediated triazolam α- and 4-hydroxylation by human liver microsomes.

    PubMed

    Kudo, Toshiyuki; Ozaki, Yuya; Kusano, Tomomi; Hotta, Eri; Oya, Yuka; Komatsu, Seina; Goda, Hitomi; Ito, Kiyomi

    2016-01-01

    1. Buffer conditions in in vitro metabolism studies using human liver microsomes (HLM) have been reported to affect the metabolic activities of several cytochrome P450 (CYP) isozymes in different ways, although there are no reports about the dependence of CYP2C8 activity on buffer conditions. 2. The present study investigated the effect of buffer components (phosphate or Tris-HCl) and their concentration (10-200 mM) on the CYP2C8 and CYP3A4 activities of HLM, using paclitaxel and triazolam, respectively, as marker substrates. 3. The Km (or S50) and Vmax values for both paclitaxel 6α-hydroxylation and triazolam α- and 4-hydroxylation, estimated by fitting analyses based on the Michaelis-Menten or Hill equation, greatly depended on the buffer components and their concentration. 4. The CLint values in phosphate buffer were 1.2-3.0-fold (paclitaxel) or 3.1-6.4-fold (triazolam) higher than in Tris-HCl buffer at 50-100 mM. These values also depended on the buffer concentration, with a maximum 2.3-fold difference observed between 50 and 100 mM which are both commonly used in drug metabolism studies. 5. These findings suggest the necessity for optimization of the buffer conditions in the quantitative evaluation of metabolic clearances, such as in vitro-in vivo extrapolation and also estimating the contribution of a particular enzyme in drug metabolism. PMID:26290405

  15. HLA–B51/B5 and the Risk of Behçet’s Disease: A Systematic Review and Meta-Analysis of Case–Control Genetic Association Studies

    PubMed Central

    de MENTHON, MATHILDE; LAVALLEY, MICHAEL P.; MALDINI, CARLA; GUILLEVIN, LOÏC; MAHR, ALFRED

    2013-01-01

    Objective To quantify by meta-analysis the genetic effect of the HLA–B5 or HLA–B51 (HLA–B51/B5) allele on the risk of developing Behçet’s disease (BD) and to look for potential effect modifiers. Methods Relevant studies were identified using the PubMed Medline database and manual searches of the literature. Pooled odds ratios (ORs) and 95% confidence intervals (95% CIs) were calculated by using the random-effects model. Subgroup meta-analyses and meta-regression analyses were undertaken to investigate the effects of selected study-level parameters on the pooled OR. Heterogeneity was assessed using the I2 statistic. Pooled results were used to calculate population-attributable risks (PAR) for BD in relationship to HLA–B51/B5. Results A total of 4,800 patients with BD and 16,289 controls from 78 independent studies (published 1975–2007) were selected. The pooled OR of HLA–B51/B5 allele carriers to develop BD compared with noncarriers was 5.78 (95% CI 5.00–6.67), with moderate between-study heterogeneity (I2 = 61%). The subgroup analyses stratifying studies by geographic locations (Eastern Asia, Middle East/North Africa, Southern Europe, Northern/Eastern Europe) yielded consistent OR ranges (5.31–7.20), with I2 ranges of 52–70%. Univariate random-effects meta-regression indicated the percentage of male BD cases (P = 0.008) as a source of heterogeneity. The PAR within the various geographic areas were estimated at 32–52%. Conclusion The strength of the association between BD and HLA–B51/B5, and its consistency across populations of various ethnicities, lends further support to this allele being a primary and causal risk determinant for BD. Variations according to sex support an interaction of this allele with BD characteristics. PMID:19790126

  16. Epigenome-wide scan identifies a treatment-responsive pattern of altered DNA methylation among cytoskeletal remodeling genes in monocytes and CD4+ T cells in Behçet’s disease

    PubMed Central

    Hughes, Travis; Ture-Ozdemir, Filiz; Alibaz-Oner, Fatma; Coit, Patrick; Direskeneli, Haner; Sawalha, Amr H

    2014-01-01

    Objective Behçet’s disease (BD) is an inflammatory disease characterized by multi-system involvement including recurrent oral and genital ulcers, cutaneous lesions, and uveitis. The pathogenesis of BD remains poorly understood. We performed a genome-wide DNA methylation study in BD before and after disease remission, and in healthy matched controls. Methods We examined genome-wide DNA methylation in monocytes and CD4+ T cells from a set of 16 untreated male BD patients and age, sex, and ethnicity-matched controls. Additional samples were collected from 12 of the same BD patients after treatment and disease remission. Genome-wide DNA methylation patterns were assessed using the HumanMethylation450 DNA Analysis BeadChip array which includes over 485,000 individual methylation sites across the genome. Results We identified 383 differentially methylated CpG sites between BD patients and controls in monocytes and 125 differentially methylated CpG sites in CD4+ T cells. Bioinformatic analysis revealed a pattern of aberrant DNA methylation among genes that regulate cytoskeletal dynamics suggesting that aberrant DNA methylation of multiple classes of structural and regulatory proteins of the cytoskeleton might contribute to the pathogenesis of BD. Further, DNA methylation changes associated with treatment act to restore methylation differences observed between patients and controls. Indeed, among CpG sites differentially methylated before and after disease remission, there was almost exclusive reversal of the direction of aberrant DNA methylation observed between patients and healthy controls. Conclusions We performed the first epigenome-wide study in BD and provide strong evidence that epigenetic modification of cytoskeletal dynamics underlies the pathogenesis and therapeutic response in BD. PMID:24574333

  17. Heavy perfluorocarbons in the global atmosphere: Atmospheric histories and top-down global emission estimates for C4F10, C5F12, C6F14, C7F16 and C8F18

    NASA Astrophysics Data System (ADS)

    Ivy, D. J.; Arnold, T.; Rigby, M. L.; Baasandorj, M.; Muhle, J.; Harth, C.; Salameh, P.; Steele, P.; Leist, M.; Krummel, P. B.; Burkholder, J. B.; Fraser, P.; Weiss, R. F.; Prinn, R. G.

    2011-12-01

    The high molecular weight perfluorocarbons (PFCs) - perfluorobutane (C4F10), perfluoropentane (C5F12), perfluorohexane (C6F14), perfluoroheptane (C7F16) and perfluorooctane (C8F18) - are potent greenhouse gases with global warming potentials of ~ 9000 for a 100 year time horizon [Forster et al., 2007]. Currently, the heavy PFCs are regulated under the Kyoto Protocol of the United Nations Framework Convention on Climate Change (UNFCCC). However, no atmospheric observations or top-down emission estimates for these gases have been published. In this study, atmospheric histories of the heavy PFCs were determined through new measurements of the Cape Grim Air Archive and a collection of Northern Hemispheric archive flasks using the Advanced Global Atmospheric Gases Experiment (AGAGE) cryogenic preconcentration gas chromatography-mass spectrometry system "Medusa" [Miller et al., 2008]. Furthermore, global top-down emissions were estimated from 1973-2010 based on the atmospheric histories using an inverse method and the 3-D chemical transport model, Model of OZone and Related Tracers (MOZARTv4.5) [Emmons et al., 2009]. Comparison of the top-down emission estimates with bottom-up estimates from the Emissions Database for Global Atmospheric Research (EDGARv4.1) shows EDGARv4.1 emission estimates are underestimated by orders of magnitude for C4F10 and C5F12 [European Commission, 2009]. The bottom-up estimates from EDGARv4.1 are comparable to the top-down estimates for C6F14 and C7F16; no bottom-up emission estimates are available for C8F18. Generally, UNFCCC reported inventories by countries that have ratified the Kyoto Protocol are 5 to 10 times lower than the top-down emission estimates for C4F10, C5F12 and C6F14 (C7F16 and C8F18 are not reported to the UNFCCC). The atmospheric histories and top-down emission estimates presented are the most accurate and comprehensive compiled so far for the high molecular weight PFCs. Furthermore, this study illustrates the importance of

  18. Complementary DNA and derived amino acid sequence of the. beta. subunit of human complement protein C8: identification of a close structural and ancestral relationship to the. cap alpha. subunit and C9

    SciTech Connect

    Howard, O.M.Z.; Rao, A.G.; Sodetz, J.M.

    1987-06-16

    A cDNA clone encoding the ..beta.. subunit (M/sub r/ 64,000) of the eighth component of complement (C8) has been isolated from a human liver cDNA library. This clone has a cDNA insert of 1.95 kilobases (kb) and contains the entire ..beta.. sequence (1608 base pairs (bp)). Analysis of total cellular RNA isolated from the hepatoma cell line HepG2 revealed the mRNA for ..beta.. to be approx. 2.5 kb. This is similar to the message size for the ..cap alpha.. subunit of C8 and confirms the existence of different mRNAs for ..cap alpha.. and ..beta... This finding supports genetic evidence that ..cap alpha.. and ..beta.. are encoded at different loci. Analysis of the derived amino acid sequence revealed several membrane surface seeking segments that may facilitate ..beta.. interaction with target membranes during complement-mediated cytolysis. Determined of the carbohydrate composition indicated 1 or 2 asparagine-linked but no O-linked oligosaccharide chains. Comparison of the ..beta.. sequence to that reported earlier and to that of human C9 revealed a striking homology between all three proteins. For ..beta.. and ..cap alpha.., the overall homology is 33% on the basis of identity and 53% when conserved substitutions are allowed. For ..beta.. and C9, the values are 26% and 47/sup 5/, respectively. All three have a large internal domain that is nearly cysteine free and N- and C-termini that are cysteine-rich and homologous to the low-density lipoprotein receptor repeat and epidermal growth factor type sequences, respectively. The overall homology and similarities in size and structural organization are indicative of a close ancestral relationship. It is concluded that ..cap alpha.., ..beta.. and C9 are members of a family of structurally related proteins that are capable of interacting to produce a hydrophilic to amphiphilic transition and membrane association.

  19. Identification and yields of 1,4-hydroxynitrates formed from the reactions of C8-C16 n-alkanes with OH radicals in the presence of NO(x).

    PubMed

    Yeh, Geoffrey K; Ziemann, Paul J

    2014-09-25

    A series of C8-C16 n-alkanes were reacted with OH radicals in the presence of NOx in an environmental chamber and particulate 1,4-hydroxynitrate reaction products were collected by filtration, extracted, and analyzed by high-performance liquid chromatography with UV absorption and electron ionization mass spectrometry (HPLC/UV/MS). Observed mass spectral patterns can be explained by using proposed ion fragmentation mechanisms, permitting the identification of each hydroxynitrate isomer. Reversed-phase retention of these compounds was dictated by the length of the longer of two alkyl chains attached to the 1,4-hydroxynitrate subunit. 1,4-Hydroxynitrates were quantified in particles using an authentic analytical standard for calibration, and the results were combined with gas chromatography measurements of the n-alkanes to determine the molar yields. Yields based on analyses of particles increased with increasing carbon number from 0.00 for C8 to an average plateau value of 0.130 ± 0.008 for C14-C16, due primarily to corresponding increases in gas-to-particle partitioning. The value at the plateau, where essentially all 1,4-hydroxynitrates were in particles, was equal to the average total yield of C14-C16 1,4-hydroxynitrates. The average branching ratio for the formation of C14-C16 1,4-hydroxynitrates from the reaction of NO with the corresponding 1,4-hydroxyperoxy radicals was 0.184 ± 0.011. This value is ∼20% higher than the plateau value of 0.15 for reactions of secondary 1,2-hydroxyperoxy radicals and ∼40% lower than the plateau value of 0.29 for reactions of secondary alkyl peroxy radicals, both of which were reported previously. The branching ratios determined here were used with values reported previously to calculate the yields of C7-C18 alkyl nitrates, 1,4-hydroxynitrates, and 1,4-hydroxycarbonyls, the three products formed from the reactions of these n-alkanes. PMID:25144881

  20. Neuroprotection of Neuro2a cells and the cytokine suppressive and anti-inflammatory mode of action of resveratrol in activated RAW264.7 macrophages and C8-B4 microglia.

    PubMed

    Steiner, Nicole; Balez, Rachelle; Karunaweera, Niloo; Lind, Joanne M; Münch, Gerald; Ooi, Lezanne

    2016-05-01

    Chronic inflammation is a hallmark of neurodegenerative disease and cytotoxic levels of nitric oxide (NO) and pro-inflammatory cytokines can initiate neuronal death pathways. A range of cellular assays were used to assess the anti-inflammatory and neuroprotective action of resveratrol using murine microglial (C8-B4), macrophage (RAW264.7) and neuronal-like (Neuro2a) cell lines. We examined the release of NO by Griess assay and used a Bioplex array to measure a panel of pro- and anti-inflammatory cytokines and chemokines, in response to the inflammatory stimuli lipopolysaccharide (LPS) and interferon-γ (IFN-γ). Resveratrol was a potent inhibitor of NO and cytokine release in activated macrophages and microglia. The activity of resveratrol increased marginally in potency with longer pre-incubation times in cell culture that was not due to cytotoxicity. Using an NO donor we show that resveratrol can protect Neuro2a cells from cytotoxic concentrations of NO. The protective effect of resveratrol from pro-inflammatory signalling in RAW264.7 cells was confirmed in co-culture experiments leading to increased survival of Neuro2a cells. Together our data are indicative of the potential neuroprotective effect of resveratrol during nitrosative stress and neuroinflammation. PMID:26522689

  1. Perfluoroalkyl Substances, Sex Hormones, and Insulin-like Growth Factor-1 at 6–9 Years of Age: A Cross-Sectional Analysis within the C8 Health Project

    PubMed Central

    Lopez-Espinosa, Maria-Jose; Mondal, Debapriya; Armstrong, Ben G.; Eskenazi, Brenda; Fletcher, Tony

    2016-01-01

    Background: Exposure to some perfluoroalkyl substances (PFAS), such as perfluorohexane sulfonate (PFHxS), perfluorooctanoate (PFOA), perfluorooctane sulfonate (PFOS), and perfluorononanoic acid (PFNA), may alter levels of sex hormones and insulin-like growth factor-1 (IGF-1) in animals. Human studies on this topic are scarce, and none have been conducted in young children. Objectives: We investigated the relationship between levels of PFAS and estradiol, total testosterone, and IGF-1 in 2,292 children (6–9 years of age) from the C8 Health Project who lived near a chemical plant in the Mid-Ohio Valley (USA) with local contamination from PFOA. Methods: Serum samples were collected in 2005–2006 and analyzed for PFAS, sex hormones, and IGF-1. Results from regression models were expressed as the adjusted percentage difference (95% CI) per sex-specific interquartile range (IQR) increment of each PFAS serum concentration. Analyses by PFAS quartiles were also conducted. Results: Median concentrations of PFHxS, PFOA, PFOS, and PFNA were 8, 35, 22, and 1.7 ng/mL in boys and 7, 30, 21, and 1.7 ng/mL in girls. In boys, PFOA concentrations were significantly associated with testosterone levels (–4.9%; 95% CI: –8.7, –0.8%); PFOS with estradiol (–4.0%; 95% CI: –7.7, –0.1%), testosterone (–5.8%; 95% CI: –9.4, –2.0%), and IGF-1 (–5.9%; 95% CI: –8.3, –3.3%); and PFNA with IGF-1 (–3.5%; 95% CI: –6.0, –1.0%). In girls, significant associations were found between PFOS and testosterone (–6.6%; 95% CI: –10.1, –2.8%) and IGF-1 (–5.6%; –8.2, –2.9%); and PFNA and IGF-1 (–3.8%; 95% CI: –6.4, –1.2%). In both sexes, the magnitudes of the associations decreased monotonically across quartiles for both testosterone and IGF-1 in relation to PFOS, and for IGF-1 and PFNA in girls. Conclusions: To our knowledge, this is the first study suggesting that PFAS are associated with lower levels of IGF-1 and sex hormones in young children. Citation: Lopez

  2. Alkyl nitrate formation from the reactions of C8-C14 n-alkanes with OH radicals in the presence of NO(x): measured yields with essential corrections for gas-wall partitioning.

    PubMed

    Yeh, Geoffrey K; Ziemann, Paul J

    2014-09-18

    In this study, C8-C14 n-alkanes were reacted with OH radicals in the presence of NO(x) in a Teflon film environmental chamber and isomer-specific yields of alkyl nitrates were determined using gas chromatography. Because results indicated significant losses of alkyl nitrates to chamber walls, gas-wall partitioning was investigated by monitoring the concentrations of a suite of synthesized alkyl nitrates added to the chamber. Gas-to-wall partitioning increased with increasing carbon number and with proximity of the nitrooxy group to the terminal carbon, with losses as high as 86%. The results were used to develop a structure-activity model to predict the effects of carbon number and isomer structure on gas-wall partitioning, which was used to correct the measured yields of alkyl nitrate isomers formed in chamber reactions. The resulting branching ratios for formation of secondary alkyl nitrates were similar for all isomers of a particular carbon number, and average values, which were almost identical to alkyl nitrate yields, were 0.219, 0.206, 0.254, 0.291, and 0.315 for reactions of n-octane, n-decane, n-dodecane, n-tridecane, and n-tetradecane, respectively. The increase in average branching ratios and alkyl nitrate yields with increasing carbon number to a plateau value of ∼0.30 at about C13-C14 is consistent with predictions of a previously developed model, indicating that the model is valid for alkane carbon numbers ≥C3. PMID:24654572

  3. On-line solid phase extraction-ultra high performance liquid chromatography-tandem mass spectrometry as a powerful technique for the determination of sulfonamide residues in soils.

    PubMed

    Tetzner, Natália Fernanda; Maniero, Milena Guedes; Rodrigues-Silva, Caio; Rath, Susanne

    2016-06-24

    Sulfonamides are antimicrobials used widely as veterinary drugs, and their residues have been detected in environmental matrices. An analytical method for determining sulfadiazine, sulfathiazole, sulfamethazine, sulfamethoxazole, sulfadimethoxine and sulfaquinoxaline residues in soils employing a solid phase extraction on-line technique coupled with ultra-high performance liquid chromatography and tandem mass spectrometry (SPE-UHPLC-MS/MS) was developed and validated in this study. SPE and chromatographic separation were performed using an Oasis HLB column and an Acquity UPLC BEH C18 analytical column, respectively, at 40°C. Samples were prepared by extracting sulfonamides from soil using a solid-liquid extraction method with water:acetonitrile, 1:1v/v (recovery of 70.2-99.9%). The following parameters were evaluated to optimize the on-line SPE process: sorbent type (Oasis and C8), sample volume (100-400μL), loading solvent (water and different proportions of water:methanol) and washing volume (0.19-0.66mL). The method produced linear results for all sulfonamides from 0.5 to 12.5ngg(-1) with a linearity greater than 0.99. The precision of the method was less than 15%, and the matrix effect was -27% to -87%. The accuracy was in the range of 77-112% for all sulfonamides. The limit of quantitation in the two soils (clay and sand) was 0.5ngg(-1). The SPE column allowed for the analysis of many (more than 2000) samples without decreasing the efficiency. PMID:27234844

  4. [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. PMID:26939367

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

    PubMed Central

    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 KH2PO4 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. PMID:22396911

  6. Evaluation of Arterial Stiffness in Patients with Behçet's Disease by Using Noninvasive Radiological Methods such as Intima-Media Thickness of the Carotid, Ankle-Brachial Pressure Index, Coronary Artery Calcium Scoring, and Their Relation to Serum Fetuin-A Levels: A Case-Control Study

    PubMed Central

    Solak, Aynur; Genç, Berhan; Akyıldız, Muhittin; Şahin, Neslin; Uyar, İhsan Sami; Saklamaz, Ali

    2015-01-01

    Background Behçet's disease (BD) is a chronic, recurrent inflammatory systemic vasculitis. Evidence for increased atherosclerosis in BD has been observed. The relation between cardiovascular risk factors and increased atherosclerosis in patients with BD is still controversial. Objective We performed this study to evaluate arterial stiffness in patients with BD by using noninvasive radiological methods such as carotid artery intima-media thickness (CIMT), ankle-brachial pressure index (ABPI), coronary artery calcium score (CACaS), and their relation to serum fetuin-A levels, which was recently found to be important in vascular calcification. Methods This prospective study included 26 patients with BD and 25 control subjects. In all patients, the CIMT, ABPI, CACaS, and serum fetuin-A levels were examined. Results The CIMT and CACaS were statistically higher and the ABPI was statistically lower in BD patients than in the control group. All p-values were <0.001. Positive correlations were found between the CACaS and CIMT, and negative correlations were found between the CACaS and ABPI. Although the values of fetuin-A were higher in BD, the difference was not statistically significant (p=0.064). However, the correlations found between fetuin-A levels and CIMT and between fetuin-A levels and CACaS were significant. Conclusion The CIMT, CACaS, and ABPI are all useful in detecting structural and functional vascular damage in BD. PMID:26719639

  7. 75 FR 14082 - Ammonium Salts of Fatty Acids (C8

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-03-24

    ...-5805. II. Background and Statutory Findings In the Federal Register of September 5, 2008 (73 FR 51817... review under Executive Order 12866, entitled Regulatory Planning and Review (58 FR 51735, October 4, 1993... Supply, Distribution, or Use (66 FR 28355, May 22, 2001) or Executive Order 13045, entitled Protection...

  8. C8, a new member of the convertase family.

    PubMed Central

    Bruzzaniti, A; Goodge, K; Jay, P; Taviaux, S A; Lam, M H; Berta, P; Martin, T J; Moseley, J M; Gillespie, M T

    1996-01-01

    A novel subtilisin-like protein, PC8, was identified by PCR using degenerate primers to conserved amino acid residues in the catalytic region of members of the prohormone convertase family. PC8 was predicted to be 785 residues long and was structurally related to the mammalian convertases furin, PACE4, PC1 and PC2, sharing more than 50% amino acid identity over the catalytic region with these family members. PC8 possessed the catalytically important Asp, His, Asn and Ser amino acids, the homo B domain of this family of enzymes and a C-terminal hydrophobic sequence indicative of a transmembrane domain. Structurally, PC8 is more related to furin and PACE4 than to PC1 or PC2. Like furin and PACE4, PC8 mRNA was found to be widely expressed; this is in contrast with PC1 and PC2, which have a restricted distribution. Two transcripts, of 4.5 and 3.5 kb, were detected in both human cell lines and rat tissues. Unlike furin and PACE4, both of which map to chromosome 15, PC8 maps to chromosome 11q23-11q24, suggesting that this gene may have resulted from an ancient gene duplication event from either furin or PACE4, or conversely that these genes arose from PC8. PMID:8615762

  9. Biological activities of conjugated fatty acids: conjugated eicosadienoic (conj. 20:2delta(c11,t13/t12,c14)), eicosatrienoic (conj. 20:3delta(c8,t12,c14)), and heneicosadienoic (conj. 21:2delta(c12,t14/c13,t15)) acids and other metabolites of conjugated linoleic acid.

    PubMed

    Park, Yeonhwa; Storkson, Jayne M; Albright, Karen J; Liu, Wei; Pariza, Michael W

    2005-02-21

    The elongated form of conjugated linoleic acid (CLA), conjugated eicosadienoic acid (CEA, conj. 20:2delta(c11,t13/t12,c14)), was generated from CLA by liver microsomal fractions. Subsequent testing showed that dietary CEA significantly reduced body fat, and increased lean mass similar to CLA when compared to controls. CEA also decreased lipoprotein lipase activity and triacylglyceride, and increased glycerol release in 3T3-L1 adipocytes, correlated with the trans-12,cis-14 isomer, but CEA required a longer incubation period than cells treated with CLA. Based on the fact that CEA fed animals had CLA in tissue, we suggest that the effect of CEA is due to the CLA converted from CEA in the system. The delta-6 desaturated and elongated form of trans-10,cis-12 CLA (conjugated eicosatrienoic acid, CETA, conj. 20:3delta(c8,t12,c14)) inhibited LPL activity and increased glycerol release but was less active than trans-10,cis-12 CLA or CEA. The 21-carbon conjugated fatty acid, conjugated heneicosadienoic acid (CHDA, conj. 21:2delta(c12,t14/c13,t15)), was not active on LPL inhibition, triacylglyceride, or glycerol release in 3T3-L1 adipocytes. We also provide evidence that CLA was metabolized to conjugated dodecadienoic acid (conj. 12:2delta(c3,t5/t4,c6)). In addition, there were indications of the presence of conjugated tetradecadienoic acid (conj. 14:2delta(c5,t7/t6,c8)), suggesting that CLA can be metabolized through fatty acid beta-oxidation. This is the first work to report the presence of conjugated 12 and 14 carbon fatty acids, originated from CLA, and the biological activities of CEA, CETA and CHDA. PMID:15708360

  10. Fast separation of selected cathinones and phenylethylamines by supercritical fluid chromatography.

    PubMed

    Pauk, Volodymyr; Žihlová, Veronika; Borovcová, Lucie; Havlíček, Vladimír; Schug, Kevin; Lemr, Karel

    2015-12-01

    The chromatographic behaviour of eleven synthetic cathinones and four phenylethylamines under supercritical/subcritical fluid conditions was investigated. Four stationary phases with sub-2μm particles (Waters Acquity UPC(2) BEH silica, BEH 2-ethylpyridine, CSH Fluoro-Phenyl, and HSS C18SB) were evaluated in terms of isomer resolution, chromatographic peak shape, and analysis time. Methanol, water, formic acid, ammonium hydroxide, ammonium acetate, and ammonium formate were mixed with carbon dioxide to test their influence on analyte retention and peak shapes. Methanol and ammonium cations were essential for successful separations. Efficient separations of four isomeric pairs (R>1), and most of the remaining analytes, were achieved in less than 3.3min on BEH and Fluoro-Phenyl columns with gradient of methanolic ammonium hydroxide in CO2. Drugs were detected by positive electrospray ionization-triple quadrupole mass spectrometry in selected reaction monitoring mode. Added detection specificity and faster separation of isomers on the BEH column using a steep gradient and high flow rate reduced analysis time of the mixture of 15 drugs to 1.6min. PMID:26585202

  11. Facts about Behçet's Disease of the Eye

    MedlinePlus

    ... NEI Office of Science Communications, Public Liaison, and Education. Technical questions about this website can be addressed to the NEI Website Manager . Department of Health and Human Services | The National ...

  12. Genetics Home Reference: Behçet disease

    MedlinePlus

    ... part of a family of genes called the human leukocyte antigen (HLA) complex . The HLA complex helps the immune system distinguish the body's own proteins from proteins made by foreign invaders ( ...

  13. Bushehr Elderly Health (BEH) Programme, phase I (cardiovascular system)

    PubMed Central

    Ostovar, Afshin; Nabipour, Iraj; Larijani, Bagher; Heshmat, Ramin; Darabi, Hossein; Vahdat, Katayoun; Ravanipour, Maryam; Mehrdad, Neda; Raeisi, Alireza; Heidari, Gholamreza; Shafiee, Gita; Haeri, Mohammadjavad; Pourbehi, Mohammadreza; Sharifi, Farshad; Noroozi, Azita; Tahmasebi, Rahim; Aghaei Meybodi, Hamidreza; Assadi, Majid; Farrokhi, Shokrollah; Nemati, Reza; Amini, Mohammad Reza; Barekat, Maryam; Amini, Abdullatif; Salimipour, Houman; Dobaradaran, Sina; Moshtaghi, Darab

    2015-01-01

    Purpose The main objective of the Bushehr Elderly Health Programme, in its first phase, is to investigate the prevalence of cardiovascular risk factors and their association with major adverse cardiovascular events. Participants Between March 2013 and October 2014, a total of 3000 men and women aged ≥60 years, residing in Bushehr, Iran, participated in this prospective cohort study (participation rate=90.2%). Findings to date Baseline data on risk factors, including demographic and socioeconomic status, smoking and medical history, were collected through a modified WHO MONICA questionnaire. Vital signs and anthropometric measures, including systolic and diastolic blood pressure, weight, height, and waist and hip circumference, were also measured. 12-lead electrocardiography and echocardiography were conducted on all participants, and total of 10 cc venous blood was taken, and sera was separated and stored at –80°C for possible future use. Preliminary data analyses showed a noticeably higher prevalence of risk factors among older women compared to that in men. Future plans Risk factor assessments will be repeated every 5 years, and the participants will be followed during the study to measure the occurrence of major adverse cardiac events. Moreover, the second phase, which includes investigation of bone health and cognition in the elderly, was started in September 2015. Data are available at the Persian Gulf Biomedical Research Institute, Bushehr University of Medical Sciences, Bushehr, Iran, for any collaboration. PMID:26674503

  14. CYP2C8- and CYP3A-mediated C-demethylation of (3-{[(4-tert-butylbenzyl)-(pyridine-3-sulfonyl)-amino]-methyl}-phenoxy)-acetic acid (CP-533,536), an EP2 receptor-selective prostaglandin E2 agonist: characterization of metabolites by high-resolution liquid chromatography-tandem mass spectrometry and liquid chromatography/mass spectrometry-nuclear magnetic resonance.

    PubMed

    Prakash, Chandra; Wang, Weiwei; O'Connell, Thomas; Johnson, Kim A

    2008-10-01

    CP-533,536, (3-{[(4-tert-butyl-benzyl)-(pyridine-3-sulfonyl)-amino]-methyl}-phenoxy)-acetic acid (1), an EP2 receptor-selective prostaglandin E2 agonist, is being developed to aid in the healing of bone fractures. To support the development of this program, in vitro metabolism of 1 was investigated in human liver microsomes and major recombinant human cytochrome P450 (P450) isoforms. 1 was metabolized in vitro by at least three recombinant human P450s: CYP3A4, CYP3A5, and CYP2C8. The turnover of 1 was NADPH-dependent and was completely inhibited by ketoconazole and quercetin in the CYP3A4/5 and CYP2C8 incubations, respectively. The major metabolic pathways were caused by oxidation of the tert-butyl moiety to form the omega-hydroxy metabolite (M4), oxidation of the pyridine moiety, and/or N-dealkylation of the methylphenoxy acetic acid moiety. The alcohol metabolite M4 was further oxidized to the corresponding carboxylic acid M3. In addition to these pathways, three unusual metabolites (M22, M23, and M26) resulting from C-demethylation of the tert-butyl group were identified using high-resolution liquid chromatography/tandem mass spectrometry and liquid chromatography/mass spectrometry/NMR. The C-demethylated metabolites were not detected on incubation of carboxylic acid metabolite M3 with either human liver microsomes or CYP3A/2C8 isoforms, suggesting that these metabolites were not derived from decarboxylation of M3. A possible mechanism for C-demethylation may involve the oxidation of M4 to form an aldehyde metabolite (M24), followed by P450-mediated deformylation, to give an unstable carbon-centered radical and formic acid. The carbon-centered radical intermediate then undergoes either oxygen rebound to form an alcohol metabolite M23 or hydrogen abstraction leading to an olefin metabolite M26. PMID:18653741

  15. Cerocene Revisited: The Electronic Structure of and Interconversion Between Ce2(C8H8)3 and Ce(C8H8)2

    SciTech Connect

    Walter, Marc D.; Booth, Corwin H.; Lukens, Wayne W.; Andersen, Richard A.

    2009-02-02

    New synthetic procedures for the preparation of Ce(cot)2, cerocene, from [Li(thf)4][Ce(cot)2], and Ce2(cot)3 in high yield and purity are reported. Heating solid Ce(cot)2 yields Ce2(cot)3 and COT while heating Ce2(cot)3 with an excess of COT in C6D6 to 65oC over four months yields Ce(cot)2. The solid state magnetic susceptibility of these three organocerium compounds shows that Ce(cot)2 behaves as a TIP (temperature independent paramagnet) over the temperature range of 5-300 K, while that of Ce2(cot)3 shows that the spin carriers are antiferromagnetically coupled below 10 K; above 10 K, the individual spins are uncorrelated, and [Ce(cot)2]- behaves as an isolated f1 paramagnet. The EPR at 1.5K for Ce2(cot)3 and [Ce(cot)2]- have ground state of MJ= +- 1/2. The LIII edge XANES of Ce(cot)2 (Booth, C.H.; Walter, M.D.; Daniel, M.; Lukens, W.W., Andersen, R.A., Phys. Rev. Lett. 2005, 95, 267202) and 2Ce2(cot)3 over 30-500 K are reported; the Ce(cot)2 XANES spectra show Ce(III) and Ce(IV) signatures up to a temperature of approximately 500 K, whereupon the Ce(IV) signature disappears, consistent with the thermal behavior observed in the melting experiment. The EXAFS of Ce(cot)2 and Ce2(cot)3 are reported at 30 K; the agreement between the molecular parameters for Ce(cot)2 derived from EXAFS and single crystal X-ray diffraction data are excellent. In the case of Ce2(cot)3 no X-ray diffraction data are known to exist, but the EXAFS are consistent with a"triple-decker" sandwich structure. A molecular rationalization is presented for the electronic structure of cerocene having a multiconfiguration ground state that is an admixture of the two configurations Ce(III, 4f1)(cot1.5-)2 and Ce(IV, 4f0)(cot2-)2; the multiconfigurational ground state has profound effects on the magnetic properties and on the nature of the chemical bond in cerocene and, perhaps, other molecules.

  16. UFLC-MS/MS determination and pharmacokinetic studies of six Saikosaponins in rat plasma after oral administration of Bupleurum Dropping Pills.

    PubMed

    Guan, Xiufeng; Wang, Xiangyang; Yan, Kaijing; Chu, Yang; Li, Shuming; Li, Wei; Yan, Xueying; Ma, Xiaohui; Zhou, Shuiping; Sun, He; Liu, Changxiao

    2016-05-30

    A rapid and sensitive ultra fast liquid chromatography tandem mass spectrometry method (UFLC-MS/MS) was developed and validated for the simultaneous determination of six Saikosaponins (SSs) (SSa, SSb1, SSb2, SSd, SSc, SSf) of Bupleurum Dropping Pills (BDP) in rat plasma using chloramphenicol as the internal standard (IS). The SSs were separated using an ACQUITY UPLC(®) BEH C18 column (50mm×2.1mm, 1.7μm) and detection of these compounds were done by using a Qtrap 5500 mass spectrometer coupled with negative electrospray ionization (ESI) source under the multiple reaction monitoring (MRM) mode. According to regulatory guidelines, the established method was fully validated and results were showed within acceptable limits. The lower limit of quantifications (LLOQs) of all analytes were 0.2ng/mL. The validated method was successfully applied into a pharmacokinetic study of orally administered BDP in rats. PMID:26970984

  17. A Fast and Reliable UPLC-PAD Fingerprint Analysis of Chimonanthus salicifolius Combined with Chemometrics Methods.

    PubMed

    Liang, Xianrui; Zhao, Cui; Su, Weike

    2016-08-01

    A novel fingerprinting approach was developed by means of ultra-high-performance liquid chromatography with photodiode array detector (UPLC-PAD) for the quality control of Chimonanthus salicifolius (C. salicifolius). All UPLC analyses were carried out on a Waters Acquity BEH Phenyl column (2.1 × 50 mm, 1.7 μm particle size) at 48°C, with a gradient mobile phase composed of 0.1% aqueous phosphoric acid and acetonitrile at a flow rate of 0.2 mL/min. The method validation results demonstrated the developed method possessing desirable precision [<0.88% relative standard deviation (RSD)], reproducibility (<1.87% RSD), stability (<1.42% RSD) and allowing fingerprint analysis in one chromatographic run within 21 min. The quality assessment was achieved by using chemometrics methods including similarity analysis, hierarchical clustering analysis and principal component analysis. The developed method can be used for further quality control of C. salicifolius. PMID:27226461

  18. 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. PMID:21499967

  19. Validation of a method for the determination of chloramphenicol in poultry and swine liver by ultra-performance liquid chromatography coupled with tandem mass spectrometry.

    PubMed

    Xia, Xi; Li, Xiaowei; Ding, Shuangyang; Shen, Jianzhong

    2010-01-01

    A sensitive and reliable method has been developed and validated for the determination of chloramphenicol in poultry and swine liver using SPE and ultra-performance liquid chromatography (UPLC)/MS/MS. The liver samples were extracted with ethyl acetate, defatted with n-hexane, and further cleaned up using SPE cartridges with polymeric sorbent. An Acquity BEH C18 column was used for gradient UPLC separation, with water and acetonitrile as the mobile phase. The multiple reaction monitoring mode was used for two precursor-product ion transitions for chloramphenicol and one for the internal standard. The method was validated at 0.1, 0.3, and 1.0 microg/kg. Mean recoveries from fortified samples ranged from 95.5 to 106.7% with an RSD of 12.2%. The method LOD was < 0.02 microg/kg. PMID:21140679

  20. [Simultaneous determination of artificial sweeteners in beverage by ultra performance liquid chromatography].

    PubMed

    Ji, Chao; Sun, Yanyan; Li, Xiuqin; Chu, Xiaogang; Chen, Zhengxing

    2009-01-01

    An ultra performance liquid chromatographic (UPLC) method for the simultaneous separation and determination of four artificial sweeteners (sodium saccharin, aspartame, acesulfame and neotame) in a single injection was developed. The separation was performed on an ACQUITY UPLC BEH C18 column with gradient program and detection at 220 nm. The good linearities between the concentrations of all analytes and peak area responses were achieved over the range from 0.5 to 20.0 mg/L. The average recoveries in samples were 80.5% - 95.2% with the relative standard deviations of 0.50% - 8.7%. The method has been successfully applied to the determination of the four sweeteners in drinks and powdered tabletop sweeteners. PMID:19449553

  1. A validated LC-MS-MS method for simultaneous identification and quantitation of rodenticides in blood.

    PubMed

    Bidny, Sergei; Gago, Kim; David, Mark; Duong, Thanh; Albertyn, Desdemona; Gunja, Naren

    2015-04-01

    A rapid, highly sensitive and specific analytical method for the extraction, identification and quantification of nine rodenticides from whole blood has been developed and validated. Commercially available rodenticides in Australia include coumatetralyl, warfarin, brodifacoum, bromadiolone, difenacoum, flocoumafen, difethialone, diphacinone and chlorophacinone. A Waters ACQUITY UPLC TQD system operating in multiple reaction monitoring mode was used to conduct the analysis. Two different ionization techniques, ES+ and ES-, were examined to achieve optimal sensitivity and selectivity resulting in detection by MS-MS using electrospray ionization in positive mode for difenacoum and brodifacoum and in negative mode for all other analytes. All analytes were extracted from 200 µL of whole blood with ethylacetate and separated on a Waters ACQUITY UPLC BEH-C18 column using gradient elution. Ammonium acetate (10 mM, pH 7.5) and methanol were used as mobile phases with a total run time of 8 min. Recoveries were between 70 and 105% with limits of detection ranging from 0.5 to 1 ng/mL. The limit of quantitation was 2 ng/mL for all analytes. Calibration curves were linear within the range 2-200 ng/mL for all analytes with the coefficient of determination ≥0.98. The application of the proposed method using liquid-liquid extraction in a series of clinical investigations and forensic toxicological analyses was successful. PMID:25595137

  2. 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. PMID:26129833

  3. Quantitative determination of alkaloids from roots of Hydrastis canadensis L. and dietary supplements using ultra-performance liquid chromatography with UV detection.

    PubMed

    Avula, Bharathi; Wang, Yan-Hong; Khan, Ikhlas A

    2012-01-01

    Ultra-performance liquid chromatography (UPLC) with UV detection was used for the quantification of alkaloids from roots of Hydrastis canadensis L. (goldenseal) and dietary supplements claiming to contain goldenseal. The analysis was performed on a Waters Acquity UPLC system with an Acquity UPLC BEH Shield RP18 column using gradient elution with ammonium formate and acetonitrile containing formic acid. The chromatographic run time was less than 6 min. The detection wavelength used for beta-hydrastine and canadine was 290 nm; for hydrastinine, coptisine, jatrorrhizine, palmatine, and berberine, it was 344 nm. A total of five different extraction solvents, including 100% methanol, 90% methanol, 90% methanol + 1% acetic acid, 90% acetonitrile + 0.1% phosphoric acid, and 100% acetonitrile, were tested for recovery of the major compounds. The samples extracted with the 90% methanol + 1% acetic acid displayed the best recovery (>97%). The analytical method was validated for linearity, repeatability, LOD, and LOQ. The RSDs for intraday and interday experiments were less than 3.5%, and the recovery was 98-103%. UPLC/MS with a quadrupole mass analyzer and electrospray ionization source was used to confirm the identity of seven alkaloids. The analytical method was successfully applied to confirm the identification of seven alkaloids from the roots of H. canadensis, dietary supplements that claimed to contain goldenseal, and possible adulterant species. PMID:23175972

  4. Prostate-Specific Antigen and Perfluoroalkyl Acids in the C8 Health Study Population

    PubMed Central

    Zhang, Jianjun; Fan, Hongmin

    2015-01-01

    Purpose: To inform questions raised by inconsistent findings regarding an association between perfluoroalkyl acids (PFAAs) and prostate cancer by assessing the relationship of PFAAs in human serum to prostate-specific antigen (PSA). Materials and Methods: Using 2005 to 2006 survey data from a large survey population, we compared serum PFAA concentrations in adult males with PSA concentrations adjusted for risk factors including age, body mass index, smoking status, and socioeconomic status. Results: Perfluoroalkyl acids are not consistently associated with PSA concentration in general, or with PSA more than 4.0. Discussion: These findings do not provide evidence that PFAA exposure is associated with PSA. PMID:25563548

  5. Age-Dependent Changes in Human Hepatic CYP2C8 and 1A2 Expression

    EPA Science Inventory

    Predicting age-specific metabolism of pyrethroids is important in evaluating age-related sensitivity. Our goal is to use an in vitro to in vivo extrapolation (IVIVE) approach to predict pyrethroid metabolism for different ages incorporating enzyme ontogeny and expressed enzyme ki...

  6. Materials Data on H12RhC8NO6 (SG:62) by Materials Project

    DOE Data Explorer

    Kristin Persson

    2014-11-02

    Computed materials data using density functional theory calculations. These calculations determine the electronic structure of bulk materials by solving approximations to the Schrodinger equation. For more information, see https://materialsproject.org/docs/calculations

  7. An ab initio study on (C5H5V)2C8H8

    NASA Technical Reports Server (NTRS)

    Luthi, Hans P.; Bauschlicher, Charles W., Jr.

    1987-01-01

    The bonding in the organometalic compound nu-(eta exp 5-(cyclooctatetraene) bis (eta exp 2 cyclopentadienyl) vanadium) involves a complex mixture of metal-metal and metal-ligand contributions. Although there is a direct V-V 3d interaction it is not as strong as a double bond with some triple bond character as has been suggested based upon experiment. The balance between metal-metal and metal-ligand bonding results in the appearance of a low-lying triplet state which retains the V-V 3d bonding. A small singlet-triplet separation is consistent with the change in magnetic properties with temperature.

  8. Chemical shifts and coupling constants of C8H10N4O2

    NASA Astrophysics Data System (ADS)

    Jain, M.

    This document is part of Subvolume D3 `Chemical Shifts and Coupling Constants for Carbon-13: Heterocycles' of Volume 35 `Nuclear Magnetic Resonance (NMR) Data' of Landolt-Börnstein Group III `Condensed Matter'

  9. Nuclear magnetic resonance data of C8H10N4O2

    NASA Astrophysics Data System (ADS)

    Jain, M.

    This document is part of Subvolume C `Chemical Shifts and Coupling Constants for Hydrogen-1, Heterocycles' of Landolt-Börnstein III/40 `Nuclear Magnetic Resonance Data', Group III `Condensed Matter'.

  10. Materials Data on CsC8 (SG:191) by Materials Project

    SciTech Connect

    Kristin Persson

    2014-11-02

    Computed materials data using density functional theory calculations. These calculations determine the electronic structure of bulk materials by solving approximations to the Schrodinger equation. For more information, see https://materialsproject.org/docs/calculations

  11. Jet noise suppressor nozzle development for augmentor wing jet STOL research aircraft (C-8A Buffalo)

    NASA Technical Reports Server (NTRS)

    Harkonen, D. L.; Marks, C. C.; Okeefe, J. V.

    1974-01-01

    Noise and performance test results are presented for a full-scale advanced design rectangular array lobe jet suppressor nozzle (plain wall and corrugated). Flight design and installation considerations are also discussed. Noise data are presented in terms of peak PNLT (perceived noise level, tone corrected) suppression relative to the existing airplane and one-third octave-band spectra. Nozzle performance is presented in terms of velocity coefficient. Estimates of the hot thrust available during emergency (engine out) with the suppressor nozzle installed are compared with the current thrust levels produced by the round convergent nozzles.

  12. Palladium-catalyzed directing group-assisted C8-triflation of naphthalenes.

    PubMed

    Yang, Zhi-Wei; Zhang, Qi; Jiang, Yuan-Ye; Li, Lei; Xiao, Bin; Fu, Yao

    2016-05-10

    The transition-metal-catalyzed direct triflation of naphthyl amides and naphthyl ketones has been accomplished for the first time. Benzophenone (BP) was found to be a suitable ligand for the cross-coupling reactions. Density functional theory (DFT) calculations revealed that excessive amounts of HOTf inhibit the reductive elimination of the C-F bond to realize the unusual reductive elimination of the C-OTf bond. PMID:27117543

  13. C8-glycosphingolipids preferentially insert into tumor cell membranes and promote chemotherapeutic drug uptake.

    PubMed

    Cordeiro Pedrosa, Lília R; van Cappellen, Wiggert A; Steurer, Barbara; Ciceri, Dalila; ten Hagen, Timo L M; Eggermont, Alexander M M; Verheij, Marcel; Goñi, Felix María; Koning, Gerben A; Contreras, F-Xabier

    2015-08-01

    Insufficient drug delivery into tumor cells limits the therapeutic efficacy of chemotherapy. Co-delivery of liposome-encapsulated drug and synthetic short-chain glycosphingolipids (SC-GSLs) significantly improved drug bioavailability by enhancing intracellular drug uptake. Investigating the mechanisms underlying this SC-GSL-mediated drug uptake enhancement is the aim of this study. Fluorescence microscopy was used to visualize the cell membrane lipid transfer intracellular fate of fluorescently labeled C6-NBD-GalCer incorporated in liposomes in tumor and non-tumor cells. Additionally click chemistry was applied to image and quantify native SC-GSLs in tumor and non-tumor cell membranes. SC-GSL-mediated flip-flop was investigated in model membranes to confirm membrane-incorporation of SC-GSL and its effect on membrane remodeling. SC-GSL enriched liposomes containing doxorubicin (Dox) were incubated at 4°C and 37°C and intracellular drug uptake was studied in comparison to standard liposomes and free Dox. SC-GSL transfer to the cell membrane was independent of liposomal uptake and the majority of the transferred lipid remained in the plasma membrane. The transfer of SC-GSL was tumor cell-specific and induced membrane rearrangement as evidenced by a transbilayer flip-flop of pyrene-SM. However, pore formation was measured, as leakage of hydrophilic fluorescent probes was not observed. Moreover, drug uptake appeared to be mediated by SC-GSLs. SC-GSLs enhanced the interaction of doxorubicin (Dox) with the outer leaflet of the plasma membrane of tumor cells at 4°C. Our results demonstrate that SC-GSLs preferentially insert into tumor cell plasma membranes enhancing cell intrinsic capacity to translocate amphiphilic drugs such as Dox across the membrane via a biophysical process. PMID:25917957

  14. 76 FR 6335 - Sodium and Potassium Salts of N-alkyl (C8

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-02-04

    ... March 19, 2010 (75 FR 132771) (FRL-8813- 2), EPA issued a notice pursuant to section 408 of FFDCA, 21 U...) under 40 CFR 180.920 in the Federal Register of July 29, 2009 (74 FR 37584) (FRL-8425-5). That final... Planning and Review (58 FR 51735, October 4, 1993). Because this final rule has been exempted from...

  15. Development of an achiral supercritical fluid chromatography method with ultraviolet absorbance and mass spectrometric detection for impurity profiling of drug candidates. Part I: Optimization of mobile phase composition.

    PubMed

    Lemasson, Elise; Bertin, Sophie; Hennig, Philippe; Boiteux, Hélène; Lesellier, Eric; West, Caroline

    2015-08-21

    to provide very comparable overall scores. However, ammonium acetate was selected for slightly better chromatographic quality. In a second step, we investigated the effects of ammonium acetate concentration (between 0 and 25mM in the methanol co-solvent) on retention and peak efficiency. Two types of silica supports were tested by working with ACQUITY UPC(2) HSS C18 SB and BEH columns. 20mM ammonium acetate in methanol with 2% water was finally selected as the best co-solvent composition. PMID:26195034

  16. Materials Data on Be(H2N)2 (SG:142) by Materials Project

    SciTech Connect

    Kristin Persson

    2014-11-02

    Computed materials data using density functional theory calculations. These calculations determine the electronic structure of bulk materials by solving approximations to the Schrodinger equation. For more information, see https://materialsproject.org/docs/calculations

  17. NOD2 is highly expressed in Behçet disease with pulmonary manifestations

    PubMed Central

    2012-01-01

    Background Excessive Th1 cells and TLRs functions are involved in the pathogenesis of Behcet's disease (BD) in response to bacterial antigens. NOD2, an intracellular pathogen recognition sensor, modulates innate defence to muropeptides derived from various bacterial species. To further define a role for NOD2 in BD, we analysed NOD2 transcriptional responses in BAL-MNC from BD patients with pulmonary manifestations. Methods We analysed NOD1, NOD2, T-bet and TLRs mRNA expression with real-time polymerase chain-reaction in BAL cells obtained from 23 BD patients with pulmonary manifestations and their matched controls. Results We found that NOD2 mRNA expression was highly up-regulated in BAL cells from BD and sarcoidosis patients compared to healthy control group (P = 0.001). In BD patients, significant correlation was found between NOD2 and T-bet mRNA expression (r = 0.602; P = 0.0009). In BAL from BD patients, NOD2 and T-bet mRNA expression were significantly correlated with BAL-lymphocytes (r = 0.485, P = 0.010; r = 0684, P = 0.0001 respectively). NOD2 in BD was also correlated with TLR 2(r = 0.444; P = 0.021) and TLR 4 (r = 0.574; P = 0.001) mRNA expression. Conclusion Our results indicate that BAL-MNC from BD patients expressed NOD2 as a result of lung inflammation. TLRs and NOD2 synergize for the induction of proinflammatory cytokines. BAL inflammatory cells showed an increased Th1 situation as indicated by increased T-bet mRNA expression. PMID:22330585

  18. Exploration of stable compounds, crystal structures, and superconductivity in the Be-H system

    SciTech Connect

    Yu, Shuyin Zeng, Qingfeng; Zhang, Litong; Oganov, Artem R.; Hu, Chaohao; Frapper, Gilles

    2014-10-15

    Using first-principles variable-composition evolutionary methodology, we explored the high-pressure structures of beryllium hydrides between 0 and 400 GPa. We found that BeH{sub 2} remains the only stable compound in this pressure range. The pressure-induced transformations are predicted as Ibam→P3{sup -}m1→R3{sup -}m→Cmcm→P4/nmm, which occur at 24, 139, 204 and 349 GPa, respectively. P3{sup -}m1 and R3{sup -}m structures are layered polytypes based on close packings of H atoms with Be atoms filling all octahedral voids in alternating layers. Cmcm and P4/nmm contain two-dimensional triangular networks with each layer forming a kinked slab in the ab-plane. P3{sup -}m1 and R3{sup -}m are semiconductors while Cmcm and P4/nmm are metallic. We have explored superconductivity of both metal phases, and found large electron-phonon coupling parameters of λ = 0.63 for Cmcm with a T{sub c} of 32.1-44.1 K at 250 GPa and λ = 0.65 for P4/nmm with a T{sub c} of 46.1-62.4 K at 400 GPa. The dependence of T{sub c} on pressure indicates that T{sub c} initially increases to a maximum of 45.1 K for Cmcm at 275 GPa and 97.0 K for P4/nmm at 365 GPa, and then decreases with increasing pressure for both phases.

  19. Symmetric tensor decomposition-configuration interaction study of BeH2

    NASA Astrophysics Data System (ADS)

    Kasamatsu, Shusuke; Uemura, Wataru; Sugino, Osamu

    2014-03-01

    The configuration interaction (CI) is a straightforward approach to describing interacting fermions. However, its application is hampered by the non-polynomially increasing computational time and memory requirements with the system size. To overcome this problem, we have been developing a variational method based on the canonical decomposition of the full-CI coefficients, which we call the symmetric tensor decomposition (STD)-CI. The applicability of STD-CI was tested for simple molecular systems, but here we test it using a stringent benchmark system, i.e., the insertion of Be into H2. The Be + H2 system is known for strong configurational degeneracy along the insertion pathway, and has been used for assessing a method's capability to treat correlated systems. We obtained errors compared to full CI results of ~10 mHartrees when using a rank 2 decomposition of the full CI coefficients. This is a huge improvement over Hartree-Fock results having errors of up to ~100 mHartrees in worst cases, although not as good as, e.g., CAS-CCSD with errors less than 1 mHartree.

  20. Materials Data on BeH8(NF2)2 (SG:33) by Materials Project

    SciTech Connect

    Kristin Persson

    2014-11-02

    Computed materials data using density functional theory calculations. These calculations determine the electronic structure of bulk materials by solving approximations to the Schrodinger equation. For more information, see https://materialsproject.org/docs/calculations

  1. [A case of Behçet's disease associated with aortic regurgitation and nephrotic syndrome].

    PubMed

    Akiyama, Y; Suzuki, T; Tanaka, M; Ohno, S; Imai, F; Kobayashi, K; Matsuo, H; Shibata, T

    1995-12-01

    A 50-year-old housewife with a main complaint of dyspnea was admitted to our hospital in September, 1992. In 1975, the patient developed aphthous stomatitis, genital aphthous ulcers, uveitis and erythema nodosum appeared and diagnosed as having Behcet's disease at Department of Dermatology of our hospital. Aortic regurgitation was pointed out in 1984. Hyperlipidemia appeared in January and Oral prednisolone was started in May, 1985. From April in 1987, proteinuria appeared. From January, 1988, urinal protein was greater than 300 mg/dl. Orthopnea appeared in July, 1992. Physical examinations revealed systolic and diastolic murmur and pretibial edema. Laboratory findings showed proteinuria (3.8 g/day) and hypoproteinemia (serum total protein 5.1 g/dl, serum albumin 3.1 g/dl). Microscopic findings of renal biopsy revealed mesangial proliferative glomerulonephritis and arteriosclerosis. Immunofluorescent studies demonstrated deposits of Apo B in the basement membrane and the mesangium. She was discharged from our hospital as proteinuria was decreased after a combination treatment with camostat mesilate 600 mg and SAIREITO 9.0 g. This patient developed nephrotic syndrome, which was caused by hypertension and hyperlipidemia in addition to Behcet's disease. This case is noteworthy because Behcet's disease is rarely complicated with nephrotic syndrome. PMID:8720269

  2. Materials Data on BeH8SO8 (SG:120) by Materials Project

    SciTech Connect

    Kristin Persson

    2014-11-02

    Computed materials data using density functional theory calculations. These calculations determine the electronic structure of bulk materials by solving approximations to the Schrodinger equation. For more information, see https://materialsproject.org/docs/calculations

  3. Materials Data on Li2BeH4 (SG:1) by Materials Project

    DOE Data Explorer

    Kristin Persson

    2016-04-23

    Computed materials data using density functional theory calculations. These calculations determine the electronic structure of bulk materials by solving approximations to the Schrodinger equation. For more information, see https://materialsproject.org/docs/calculations

  4. Pharmacokinetics screening for multi-components absorbed in the rat plasma after oral administration of traditional Chinese medicine Flos Lonicerae Japonicae-Fructus Forsythiae herb couple by sequential negative and positive ionization ultra-high-performance liquid chromatography/tandem triple quadrupole mass spectrometric detection.

    PubMed

    Zhou, Wei; Tam, Kin Y; Meng, Minxin; Shan, Jinjun; Wang, Shouchuan; Ju, Wenzheng; Cai, Baochang; Di, Liuqing

    2015-01-01

    The current study aims to investigate the pharmacokinetics of multi-components (caffeic acid, quinic acid, genistein, luteolin, quercetin, neochlorogenic acid, chlorogenic acid, cryptochlorogenic acid, arctigenin, genistin, luteoloside, astragalin, hyperoside, isoquercitrin, 3,5-dicaffeoylquinic acid, 3,4-dicaffeoylquinic acid, rutin, loganin, pinoresinol-β-d-glucoside, phillyrin, isoforsythoside, forsythoside A and forsythoside B) following oral administration of Flos Lonicerae Japonicae-Fructus Forsythiae herb couple in rats. A rapid and sensitive UPLC-ESI-MS/MS with sequential positive and negative ionization modes was developed to determine the 23 absorbed ingredients using one sample preparation combined with three chromatographic conditions in rat plasma. After mixing with internal standard (IS) (tinidazole and chloramphenicol), samples were pretreated by liquid-liquid extraction (LLE) with n-butyl alcohol/ethyl acetate (1:1, v/v). The separations for pinoresinol-β-d-glucoside, phillyrin, isoforsythoside, forsythoside A and forsythoside B were performed on an ACQUITY UPLC BEH C18 column (100mm×2.1mm, 1.7μm) with acetonitrile/methanol (4:1, v/v)-water as mobile phase. For analyzing quinic acid, an ACQUITY UPLC HSS T3 column (100mm×2.1mm, 1.8μm) was applied with acetonitrile/methanol (4:1, v/v)-0.01% formic acid as mobile phase after dilution up to 25-fold. The same column was applied to the other components with acetonitrile/methanol (4:1, v/v)-0.4% formic acid as mobile phase. The method validation results demonstrated that the proposed method was sensitive, specific and reliable, which was successfully applied to the pharmacokinetic study of the multi-components after oral administration of Flos Lonicerae Japonicae-Fructus Forsythiae herb couple. PMID:25533397

  5. Potential and limitations of on-line comprehensive reversed phase liquid chromatography×supercritical fluid chromatography for the separation of neutral compounds: An approach to separate an aqueous extract of bio-oil.

    PubMed

    Sarrut, Morgan; Corgier, Amélie; Crétier, Gérard; Le Masle, Agnès; Dubant, Stéphane; Heinisch, Sabine

    2015-07-10

    On-line comprehensive Reversed Phase Liquid Chromatography×Supercritical Fluid Chromatography (RPLCxSFC) was investigated for the separation of complex samples of neutral compounds. The presented approach aimed at overcoming the constraints involved by such a coupling. The search for suitable conditions (stationary phases, injection solvent, injection volume, design of interface) are discussed with a view of ensuring a good transfer of the compounds between both dimensions, thereby allowing high effective peak capacity in the second dimension. Instrumental aspects that are of prime importance in on-line 2D separations, were also tackled (dwell volume, extra column volume and detection). After extensive preliminary studies, an on-line RPLCxSFC separation of a bio-oil aqueous extract was carried out and compared to an on-line RPLCxRPLC separation of the same sample in terms of orthogonality, peak capacity and sensitivity. Both separations were achieved in 100min. For this sample and in these optimized conditions, it is shown that RPLCxSFC (with Hypercarb and Acquity BEH-2EP as stationary phases in first and second dimension respectively) can generate a slightly higher peak capacity than RPLCxRPLC (with Hypercarb and Acquity CSH phenyl-hexyl as stationary phases in first and second dimension respectively) (620 vs 560). Such a result is essentially due to the high degree of orthogonality between RPLC and SFC which may balance for lesser peak efficiency obtained with SFC as second dimension. Finally, even though current limitations in SFC instrumentation (i.e. large extra-column volume, large dwell volume, no ultra-high pressure) can be critical at the moment for on-line 2D-separations, RPLCxSFC appears to be a promising alternative to RPLCxRPLC for the separation of complex samples of neutral compounds. PMID:26037315

  6. 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

  7. Materials Data on InH8C8N4Cl7 (SG:18) by Materials Project

    SciTech Connect

    Kristin Persson

    2014-10-02

    Computed materials data using density functional theory calculations. These calculations determine the electronic structure of bulk materials by solving approximations to the Schrodinger equation. For more information, see https://materialsproject.org/docs/calculations

  8. Production and EPR characterization of exohedrally perfluoroalkylated paramagnetic lanthanum metallofullerenes: (La@C 82)-(C 8F 17) 2

    NASA Astrophysics Data System (ADS)

    Tagmatarchis, Nikos; Taninaka, Atsushi; Shinohara, Hisanori

    2002-04-01

    A strategy to chemically derivatize the outer sphere of endohedral metallofullerenes by using a fluorous synthesis-partitioning approach has been developed. The newly synthesized materials were found to be paramagnetic species and were characterized by electron paramagnetic resonance spectroscopy (EPR), laser desorption time-of-flight spectrometry (LD-TOF) and electronic absorption spectroscopy (UV-VIS-NIR). The fluorous-phase partitioning method (or liquid-liquid extraction), successfully applied for the first time in fullerene chemistry, aided by multi-stage recycling high performance liquid chromatography (HPLC) resulted in their isolation in isomer-free form. The present study opens the way to organic transformations of fullerene-based materials as a powerful separation technique.

  9. Synthesis and crystal structure of a chiral aromatic amine chloride salt (C8H12N)Cl

    NASA Astrophysics Data System (ADS)

    Ben Salah, A. M.; Naїli, H.; Mhiri, T.; Bataille, T.

    2015-12-01

    The new organic chloride salt incorporating an aromatic primary amine with a chiral functional group, (S)-α-methylbenzylammonium), has been synthesized by slow evaporation method at room temperature. The crystals are trigonal with non-centrosymmetric sp. gr. R3. The crystal packing is determined by N-H···Cl hydrogen bonds and C-H···π interactions between the aromatic rings of the organic moieties, resulting in supramolecular architecture.

  10. Materials Data on CuH36C8(N5O4)2 (SG:15) by Materials Project

    DOE Data Explorer

    Kristin Persson

    2016-07-14

    Computed materials data using density functional theory calculations. These calculations determine the electronic structure of bulk materials by solving approximations to the Schrodinger equation. For more information, see https://materialsproject.org/docs/calculations

  11. Materials Data on CuH22C8N10O (SG:15) by Materials Project

    DOE Data Explorer

    Kristin Persson

    2016-07-29

    Computed materials data using density functional theory calculations. These calculations determine the electronic structure of bulk materials by solving approximations to the Schrodinger equation. For more information, see https://materialsproject.org/docs/calculations

  12. Comprehensive chemical kinetic modeling of the oxidation of C8 and larger n-alkanes and 2-methylalkanes

    SciTech Connect

    Sarathy, S M; Westbrook, C K; Pitz, W J; Mehl, M; Togbe, C; Dagaut, P; Wang, H; Oehlschlaeger, M; NIemann, U; Seshadri, K; Veloo, P S; Ji, C; Egolfopoulos, F; Lu, T

    2011-03-16

    Conventional petroleum jet and diesel fuels, as well as alternative Fischer-Tropsch (FT) fuels and hydrotreated renewable jet (HRJ) fuels, contain high molecular weight lightly branched alkanes (i.e., methylalkanes) and straight chain alkanes (n-alkanes). Improving the combustion of these fuels in practical applications requires a fundamental understanding of large hydrocarbon combustion chemistry. This research project presents a detailed and reduced chemical kinetic mechanism for singly methylated iso-alkanes (i.e., 2-methylalkanes) ranging from C{sub 8} to C{sub 20}. The mechanism also includes an updated version of our previously published C{sub 8} to C{sub 16} n-alkanes model. The complete detailed mechanism contains approximately 7,200 species 31,400 reactions. The proposed model is validated against new experimental data from a variety of fundamental combustion devices including premixed and nonpremixed flames, perfectly stirred reactors and shock tubes. This new model is used to show how the presence of a methyl branch affects important combustion properties such as laminar flame propagation, ignition, and species formation.

  13. Quantification of L-ergothioneine in whole blood by hydrophilic interaction ultra-performance liquid chromatography and UV-detection.

    PubMed

    Sotgia, Salvatore; Zinellu, Angelo; Pintus, Gianfranco; Pinna, Gerard Aime; Deiana, Luca; Carru, Ciriaco

    2013-03-01

    A new hydrophilic interaction ultra-performance LC method was established for the whole blood measurement of L-ergothioneine. Chromatographic separation was achieved in a fairly short time, less than 4 min, on a 100 × 2.1 mm Acquity UPLC BEH HILIC 1.7 μm column with a mobile phase consisting of a mixture of 100 mmol/L ammonium acetate/ACN/water (5:85:10, v/v/v) that flowed isocratically at 0.250 mL/min. The LOD and the limit of quantification were 3.85 and 11.67 μmol/L, respectively. The method exhibited linearity in a concentration range of 15.63-1000 μmol/L (R(2) > 0.999). Mean recovery was 96.34% whereas intraassay and interassay precision were 1.52 and 1.82% RSD, respectively. On the whole, the developed method is simple, fast, precise, accurate, and sensitive and may be useful for routine analyses. PMID:23418129

  14. Rapid determination of eight oxoisoaporphine alkaloids in Rhizoma Menispermi by the optimal homogenate extraction followed by UPLC-MS/MS.

    PubMed

    Wei, Jinxia; Jiang, Zhen; Cui, Zhi; Guo, Xingjie

    2015-07-01

    The objective of this study was to develop a rapid and reliable homogenate extraction (HGE) and ultra high-performance liquid chromatography-tandem mass spectrometric (UPLC-MS/MS) method for simultaneous analysis of eight bioactive oxoisoaporphine alkaloids (including two new alkaloids) in Rhizoma Menispermi. HGE was optimized by response surface methodology (RSM) to obtain the maximum extraction efficiency of eight alkaloids. Separation was achieved on a Waters ACQUITY UPLC® BEH C18 column (50 × 2.1 mm(2), 1.7 μm) using gradient elution with a mobile phase consisting of acetonitrile and 0.2% formic acid in water. Quantification was performed with multiple reaction monitoring (MRM) mode using positive ESI as an interface. This is the first report of the simultaneous analysis of eight oxoisoaporphine alkaloids in Rhizoma Menispermi using a UPLC-MS/MS method; this analysis afforded good linearity, precision, and accuracy. Then, the method was successfully applied to determine the alkaloids in Rhizoma Menispermi from different sources. PMID:25948242

  15. UPLC-MS/MS determination of voriconazole in human plasma and its application to a pharmacokinetic study.

    PubMed

    Wang, Zhe; Huang, Cheng-ke; Sun, Wei; Xiao, Cui; Wang, Zeng-shou

    2015-02-01

    A sensitive and rapid ultra performance liquid chromatography tandem mass spectrometry (UPLC-MS/MS) method was developed to determine voriconazole in human plasma. Sample preparation was accomplished through a simple one-step protein precipitation with methanol. Chromatographic separation was carried out on an Acquity UPLC BEH C18 column using an isocratic mobile phase system composed of acetonitrile and water containing 1% formic acid (45:55, v/v) at a flow rate of 0.50 mL/min. Mass spectrometric analysis was performed using a QTrap5500 mass spectrometer coupled with an electrospray ionization source in the positive ion mode. The multiple reaction monitoring transitions of m/z 351.0 → 281.5 and m/z 237.1 → 194.2 were used to quantify voriconazole and carbamazepine (internal standard), respectively. The linearity of this method was found to be within the concentration range of 2.0-1000 ng/mL with a lower limit of quantification of 2.0 ng/mL. Only 1.0 min was needed for an analytical run. This fully validated method was successfully applied to the pharmacokinetic study after oral administration of 200 mg voriconazole to 20 Chinese healthy male volunteers. PMID:24925071

  16. Quantification of carbamazepine and its 10,11-epoxide metabolite in rat plasma by UPLC-UV and application to pharmacokinetic study.

    PubMed

    Beig, Avital; Dahan, Arik

    2014-07-01

    A rapid, selective and sensitive UPLC-UV method was developed and validated for the quantitative analysis of carbamazepine and its epoxide metabolite in rat plasma. A relatively small volume of plasma sample (200 μL) is required for the described analytical method. The method includes simple protein precipitation, liquid-liquid extraction, evaporation, and reconstitution steps. Samples were separated on a Waters Acquity UPLC BEH C18 column (1.7 µm, 2.1 × 100 mm) with a gradient mobile phase consisted of 60:40 going to 40:60 (v/v) water-acetonitrile at a flow rate of 0.5 mL/min. The total run time was as low as 6 min, representing a significant improvement in comparison to existing methods. Excellent linearity (r(2)  > 0.999) was achieved over a wide concentration range. Close to complete recovery, short analysis time, high stability, accuracy, precision and reproducibility, and low limit of quantitation were demonstrated. Finally, we successfully applied this analytical method to a pre-clinical oral pharmacokinetic study, revealing the plasma profiles of both carbamazepine and carbamazepine-10,11-epoxide following oral administration of carbamazepine to rats. The advantages demonstrated in this work make this analytical method both time- and cost-efficient approach for drug and metabolite monitoring in the pre-clinical/clinical laboratory. PMID:24327551

  17. Chemical Fingerprint Analysis and Quantitative Determination of Steroidal Compounds from Dioscorea villosa, Dioscorea Species, and Dietary Supplements using UHPLC-ELSD

    PubMed Central

    Avula, Bharathi; Wang, Yan-Hong; Ali, Zulfiqar; Smillie, Troy J.

    2014-01-01

    Ultra high-performance liquid chromatography (UHPLC) with evaporative light scattering (ELS) detection was used for the quantification of steroidal saponins and diosgenin from the rhizomes or tubers of various Dioscorea species and dietary supplements that were purported to contain Dioscorea. The analysis was performed on an Acquity UPLC™ system with an UPLC™ BEH Shield RP18 column using a gradient elution with water and acetonitrile. Due to their low UV absorption, the steroidal saponins were observed by evaporative light scattering detection. The twelve compounds could be separated within 15 minutes using the developed UHPLC method with detection limits of 5–12 μg/mL with 2μL injection volume. The analytical method was validated for linearity, repeatability, accuracy, limits of detection (LOD) and limits of quantification (LOQ). The Relative Standard Deviations (RSD) for intra- and inter-day experiments were less than 3.1 %, and the recovery efficiency was 97–101 %. The total content of standard compounds was found to be in the range from 0.01–14.5% and 0.9–28.6 mg daily intake for dry plant materials and solid commercial preparations, respectively. UHPLC-mass spectrometry with a quadrupole mass analyzer and ESI source was used only for confirmation of the identity of the various saponins. The developed method is simple, rapid and especially suitable for quality control analysis of commercial products. PMID:24019066

  18. Development and validation of a stability-indicating RP-UPLC method for the quantitative analysis of nabumetone in tablet dosage form.

    PubMed

    Sethi, Neha; Anand, Ankit; Chandrul, Kaushal K; Jain, Garima; Srinivas, Kona S

    2012-02-01

    High efficiency and less run time are the basic requirements of high-speed chromatographic separations. To fulfill these requirements, a new separation technique, ultra-performance liquid chromatography (UPLC), has shown promising developments. A rapid, specific, sensitive, and precise reverse-phase UPLC method is developed for the determination of nabumetone in tablet dosage form. In this work, a new isocratic chromatographic method is developed. The newly developed method is applicable for assay determination of the active pharmaceutical ingredient. The chromatographic separation is achieved on a Waters Acquity BEH column (100 mm, i.d., 2.1 mm, 1.7 µm) within a short runtime of 2 min using a mobile phase of 5 mM ammonium acetate-acetonitrile (25:75, v/v), at a flow rate of 0.3 mL/min at an ambient temperature. Quantification is achieved with photodiode array detection at 230 nm, over the concentration range of 0.05-26 µg/mL. Forced degradation studies are also performed for nabumetone bulk drug samples to demonstrate the stability-indicating power of the UPLC method. Comparison of system performance with conventional high-performance liquid chromatography is made with respect to analysis time, efficiency, and sensitivity. The method is validated according to the ICH guidelines and is applied successfully for the determination of nabumetone in tablets. PMID:22298755

  19. 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. PMID:27475405

  20. 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. PMID:26383987

  1. A rapid and simple UPLC-MS-MS method for determination of glipizide in human plasma and its application to bioequivalence study.

    PubMed

    Qiu, Xiangjun; Zheng, Shuang-li; Wang, Yingfei; Wang, Rong; Ye, Lei

    2015-01-01

    In this study, a simple, rapid and sensitive ultra performance liquid chromatography-tandem mass spectrometry method is described for the determination of glipizide in human plasma samples using carbamazepine as the internal standard (IS) from bioequivalence assays. Sample preparation was accomplished through protein precipitation with methanol, and chromatographic separation was performed on an Acquity BEH C18 column (2.1 mm × 50 mm, 1.7 μm) with gradient profile at a flow rate of 0.4 mL/min. Mass spectrometric analysis was performed using an QTrap5500 mass spectrometer coupled with an electrospray ionization source in the positive ion mode. The multiple reaction monitoring transitions of m/z 446.1 → 321.0 and m/z 237.1 → 194.2 were used to quantify for glipizide and IS. The linearity of this method was found to be within the concentration range of 10-1,500 ng/mL for glipizide in human plasma. Only 1.0 min was needed for an analytical run. The method was applied to a bioequivalence study of two drug products containing glipizide in human plasma samples. PMID:24771054

  2. Simultaneous determination of loganin, morroniside, catalpol and acteoside in normal and chronic kidney disease rat plasma by UPLC-MS for investigating the pharmacokinetics of Rehmannia glutinosa and Cornus officinalis Sieb drug pair extract.

    PubMed

    Zhao, Min; Tao, Jinhua; Qian, Dawei; Liu, Pei; Shang, Er-xin; Jiang, Shu; Guo, Jianming; Su, Shu-lan; Duan, Jin-ao; Du, Leyue

    2016-01-15

    A sensitive and rapid method for determination of loganin, morroniside, catalpol and acteoside in rat plasma after oral administration of Rehmannia glutinosa Libosch and Cornus officinalis Sieb drug pair based on ultra-high performance liquid chromatography coupled with tandem mass spectrometry (UPLC-MS). Chromatographic separation was achieved using an Acquity UPLC BEH C18 column (100mm×2.1mm, 1.7μm) at a flow rate of 0.4mL/min, using gradient mode containing 0.1% formic acid in water and acetonitrile were used as the mobile phase A and B. Loganin, morroniside, catalpol, acteoside and the internal standard (chloramphenicol) were detected by selected reaction monitoring in the negative ion mode with the mass transition of m/z 451.0→179.0 (morroniside), m/z 435.0→227.0 (loganin), m/z 407.1→199.1 (catalpol), m/z 623.2→161.0 (acteoside) and m/z 320.8→151.9 (chloramphenicol), respectively. All calibration curves showed good linearity (r>0.991). The precision was evaluated by intra-day and inter-day assays and the RSD% were all within 9.58%. The recovery ranged from 67.62 to 80.14%. The method was successfully applied to pharmacokinetic study of the analytes in normal and doxorubicin-induced chronic kidney disease rat plasma. PMID:26720701

  3. A SIMPLE AND-SENSITIVE STABILITY-INDICATING UHPLC-DAD METHOD FOR THE DETERMINATION OF CEFETAMET PIVOXIL HYDROCHLORIDE.

    PubMed

    Garbacki, Piotr; Cielecka-Piontek, Judyta; Zalewski, Przemysław; Oszczapowicz, Irena; Jelińska, Anna

    2016-01-01

    A fast and sensitive UHPLC-DAD method was developed and subsequently validated for determination of cefetamet pivoxil hydrochloride in the presence of its degradation products. The chromatographic separation was carried out on a Waters Acquity BEH C18, (2.1 x 100 mm, 1.7 µm) column. The mobile phase was composed of 0.1% formic acid and acetonitrile (40 : 60, v/v) at the flow rate 0.7 mL/min. The detection wavelength was 265 nm and the temperature was 30 °C. Cefetamet pivoxil hydrochloride was susceptible to degradation under the influence of sodium hydroxide, hydrochloric acid and in the conditions of increased temperature and relative humidity. However, it was stable after irradiation, in increased temperature in dry air and in the presence of oxidizing agent. The developed UHPLC-DAD method was linear over the concentration range of 10-240 µg/mL (r2 = 0.9999; n = 12). The obtained RSD values were less than 2%, demonstrating that the described procedure is precise. The accuracy was also confirmed (mean recoveries were 97.79-102.08%). Under applied chromatographic conditions LOD and LOQ values were 2.08 mg/mL and 6.29 mg/mL, respectively. The proposed method was successfully applied in determination of cefetamet pivoxil hydrochloride in aqueous solutions as well as in the solid state. PMID:27476279

  4. 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). PMID:25965875

  5. 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. PMID:25030991

  6. Ultra high performance liquid chromatography with electrospray ionization tandem mass spectrometry coupled with hierarchical cluster analysis to evaluate Wikstroemia indica (L.) C. A. Mey. from different geographical regions.

    PubMed

    Wei, Lan; Wang, Xiaobo; Mu, Shanxue; Sun, Lixin; Yu, Zhiguo

    2015-06-01

    A sensitive, rapid and simple ultra high performance liquid chromatography with electrospray ionization tandem mass spectrometry method was developed to determine seven constituents (umbelliferone, apigenin, triumbelletin, daphnoretin, arctigenin, genkwanin and emodin) in Wikstroemia indica (L.) C. A. Mey. The chromatographic analysis was performed on an ACQUITY UPLC® BEH C18 column (2.1 × 50 mm, 1.7 μm) by gradient elution with the mobile phase of 0.05% formic acid aqueous solution (A) and acetonitrile (B). Multiple reaction monitoring mode with positive and negative electrospray ionization interface was carried out to detect the components. This method was validated in terms of specificity, linearity, accuracy, precision and stability. Excellent linear behavior was observed over the certain concentration ranges with the correlation coefficient values higher than 0.999. The intraday and innerday precisions were within 2.0%. The recoveries of seven analytes were 99.4-101.1% with relative standard deviation less than 1.2%. The 18 Wikstroemia indica samples from different origins were classified by hierarchical clustering analysis according to the contents of seven components. The results demonstrated that the developed method could successfully be used to quantify simultaneously of seven components in Wikstroemia indica and could be a helpful tool for the detection and confirmation of the quality of traditional Chinese medicines. PMID:25866087

  7. Isolation, Identification, and Characterisation of Degradation Products and the Development and Validation of a Stability-Indicating Method for the Estimation of Impurities in the Tolterodine Tartrate Formulation

    PubMed Central

    Prakash, Lakkireddy; Himaja, Malipeddi; Vasudev, Rudraraju

    2015-01-01

    A short and sensitive stability-indicating gradient RP-UPLC method was developed for the quantitative determination of process-related impurities and degradation products of tolterodine tartrate in pharmaceutical formulations. The method was developed by using the Waters ACQUITY UPLC™ BEH shield RP18 (2.1 × 100 mm, 1.7 μm) column with a mobile phase containing a gradient mixture of solvent A and B at a detection wavelength of 210 nm. During the stress study, the degradation products of tolterodine tartrate were well-resolved from tolterodine and its impurities and the mass balances were found to be satisfactory in all the stress conditions, thus proving the stability-indicating capability of the method. The developed method was validated as per ICH guidelines with respect to specificity, linearity, limit of detection and quantification, accuracy, precision, ruggedness, and robustness. During the stability (40°C/75% RH, 3 months) analysis of the drug product, one unknown impurity was detected by the above stability-indicating method. The unknown impurity was isolated by preparative HPLC and subjected to mass and NMR studies. Based on the spectral data, the unknown impurity was characterised as 2-(3-amino-1-phenylpropyl)-4-methylphenol (des-N,N-diisopropyl tolterodine). Structural elucidation of the impurity by spectral data is discussed in detail. PMID:26839802

  8. [Fast analysis of indole alkaloids from Evodiae fructus by supercritical fluid chromatography].

    PubMed

    Li, Zhenyu; Fu, Qing; Li, Kuiyong; Liang, Tu; Jin, Yu

    2014-05-01

    A fast chromatographic separation of indole alkaloids from Evodiae fructus was developed by supercritical fluid chromatography (SFC). The initial screening of four stationary phases was investigated with a standard mixture of evodiamine and rutaecarpine, and a complex sample of indole alkaloids prepared from Evodiae fructus as probes. Later, the effects of chromatographic parameters on separation were studied including injection volume, organic modifier, additive, temperature and back pressure. The injection volume had significant impact on the peak shape. With the additives in the mobile phase, slight changes in peak shape and retention time were observed in separation. Variation in organic modifier led to dramatic change in chromatographic behavior. Both decreased temperature and increased back pressure shortened the retention time. Finally, a fast analytical method using SFC, on a Waters ACQUITY UPC2 BEH column, methanol as modifier, under 35 degrees C and 2.07 x 10(7) Pa, was developed to separate a complex sample of indole alkaloids in less than 15 min. Another rapid approach for the separation of a complex sample of indole alkaloids was developed by using ultra-high performance liquid chromatography (UHPLC). As a result, SFC can be used in the separation of natural products, giving high performance, good resolution and fast analysis speed. The difference in selectivity with UHPLC can be used to the development of natural product separation. PMID:25185311

  9. High-throughput analysis of 19 endogenous androgenic steroids by ultra-performance convergence chromatography tandem mass spectrometry.

    PubMed

    Quanson, Jonathan L; Stander, Marietjie A; Pretorius, Elzette; Jenkinson, Carl; Taylor, Angela E; Storbeck, Karl-Heinz

    2016-09-15

    11-Oxygenated steroids such as 11-ketotestosterone and 11-ketodihydrotestosterone have recently been shown to play a putative role in the development and progression of castration resistant prostate cancer. In this study we report on the development of a high throughput ultra-performance convergence chromatography tandem mass spectrometry (UPC(2)-MS/MS) method for the analysis of thirteen 11-oxygenated and six canonical C19 steroids isolated from a cell culture matrix. Using an Acquity UPC(2) BEH 2-EP column we found that UPC(2) resulted in superior selectivity, increased chromatographic efficiency and a scattered elution order when compared to conventional reverse phase ultra-performance liquid chromatography (UPLC). Furthermore, there was a significant improvement in sensitivity (5-50 times). The lower limits of quantification ranged between 0.01-10ngmL(-1), while the upper limit of quantification was 100ngmL(-1) for all steroids. Accuracy, precision, intra-day variation, recovery, matrix effects and process efficiency were all evaluated and found to be within acceptable limits. Taken together we show that the increased power of UPC(2)-MS/MS allows the analyst to complete in vitro assays at biologically relevant concentrations for the first time and in so doing determine the routes of steroid metabolism which is vital for studies of androgen responsive cancers, such as prostate cancer, and could highlight new mechanisms of disease progression and new targets for cancer therapy. PMID:27479683

  10. A fast ultra high pressure liquid chromatographic method for qualification and quantification of pharmaceutical combination preparations containing paracetamol, acetyl salicylic acid and/or antihistaminics.

    PubMed

    Deconinck, E; Sacré, P Y; Baudewyns, S; Courselle, P; De Beer, J

    2011-09-10

    A fully validated UHPLC method for the identification and quantification of pharmaceutical preparations, containing paracetamol and/or acetyl salicylic acid, combined with anti-histaminics (phenylephrine, pheniramine maleate, diphenhydramine, promethazine) and/or other additives as quinine sulphate, caffeine or codeine phosphate, was developed. The proposed method uses a Waters Acquity BEH C18 column (2 mm × 100 mm, 1.7 μm) with a gradient using an ammonium acetate buffer pH 4.0 as aqueous phase and methanol as organic modifier. The obtained method was fully validated based on its measurement uncertainty (accuracy profile) and robustness tests. Calibration lines for all components were linear within the studied ranges. The relative bias and the relative standard deviations for all components were respectively smaller than 1.5% and 2%, the β-expectation tolerance limits did not exceed the acceptance limits of 10% and the relative expanded uncertainties were smaller than 5% for all of the considered components. A UHPLC method was obtained for the identification and quantification of these kind of pharmaceutical preparations, which will significantly reduce analysis times and workload for the laboratories charged with the quality control of these preparations. PMID:21665401

  11. Preclinical pharmacokinetics, tissue distribution and excretion studies of a potential analgesics - corydaline using an ultra performance liquid chromatography-tandem mass spectrometry.

    PubMed

    Wang, Jianfeng; Liang, Lishuang; Zhang, Qiongyu; Li, Xingang; Fu, Zhijian

    2013-12-30

    A rapid resolution ultra performance liquid chromatography (UPLC) coupled with electrospray ionization (ESI) mass spectrometry method was developed and validated for the quantitative analysis of corydaline in rats' plasma and various tissues for pharmacokinetic, tissue distribution and excretion studies of corydaline. The analytes were separated on an Acquity UPLC BEH C18 column (2.1mm×100mm, 1.7μm) and detected with a triple quadrupole mass spectrometer using positive ion ESI in the multiple reaction monitoring (MRM) mode. The MS/MS ion transitions monitored were m/z 370.0→192.0 for corydaline and 354.1→188.0 for IS, respectively. Calibration curves (1/x(2) weighted) offered satisfactory linearity (r(2)>0.9984) within 1-1000ng/mL. The accuracy and precision ranged from -7.4% to 8.5% and 3.4% to 12.8%, respectively. The absolute matrix effect (94.2-119.2%), relative matrix effect (1.7-9.6%) and recoveries (81.4-93.7%) were satisfactory in all the biological matrices examined. The assay was successfully applied to the plasma pharmacokinetics, tissue distribution and excretion studies of corydaline in rats. The pharmacokinetic parameters such as half-life (t1/2), mean residence time (MRT) and maximum concentration (Cmax) were determined. These preclinical data of corydaline would be useful for the clinical reference. PMID:24216274

  12. [Rapid screening and confirming carcinogenic banned azo colorants in textiles by high performance liquid chromatography-linear ion trap/orbitrap high-resolution mass spectrometry].

    PubMed

    Yun, Huan; Liu, Xin; Wang, Jing; Yan, Hua; Cui, Fengyun; Zhang, Zhaohui

    2013-09-01

    A method of high performance liquid chromatography-linear ion trap/orbitrap highresolution mass spectrometry (HPLC-LTP/Orbitrap MS) was ued to screen and confirm-banned azo colorants in textiles rapidly. The analytes were reduced to carcinogenic aromatic amines with sodium dithionite in citrate buffer solution. The reduced solution was extracted bydiatomite, and loadd onto an Acquity UPLC BEH C18 column (50 mm x 2.1 MM. 1.7 microm) with a gradient elution of methanol and 0.1% (v/v) methane acid aqueous solution, and finally detected by linear ion trap/orbitrap high-resolution mass spectrometry in positive ESI mode. In mass spectrometry method, the MS spectrum of high-resolution and the collision induced dissociation (CID) spectrum of data-dependent scan mode were used for screening analysis and conformation, respectively. The calibration curves showed a good linearity in the range of 0.05 -2.00 mg/b, and the correlation coefficients (r) were higher than 0.99. By detecting spiked samples, the limits of quantification were 0.08 mg/kg for all the residues and the recoveries were in the range of 65.5% - 111.5% with the relative standard deviations (RSDs) between 0.87% and 2.49%. The results indicate that the method is simple, rapid, sensitive and suitable for the qualitative and quantitative analysis of carcinogenic aromatic amines in textiles. PMID:24392621

  13. Separation and characterization of ciprofloxacin, difloxacin, lomefloxacin, norfloxacin, and ofloxacin oxidation products under potassium permanganate treatment in acidic medium by UPLC-MS/MS.

    PubMed

    Hubicka, Urszula; Zmudzki, Paweł; Zuromska-Witek, Barbara; Zajdel, Paweł; Pawłowski, Maciej; Krzek, Jan

    2013-05-15

    A simple, sensitive and reproducible ultra-performance liquid chromatography method for determination of ciprofloxacin, difloxacin, lomefloxacin, norfloxacin and ofloxacin oxidation stability under permanganate treatment in acidic conditions at pH from 3.0 to 6.0, was developed. Chromatographic separations were carried out using the Acquity UPLC BEH C18 column; (2.1×100 mm, 1.7 μm particle size). The column was maintained at 40°C, and eluted under isocratic conditions using 83% of eluent A and 17% of eluent B over 6.5 min, at a flow rate of 0.3 mL min(-1). Eluent A: water/formic acid (0.1 v/v%); eluent B: acetonitrile/formic acid (0.1 v/v%). An oxidation process followed kinetic of the second order reaction and depended upon solution acidity. Oxidation of fluoroquinolones proceeded at piperazine moiety yielding respective hydroxy and oxo analogs, and remaining the quinolone fragment intact. Structures of products formed were assigned on a basis of UPLC/MS/MS fragmentation pathways. PMID:23618144

  14. Ultra performance liquid chromatography tandem mass spectrometry performance evaluation for analysis of antibiotics in natural waters.

    PubMed

    Tamtam, Fatima; Mercier, Fabien; Eurin, Joëlle; Chevreuil, Marc; Le Bot, Barbara

    2009-03-01

    An ultra performance liquid chromatography electrospray tandem mass spectrometry (UPLC/MS/MS) method was developed and validated for the determination of 17 antibiotics in natural waters in one single extraction and chromatographic procedure. Gradient separation conditions were optimised for 17 compounds belonging to five different antibiotic groups: quinolones (oxolinic acid, nalidixic acid, pipemidic acid, flumequine), fluoroquinolones (enoxacin, ciprofloxacin, norfloxacin, ofloxacin, enrofloxacin, sarafloxacin, danofloxacin, difloxacin, lomefloxacin), sulphonamides (sulphamethoxazole, sulphamethazine), nitro-imidazole (ornidazole) and diaminopyrimidine (trimethoprim). The separation of all compounds, obtained using a 1.7 microm particle size column (100 mm x 2.1 mm), was achieved within 10 min time. Water samples were adjusted to pH 7 and extracted using Oasis hydrophilic-lipophilic balance (HLB) solid phase extraction cartridges. After elution with methanol and concentration, extracts were injected in a C18 column (Acquity UPLC BEH C18) and detected by tandem mass spectrometry. Average recovery from 100 ng L(-1) fortified samples was higher than 70% for most of the compounds, with relative standard deviations below 20%. Performances of the method (recoveries, detection limit, quantification limit and relative standard deviation) and matrix effects were studied, and results obtained showed that method was suitable for routine analysis of antibiotics in surface water. Samples analysis from Seine River (France) confirmed the interest of antibiotic contamination evaluation in that area. PMID:19148627

  15. [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. PMID:25185307

  16. Development and validation of a fast chromatographic method for screening and quantification of legal and illegal skin whitening agents.

    PubMed

    Desmedt, B; Rogiers, V; Courselle, P; De Beer, J O; De Paepe, K; Deconinck, E

    2013-09-01

    During the last years, the EU market is flooded by illegal cosmetics via the Internet and a so-called "black market". Among these, skin-bleaching products represent an important group. They contain, according to the current European cosmetic legislation (Directive 76/768/EEC), a number of illegal active substances including hydroquinone, tretinoin and corticosteroids. These may provoke as well local as systemic toxic effects, being the reason for their banning from the EU market. To control this market there is a need for a fast screening method capable of detecting illegal ingredients in the wide variety of existing bleaching cosmetic formulations. In this paper the development and validation of an ultra high pressure liquid chromatographic (UHPLC) method is described. The proposed method makes use of a Waters Acquity BEH shield RP18 column with a gradient using 25 mM ammonium borate buffer (pH 10) and acetonitrile. This method is not only able to detect the major illegal (hydroquinone, tretinoin and six dermatologic active corticosteroids) and legal whitening agents, the latter having restrictions with respect to concentration and application (kojic acid, arbutin, nicotinamide and salicylic acid), but can also quantify these in a run time of 12 min. The method was successfully validated using the "total error" approach in accordance with the validation requirements of ISO-17025. During the validation a variety of cosmetic matrices including creams, lotions and soaps were taken into consideration. PMID:23708434

  17. Chemical fingerprint analysis and quantitative determination of steroidal compounds from Dioscorea villosa, Dioscorea species and dietary supplements using UHPLC-ELSD.

    PubMed

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

    2014-02-01

    Ultra high-performance liquid chromatography (UHPLC) with evaporative light scattering detection was used for the quantification of steroidal saponins and diosgenin from the rhizomes or tubers of various Dioscorea species and dietary supplements that were purported to contain Dioscorea. The analysis was performed on an Acquity UPLC™ system with an UPLC™ BEH Shield RP18 column using a gradient elution with water and acetonitrile. Owing to their low UV absorption, the steroidal saponins were observed by evaporative light scattering detection. The 12 compounds could be separated within 15 min using the developed UHPLC method with detection limits of 5-12 µg/mL with 2 μL injection volume. The analytical method was validated for linearity, repeatability, accuracy, limits of detection and limits of quantification. The relative standard deviations for intra- and inter-day experiments were <3.1%, and the recovery efficiency was 97-101%. The total content of standard compounds was found to be in the ranges 0.01-14.5% and 0.9-28.6 mg daily intake for dry plant materials and solid commercial preparations, respectively. UHPLC-mass spectrometry with a quadrupole mass analyzer and ESI source was used only for confirmation of the identity of the various saponins. The developed method is simple, rapid and especially suitable for quality control analysis of commercial products. PMID:24019066

  18. Fingerprint Analysis of Desmodium Triquetrum L. Based on Ultra Performance Liquid Chromatography with Photodiode Array Detector Combined with Chemometrics Methods.

    PubMed

    Zhang, Meiling; Zhao, Cui; Liang, Xianrui; Ying, Yin; Han, Bing; Yang, Bo; Jiang, Cheng

    2016-01-01

    A fingerprinting approach was developed by means of ultra high-performance liquid chromatography with photodiode array detector for the quality control of Desmodium triquetrum L., an herbal medicine widely used for clinical purposes. Ten batches of raw material samples of D. triquetrum were collected from different regions of China. All UPLC analyses were carried out on a Waters ACQUITY UPLC BEH shield RP18 column (2.1 × 50 mm, 1.7 µm particle size) at 60°C, with a gradient mobile phase composed of 0.1% aqueous formic acid and acetonitrile at a flow rate of 0.45 mL/min. The method validation results demonstrated the developed method possessing desirable reproducibility, efficiency, and allowing fingerprint analysis in one chromatographic run within 13 min. The quality assessment was achieved by using chemometrics methods including similarity analysis, hierarchical clustering analysis and principal component analysis. The developed method can be used for further quality control of D. triquetrum. PMID:26791345

  19. Determination of Apremilast in Rat Plasma by UPLC-MS-MS and Its Application to a Pharmacokinetic Study.

    PubMed

    Chen, Lian-Guo; Wang, Zhe; Wang, Shujun; Li, Tao; Pan, Yongyang; Lai, Xixi

    2016-09-01

    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 apremilast 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 apremilast was at 1.27 min. The detection was performed on a triple quadrupole tandem mass spectrometer in the multiple reaction-monitoring mode using the respective transitions m/z 461.3 → 257.1 for apremilast and m/z 237.2 → 194.2 for carbamazepine (internal standard). The calibration curve was linear over the range of 0.1-100 ng/mL with a lower limit of quantitation of 0.1 ng/mL. The mean recovery of apremilast in plasma was in the range of 83.2-87.5%. Both intraday and interday precision were <9.6%. This method was successfully applied in the pharmacokinetic study after oral administration of 6.0 mg/kg apremilast in rats. PMID:27165568

  20. Quantification of sofosbuvir and ledipasvir in human plasma by UPLC-MS/MS method: Application to fasting and fed bioequivalence studies.

    PubMed

    Rezk, Mamdouh R; Bendas, Ehab R; Basalious, Emad B; Karim, Iman A

    2016-08-15

    A rapid and sensitive LC-MS/MS method was developed, optimized and validated for quantification of sofosbuvir (SF) and ledipasvir (LD) in human plasma using eplerenone as an internal standard (IS). Analytes and IS were extracted from plasma by simple liquid-liquid extraction technique using methyl tertiary butyl ether. The prepared samples were chromatographed on Acquity UPLC BEH C18 column. Separation was done using a mobile phase formed of 0.1% formic acid and acetonitrile (50:50, v/v) in an isocratic mode at a flow rate of 0.4ml/min. The Xevo TQD LC-MS/MS was operated under the multiple-reaction monitoring mode using electrospray ionization. A full validation of the method was performed according to the FDA guidelines. Linearity was found to be in the range of 0.25-3500ng/ml for SF and 5-2000ng/ml for LD. The intra-day and inter-day precision and accuracy results were within the acceptable limits. A short run time of 2min allows analysis of more than 400 plasma samples per day. The developed method was successfully applied to both fasting and fed bioequivalence studies in healthy human volunteers. PMID:27322631

  1. Development and validation of a UPLC-MS/MS method for quantitation of droxidopa in human plasma: Application to a pharmacokinetic study.

    PubMed

    Wang, Haidong; Yang, Guangsheng; Zhou, Jinyu; Pei, Jiang; Zhang, Qiangfeng; Song, Xingfa; Sun, Zengxian

    2016-08-01

    In this study, a simple and sensitive ultra performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) method was developed and validated for quantitation of droxidopa in human plasma for the first time. A simple plasma protein precipitation method using methanol containing 3% formic acid was selected, and the separation was achieved by an Acquity UPLC™ BEH Amide column (2.1mm×50mm, 1.7μm) with a gradient elution using acetonitrile, ammonium formate buffer and formic acid as mobile phase. The detection of droxidopa and benserazide (internal standard, IS) was performed using positive-ion electrospray tandem mass spectrometry via multiple reaction monitoring (MRM). The precursor-to-product ion transitions m/z 214.2→m/z 152.0 for droxidopa, and m/z 258.1→m/z 139.1 for IS were used for quantification. A lower limit of quantification of 5.00ng/mL was achieved and the linear curve range was 5.00-4000ng/mL using a weighted (1/x(2)) linear regression model. Intra-assay and inter-assay precision was less than 10.2%, and the accuracy ranged from 0.1% to 2.1%. Stability, recovery and matrix effects were within the acceptance criteria recommended by the regulatory bioanalytical guidelines. The method was successfully applied to a pharmacokinetic study of droxidopa in healthy Chinese volunteers. PMID:27311027

  2. Determination of dexmedetomidine in children's plasma by ultra-performance liquid chromatography tandem mass spectrometry and application to pharmacokinetic study.

    PubMed

    Liu, Hua-Cheng; Sun, Wei; Wang, Cheng-Yu; Ying, Wei-Yang; Zheng, Li-Dan; Zeng, Rui-Feng; Wang, Zhe; Ge, Ren-Shan

    2016-06-15

    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 dexmedetomidine in children's plasma. Sample preparation was accomplished through a simple one-step deproteinization procedure with 0.2mL of acetonitrile 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 3.1min and the elution of dexmedetomidine was at 1.24min. The detection was performed on a triple quadrupole tandem mass spectrometer in the multiple reaction-monitoring mode using the respective transitions m/z 201.3→95.1 for dexmedetomidine and m/z 204.2→98.0 for the internal standard, respectively. The calibration curve was linear over the range of 0.05-10ng/mL with a lower limit of quantitation of 0.05ng/mL. Mean recovery rate of dexmedetomidine in plasma was in the range of 86.7-89.1%. Intra-day and inter-day precision were both <11.6%. This method was successfully applied in pharmacokinetic study after commencement of 1.0μg/kg dexmedetomidine infusion in children. PMID:27179189

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

    PubMed Central

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

    2016-01-01

    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). PMID:27187471

  4. Development and Validation of a Stability-Indicating RP-UPLC Method for the Estimation of Impurities in Cinacalcet Hydrochloride API and its Formulation.

    PubMed

    Sunil Reddy, Pingili; Raju, Thummala Veera Raghava; Raju, Penmetsa Satyanarayana; Varma, Nadimpalli Sunil; Babu, Kondra Sudhakar

    2015-01-01

    A sensitive, stability-indicating, gradient reversed-phase ultra-performance liquid chromatography method has been developed for the quantitative estimation of cinacalcet hydrochloride impurities in active pharmaceutical ingredients and pharmaceutical formulations. Efficient chromatographic separation was achieved on an Acquity BEH Shield RP18, 100 × 2.1 mm, 1.7 µm column with the mobile phase containing pH 6.6 phosphate buffer and acetonitrile. The flow rate of the mobile phase was 0.3 mL min(-1) with a column temperature of 35°C and detection wavelength at 223 nm. The relative response factor values of (+)-R-1-(1-Naphthyl)ethylamine, regioisomer, diastereomer isomer-1, and diastereomer isomer-2 were 1.79, 0.99, 0.89, and 0.88, respectively. The cinacalcet hydrochloride formulation sample was subjected to the stress conditions of acid, base, oxidative, hydrolytic, thermal, humidity, and photolytic degradation. Cinacalcet hydrochloride was found to degrade significantly under the peroxide stress conditions. The degradation products were well-resolved from cinacalcet hydrochloride and its impurities. The peak purity test results confirmed that the cinacalcet hydrochloride peak was homogenous in all stress samples and the mass balance was found to be more than 96%, thus proving the stability-indicating power of the method. The developed method was validated according to ICH guidelines. PMID:26839840

  5. Quantification of Oxidized and Unsaturated Bile Alcohols in Sea Lamprey Tissues by Ultra-High Performance Liquid Chromatography-Tandem Mass Spectrometry.

    PubMed

    Li, Ke; Scott, Anne M; Chung-Davidson, Yu-Wen; Bussy, Ugo; Patel, Trinkal; Middleton, Zoe E; Li, Weiming

    2016-01-01

    A sensitive and reliable method was developed and validated for the determination of unsaturated bile alcohols in sea lamprey tissues using liquid-liquid extraction and ultra-high performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS). The liver, kidney, and intestine samples were extracted with acetonitrile and defatted by n-hexane. Gradient UHPLC separation was performed using an Acquity BEH C18 column with a mobile phase of water and methanol containing 20 mM triethylamine. Multiple reaction monitoring modes of precursor-product ion transitions for each analyte was used. This method displayed good linearity, with correlation coefficients greater than 0.99, and was validated. Precision and accuracy (RSD %) were in the range of 0.31%-5.28%, while mean recoveries were between 84.3%-96.3%. With this technique, sea lamprey tissue samples were analyzed for unsaturated bile alcohol analytes. This method is practical and particularly suitable for widespread putative pheromone residue analysis. PMID:27563866

  6. Simultaneous determination of carbamate insecticides and mycotoxins in cereals by reversed phase liquid chromatography tandem mass spectrometry using a quick, easy, cheap, effective, rugged and safe extraction procedure.

    PubMed

    Zhang, Jin-Ming; Wu, Yin-Liang; Lu, Yao-Bin

    2013-02-01

    A simple, sensitive and reliable analytical method was developed for the simultaneous determination of 22 carbamate insecticides and 17 mycotoxins in cereals by ultra high performance liquid chromatography electrospray ionization tandem mass spectrometry (UHPLC-ESI-MS/MS). Carbamates and mycotoxins were extracted from cereal samples using a QuEChERS (Quick, Easy, Cheap, Effective, Rugged and Safe) procedure without any further clean-up step. The extract was diluted with water containing 0.1% formic acid and 5.0mM ammonium acetate, and analyzed by LC-MS/MS on a Waters Acquity BEH C(18) column with water (0.1% formic acid, 0.50mM ammonium acetate)/methanol as mobile phase with gradient elution. Matrix-matched calibration was used for quantification. Blank samples (rice, wheat and corn) were fortified at 5, 10 and 50 μg/kg except for five zearalenonic compounds at 25, 50 and 250 μg/kg, and recoveries were in the range of 70-120%. Relative standard deviations were lower than 20% in all cases. The LOQ values were in the range of 0.20-29.7 μg/kg. The method is suitable for the simultaneous determination of carbamate insecticides and mycotoxins in cereals. The total time required for the analysis of one sample, including sample preparation, was about 35 min. PMID:23314399

  7. Development and validation of an ultra high performance liquid chromatography tandem mass spectrometry method for determination of 10 cephalosporins and desacetylcefapirin in milk.

    PubMed

    Hou, Xiao-Lin; Wu, Yin-Liang; Lv, Yan; Xu, Xiu-Qin; Zhao, Jian; Yang, Ting

    2013-07-15

    A simple, sensitive and reliable analytical method was developed for the simultaneous determination of 10 cephalosporins and desacetylcefapirin in bovine milk by ultra high performance liquid chromatography-positive electrospray ionization tandem mass spectrometry (UHPLC-ESI-MS/MS). Samples were directly purified through HLB cartridge after dilution with 50mM phosphate buffer solution (pH 8.5). Then the eluate was dried under nitrogen and the residue was redissolved in mobile phase. Samples were analyzed by LC-MS/MS on an Acquity UPLC BEH Shield RP18 column with gradient elution. The samples were quantified using ceftiofur-D3 as internal standard. The proposed method was validated according to the European Commission Decision 2002/657/EC. The CCα values were 111, 0.04, 140, 55, 55, 67, 23, 23, 68, 0.10 and 113μg/kg for cefalexin, cefradine, cefacetrile, cefazolin, cefoperazone, cefapirin, cefalonium, cefquinome, desacetylcefapirin, cefotaxime and ceftiofur, respectively. The mean recoveries, repeatability (expressed as coefficient of variation, CVr), and reproducibility (CVR) varied from 94.6% to 117.1%, from 5.6% to 13.6% (CVr), and from 5.9% to 27.9% (CVR), respectively. The method is demonstrated to be suitable for the determination of 10 cephalosporins and desacetylcefapirin in bovine milk. The total time required for the analysis of one sample, including sample preparation, was about 40min. PMID:23747425

  8. 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. PMID:26228849

  9. Ultra High Performance Liquid Chromatography Method for the Determination of Two Recently FDA Approved TKIs in Human Plasma Using Diode Array Detection

    PubMed Central

    Fouad, Marwa; Blankert, Bertrand

    2015-01-01

    Generally, tyrosine kinase inhibitors have narrow therapeutic window and large interpatient variability compared to intrapatient variability. In order to support its therapeutic drug monitoring, two fast and accurate methods were developed for the determination of recently FDA approved anticancer tyrosine kinase inhibitors, afatinib and ibrutinib, in human plasma using ultra high performance liquid chromatography coupled to PDA detection. Diclofenac sodium was used as internal standard. The chromatographic separation was achieved on an Acquity UPLC BEH C18 analytical column using a mobile phase combining ammonium formate buffer and acetonitrile at a constant flow rate of 0.4 mL/min using gradient elution mode. A µSPE (solid phase extraction) procedure, using Oasis MCX µElution plates, was processed and it gave satisfying and reproducible results in terms of extraction yields. Additionally, the methods were successfully validated using the accuracy profiles approach (β = 95% and acceptance limits = ±15%) over the ranges 5–250 ng/mL for afatinib and from 5 to 400 ng/mL for ibrutinib in human plasma. PMID:26101692

  10. Simultaneous quantification of trantinterol and its metabolites in human urine by ultra performance liquid chromatography-tandem mass spectrometry.

    PubMed

    Qin, Feng; Wang, Lijuan; Li, Kunjie; Xiong, Zhili; Li, Famei

    2015-08-01

    A rapid, selective and sensitive ultra performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) method was developed to simultaneously determine trantinterol and its major metabolites in human urine. Waters Oasis HLB C18 solid phase extraction cartridges were used in the urine sample preparation. The separation was carried out on an ACQUITY UPLC™ BEH C18 column with methanol-0.2% formic acid (30:70, v/v) as the mobile phase at a flow rate of 0.25mL/min. The detection was performed on a triple quadrupole tandem mass spectrometer by multiple reaction monitoring (MRM) mode via electrospray ionization (ESI) source. The linear calibration curves for trantinterol, arylhydroxylamine trantinterol (N-OH-trantinterol), the tert-butyl hydroxylated trantinterol (tert-OH-trantinterol) and the 1-carbonyl trantinterol (trantinterol-COOH) were obtained in the concentration range of 0.414-207, 0.578-385, 0.168-84.0, and 0.954-477ng/mL, respectively. The linear correlation coefficients were greater than 0.990. The intra and inter-day precision (relative standard deviation, RSD) values were less than 12% and the accuracy (relative error, RE) was 6.7-11%. The method herein described was superior to previous methods in sample throughput and sensitivity and successfully applied to the human excretion study. PMID:26093121

  11. Detection and chemical profiling of Ling-Gui-Zhu-Gan decoction by ultra performance liquid chromatography-hybrid linear ion trap-Orbitrap mass spectrometry.

    PubMed

    Wang, Pei; Wang, Bo; Xu, Jingyao; Sun, Jianbo; Yan, Qin; Ji, Bin; Zhao, Yunli; Yu, Zhiguo

    2015-02-01

    Ling-Gui-Zhu-Gan decoction (LGZGD), a well-known traditional Chinese medicine (TCM) formula, has been extensively used for the treatment of cardiovascular disease in clinic. However, the chemical constituents in LGZGD had not been investigated so far. In this study, an ultra performance liquid chromatography-hybrid electrospray ionization linear ion trap-Orbitrap mass spectrometry (UPLC-LTQ-Oribitrap-MS/MS) method was established for rapid separation and structural identification of the constituents in LGZGD. Separation was performed on an ACQUITY(TM) UPLC BEH C18 column (50 × 2.1 mm, 1.7 μm) by gradient elution mode, using acetonitrile-water containing 0.1% formic acid as mobile phase at the flow rate of 0.2 mL/min. Accurate mass measurement for molecular ions and characteristic fragment ions could represent identification criteria for these compounds. As a result, 95 compounds including triterpene acids, triterpene saponins, flavonoids, coumarins, coumestans, benzofurans, phenylpropanoids and sesquiterpenoid lactones were detected, and 90 of them were tentatively identified. All compounds were further assigned in the individual raw material. In conclusion, the UPLC-LTQ-Orbitrap-MS/MS is a highly efficient technique to separate and identify constituents in complex matrices of TCMs. These results obtained in this research will provide a basis for quality control and further in vivo study of LGZGD. PMID:24920655

  12. 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. PMID:19061153

  13. 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

    2016-01-01

    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). PMID:27187471

  14. Simultaneous determination of 21 preservatives in cosmetics by ultra performance liquid chromatography.

    PubMed

    Wu, T; Wang, C; Wang, X; Ma, Q

    2008-10-01

    An ultra performance liquid chromatography (UPLC) method has been developed for the simultaneous determination of 21 preservatives: 2-methyl-4-isothiazoline-3-ketone, bronopol, 5-chloro-2-methyl-4-isothiazoline-3-ketone, benzyl alcohol, 2-phenoxyethanol, methyl-p-hydroxy benzoate, ethyl-p-hydroxy benzoate, methyl benzoate, 4-hydroxybenzoic acid iso-propyl ester, propyl-p-hydroxy benzoate, 4-chloro-3-methylphenol, ethyl benzoate, 2-phenylphenol, 4-hydroxybenzoic acid iso-butyl ester, butyl-p-hydroxy benzoate, 4-chloro-3,5-dimethylphenol, phenyl benzoate, 2,4-dichloro-3,5-dimethylphenol, 2-benzyl-4-chlorophenol, triclocarban and triclosan in cosmetics. A Waters ACQUITY UPLC BEH C(18) column was used with 0.1% formic acid solution as the mobile phase under the condition of gradient elution. Preservatives were extracted with methanol by ultrasonicator, and then they were analysed by UPLC-PDA detector. All these preservatives were baseline separated in 8.5 min. The pre-treatment method of samples and the chromatographic condition of analysis were critically examined in this study. The recoveries ranged from 90.5 to 97.8%, with RSD values below 3.2%, and all correlation coefficients (r) were no less than 0.9997. Thus, this method could be used for analysing the preservatives in cosmetic products. PMID:18822043

  15. Novel and sensitive UPLC-MS/MS method for quantification of sofosbuvir in human plasma: application to a bioequivalence study.

    PubMed

    Rezk, Mamdouh R; Basalious, Emad B; Amin, Mohammed E

    2016-09-01

    A novel and sensitive LC-MS/MS method was developed and validated for determination of sofosbuvir (SF) using eplerenone as an internal standard. The Xevo TQD LC-MS/MS was operated under the multiple-reaction monitoring mode using electrospray ionization. Extraction with tert-butyl methyl ether was used in sample preparation. The prepared samples were chromatographed on Acquity UPLC BEH C18 (50 × 2.1 mm, 1.7 μm) column by pumping 0.1% formic acid and acetonitrile in an isocratic mode at a flow rate of 0.35 mL/min. Method validation was performed as per the US Food and Drug Administration guidelines and the standard curves were found to be linear in the range of 0.25-3500 ng/mL for SF. The intra- and inter-day precision and accuracy results were within the acceptable limits. A very short run time of 1 min made it possible to analyze more than 500 human plasma samples per day. A very low quantification limit of SF allowed the applicability of the developed method for determination of SF in a bioequivalence study in human volunteers. Copyright © 2016 John Wiley & Sons, Ltd. PMID:26821881

  16. An Ultra-Performance Liquid Chromatography Photodiode Array Detection Tandem Mass Spectrometric Method for Simultaneous Determination of Seven Major Bioactive Constituents in Xiaochaihutang and Its Application to Fourteen Compatibilities Study.

    PubMed

    Wang, Lijuan; Wu, Chunfu; Zhao, Longshan; Lu, Xiumei; Wang, Fang; Yang, Jingyu; Xiong, Zhili

    2015-10-01

    A rapid and sensitive ultra-performance liquid chromatography photodiode array detection tandem mass spectrometric method (UPLC-PDA-MS-MS) was developed and validated to simultaneously determine seven major bioactive constituents in the formula of traditional Chinese medicines Xiaochaihutang (XCHT). To investigate the discipline of compatibility in XCHT, 14 kinds of compatibilities designed by orthogonal array were also analyzed. The separation was performed on an ACQUITY UPLC™ BEH C18 column (100 × 2.1 mm, 1.7 µm) using gradient elution with a mobile phase of 0.1% formic acid and acetonitrile at a flow rate of 0.2 mL/min. Two detection techniques of PDA detector and MS-MS detector were proposed, respectively. The concentrations of baicalin and wogonoside were high enough for PDA detection while low-concentration bioactive constituents including saikosaponin a, ginsenoside Rg1, liquiritin, baicalein and wogonin were quantified by MS-MS detection. The proposed method was fully validated in terms of sensitivity, linearity, specificity, precision, repeatability and recovery. This is the first report on the simultaneous determination of the major bioactive constituents of XCHT by UPLC-PDA-MS-MS, which could be used to evaluate the quality of XCHT and to investigate the discipline of compatibility in XCHT. PMID:26024854

  17. Simultaneous determination of saponins and a flavonoid from aerial parts of Zygophyllum coccineum L.

    PubMed

    Amin, Elham; Wang, Yan-Hong; Avula, Bharathi; El-Hawary, Seham S; Fathy, Magda M; Mohammed, Rabab; Khan, Ikhlas A

    2012-01-01

    Triterpenoid saponins are a class of glycosides with a wide range of bioactivities, which make them interesting research candidates. Zygophyllum coccineum is an Egyptian desert plant rich in triterpenoid saponins. Reviewing the relevant literature, no data concerning the HPLC or ultra-performance LC (UPLC) analysis of Zygophyllum content were found. This paper presents two methods, HPLC-UV and UPLC-UV-evaporative light scattering detector (ELSD)/MS, for the simultaneous determination of 10 compounds in the alcohol extract of Z. coccineum. The HPLC method uses a C18 column and water-acetonitrile (both containing 0.1% trifluoroacetic acid) gradient system. The separation was achieved within 32 min. The developed UPLC method simultaneously detects and quantifies the 10 compounds using an Acquity UPLC BEH Shield RP18 column and reagent alcohol-acetonitrile (80/20, v/v) and water (both containing 0.5% formic acid) gradient system within 14 min with UV, ELS, and MS detectors. The methods were used to analyze another species, Z. simplex, and results revealed a great variation between the secondary metabolite pattern of both species. PMID:22816267

  18. Effects of berberine and pomegranate seed oil on plasma phospholipid metabolites associated with risks of type 2 diabetes mellitus by U-HPLC/Q-TOF-MS.

    PubMed

    Wu, Xia; Li, Yan; Wang, Qiu; Li, Weimin; Feng, Yifan

    2015-12-15

    A rapid and reliable ultra-performance liquid chromatography coupled with electrospray ionization/quadrupole-time-of-flight mass spectrometry (U-HPLC/Q-TOF-MS) has been firstly used to analyze the changes of plasma phospholipids, in type 2 diabetes mellitus (T2DM) mice after administration of berberine and pomegranate seed oil (PSO). The separation of plasma phospholipids was carried out on an Acquity U-HPLC BEH C18 column (2.1mm×50mm, 1.7μm, Waters) by linear gradient elution using a mobile phase consisting of 10mM ammonium formate in water and acetonitrile: isopropanol (1:1, v/v) mixed solution added by 0.25% water and 10mM ammonium formate. The method demonstrated a good precision and reproducibility. Linear regression analysis showed a good linearity. And potential biomarkers were discovered based on their mass spectra and chemometrics methods. The results demonstrated that the proposed U-HPLC/Q-TOF-MS method was successfully applied to analyze the dynamic changes of phospholipids components in plasma of T2DM mice after drug treatment and could provide a useful data base for meriting further study in humans and investigating pharmacological actions of drugs. PMID:26590882

  19. Chemical profiling of Wu-tou decoction by UPLC-Q-TOF-MS.

    PubMed

    Qi, Yao; Li, Shizhe; Pi, Zifeng; Song, Fengrui; Lin, Na; Liu, Shu; Liu, Zhiqiang

    2014-01-01

    Wu-tou decoction (WTD), a traditional Chinese medicine (TCM) formula, is composed of Aconiti Radix Cocta, Ephedrae Herba, Paeoniae Radix Alba, Astragali Radix and Glycyrrhiza Radix Preparata, and it has been used for more than a thousand years to treat rheumatic arthritis, rheumatoid arthritis and pain of joints, while the active constitutions of WTD are unclear. In this research, an ultra performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF-MS) method in both positive and negative ion mode was established to investigate the major constitutions in WTD. A Waters ACQUITY UPLC BEH C18 column was used to separate the aqueous extract of WTD. Acetonitrile and 0.1% aqueous formic acid (v/v) were used as the mobile phase. 74 components including alkaloids, monoterpene glycosides, triterpene saponins, flavones and flavone glycosides were identified or tentatively characterized in WTD based on the accurate mass within 15 ppm error and tandem MS behavior. All the constitutions were also detected in the corresponding individual herbs. These results will provide a basis for further study in vivo of WTD and the information of potential new drug structure for treating rheumatic arthritis and rheumatoid arthritis. PMID:24274266

  20. Development and validation of a UPLC-MS/MS method for quantification of SKLB010, an investigational anti-inflammatory compound, and its application to pharmacokinetic studies in beagle dogs.

    PubMed

    Ye, Xia; Tang, Minghai; Liu, Juan; Wang, Xianhuo; Ma, Liang; Zheng, Hao; Hu, Jia; Chen, Xiang; Duan, Xingmei; Chen, Lijuan

    2011-09-10

    SKLB010 is currently under development as a potential therapeutic agent for the treatment of acute hepatitis and rheumatoid arthritis. The purpose of this paper was to investigate the pre-clinical pharmacokinetics of SKLB010 in beagle dogs. An ultra performance liquid chromatographic tandem mass spectroscopy (UPLC-MS/MS) method was developed and validated for the quantitative determination of SKLB010 in dog plasma, using rosiglitazone as the internal standard (I.S.). Plasma samples were prepared by a simple solid phase extraction (SPE) method. The analyte and internal standard were separated by an Acquity UPLC BEH C18 (2.1 mm × 50 mm) column with a mobile phase of methanol-water (80/20, v/v) over 2 min. Detection was based on the multiple reaction monitoring with the precursor-to-product ion transitions m/z 234.10→147.92 (SKLB010) and m/z 356.15→150.00 (I.S.). The method was validated according to FDA guidelines on bio-analytical method validation. The selectivity, sensitivity, linearity, accuracy, precision, extraction recovery, ion suppression and stability were within the acceptable ranges. The method described above was successfully applied to reveal the single- and multi-pharmacokinetic profiles of SKLB010 in beagle dogs and should be extendable to pharmacokinetic studies in other species as well. PMID:21680128

  1. [UPLC fingerprint of xanthii fructus from different habitats].

    PubMed

    Hong, Yan; Han, Yan-Quan; Xia, Lun-Zhu; Gui, Jie; Chen, Xi; Sun, Yan-Hua

    2013-06-01

    This study was establish an UPLC fingerprint of Xanthii Fructus from different habitats, to provide a comprehensive evaluation for its quality control. UPLC-PDA was adopted to analysis of 26 baches of Xanthii Fructus from different habitats. The chromatographic condition was as follow: ACQUITY BEH C18 Column (2.1 mm x 100 mm,1.7 microm) eluted with the mobile phases of acetonitrile and 0.1% phosphoric acid water in gradient mode. The flow rate was 0.25 mL x min(-1) and the detection wavelength was set at 220 nm. The fingerprints of 26 batches Xanthii Fructus were carried out by similarity comparation, cluster and the principal component analysis (PCA). There were nineteen common peaks, nine of which had been identified, and the similarity degrees of the twenty-six batches of the samples were between 0.804 and 0.990. All the samples were classified into six categories, and the PCA value of each fingerprint peak was calculated, and six principal components accounted for over 81. 140% of the total variance were extracted from the original data This method can be used to assess the quality of Xanthii Fructus. PMID:24010293

  2. Force degradation behavior of glucocorticoid deflazacort by UPLC: isolation, identification and characterization of degradant by FTIR, NMR and mass analysis

    PubMed Central

    Deshmukh, Rajesh; Sharma, Lata; Tekade, Muktika; Kesharwani, Prashant; Trivedi, Piyush; Tekade, Rakesh K.

    2016-01-01

    Abstract In this investigation, sensitive and reproducible methods are described for quantitative determination of deflazacort in the presence of its degradation product. The method was based on high performance liquid chromatography of the drug from its degradation product on reverse phase using Acquity UPLC BEH C18 columns (1.7 µm, 2.1 mm × 150 mm) using acetonitrile and water (40:60 V/V) at a flow rate of 0.2 mL/minute in UPLC. UV detection was performed at 240.1 nm. Deflazacort was subjected to oxidative, acid, base, hydrolytic, thermal and photolytic degradation. The drug was found to be stable in water and thermal stress, as well as under neutral stress conditions. However, forced-degradation study performed on deflazacort showed that the drug degraded under alkaline, acid and photolytic stress. The degradation products were well resolved from the main peak, which proved the stability-indicating power of the method. The developed method was validated as per ICH guidelines with respect to accuracy, linearity, limit of detection, limit of quantification, accuracy, precision and robustness, selectivity and specificity. Apart from the aforementioned, the results of the present study also emphasize the importance of isolation characterization and identification of degradant. Hence, an attempt was made to identify the degradants in deflazacort. One of the degradation products of deflazacort was isolated and identified by the FTIR, NMR and LC-MS study.

  3. Study on the destructive effect to inherent quality of Fritillaria thunbergii Miq. (Zhebeimu) by sulfur-fumigated process using chromatographic fingerprinting analysis.

    PubMed

    Duan, Baozhong; Huang, Linfang; Chen, Shilin

    2012-04-15

    The after-harvesting sun-dried processing of Fritillariae thunbergii bulbus (Zhebeimu) was the traditional treatment for commodity. Over recent decades the natural drying process for bulbus of Fritillariae has been replaced by sulfur-fumigation for reducing the drying duration and pest control. We used ultra-performance liquid chromatography coupled with evaporative light scattering detection (UPLC-ELSD) fingerprinting analysis and major alkaloids determination to investigate the potential damaging effect of the sulfur-fumigating process. The experimental conditions were as follows: Chromatography was proceeded on Waters Acquity UPLC BEH C(18) column; the linear gradient elution was conducted with mobile phase prepared from acetonitrile-0.02% triethylamine; the drift tube temperature was set at 40°C with a nitrogen flow-rate of 30psi, and the spray parameter was set 40%. All calibration curves showed good linear regression (R>0.9991) within the tested range. The method was validated for precision, accuracy, limit of detection and quantification. The study also has shown that sulfur-fumigated samples had significant loss of the main active compounds and a more destructive fingerprint profile when compared to the sun-dried samples. PMID:22326548

  4. Determination of nine sensitizing disperse dyes in activated sludge by ultrasound-assisted liquid-liquid extraction-ultra-performance liquid chromatography-electrospray ionization-tandem mass spectrometry.

    PubMed

    Zhou, Linjun; Shi, Lili; Liu, Jining; Lv, Fenglan; Xu, Yanhua

    2016-01-01

    A method was developed on the basis of ultrasound-assisted liquid-liquid extraction ultra-performance liquid chromatography coupled with electrospray ionization tandem mass spectrometry (ULLE-UPLC-ESI-MS/MS) to determine nine sensitizing disperse dyes in activated sludge. The samples were extracted using ULLE and separated through UPLC on an ACQUITY UPLCTM BEH C18 column with a gradient elution program of acetonitrile and acidified water (containing 2% acetonitrile, 0.2% formic acid, and 0.005 mol/L ammonium; pH 2.7) as the mobile phase. The samples were then identified and quantified through UPLC-ESI-MS/MS in a positive mode and multiple reaction monitoring. Results showed good linearity (10-1000 μg/L, 0.9934-0.9998), detection limit (0.08-2.17 μg/L), and quantification limit (0.27-7.38 μg/L) for the nine sensitizing disperse dyes, with recoveries ranging from 65.0 to 111.3%. The proposed method was applied to detect and determine the concentration of sensitizing disperse dyes in sludge samples obtained from various sewage treatment plants (six dyeing enterprises and one dye manufacturer). Three sensitizing disperse dyes were identified, and the lowest concentration detected was 10 μg/kg. PMID:26521175

  5. Determination of Pinaverium Bromide in Human Plasma by a Sensitive and Robust UPLC-MS-MS Method and Application to a Pharmacokinetic Study in Mexican Subjects.

    PubMed

    Patiño-Rodríguez, Omar; Zapata-Morales, Juan Ramón; Escobedo-Moratilla, Abraham; Díaz de León-Cabrero, Manuel; Torres-Roque, Irma; Pérez-Urizar, José

    2015-09-01

    A high-throughput ultra-performance liquid chromatography coupled to tandem mass spectrometry (LC-ESI-MS-MS) method was developed for the determination of pinaverium bromide in human plasma. Protein precipitation with acetonitrile was used to extract pinaverium and itraconazole (as internal standard) from 500 µL plasma samples. The chromatographic separation was achieved with an Acquity UPLC BEH C18 column (1.7 µm, 2.1 × 100 mm) using a mixture of acetonitrile-5 mM ammonium formate (80:20, v/v) as mobile phase. Isocratic elution at 0.3 mL/min was used. Detection was performed by positive ion electrospray tandem mass spectrometry on a XEVO TQ-S by multiple reaction monitoring mode. The mass transitions monitorized were as follows: m/z 511.2 → 230 for pinaverium bromide, and m/z 705.29 → 392.18 for the itraconazole. The method was validated over a concentration range of 12-12,000 pg/mL. The chromatographic method runtime is 2.5 min and was applied to characterize the pharmacokinetics of pinaverium bromide after the oral administration of 100 mg to healthy Mexican subjects. PMID:25862744

  6. [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. PMID:27062811

  7. Simultaneous determination of sweeteners in beverages by LC-MS/MS.

    PubMed

    Sakai, Hiroaki; Yamashita, Azusa; Tamura, Masayoshi; Uyama, Atsuo; Mochizuki, Naoki

    2015-01-01

    A new method was established for the simultaneous determination of 10 sweeteners and a degradation product in beverages by using LC-MS/MS. An ACQUITY UPLC BEH C18 (2.1 × 100 mm, 1.7 μm) was used as the LC column and 0.1% each of aqueous formic acid and formic acid in acetonitrile were used as the mobile phase. A simple and rapid determination of sweeteners was possible by diluting with a solvent, and in the case of some samples containing a large amount of foreign matter, after pre-treatment by diluting with solvent and clean-up of the sample using an Oasis HLB cartridge. All the validation results were satisfactory. As the regulations and standards for sweeteners vary from country to country, a field survey of 58 beverages marketed in Japan was performed using the present method. No issues concerning the labelling or food sanitation law were found in the tested samples. PMID:25794347

  8. Determination of Sertraline in Human Plasma by UPLC-MS/MS and its Application to a Pharmacokinetic Study.

    PubMed

    Yue, Xiao-Hong; Wang, Zhen; Tian, Dong-Dong; Zhang, Jian-Wei; Zhu, Kang; Ye, Qiang

    2016-02-01

    A sensitive and rapid ultra-performance liquid chromatography tandem mass spectrometry (UPLC-MS-MS) method was developed to determine sertraline in human plasma. Sample preparation was accomplished through a simple liquid-liquid extraction with ethyl acetate. Chromatographic separation was carried out on an Acquity UPLC BEH C18 column using a gradient mobile phase system composed of acetonitrile and 1% formic acid in water at a flow rate of 0.40 mL/min. Mass spectrometric analysis was performed using a XEVO TQD mass spectrometer coupled with an electrospray ionization source in the positive ion mode. The multiple reaction monitoring transitions of m/z 306.3 → 275.2 and 326.2 → 291.1 were used to quantify for sertraline and midazolam (internal standard), respectively. The linearity of this method was found to be within the concentration range of 1.0-100.0 ng/mL with a lower limit of quantification of 1.0 ng/mL. Only 2.0 min was needed for an analytical run. This fully validated method was successfully applied to the pharmacokinetic study after an oral administration of 100 mg sertraline to 20 Chinese healthy male volunteers. PMID:26324195

  9. [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. PMID:23947129

  10. 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. PMID:20155752

  11. 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. PMID:26683023

  12. Simultaneous determination of nineteen major active compounds in Qiangshen tablet by UPLC-ESI-MS/MS.

    PubMed

    Gao, Jinwei; Qiu, Ying; Chen, Jinmei; Mu, Shanxue; Sun, Lixin

    2016-09-01

    An ultra high performance liquid chromatography coupled with triple quadrupole mass spectrometry method has been developed to evaluate the quality of a pharmaceutical herbal preparation, Qiangshen tablet, through a simultaneous determination of 19 major active compounds (stachydrine hydrochloride, betaine, gallic acid, sodium danshensu, morroniside, loganin, protocatechuic aldehyde, gardenoside, sweroside, acteoside, paeoniflorin, ginsenoside Re, rosmarinic acid, salvianolic acid B, ginsenoside Rg1, psoralen, isopsoralen, ginsenoside Rb1, paeonol). Chromatographic separation was achieved on an ACQUITY UPLC(®) BEH C18 column (2.1×100mm, 1.7μm) by gradient elution with the mobile phase of 0.1% formic acid aqueous solution (A) and acetonitrile (B). Multiple reaction monitoring (MRM) mode with positive and negative electrospray ionization interface was operated to detect the 19 compounds. All calibration curves showed excellent linear regressions (r>0.999) within the test range. The precision, repeatability and stability of the 19 compounds were below 2.0% in terms of RSD. The recoveries were 97.5-102.2% with RSD of 1.0-1.9% for Qiangshen tablet samples. The method was successfully used for the analysis of samples of Qiangshen tablet. In conclusion, a rapid, sensitive, precise, accurate and reliable UPLC-ESI-MS/MS method has been developed for the simultaneous detection of 19 active compounds with large difference in level of content in the pharmaceutical samples of Qiangshen tablet, which can be applied for the quality control of Qiangshen tablet. PMID:27416474

  13. Development and Validation of a Stability-Indicating RP-UPLC Method for the Estimation of Impurities in Cinacalcet Hydrochloride API and its Formulation

    PubMed Central

    Sunil Reddy, Pingili; Raju, Thummala Veera Raghava; Raju, Penmetsa Satyanarayana; Varma, Nadimpalli Sunil; Babu, Kondra Sudhakar

    2015-01-01

    A sensitive, stability-indicating, gradient reversed-phase ultra-performance liquid chromatography method has been developed for the quantitative estimation of cinacalcet hydrochloride impurities in active pharmaceutical ingredients and pharmaceutical formulations. Efficient chromatographic separation was achieved on an Acquity BEH Shield RP18, 100 × 2.1 mm, 1.7 µm column with the mobile phase containing pH 6.6 phosphate buffer and acetonitrile. The flow rate of the mobile phase was 0.3 mL min−1 with a column temperature of 35°C and detection wavelength at 223 nm. The relative response factor values of (+)-R-1-(1-Naphthyl)ethylamine, regioisomer, diastereomer isomer-1, and diastereomer isomer-2 were 1.79, 0.99, 0.89, and 0.88, respectively. The cinacalcet hydrochloride formulation sample was subjected to the stress conditions of acid, base, oxidative, hydrolytic, thermal, humidity, and photolytic degradation. Cinacalcet hydrochloride was found to degrade significantly under the peroxide stress conditions. The degradation products were well-resolved from cinacalcet hydrochloride and its impurities. The peak purity test results confirmed that the cinacalcet hydrochloride peak was homogenous in all stress samples and the mass balance was found to be more than 96%, thus proving the stability-indicating power of the method. The developed method was validated according to ICH guidelines. PMID:26839840

  14. [Determination of ten sedative residues in pork and kidney by ultra performance liquid chromatography-tandem mass spectrometry].

    PubMed

    Sun, Lei; Zhang, Li; Xu, Qian; Wang, Shuhuai; Wang, Xia

    2010-01-01

    An ultra performance liquid chromatography-tandem mass spectrometry (UPLC-MS/ MS) method was established for the determination of methaqualone, chloropromazine, promethazine, diazepam, nitrazepam, oxazepam, temazepam, midazolam, triazolam and zolpidem residues in pork and kidney. After enzymolysis, the samples were extracted by ethyl acetate and tert-butyl methyl ether, separately. The separation of the ten sedatives was performed on a Waters Acquity UPLC system with a BEH C18 column. The mobile phases were acetonitrile (containing 0.1% formic acid) and water (containing 0.1% formic acid) at a flow rate of 0.3 mL/min. The electrospray was operated in the positive ionization mode and the ten sedatives were identified by multiple reaction monitoring (MRM) mode. The method of matrix-matched standard solution was adopted as the quantitative method. The calibration curves showed good linearity within the concentrations of 2 - 100 microg/L with the correlation coefficients r > 0. 998. The limits of detection of the ten sedatives were 0.5 microg/kg, and the limit of quantification was 1 microg/kg. The recoveries of the ten sedatives were 64.5% - 111.4% at the spiked levels of 2, 5 and 10 microg/kg. The relative standard deviations of intra- and inter-day coefficients of variation were both less than 15%. This method is simple, sensitive and accurate in the determination of sedative residues. PMID:20458918

  15. 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 5-2000ng/mL for mangiferin, and 2-1000ng/mL for neomangiferin in rat plasma, respectively. Only 3.0min 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. PMID:26945635

  16. [Fast analysis of common fatty acids in edible vegetable oils by ultra-performance convergence chromatography-mass spectrometry].

    PubMed

    Lin, Chunhua; Xie, Xianqing; Fan, Naili; Tu, Yuanhong; Chen, Yan; Liao, Weilin

    2015-04-01

    A fast analytical method for five common fatty acids in six edible vegetable oils was developed by ultra-performance convergence chromatography-mass spectrometry (UPC2-MS). The five fatty acids are palmitic acid, stearic acid, oleic acid, linoleic acid and linolenic acid. Their contents in the corn oil, sunflower oil, soybean oil, tea oil, rapeseed oil and peanut oil were compared. The chromatographic separation was performed on an ACQUITY UPC2 BEH 2-EP column (100 mm x 2.1 mm, 1.7 µm) using the mobile phases of carbon dioxide and methanol/acetonitrile (1:1, v/v) with gradient elution. The separated compounds were detected by negative electrospray ionization ESF-MS. The results showed that the reasonable linearities were achieved for all the analytes over the range of 0.5-100 mg/L with the correlation coefficients (R2) of 0.9985-0.9998. The limits of quantification (S/N ≥ 10) of the five fatty acids were 0.15-0.50 mg/L. The recoveries of the five fatty acids at three spiked levels were in the range of 89.61%-108.50% with relative standard deviations of 0.69%-3.01%. The developed method showed high performance, good resolution and fast analysis for the underivatized fatty acids. It has been successfully used to detect the five fatty acids from corn oil, sunflower oil, soybean oil, tea oil rapeseed oil and peanut oil. PMID:26292410

  17. Simultaneous Analysis of Quercetin and Naringenin in Rat Plasma by Liquid Chromatography-Tandem Mass Spectrometry: Application to a Pharmacokinetic Study After Oral Administration.

    PubMed

    Ni, Boran; Cao, Sali; Feng, Lijun; Yin, Xingbin; Wang, Wenping; Zhang, Xin; Ni, Jian

    2016-09-01

    A rapid and specific LC-MS-MS method has been developed for simultaneous analysis of quercetin and naringenin in rat plasma. The method was applied to the pharmacokinetics studies of quercetin and naringenin after oral administration of Pollen Typhae extract. The samples were prepared by the protein precipitation method. The analysis was carried out on an ACQUITY UPLC™ BEH C18 column with gradient elution using mobile phase, which included acetonitrile and water (containing 0.1% formic acid). The flow rate was 0.4 mL/min. All analytes including internal standard (IS) were monitored by selected reaction monitoring with an electrospray ionization source. Linear responses were obtained for quercetin ranging from 0.5 to 100 ng/mL and naringenin ranging from 5 to 1000 ng/mL. The intra- and interday precisions (RSD) were less than 10.78 and 11.20%. The extraction recovery of the analytes was acceptable. Stability studies showed that quercetin and naringenin were stable in the preparation and analytical process. The validated method was successfully used to determine the concentration-time profiles of quercetin and naringenin. PMID:27199443

  18. Multiwalled Carbon Nanotubes-Dispersive Solid-Phase Extraction Coupled with UPLC-ESI-MS-MS for Simultaneous Determination of 10 Illegal Adulterants in Antihypertensive Functional Foods.

    PubMed

    Hu, Jielan; Zeng, Li; He, Ling; You, Fan; Sun, Chengjun

    2016-05-01

    A reliable method for simultaneous determination of 10 illegal adulterants including chlortalidone, hydrochlorothiazide, indapamide, metoprolol, nifedipine, nimodipine, nitrendipine, reserpine, triamterene and valsartan in antihypertensive functional foods by ultra-high-performance liquid chromatography coupled with electrospray ionization-tandem mass spectrometry is presented in this article. The target chemicals were extracted with acetonitrile ultrasonically and cleaned up using multiwalled carbon nanotubes-dispersive solid-phase extraction. The separation was performed on a Waters ACQUITY UPLC BEH C18 Column (2.1 × 100 mm, 1.7 µm) with acetonitrile, 0.1% formic acid and 10 mmol/L ammonium acetate solution as mobile phase at a flow rate of 0.2 mL/min. Multiple reaction monitoring was applied for detection and sildenafil was used as the internal standard. The correlation coefficients of the method were >0.995, with the limits of detection of 0.022-0.30 ng/mL and the limits of quantification of 0.075-0.99 ng/mL. The interday and intraday relative standard deviations were <9.77% and the recoveries were in the range of 85.8-109%. The established method has been applied for the analysis of real samples, and reserpine was detected in a tonic wine sample with a content of 60.1 ± 3.2 mg/L. PMID:26850731

  19. [Simultaneous determination of 24 industrial dyes in grain and meat products by ultra performance liquid chromatography-tandem mass spectrometry].

    PubMed

    Feng, Yuechao; Jia, Li; He, Yahui; Wang, Jianfeng; Liu, Yan; Fan, Xiaojing

    2013-10-01

    An ultra performance liquid chromatography-tandem mass spectrometry (UPLC-MS/ MS) analytical method was established for the simultaneous determination of 24 forbidden industrial dyes in grain and meat products. The sample was extracted with methanol and acetonitrile, and cleaned-up by a WAX solid phase extraction column. The solution was separated on an ACQUITY UPLC BEH C18 column eluted with a mixture of 10 mmol/L ammonium acetate-0.2% formic acid aqueous solution and methanol-acetonitrile (7:3, v/v) as the mobile phases, and then analyzed in multiple reaction monitoring (MRM) mode. The correlation coefficients were above 0.99, the average recoveries were 61%-116%, and the relative standard deviations (RSD, n = 6) were lower than 13%. The quantification limits were 0.1-4.0 microg/kg. This method is simple, effective, sensitive, and suitable for the determination and confirmation of the 24 forbidden industrial dyes in grain and meat products. PMID:24432648

  20. Development, optimization and validation of a highly sensitive UPLC-ESI-MS/MS method for simultaneous quantification of amlodipine, benazeprile and benazeprilat in human plasma: application to a bioequivalence study.

    PubMed

    Rezk, Mamdouh R; Badr, Kamal A

    2014-09-01

    A rapid, simple, sensitive and specific LC-MS/MS method has been developed and validated for the simultaneous estimation of amlodipine (AML), benazepril (BEN) and benazeprilat (BNT) using eplerenone and torsemide as internal standards (IS). The Xevo TQD LC-MS/MS was operated under the multiple-reaction monitoring mode using electrospray ionization. Sample preparation involves both extraction and precipitation techniques. The reconstituted samples were chromatographed on Acquity UPLC BEH C18 (50mm×2.1mm, 1.7μm) column by pumping 0.1% formic acid and acetonitrile in a gradient mode at a flow rate of 0.45ml/min. A detailed validation of the method was performed as per the FDA guidelines and the standard curves were found to be linear in the range of 0.1-5ng/ml for AML; 5-1200ng/ml for both BEN and BNT. The intra-day and inter-day precision and accuracy results were within the acceptable limits. A run time of 2.5min for each sample made it possible to analyze more than 300 human plasma samples per day. The developed assay method was successfully applied to a bioequivalence study in human volunteers. PMID:24863555