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61.
Ayaz M Lodhi MA Riaz M Ul-haq A Malik A Choudhary MI 《Journal of enzyme inhibition and medicinal chemistry》2006,21(5):527-529
Phytochemical investigations on the chloroform and ethyl acetate soluble fractions of the roots of the Daphne oleoids led to the isolation of the coumarin glycosides 1-6. Compound 5 with IC50 values 22.05 and 26.30 microM repectively, was found to be the most active of these compounds when screened against Bacillus pasteurii and jack bean urease enzymes in a concentration-dependent fashion. 相似文献
62.
Neutrophil apoptosis is delayed under trauma and/or sepsis conditions. The mechanism for the delay has remained unclear. We hypothesize that modulation of the mitochondrial pathway of apoptosis contributes to the delay in neutrophil apoptosis with burn injury. Rats were subjected to burn injury (30% of total body surface area, 98°C for 10 s) and euthanatized 24 h postinjury. Blood neutrophils from sham and burn-injured rats were isolated by Ficoll gradient centrifugation and cultured for 2 or 8 h. Neutrophil apoptosis was determined by annexin V and propidium iodide (PI) labeling and flow cytometry. Neutrophil mitochondrial morphology was assessed via histochemical staining (MitoTracker GreenFM) and confocal microscopy. Neutrophils from rats with burn injury showed a decreased level of apoptosis compared with sham rat neutrophils at both 2 and 8 h of incubation. In incubated sham rat neutrophils, mitochondria showed a change from normal "tubular" to an "aggregated" morphology. In contrast, cultured neutrophils from burn rats did not exhibit this mitochondrial morphological transition until 8 h of incubation. Compared with sham rat neutrophils, neutrophils from burn rats showed decreased levels of active caspase-9 and -3. Whereas an upregulation of Bcl-xL and a downregulation of Bax seemed to contribute to decreased apoptosis in burn rat neutrophils at 2 h of incubation, the decreased apoptosis at 8 h appeared to be associated with a decrease in Bax and increased phosphorylated Bad. These data suggest that suppression of the mitochondrial pathway plays an essential role in the delay of polymorphonuclear neutrophil apoptosis with burn injury. burn; rat; polymorphonuclear leukocytes; caspase-3; caspase-9; cytochrome c; Bcl-xL; Bax; Bad; MitoTracker GreenFM; confocal microscopy 相似文献
63.
Protective effect of selenium treatment on diabetes-induced myocardial structural alterations 总被引:2,自引:0,他引:2
One of the main causes leading to mortality in diabetes is myocardial disease. Using streptozotocin (STZ)-induced diabetic
animals, it has been possible to characterize diabetes-induced myocardial abnormalities. Interstitial and microvascular disorders
are known to be a characteristic part of the diabetic cardiomyopathy and partly resist insulin therapy. Because diabetic damage
is partly attributed to oxidative stress, antioxidant treatment may be able to reduce this damage. The aim of this study was
to investigate the cardioprotective effect of sodium selenite, known as an antioxidant agent. The diabetes was induced by
ip injection of 50 mg/kg body wt STZ. The duration of diabetes was 5 wk. The protected group received (ip) 5 μmol/kg body
wt/d sodium selenite (Na2SeO3) over 4 wk following diabetes induction. Electron and light microscopic morphometry of heart samples revealed typical diabetic
alterations consisting in an increase in collagen content, vacuolation, diminishing of the cardiomyocyte diameter, alteration
in myofilaments and Z-lines of myofibers, and myofibrillary degeneration. Sodium selenite treatment could prevent the loss
of myofibrills and reduction of myocyte diameter. In the sodium-selenite-treated diabetic rat heart, alterations of the discus
intercalaris and nucleus were corrected, and degenerations seen in myofilaments and Z-lines were reversed by this treatment.
Under these findings, one can suggest that sodium selenite treatment may alleviate late diabetic complications when it is
used under control conditions. 相似文献
64.
The effect of sodium selenite (0.05, 0.1, and 0.2 mg/kg body weight, ip) on the contents of lipids (phospholipids, cholesterol,
esterified fatty acids, gangliosides), thiobarbituric acid reactive substance (TBARS), and thiol group in circadian rhythm
centers (preoptic area, brainstem, and posterior hypothalamus) of male Wistar rats was studied after 7 d of treatment. The
content of phospholipids was elevated significantly with a dose of 0.1 mg/kg of selenite in the preoptic area and brainstem,
but a 0.2-mg/kg dose has depleted its level significantly in these regions. The alteration of phospholipids in posterior hypothalamus
was not significant with three doses of sodium selenite. The level of cholesterol in the preoptic area was inhibited significantly
with a dose of 0.05 mg/kg sodium selenite, but its level was elevated significantly with a dose of 0.2 mg/kg selenite in the
preoptic area and brainstem. Alteration with three doses of sodium selenite in the posterior hypothalamus was not significant.
The ganglioside level in the preoptic area and brainstem was elevated significantly with a 0.1-mg dose of sodium selenite;
conversely, a 0.2 mg dose of sodium selenite caused a significant depletion on its content in these areas. In the posterior
hypothalamus, the ganglioside level was depleted significantly with a dose of 0.1 mg, but elevated significantly with a dose
of 0.2 mg of sodium selenite. The level of esterified fatty acids was decreased significantly in the preoptic area and brainstem
with a dose of 0.1 mg/kg sodium selenite, but in these regions, its level was elevated with a dose of 0.2 mg/kg sodium selenite
and its elevation was significant in the preoptic area. In the posterior hypothalamus, the alteration of esterified fatty
acids with three doses of sodium selenite was not significant. The effect of 0.1 and 0.2 mg/kg sodium selenite on the TBARS
level and thiol group in sleep centers was significantly opposite to the wakefulness center. A sodium selenite dose of 0.1
mg/kg had depleted the content of TBARS in the preoptic area and brainstem but elevated the content of the thiol group significantly
in the posterior hypothalamus. On the other hand, a 0.2-mg/kg dose of sodium selenite has significantly elevated the content
of TBARS but depleted the content of the thiol group significantly in the posterior hypothalamus. No dose-dependent alteration
was observed on the content of lipids, TBARS, and thiol group in the circadian rhythm centers of rats. 相似文献
65.
Selenium (Se) has long been recognized as both an essential mammalian nutrient and a hazardous element. Sodium selenite is
commonly used as a dietary supplement for the treatment of Se deficiency. On the other hand, chronic Se toxicity has been
demonstrated to affect the major organs, including the heart, in experimental animals.
This study examines the effects of high concentrations of extracellular selenite (in the range of 0.001–1 mM) application into the recording bath on the electrical properties of rat papillary muscles. Conventional glass semifloating
microelectrodes were used to record intracellular action potentials (APs) in isolated rat papillary muscles. The amplitude
of APs and the resting membrane potential of papillary muscles were not changed following a 20-min selenite (1 mM) application compared to the first minute of its application. Freshly isolated ventricular myocytes by an enzymatic method
were used to determine the selenite-induced alterations in Na+ currents. Na+ currents, measured at 22°C, by the whole-cell patch-clamp technique, decreased by 38±8% in the presence of 1 mM selenite for 5 min. These selenite-induced effects were not reversed, but are restored by dithiothreitol (1 mM).
These results demonstrated that toxic concentrations of selenite induced a significant shortening in AP duration as a result
of an increase in the rate of repolarization. Our findings also suggest that a decrease in Na+ currents, in addition to Ca2+ currents, may play a role in the shortening of AP duration in rat papillary muscles. 相似文献
66.
D Konukoglu M Ercan M Ayaz S Onen 《Journal of trace elements in medicine and biology》2001,15(2-3):119-122
The objective of the study was to investigate the effect of moderate glomerular dysfunction on oxidative stress. We determined the plasma and erythrocyte malondialdehyde (MDA) levels, as a marker of lipid peroxidation, erythrocyte glutathione (GSH) levels and activities of GSH-Px, GSH Red and SOD as an antioxidant enzymes, and plasma trace element levels containing Fe, Cu and Zn in twenty proteinuric patients (6.8 +/- 5.1 g/day) with moderate glomerular function and in 20 anemic control subjects. We found that the erythrocyte and plasma MDA levels and erythrocyte GSH-Px activities were significantly higher (p < 0.001, p < 0.001, p < 0.001, respectively) and the erythrocyte GSH levels and activities of GSH-Red and SOD activities were significantly lower (p < 0.001, p < 0.001, p < 0.001, respectively) in the patients than in the anemic subjects. Plasma Fe and Zn levels were not to be found significantly different in the patients compared to the anemic subjects. But plasma Cu levels were significantly higher in the patients (p < 0.05) when compared with the levels of anemic subjects. This study was concluded that cellular antioxidant activity decreases in proteinuric patients with moderate glomerular function. This may increase lipid peroxidation reactions by causing oxidative stress in erythrocyte membranes. 相似文献
67.
Ayaz M Ozdemir S Yaras N Vassort G Turan B 《Biochemical and biophysical research communications》2005,327(1):163-173
In the present study, rats were treated with sodium selenite (5 micromol/kg body weight/day, ip) for 4 weeks and the parameters of contractile activity, action potential, L-type Ca2+-current (ICaL), as well as transient outward (Ito), inward rectifier (IK1), and steady state (Iss) K+-currents were investigated. Sodium selenite treatment increased rat blood glucose level and lowered plasma insulin level, significantly. This treatment also caused slightly prolongation in action potential with no significant effects on spontaneous contraction parameters and intracellular Ca2+ transients of the heart preparations. These effects were associated with marked alterations in the kinetics of both ICaL and Ito including a significant slowing in both inactivation time constants of ICaL and a significant shift to negative potential at half-inactivation of these channels without any change in the current density. Also, there was a significantly faster inactivation of Ito and no shift in half-inactivation of this channel without any change in its current density. Consequently, there was a approximately 50% increase in total charges carried by Ca2+ current and approximately 50% decrease in total charges carried by K+ currents of the treated rat cardiomyocytes. Additionally we observed a significant inhibition in IK1 density in treated rat cardiomyocytes. Oxidized glutathione level was significantly increased (70%) while the observed decrease in reduced glutathione was much less. Since a shift in redox state of regulatory proteins is related with cell dysfunction, selenium-induced increase in blood glucose and decrease in plasma insulin may correlate these alterations. These alterations, in the kinetics of the channels and in IK1 density, might lead to proarrhythmic effect of chronic selenium supplementation. 相似文献
68.
Md. Abu Sayeed Meagan Kelly Bufano Peng Xu Grace Eckhoff Richelle C. Charles Mohammad Murshid Alam Tania Sultana Md. Rasheduzzaman Rashu Amanda Berger Geoffrey Gonzalez-Escobedo Anjali Mandlik Taufiqur Rahman Bhuiyan Daniel T. Leung Regina C. LaRocque Jason B. Harris Stephen B. Calderwood Firdausi Qadri W. F. Vann Pavol Ková? Edward T. Ryan 《PLoS neglected tropical diseases》2015,9(7)
Background
Vibrio cholerae is the cause of cholera, a severe watery diarrhea. Protection against cholera is serogroup specific. Serogroup specificity is defined by the O-specific polysaccharide (OSP) component of lipopolysaccharide (LPS).Methodology
Here we describe a conjugate vaccine for cholera prepared via squaric acid chemistry from the OSP of V. cholerae O1 Inaba strain PIC018 and a recombinant heavy chain fragment of tetanus toxin (OSP:rTTHc). We assessed a range of vaccine doses based on the OSP content of the vaccine (10-50 μg), vaccine compositions varying by molar loading ratio of OSP to rTTHc (3:1, 5:1, 10:1), effect of an adjuvant, and route of immunization.Principle Findings
Immunized mice developed prominent anti-OSP and anti-TT serum IgG responses, as well as vibriocidal antibody and memory B cell responses following intramuscular or intradermal vaccination. Mice did not develop anti-squarate responses. Intestinal lamina proprial IgA responses targeting OSP occurred following intradermal vaccination. In general, we found comparable immune responses in mice immunized with these variations, although memory B cell and vibriocidal responses were blunted in mice receiving the highest dose of vaccine (50 μg). We found no appreciable change in immune responses when the conjugate vaccine was administered in the presence or absence of immunoadjuvant alum. Administration of OSP:rTTHc resulted in 55% protective efficacy in a mouse survival cholera challenge model.Conclusion
We report development of an Inaba OSP:rTTHc conjugate vaccine that induces memory responses and protection against cholera in mice. Development of an effective cholera conjugate vaccine that induces high level and long-term immune responses against OSP would be beneficial, especially in young children who respond poorly to polysaccharide antigens. 相似文献69.
Zul Kamal Farhat Ullah Muhammad Ayaz Abdul Sadiq Sajjad Ahmad Anwar Zeb Abid Hussain Muhammad Imran 《Biological research》2015,48(1)
Background
Atriplex laciniata L. was investigated for phenolic, flavonoid contents, antioxidant, anticholinesterase activities, in an attempt to explore its effectiveness in Alzheimer’s and other neurological disorders. Plant crude methanolic extract (Al.MeF), subsequent fractions; n-hexane (Al.HxF), chloroform (Al.CfF), ethyl acetate (Al.EaF), aqueous (Al.WtF), Saponins (Al.SPF) and Flavonoids (Al.FLVF) were investigated for DPPH, ABTS and H2O2 free radical scavenging activities. Further these extracts were subjected to acetylcholinesterase (AChE) & butyrylcholinesterase (BChE) inhibitory activities using Ellman’s assay. Phenolic and Flavonoid contents were determined and expressed in mg Gallic acid GAE/g and Rutin RTE/g of samples respectively.Results
In DPPH free radicals scavenging assay, Al.FLVF, Al.SPF and Al.MeF showed highest activity causing 89.41 ± 0.55, 83.37 ± 0.34 and 83.37 ± 0.34% inhibition of free radicals respectively at 1 mg/mL concentration. IC50 for these fractions were 33, 83 and 82 μg/mL respectively. Similarly, plant extracts showed high ABTS scavenging potential, i.e. Al.FLVF (90.34 ± 0.55), Al.CfF (83.42 ± 0.57), Al.MeF (81.49 ± 0.60) with IC50 of 30, 190 and 70 μg/ml respectively. further, H2O2 percent scavenging was highly appraised in Al.FLVF (91.29 ± 0.53, IC50 75), Al.SPF (85.35 ± 0.61, IC50 70) and Al.EaF (83.48 ± 0.67, IC50 270 μg/mL). All fractions exhibited concentration dependent AChE inhibitory activity as; Al.FLVF, 88.31 ± 0.57 (IC50 70 μg/mL), Al.SPF, 84.36 ± 0.64 (IC50 90 μg/mL), Al.MeF, 78.65 ± 0.70 (IC50 280 μg/mL), Al.EaF, 77.45 ± 0.46 (IC50 270 μg/mL) and Al.WtF 72.44 ± 0.58 (IC50 263 μg/mL) at 1 mg/mL. Likewise the percent BChE inhibitory activity was most obvious in Al.FLVF 85.46 ± 0.62 (IC50 100 μg/mL), Al.CfF 83.49 ± 0.46 (IC50 160 μg/mL), Al.MeF 82.68 ± 0.60 (IC50 220 μg/mL) and Al.SPF 80.37 ± 0.54 (IC50 120 μg/mL).Conclusions
These results stipulate that A. laciniata is enriched with phenolic and flavonoid contents that possess significant antioxidant and anticholinestrase effects. This provide pharmacological basis for the presence of compounds that may be effective in Alzheimer’s and other neurological disorders. 相似文献70.
Xiaoming Xu Abhay Gupta Patrick Faustino Pradeep M. Sathe Vilayat A. Sayeed Mansoor A. Khan 《AAPS PharmSciTech》2013,14(3):959-967
To assay the dissolution samples of a drug product from several sources, a simple but broadly applicable analytical method is always desired. For the liquid-filled cyclosporine capsules, while analyzing the dissolution samples, the current compendial and literature HPLC methods have been found to be inadequate to provide satisfactory separation of the drug and the excipient peaks. Accordingly, a suitable isocratic reverse-phase HPLC method was developed for the analysis of dissolution samples of liquid-filled cyclosporine capsules. The method successfully separated the cyclosporine peak from the interfering chromatographic peaks of the excipients. The method was validated according to the ICH and FDA guidelines. Specificity, selectivity, linearity, accuracy, precision, and robustness were established over 3 days as part of method validation. Additionally, the degradation kinetics of cyclosporine in dissolution media was determined. Cyclosporine degradation followed a zero-order kinetics in the dissolution media with the respective rate constants of −3.5, −1.5, and −0.3%/h at 37°C, 25°C, and 10°C.Key words: cyclosporine, degradation, dissolution, HPLC, liquid-filled capsules 相似文献