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Effect Dependent (effect + dependent)

Distribution by Scientific Domains

Medical Sciences	40%

Selected Abstracts

Hepatotoxic effect of cyclosporin A in the mitochondrial respiratory chain

JOURNAL OF APPLIED TOXICOLOGY, Issue 4 2007
Lilia Cristina De la Cruz Rodríguez
Abstract Cyclosporin A (CyA), a potent immunosuppressant, was used to determine the hepatotoxic effect in long-term treatments. Male Wistar rats were used in these experiments. They were given CyA chronically at doses used in patients for 120 days, and at doses of 5, 10, 15 and 20 mg kg,1 day,1. These doses amount to CyA values in blood of 200 ± 24, 314 ± 40, 445 ± 33 and 598 ± 53 ng ml,1, respectively. A significant increase in glutamate dehydrogenase (GLDH) was found in the groups treated with 15 and 20 mg kg,1 day,1, which would point to mitochondria as the potential target of the toxic action of CyA. The mitochondrial respiratory chain of rat livers was studied in enzyme complexes I and II. Enzyme complex I was determined by spectrophotometry at 340 nm using NADH oxidase with the respirable substrate 10 mm NADH; enzyme complex II was determined by monitoring succinate dehydrogenase by oxymetry using the respirable substrate 10 mm succinate. The results show the inhibition of NADH oxidase in the groups treated with 10, 15 and 20 mg kg,1 day,1, an effect dependent both on time and on CyA concentration. Enzyme complex II showed a decrease in oxygen consumption. These findings were confirmed by histological studies (hematoxylin-eosin technique). Conclusions: Long-term treatment with CyA at doses of 15 and 20 mg kg,1 day,1, amounting to concentrations in blood of 445 ± 33 and 598 ± 53 ng ml,1, causes alterations in the mitochondria, revealed by the increase in serum GLDH and by the functional alteration of enzyme complexes I and II of the mitochondrial respiratory chain. Copyright © 2007 John Wiley & Sons, Ltd. [source]

In Vitro and In Vivo Transfer of bcl-2 Gene into Keratinocytes Suppresses UVB-induced Apoptosis,

PHOTOCHEMISTRY & PHOTOBIOLOGY, Issue 4 2001
Hidetoshi Takahashi
ABSTRACT Bcl-2 is a member of the large Bcl-2 family and protects cells from apoptosis. Ultraviolet B (UVB) irradiation induces apoptosis of keratinocytes that is known as "sunburn cells." Previously we reported that UVB irradiation induces apoptosis accompanied by sequential activation of caspase 8, 3 and 1 in keratinocytes, and that the process is inhibited by various caspase inhibitors. Using bcl-2,expressing adenovirus vector we investigated the effect of Bcl-2 on UVB-induced apoptosis. Adenovirus vector efficiently introduced bcl-2 gene in cultured normal mouse keratinocytes (NMK cells); almost all NMK cells (1 × 106) were transfected at 1 × 108 plaque-forming unit (PFU)/mL. Bcl-2,transfected NMK cells were significantly resistant to UVB-induced apoptosis with the suppressive effect dependent on the Bcl-2 expression level. Following UVB irradiation caspase 8, 3 and 9 activities were stimulated in NMK cells, whereas in bcl-2,transfected cells only caspase 8, but not caspase 3 or 9, activity was stimulated. In order to investigate the effect of Bcl-2 in vivo topical application of Ad-bcl-2 on tape-stripped mouse skin was performed. Following the application Bcl-2 was efficiently overexpressed in almost all viable keratinocytes. The expression was transient with the maximal expression of Bcl-2 on the first day following the application of 1 × 109 PFU in 200 ,L. The introduced Bcl-2 remained at least for 6 days. UVB irradiation (1250 J/m2) induced apoptosis within 12 h and the maximal effect was observed at 24 h in control mouse skin. Both bcl-2,transfected and topical caspase 3 inhibitor-treated mice skin were resistant to UVB-induced apoptosis. The suppressive effect of Bcl-2 was more potent than that of caspase 3 inhibitor application. Topical application of empty adenovirus vector alone had no effect on Bcl-2 expression or UVB-induced apoptosis. These results indicate that adenovirus vector is an efficient gene delivery system into keratinocytes and that Bcl-2 is a potent inhibitor of UVB-induced apoptosis both in vitro and in vivo. [source]

Intermediate-term variations in solar radius during solar cycle 23

ASTRONOMISCHE NACHRICHTEN, Issue 4 2009
H. Kiliç
Abstract In this study, we look for the mid-term variations in the daily average data of solar radius measurements made at the Solar Astrolabe Station of TUBITAK National Observatory (TUG) during solar cycle 23 for a time interval from 2000 February 26 to 2006 November 15. Due to the weather conditions and seasonal effect dependent on the latitude, the data series has the temporal gaps. For spectral analysis of the data series, thus, we use the Date Compensated Discrete Fourier Transform (DCDFT) and the CLEANest algorithm, which are powerful methods for irregularly spaced data. The CLEANest spectra of the solar radius data exhibit several significant mid-term periodicities at 393.2, 338.9, 206.5, 195.2, 172.3 and 125.4 days which are consistent with periods detected in several solar time series by several authors during different solar cycles. The knowledge relating to the origin of solar radius variations is not yet present. To see whether these variations will repeat in next cycles and to understand how the amplitudes of such variations change with different phases of the solar cycles, we need more systematic efforts and the long-term homogeneous data. Since most of the periodicities detected in the present study are frequently seen in solar activity indicators, it is thought that the physical mechanisms driving the periodicities of solar activity may also be effective in solar radius variations (© 2009 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim) [source]

Interleukin-1, attenuates endothelin B receptor-mediated airway contractions in a murine in vitro model of asthma: roles of endothelin converting enzyme and mitogen-activated protein kinase pathways

CLINICAL & EXPERIMENTAL ALLERGY, Issue 9 2004
Y. Zhang
Summary Background Asthma is a chronic airway disease, known to involve several inflammatory mediators. Little is known about how these mediators interact in order to produce or attenuate even basic features of the disease, like airway hyper-reactivity and remodelling. Endothelin-1 (ET-1) and IL-1, are two mediators suggested to play important roles in the induction of airway inflammation. Objective To investigate the interactions between ET-1 and IL-1,, using a novel in vitro model of asthma, focusing on airway smooth muscle contractility. Methods Isolated murine tracheal segments were cultured from 1 to 8 days in the absence and presence of IL-1,. The subsequent contractile responses to sarafotoxin 6c (S6c) (selective agonist for ETB receptor) and sarafotoxin 6b (S6b) (ETA and ETB receptor agonist) were recorded by a myographs system. In all experiments, ETB receptors were desensitized before the contractile response to S6b was recorded. Thus, the response to S6b is only mediated by ETA receptors in the present study. The mRNA expressions for ET-1 and endothelin (ET) receptors were quantified by real-time PCR. Results Organ culture in the presence of IL-1, attenuated the maximal contraction induced by S6c, but not S6b. This reduction was concentration-dependent and was significant after 2, 4 and 8 days of culture. To investigate the mechanisms behind this, inhibitors for endothelin converting enzyme (ECE) phosphoramidon, c-JUN N-terminal kinase (JNK) SP600125, extracellular-signal-regulated kinase 1/2(ERK 1/2) PD98059 and p38 pathway SB203580 were used. Individually, SP600125 and PD98059, but not SB203580, could partly reverse the reduction induced by IL-1,. An additional effect was obtained when SP600125 and PD98059 were combined. The mRNA expressions for ET-1 and ETB receptor were up- and down-regulated, respectively, by IL-1,. Conclusion Presence of IL-1, in the airways attenuate the contractile response mediated via ETB receptors, an effect dependent on ECE, JNK and ERK 1/2 pathways. [source]

Modulation of growth hormone action by sex steroids

CLINICAL ENDOCRINOLOGY, Issue 4 2006
Udo J. Meinhardt
Summary Growth hormone (GH) is a major regulator of growth, somatic development and body composition. Sex steroids can act centrally by regulating GH secretion and peripherally modulating GH responsiveness. This review addresses data of potential clinical relevance on how sex steroids modulate GH secretion and action, aiming to increase the understanding of sex steroid/GH interactions and leading to improved management of patients. Sex steroids regulate GH secretion directly as well as indirectly through IGF-I modulation. Testosterone stimulates GH secretion centrally, an effect dependent on prior aromatization to oestrogen. Oestrogen stimulates GH secretion indirectly by reducing IGF-I feedback inhibition. Whether oestrogen stimulates GH secretion centrally in females is unresolved. Gonadal steroids modify the metabolic effects of GH. Testosterone amplifies GH stimulation of IGF-I, sodium retention, substrate metabolism and protein anabolism while exhibiting similar but independent actions of its own. Oestrogen attenuates GH action by inhibiting GH-regulated endocrine function of the liver. This is a concentration-dependent phenomenon that arises invariably from oral administration of therapeutic doses of oestrogen, an effect that can be avoided by using a parenteral route. This strong modulatory effect of gonadal steroids on GH responsiveness provides insights into the biological basis of sexual dimorphism in growth, development and body composition and practical information for the clinical endocrinologist. It calls for an appraisal of the diagnostic criteria for GH deficiency of GH stimulation tests, which currently are based on arbitrary cut-offs that do not take into account the shifting baseline from the changing gonadal steroid milieu. In the management of GH deficiency in the hypopituitary female, oestrogen should be administered by a nonoral route. In hypopituitary men, androgens should be replaced concurrently to maximize the benefits of GH. In the general population, the metabolic consequences of long-term treatment of women with oral oestrogen compounds, including selective oestrogen receptor modulators, are largely unknown and warrant study. [source]