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1.
Deep Sea Res 2 Top Stud Oceanogr ; 138: 63-73, 2017 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-28515575

RESUMO

The Antarctic Circumpolar Current has a high potential for primary production and carbon sequestration through the biological pump. In the current study, two large-scale blooms observed in 2012 during a cruise with R.V. Polarstern were investigated with respect to phytoplankton standing stocks, primary productivity and nutrient budgets. While net primary productivity was similar in both blooms, chlorophyll a -specific photosynthesis was more efficient in the bloom closer to the island of South Georgia (39 °W, 50 °S) compared to the open ocean bloom further east (12 °W, 51 °S). We did not find evidence for light being the driver of bloom dynamics as chlorophyll standing stocks up to 165 mg m-2 developed despite mixed layers as deep as 90 m. Since the two bloom regions differ in their distance to shelf areas, potential sources of iron vary. Nutrient (nitrate, phosphate, silicate) deficits were similar in both areas despite different bloom ages, but their ratios indicated more pronounced iron limitation at 12 °W compared to 39 °W. While primarily the supply of iron and not the availability of light seemed to control onset and duration of the blooms, higher grazing pressure could have exerted a stronger control toward the declining phase of the blooms.

2.
Eur J Ophthalmol ; 18(2): 320-3, 2008.
Artigo em Inglês | MEDLINE | ID: mdl-18320533

RESUMO

PURPOSE: The incidence of eye disease increases with age and can often be linked to worsening cardiovascular function and increasing intraocular pressure. Estrogen is known to have vasodilatory effects in the systemic circulation. Decreased estrogen levels during menopause may therefore complicate or contribute to ocular pathologies as estrogen receptors are found in both retinal and choroidal tissue. The purpose of this investigation was to determine the effects of menopause on visual function and cardiovascular and ocular hemodynamics. METHODS: Twelve premenopausal and 24 postmenopausal women were evaluated at the Indiana University School of Medicine during a single study visit. Vision screening and ocular blood flow evaluations were performed, including blood pressure, heart rate, visual acuity, contrast sensitivity, intraocular pressure, and retinal capillary and retrobulbar blood flow imaging. Vision and ocular hemodynamics were compared using unpaired Student t-tests with p<0.05 regarded as statistically significant. RESULTS: The premenopausal group had significantly lower heart rate (-16.1 b/m, p=0.0001) and systolic blood pressure (-17.7 mmHg, p=0.003) than postmenopausal subjects. Contrast sensitivity was significantly higher (measured in log units) in premenopausal women in both the right (0.25, p=0.039; 0.16, p=0.039) and left (0.45, p=0.001; 0.27, p=0.032) eyes at 9 and 18 cycles per degree, respectively. Premenopausal women also had significantly lower intraocular pressure in both the right (-2.19 mmHg, p=0.024) and left (-1.74 mmHg, p=0.035) eyes. Total ocular perfusion was not significantly different between groups. CONCLUSIONS: This pilot work suggests that postmenopausal women have lower contrast sensitivity detection and elevated intraocular pressures compared to premenopausal women. Premenopausal women have lower cardiovascular risk factors, while total ocular circulation was similar to postmenopausal women.


Assuntos
Artérias Ciliares/fisiologia , Sensibilidades de Contraste/fisiologia , Artéria Oftálmica/fisiologia , Pós-Menopausa/fisiologia , Pré-Menopausa/fisiologia , Artéria Retiniana/fisiologia , Acuidade Visual/fisiologia , Adulto , Velocidade do Fluxo Sanguíneo , Pressão Sanguínea/fisiologia , Feminino , Frequência Cardíaca/fisiologia , Humanos , Pressão Intraocular , Fluxometria por Laser-Doppler , Pessoa de Meia-Idade , Disco Óptico/irrigação sanguínea , Ultrassonografia Doppler em Cores
3.
Bioorg Med Chem ; 10(9): 2855-61, 2002 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-12110305

RESUMO

Human neutrophil elastase (HNE) is a serine protease that has been implicated in the abnormal turnover of connective tissue proteins and has been described as an important pathogenic factor in several inflammatory diseases such as rheumatoid arthritis or cystic fibrosis. Here we investigated 17 sesquiterpene lactones (SLs) for their ability to inhibit human neutrophil elastase in an in vitro assay. Podachaenin was the most active compound with an IC(50) value of 7 microM. SLs do not covalently bind to the amino acids of the catalytic triad, thus differing from other elastase inhibitors with a lactone moiety. In contrast to most other biological activities of SLs HNE inhibition is not mediated by alpha,beta-unsaturated carbonyl functions. Ligand binding calculations using the X-ray structure of HNE and the program FlexX revealed structural elements which are a prerequisite for their inhibitory activity.


Assuntos
Lactonas/química , Elastase de Leucócito/antagonistas & inibidores , Sesquiterpenos/química , Inibidores Enzimáticos/química , Inibidores Enzimáticos/farmacologia , Humanos , Concentração Inibidora 50 , Lactonas/farmacologia , Modelos Moleculares , Estrutura Molecular , Ligação Proteica , Sesquiterpenos/farmacologia , Relação Estrutura-Atividade
4.
Biochem Pharmacol ; 62(6): 795-801, 2001 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-11551526

RESUMO

Many sesquiterpene lactones (Sls) are known to possess anti-inflammatory activities. To gain further insight into their structure-activity relationships and the molecular mechanism of action, four germacranolide sesquiterpene lactones which differ in the skeleton and the number of reactive centers (4beta,15-epoxy-miller-9E-enolide (1), 15-acetoxy-eremantholide B (2), a mixture of 15-(isovaleroyl)/15-(2-methyl-butyryl)-2alpha-acetoxy-miguanin (3), and 15-(2-hydroxy)-isobutyryloxy-micrantholide (4)) were investigated for their effect on production of proinflammatory cytokines (interleukin-1beta [IL-1beta], IL-6, and tumor necrosis factor-alpha [TNF-alpha]) as well as proliferation of concanavalin A (Con A) and lipopolysaccharide (LPS)-stimulated mouse lymphocytes. Compounds 1 and 3 which possess an alpha-methylene-gamma-lactone function and a conjugated carbonyl group induced a half-maximal inhibition of cytokine synthesis in adherent mouse peritoneal exudate cells at micromolar concentrations (IC(50) 0.69-1.70 microM), while compound 4 which contains only an alpha-methylene-gamma-lactone residue was less active (IC(50) > or 38 microM). Interestingly, compound 2, which carries only a conjugated keto group, displayed a potency similar to those of the bifunctional compounds 1 and 3. All four Sls suppressed proliferation of murine lymphocyte at IC(50) concentrations between 0.22 and 5.03 microM. The rank order of potency was 1 = 2 > 3 > 4. Generally, the growth of LPS-stimulated cells was more strongly influenced than those of Con A-activated lymphocytes. This effect was particularly pronounced with 4. Inhibitory concentrations correlated well with those necessary for inhibition of the transcription factor nuclear factor kappaB (NF-kappaB) observed in a previous investigation. Therefore, it can be assumed that NF-kappaB may be involved in the suppressive effect of Sls on cytokine production and lymphocyte proliferation.


Assuntos
Citocinas/biossíntese , Lactonas/farmacologia , Ativação Linfocitária/efeitos dos fármacos , NF-kappa B/metabolismo , Animais , Linfócitos B/efeitos dos fármacos , Linfócitos B/metabolismo , Divisão Celular/efeitos dos fármacos , Citocinas/efeitos dos fármacos , Relação Dose-Resposta a Droga , Interleucina-1/metabolismo , Interleucina-1beta , Interleucina-6/metabolismo , Masculino , Camundongos , Fragmentos de Peptídeos/metabolismo , Sesquiterpenos/química , Sesquiterpenos/farmacologia , Fator de Necrose Tumoral alfa/metabolismo
5.
Planta Med ; 66(7): 591-5, 2000 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-11105560

RESUMO

Investigation of Podachaenium eminens afforded nine sesquiterpene lactones (Sls) from which costunolide, 7-hydroxycostunolide, santamarin as well as 3-chlorodehydroleucodin are new for this plant and 3,4-dehydro-4-dehydroxypodachaenin (= 3-costoyloxydehydroleucodin) is found for the first time in nature. All isolated Sls were studied for their anti-inflammatory activity using the transcription factor NF-kappa B as a molecular target. NF-kappa B is involved in the synthesis of inflammatory mediators, such as cytokines and chemokines. Except for podachaenin, all compounds completely inhibited NF-kappa B DNA binding in an electrophoretic mobility shift assay at concentrations between 5 and 200 microM without showing any cytotoxic effects. 3,4-Epoxydehydroleucodin possessing an alpha-methylene-gamma-butyrolactone and a second reactive structure element by its epoxy ring alpha,beta to a carbonyl group was most active. Although the majority of the Sls tested in this study were monofunctional only low concentrations of 50 microM were often needed for complete inhibition. Possible reasons are discussed for this result.


Assuntos
Asteraceae/química , Lactonas/farmacologia , NF-kappa B/antagonistas & inibidores , Sesquiterpenos/química , Humanos , Células Jurkat , Lactonas/química
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