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1.
Phys Rev Lett ; 131(3): 033602, 2023 Jul 21.
Artigo em Inglês | MEDLINE | ID: mdl-37540849

RESUMO

Large-momentum-transfer (LMT) atom interferometers using elastic Bragg scattering on light waves are among the most precise quantum sensors to date. To advance their accuracy from the mrad to the µrad regime, it is necessary to understand the rich phenomenology of the Bragg interferometer, which differs significantly from that of a standard two-mode interferometer. We develop an analytic model for the interferometer signal and demonstrate its accuracy using comprehensive numerical simulations. Our analytic treatment allows the determination of the atomic projection noise limit of a LMT Bragg interferometer and provides the means to saturate this limit. It affords accurate knowledge of the systematic phase errors as well as their suppression by 2 orders of magnitude down to a few µrad using appropriate light-pulse parameters.

2.
Phys Rev Lett ; 127(14): 140402, 2021 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-34652182

RESUMO

Compared to light interferometers, the flux in cold-atom interferometers is low and the associated shot noise is large. Sensitivities beyond these limitations require the preparation of entangled atoms in different momentum modes. Here, we demonstrate a source of entangled atoms that is compatible with state-of-the-art interferometers. Entanglement is transferred from the spin degree of freedom of a Bose-Einstein condensate to well-separated momentum modes, witnessed by a squeezing parameter of -3.1(8) dB. Entanglement-enhanced atom interferometers promise unprecedented sensitivities for quantum gradiometers or gravitational wave detectors.

3.
Clin Psychol Psychother ; 24(3): 785-792, 2017 May.
Artigo em Inglês | MEDLINE | ID: mdl-27699920

RESUMO

While there is a plethora of evidence for the efficacy of cognitive-behavioural therapy (CBT) in obsessive-compulsive disorder (OCD), studies on change factors of the therapeutic process that account for this success are scarce. In the present study, 155 participants with primary OCD were investigated during CBT inpatient treatment. The Yale-Brown Obsessive-Compulsive Scale-SR served as a measure of symptom severity. In addition, the following process change factors were measured: therapeutic relationship, experience of self-esteem during therapy, experience of mastery, problem actualization and clarification. All variables were assessed on a weekly basis for seven weeks. Linear mixed growth curve analyses were conducted to model the decrease of symptoms over time and to analyse whether the change factors predicted symptom reduction. The analyses revealed a linear decrease of symptoms with high inter-individual variation. Results further showed that increase in self-esteem and mastery experiences as well as the initial score on mastery experience and clarification predicted decrease on the Y-BOCS. We conclude that CBT therapists should focus on clarification in the very first sessions, and try to boost self-esteem and self-efficacy, which is related to mastery, throughout the treatment of OCD. Copyright © 2016 John Wiley & Sons, Ltd. KEY PRACTITIONER MESSAGE: Increase in mastery and self-esteem experiences are associated with symptom decrease in obsessive-compulsive disorder (OCD) during cognitive-behavioural therapy (CBT). Initial score of mastery experiences and problem clarification predict symptom decrease in OCD during CBT. CBT therapists should focus on problem clarification in the very first sessions and try to boost self-esteem and self-efficacy throughout the treatment of OCD.


Assuntos
Terapia Cognitivo-Comportamental/métodos , Transtorno Obsessivo-Compulsivo/psicologia , Transtorno Obsessivo-Compulsivo/terapia , Autoimagem , Adolescente , Adulto , Feminino , Alemanha , Humanos , Masculino , Pessoa de Meia-Idade , Índice de Gravidade de Doença , Resultado do Tratamento , Adulto Jovem
4.
Phys Rev Lett ; 117(20): 203003, 2016 Nov 11.
Artigo em Inglês | MEDLINE | ID: mdl-27886486

RESUMO

We demonstrate a quantum gravimeter by combining the advantages of an atom chip for the generation, delta-kick collimation, and coherent manipulation of freely falling Bose-Einstein condensates (BECs) with an innovative launch mechanism based on Bloch oscillations and double Bragg diffraction. Our high-contrast BEC interferometer realizes tens of milliseconds of free fall in a volume as little as a one centimeter cube and paves the way for measurements with sub-µGal accuracies in miniaturized, robust devices.

5.
Chem Soc Rev ; 44(4): 988-98, 2015 Feb 21.
Artigo em Inglês | MEDLINE | ID: mdl-25316408

RESUMO

In this review we highlight recent progress in the field of photochemically and thermally induced electron transport through molecular bridges as integrative parts of electron donor-bridge-acceptor conjugates. The major emphasis is hereby on the design and the modular composition of the bridges. To this end, we will demonstrate that control over attenuation factors and reorganization energies, on one hand, as well as electronic and electron-vibration couplings, on the other hand, enables tuning electron transport over distances as short as 3.5 Å and as large as 50 Å by up to nine orders of magnitude. In terms of electron transport, the maximum extreme is given by carbon-bridged oligo-p-phenylenevinylenes of different lengths, while a zinc tetraphenylporphyrin free base tetraphenylporphyrin dyad constitutes the minimum extreme.


Assuntos
Metaloporfirinas/química , Transporte de Elétrons , Elétrons , Fulerenos/química , Luz , Teoria Quântica
6.
Phys Rev Lett ; 114(6): 063002, 2015 Feb 13.
Artigo em Inglês | MEDLINE | ID: mdl-25723216

RESUMO

We realize beam splitters and mirrors for atom waves by employing a sequence of light pulses rather than individual ones. In this way we can tailor atom interferometers with improved sensitivity and accuracy. We demonstrate our method of composite pulses by creating a symmetric matter-wave interferometer which combines the advantages of conventional Bragg- and Raman-type concepts. This feature leads to an interferometer with a high immunity to technical noise allowing us to devise a large-area Sagnac gyroscope yielding a phase shift of 6.5 rad due to the Earth's rotation. With this device we achieve a rotation rate precision of 120 nrad s(-1) Hz(-1/2) and determine the Earth's rotation rate with a relative uncertainty of 1.2%.

7.
Laryngorhinootologie ; 94(9): 601-8, 2015 Sep.
Artigo em Alemão | MEDLINE | ID: mdl-25739072

RESUMO

BACKGROUND: High resolution manometry (HRM) can provide information about the muscular contraction of the pharynx and the upper esophageal sphincter (UES) and represents an important tool in the diagnostics of dysphagia. To compare the results of swallowing studies interindividually and to identify pathological swallows, normative data are necessary. Normative data for the use of an HRM-probe with a large diameter has already been published. As previously has been shown these probes can influence the normal contraction of the pharynx and the UES. In this study comprehensive normal values are presented for small HRM-probes in diameter (2 mm), that only minimally affect pharyngeal and UES contractions. METHOD: 29 healthy volunteers underwent pharyngeal and upper esophageal HRM. All subjects performed 10 water swallows of 2 ml in an upright position. Pressure and time dependent parameters of the velopharyngeal region, the tongue base and the UES have been evaluated. Mean and median values and different percentile ranges were calculated. RESULTS: The normative values for the key parameters were (mean±SD): maximum velopharyngeal pressure 269.9±113.1 mmHg, maximum tongue base pressure 278±93.6 mmHg, maximum UES pressure 205.8±64.0 mmHg, UES resting pressure 42.5±18.7 mmHg and relaxation time of the UES 681.6±86.8 ms. Further parameters have been measured. CONCLUSION: Time dependent values are comparable to those already published. Especially in the UES lower pressures can be measured when a small HRM-probe is used. The normative data established in this study might help to distinguish pathological from physiological swallows using HRM.


Assuntos
Transtornos de Deglutição/diagnóstico , Transtornos de Deglutição/fisiopatologia , Esfíncter Esofágico Superior/fisiopatologia , Manometria/métodos , Faringe/fisiopatologia , Adulto , Feminino , Humanos , Aumento da Imagem/métodos , Interpretação de Imagem Assistida por Computador/métodos , Masculino , Pessoa de Meia-Idade , Contração Muscular/fisiologia , Palato Mole/fisiopatologia , Estudos Prospectivos , Valores de Referência , Língua/fisiopatologia , Adulto Jovem
8.
Nat Cell Biol ; 1(2): 94-7, 1999 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-10559880

RESUMO

MAPKAP kinase 2 (MK2) is one of several kinases that are regulated through direct phosphorylation by p38 MAP kinase. By introducing a targeted mutation into the mouse MK2 gene, we have determined the physiological function of MK2 in vivo. Mice that lack MK2 show increased stress resistance and survive LPS-induced endotoxic shock. This is due to a reduction of approximately 90% in the production of tumor necrosis factor-alpha (TNF-alpha) and not to a change in signalling from the TNF receptor. The level and stability of TNF-alpha mRNA is not reduced and TNF-alpha secretion is not affected. We conclude that MK2 is an essential component in the inflammatory response which regulates biosynthesis of TNF-alpha at a post-transcriptional level.


Assuntos
Citocinas/genética , Regulação da Expressão Gênica/fisiologia , Lipopolissacarídeos/farmacologia , Proteínas Serina-Treonina Quinases/genética , Proteínas Serina-Treonina Quinases/metabolismo , Fator de Necrose Tumoral alfa/genética , Animais , Citocinas/biossíntese , Regulação da Expressão Gênica/efeitos dos fármacos , Inflamação/genética , Inflamação/imunologia , Peptídeos e Proteínas de Sinalização Intracelular , Camundongos , Camundongos Endogâmicos , Camundongos Knockout , Proteínas Quinases Ativadas por Mitógeno/metabolismo , Mutagênese , Fosforilação , Proteínas Serina-Treonina Quinases/deficiência , RNA Mensageiro/metabolismo , Mapeamento por Restrição , Salmonella typhi , Baço/imunologia , Transcrição Gênica , Fator de Necrose Tumoral alfa/biossíntese , Proteínas Quinases p38 Ativadas por Mitógeno
9.
Clin Nephrol ; 73(6): 413-9, 2010 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-20497752

RESUMO

BACKGROUND: Acute tubulointerstitial nephritis (ATIN) as a complication of antituberculous therapy has been most commonly reported due to rifampicin therapy. This reaction typically occurs following re-exposure to the drug. This study undertook to investigate the clinicopathological features of ATIN related to antituberculous therapy. METHODS: We performed a retrospective study of all adult patients with a biopsy-proven diagnosis of ATIN on chemotherapy for tuberculosis. The patients presented with acute renal failure at our institution during 1995 - 2007. The demographic, clinical, biochemical and histopathological features were studied. The patient outcome and management were analyzed. RESULTS: 41 patients had histologically proven ATIN. 23 (56%) were female. The mean age at presentation was 42 years. The most common regimen included rifampicin used intermittently to treat pulmonary tuberculosis. The average duration of antituberculosis therapy was 19 days before presentation and the duration of the acute illness averaged 5 days. The most common clinical manifestation included gastro-intestinal symptoms occurring in 35 (85%) patients with associated hepatitis biochemically in 20 (53%) patients. No skin rashes were observed and eosinophilia was only present in two patients. Hematuria was observed universally without any significant proteinuria. Anemia was present in 37 (90%) patients, with associated thrombocytopenia in 15 (37%). Rifampicin was discontinued in 37 (90%) cases. Nine (22%) patients required dialysis. One patient failed to recover renal function and 4 (10%) patients died. Mortality was related to overwhelming tuberculosis infection. The main factor predicting the need for dialysis was duration of oliguria. CONCLUSION: ATIN is a rare, but serious complication of repeat antituberculous therapy mainly due to re-exposure to rifampicin. Although the renal prognosis is generally good the disease does carry significant morbidity and mortality risks. A high index of suspicion is needed in re-treatment patients. A suggested screening test is for microhematuria with urine dipstix.


Assuntos
Antituberculosos/efeitos adversos , Nefrite Intersticial/induzido quimicamente , Adulto , Feminino , Humanos , Masculino , Estudos Retrospectivos , Rifampina/efeitos adversos
10.
Cell Mol Life Sci ; 66(7): 1178-97, 2009 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-19039520

RESUMO

The Williams-Beuren syndrome is a genomic disorder (prevalence: 1/7,500 to 1/20,000), caused by a hemizygous contiguous gene deletion on chromosome 7q11.23. Typical symptoms comprise supravalvular aortic stenosis, mental retardation, overfriendliness and visuospatial impairment. The common deletion sizes range of 1.5-1.8 mega base pairs (Mb), encompassing app. 28 genes. For a few genes, a genotype-phenotype correlation has been established. The best-explored gene within this region is the elastin gene; its haploinsufficiency causes arterial stenosis. The region of the Williams-Beuren syndrome consists of a single copy gene region (approximately 1.2 Mb) flanked by repetitive sequences--Low Copy Repeats (LCR). The deletions arise as a consequence of misalignment of these repetitive sequences during meiosis and a following unequal crossing over due to high similarity of LCRs. This review presents an overview of the Williams-Beuren syndrome region considering the genomic assembly, chromosomal rearrangements and their mechanisms (i.e. deletions, duplications, inversions) and evolutionary and historical aspects.


Assuntos
Genoma Humano , Síndrome de Williams/genética , Aberrações Cromossômicas , Cromossomos Humanos Par 7/genética , Deleção de Genes , Dosagem de Genes , Humanos
11.
Klin Padiatr ; 222(6): 388-90, 2010 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-21058226

RESUMO

Patients with Wiedemann-Beckwith syndrome (WBS, MIM 130650), a congenital overgrowth syndrome, have a known increased tumor risk especially for embryonic tumors. WBS belongs to the "imprinting" syndromes caused by overexpression of IGF2 and/or loss of CDKN1C on chromosome 11p15.5. A 13-year-old boy with WBS developed a spitzoid malignant melanoma (Clark level V, Breslow index 4.8 mm) on the right cheek. Genetic analyses of the patient's blood showed hypermethylation at the H19 locus on chromosome 11p. The (epi)genetic changes of the WBS locus might have played a role in the pathogenesis of melanoma development.


Assuntos
Síndrome de Beckwith-Wiedemann/diagnóstico , Cromossomos Humanos Par 11/genética , Metilação de DNA/genética , Neoplasias Faciais/diagnóstico , Impressão Genômica/genética , Melanoma/diagnóstico , Neoplasias Cutâneas/diagnóstico , Adolescente , Síndrome de Beckwith-Wiedemann/genética , Bochecha , Neoplasias Faciais/genética , Predisposição Genética para Doença/genética , Humanos , Masculino , Melanoma/genética , RNA Longo não Codificante , RNA não Traduzido/genética , Neoplasias Cutâneas/genética
12.
Sci Total Environ ; 722: 137899, 2020 Jun 20.
Artigo em Inglês | MEDLINE | ID: mdl-32197166

RESUMO

Beaver populations are increasing throughout Europe and especially in Switzerland. Beaver are major ecological engineers of fluvial systems, dramatically influencing river morphology, ecohydrology and, consequently, aquatic and terrestrial biota. This study compared macroinvertebrate assemblages and trophic structure at two beaver complexes with contrasting topography in Switzerland over an annual cycle. One complex (Marthalen) was in a low gradient open basin, whereas the other complex (Flaach) flowed through a higher gradient ravine-like basin. Both complexes were embedded in an overall agricultural landscape matrix. Water physico-chemistry differed between the two complexes with nitrogen, phosphorus, and DOC being higher at Marthalen than at Flaach. Both complexes showed strong seasonality in physico-chemistry, but retention of nutrients (N, P) was highest in summer and only at Marthalen. Both complexes also showed strong seasonality in macroinvertebrate assemblages, although assemblages differed substantially between complexes. At Marthalen, macroinvertebrate assemblages were predominantly lentic in character at 'pool' sites within the complex. At Flaach, lotic macroinvertebrate assemblages were common at most sites with some lentic taxa also being present. Dietary shifts based on carbon/nitrogen stable isotopes occurred in spring and summer among sites at both complexes (autochthonous resource use increasing over allochthonous resource use downstream), although being most pronounced at Marthalen. In contrast, similar resource use across sites occurred in winter within both complexes. Although beaver significantly influenced fluvial dynamics and macroinvertebrate assemblage structure at both complexes, this influence was most pronounced at Marthalen where beaver caused the system to become more wetland in character, e.g., via higher hydraulic residence time, than at Flaach. We conclude that topography can shape beaver effects on fluvial systems and resident biota.


Assuntos
Roedores , Animais , Ecossistema , Monitoramento Ambiental , Invertebrados , Suíça
13.
Chem Senses ; 34(5): 435-40, 2009 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-19363087

RESUMO

This study described the San Diego Odor Identification Test (SDOIT) reliability and compared the SDOIT and the Brief Smell Identification Test (B-SIT). Ninety participants aged 50-70 years completed this 2-visit olfaction study. During visit 1, the SDOIT and B-SIT were administered according to standard protocols. Three weeks later, participants returned to retake the SDOIT. The SDOIT score was the total number of odorants correctly identified out of 8 odorants presented, and olfactory impairment was defined as correctly identifying less than 6 odorants. The B-SIT score was the total number of odorants correctly identified out of 12 odorants presented, and participants correctly identifying less than 9 odorants were categorized as abnormal. The SDOIT reliability was high (concordance correlation coefficient = 0.85, 95% confidence interval [CI] = 0.79-0.91). The same score was obtained on retest for 73% of participants, whereas 18% improved, and 9% declined. Test-retest agreement was 96% for the SDOIT; 4% improved from impaired at visit 1 to unimpaired at visit 2. Overall, SDOIT impairment classification and B-SIT abnormal classification agreed in 96% of participants (kappa = 0.81, 95% CI = 0.63-0.99). In conclusion, the SDOIT showed good test-retest reliability. Agreement for impaired/abnormal olfaction was demonstrated for the SDOIT and the B-SIT.


Assuntos
Odorantes/análise , Olfato/fisiologia , Idoso , Métodos Epidemiológicos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Reconhecimento Psicológico , Reprodutibilidade dos Testes , Limiar Sensorial/fisiologia
14.
Science ; 175(4024): 888-90, 1972 Feb 25.
Artigo em Inglês | MEDLINE | ID: mdl-17781063

RESUMO

Excavations of a workshop and cemetery in the high Venezuelan Andes yielded winged artifacts made of serpentinite at various stages of finish. Serpentinites are unknown in the Venezuelan Andes, and the raw material was obtained from natural sources located in northern South American or possibly the Antilles, or by trade.

15.
Science ; 170(3953): 66-9, 1970 Oct 02.
Artigo em Inglês | MEDLINE | ID: mdl-17734671

RESUMO

Postglacial, right-lateral, strike-slip movement along the Boconó fault, measured on detailed topographic maps, averages 66 meters. The rate of movement was approximately 0.66 centimeter per year, as indicated by carbon-14 dating of associated soil. This evidence suggests that postglacial movement between the Caribbean and Americas plates occurred mainly along the Boconó fault and the north coast of Venezuela.

16.
Science ; 264(5159): 692-6, 1994 Apr 29.
Artigo em Inglês | MEDLINE | ID: mdl-17737955

RESUMO

Oxygen isotope records of cores from the central Arctic Ocean yield evidence for a major influx of meltwater at the beginning of the last deglaciation 15.7 thousand years ago (16,650 calendar years B.C.). The almost parallel trends of the isotope records from the Arctic Ocean, the Fram Strait, and the east Greenland continental margin suggest contemporaneous variations of the Eurasian Arctic and Greenland (Laurentide) ice sheets or increased export of low-saline waters from the Arctic within the East Greenland Current during the last deglaciation. On the basis of isotope and carbon data, the modern surface- and deep-water characteristics and seasonally open-ice conditions with increased surface-water productivity were established in the central Arctic at the end of Termination lb about 7.2 thousand years ago or 6,000 calendar years B.C.).

17.
Science ; 214(4527): 1299-305, 1981 Dec 18.
Artigo em Inglês | MEDLINE | ID: mdl-17812244

RESUMO

Chemical, paleontological, and mineralogical analyses of a 7.5-meter core from the middle of Lake Valencia, Venezuela, have provided information on the paleoclimatic history of this low-elevation, low-latitude site for the last 13,000 years. The data show that dry climates existed in this region from 13,000 years before present (B.P.) until about 10,000 years B.P. The Lake Valencia Basin was occupied by intermittent saline marshes at that time. About 10,000 years B.P., a permanent lake of fluctuating salinity formed and arboreal plant communities replaced the earlier dominant xeric herbaceous vegetation and marsh plants. By 8500 years B.P., Lake Valencia reached moderate to low salinities and discharged water; the modern vegetation became established at that time. After 8500 years B.P., the lake twice ceased discharging as a result of reduced watershed moisture. The second of these drying episodes is still in progress and has been aggravated by human activities in the watershed.

18.
Ophthalmic Physiol Opt ; 29(5): 509-17, 2009 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-19602142

RESUMO

PURPOSE: To establish a virtual device that can predict the effect of facial features on the visual field of humans and primates. METHODS: Virtual masks were obtained from human subjects, and macaque, chimpanzee and baboon taxidermic specimens, and aligned with upright head orientation at the center of a virtual perimeter-like dome (radius = 50 m) developed with Cinema 4D. Virtual searchlights positioned at the masks' pupils were then allowed to 'paint' facial elements obstructing their path, and demarcate the unobstructed rays at the perimetric surface and on a virtual ground floor related to eye level. Searchlight positions along the human mask's pupillary axis were identified by maximum congruence to Goldmann visual field limits. RESULTS: The human contours largely concur with large-stimulus isopters displaying the limiting role of the nasal ridge, and the relatively extended ventral and temporal limits. In contrast, the facial design of chimpanzees and baboons obstructs significant portions of the ventral foreground (>2 m cf < 0.5 m in human), while there appear to be larger binocular overlaps (125 degrees in chimp cf 90 degrees in human). CONCLUSIONS: The model provides information on anatomical constraints for monocular and binocular visual field extensions including projection of the ventral field on a virtual floor.


Assuntos
Face/anatomia & histologia , Lateralidade Funcional/fisiologia , Testes de Campo Visual/métodos , Animais , Humanos , Modelos Anatômicos , Primatas , Software
19.
SADJ ; 64(10): 470-3, 2009 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-20306866

RESUMO

UNLABELLED: Patients with end-stage renal disease (ESRD) experience a significantly increased rate of atherosclerotic complications. Inflammation plays a central role in the pathogenesis of these complications and C-reactive protein (CRP) has been found to be predictive of all-cause and cardiovascular mortality. Many patients have elevated CRP levels without an apparent infection. Periodontal diseases in the general population have been associated with both an increased prevalence of atherosclerotic complications and an elevation in serum CRP values. This study examined the association between periodontal disease and elevated CRP in patients with ESRD on chronic dialysis. METHODS: Eighty patients on chronic dialysis were included in the study. Demographic information, medical history and CRP levels were recorded. Periodontal examination was carried out by a single calibrated examiner and included gingival index (GI), bleeding on probing (BoP), probing depths (PD) and clinical attachment loss (CAL). These measurements were recorded in relation to the Ramfjord teeth. The presence in any one sextant of PD > or =4 mm or clinical loss of attachment > or =3 mm was diagnosed as periodontitis. RESULTS: Mean age of subjects was 50.3 +/- 9.06 years with a median time on dialysis of 24 months. 57.5% (n=46) of subjects were diagnosed as having periodontitis; of these 52.2% had CRP levels >10 mg/l. Of the 34 subjects with healthy periodontium, only 10 (29.4%) had elevated CRP levels. The serum CRP levels between these two groups were significantly different (p = 0.004). CONCLUSION: The results of the study showed significantly elevated levels of CRP in ESRD patients with periodontitis. Periodontal diseases may be an overlooked source of inflammation in ESRD patients.


Assuntos
Falência Renal Crônica/complicações , Periodontite/complicações , Adulto , Aterosclerose/complicações , Proteína C-Reativa/análise , Estudos Transversais , Complicações do Diabetes , Feminino , Hemorragia Gengival/complicações , Humanos , Inflamação , Falência Renal Crônica/sangue , Falência Renal Crônica/terapia , Masculino , Pessoa de Meia-Idade , Perda da Inserção Periodontal/complicações , Índice Periodontal , Bolsa Periodontal/complicações , Periodontite/sangue , Diálise Peritoneal , Diálise Renal , Método Simples-Cego , Fumar , Fatores de Tempo
20.
Curr Drug Metab ; 9(7): 622-7, 2008 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-18781914

RESUMO

Neuropsychiatric symptoms like mood changes and depression are common in patients with chronic inflammatory disorders such as infections, autoimmune diseases or cancer. The pathogenesis of these symptoms is still unclear. Pro-inflammatory stimuli interfere not only with the neural circuits and neurotransmitters of the serotonergic, but also with those of the adrenergic system. The pro-inflammatory cytokine interferon-gamma stimulates the biosynthesis of 5,6,7,8-tetrahydrobiopterin (BH4), which is cofactor for several aromatic amino acid monooxygenases and thus is strongly involved in the biosynthesis of the neurotransmitter serotonin and the catecholamines dopamine, epinephrine (adrenaline) and norepinephrine (noradrenaline). In macrophages, interferon-gamma also triggers the high output of reactive oxygen species, which can destroy the oxidation-labile BH4. Recent data suggest that oxidative loss of BH4 in chronic inflammatory conditions can reduce the biosynthesis of catecholamines, which may relate to disturbed adrenergic neurotransmitter pathways in patients.


Assuntos
Inflamação/metabolismo , Fenilalanina/metabolismo , Animais , Monoaminas Biogênicas/metabolismo , Biopterinas/análogos & derivados , Biopterinas/fisiologia , Homocisteína/metabolismo , Humanos , Sistema Imunitário/fisiologia , Interferon gama/biossíntese , Estresse Oxidativo
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