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1.
Effects of temperature on the inhibitory junction potential (IJP) mediated via intramural ‘purinergic’ nerves were studied. The IJP area and the membrane conductance of the smooth muscle cell hardly changed between 16 and 28°C. The amplitude, stimulus-top time and decay time of the IJP however, changed linearly with temperature (with +0.5 mV, ?0.2 sec and ?0.3 sec per °C respectively). A temperature dependent synchronization of transmitter release can account for the observed phenomena.  相似文献   

2.
Metal-containing granules in the mucus trails of the marine gastropod Littorina littorea from nine sites in north-east England were analysed for elemental composition by X-ray microanalysis and characterised relative to a putative gradient of pollution. Overall granule density varied significantly between sites, means of 6.5-17.0 per field of view (2688 microm2). Most granules found (64%) were poly-metal of a wide variety of compositions, but could be classified as Si+X, Mg+X, S+X, Na+X, P+Ca, P+Al, where X indicates any other combination of elements. Si+Al+X accounted for 61% of the poly-metal granules found and was considered to be contamination from the beach substratum. In single-metal granule form only Ca, Si, Fe, Ti, Al and Na were found. The most common single-metal granule at each site was of Ca, except at two sites, where the most common single-metal granule was of Si. The densities of these granule types varied between sites but differences were found to be significant only in the case of Si granules. Across all sites, single-metal granules of Si (mean = 2.49 microm +/- 1.44 SD, n = 141) and Ca (2.22 microm +/- 1.08 SD, n = 147) were significantly larger than granules of Fe (1.74 microm +/- 0.95 SD, n = 63) and Ti (1.24 microm +/- 0.52 SD, n = 18). The range of sizes was large: Ca (0.5-6 microm), Si (0.5-10 microm), Fe (0.3-4.1 microm), Ti (0.5-2.5 microm). Between the sites there were significant differences in the size of Fe and Si granules but not Ca or Ti granules. Despite these variations in granule type and size, there was no evidence of a relationship with pollution and consequently a detoxifying function of the mucus trail in metal polluted environments is not apparent.  相似文献   

3.
曹萌  曹鹏  张双全  程莹  颜怀江 《药学学报》2012,(10):1336-1340
通过注射人B淋巴细胞激活因子(hsBAFF)的全人源抗体scFv-Fc,观察其对hsBAFF引发的B细胞增殖与分化的拮抗作用。将ICR小鼠随机分为对照组、hsBAFF(1 mg.kg 1)组、hsBAFF(1 mg.kg 1)+Ab(1mg.kg 1)组、hsBAFF(1 mg.kg 1)+Ab(2 mg.kg 1)组、hsBAFF(1 mg.kg 1)+human IgG(1 mg.kg 1)组和hsBAFF(1 mg.kg 1)+human IgG(2 mg.kg 1)组。采用MTT、ELISA及流式细胞检测,分别考察各组小鼠脾脏指数、脾脏B淋巴细胞增殖活性及成熟分化和血浆中抗体水平。结果表明:通过注射scFv-Fc有效抑制了hsBAFF引起的脾脏B细胞增殖以及血浆中抗体水平的升高;同时scFv-Fc也显著抑制了hsBAFF引发的B细胞成熟分化,具有潜在的抗体药物开发价值。  相似文献   

4.
Pulmonary complications of sulfur mustard (SM) range from mild respiratory symptoms to even severe bronchial stenosis. In the present study, the protective effect of vitamin E on tracheal responsiveness (TR) and lung inflammation of SM-exposed guinea pigs were examined. Guinea pigs were exposed to ethanol (control group), 40?mg/m(3) inhaled SM and ethanol vehicle (sulfur mustard exposed (SME) group), SME treated with vitamin E (SME + E), SME with dexamethasone (SME + D) and both drugs (SME + E + D), (n?=?8 for each group). TR to methacholine, total and differential white blood cell (WBC) count of lung lavage and serum cytokines were evaluated 14 days post-exposure. TR, WBC, interleukin 4 (IL-4), interferon gamma (INF-γ), eosinophil, and monocyte levels in SME guinea pigs were significantly higher, but lymphocyte was lower than those of controls (P?相似文献   

5.
Reactivity of benzene oxide (BO), a reactive metabolite of benzene, was studied in model reactions with biologically relevant S- and N-nucleophiles by LC-ESI-MS. Reaction with N-acetylcysteine (NAC) in aqueous buffer solutions gave N-acetyl-S-(6-hydroxycyclohexa-2,4-dien-1-yl)cysteine (pre-phenylmercapturic acid, PPhMA), which was easily dehydrated in acidic solutions to phenylmercapturic acid (PhMA). The yield of PPhMA + PhMA increased exponentially with pH up to 11% in the pH range from 5.5 to 11.4. Primary 6-hydroxycyclohexa-2,4-dien-1-yl (HC) adducts were detected also in reactions of purine nucleosides and nucleotides under physiological conditions. After a vigorous acidic hydrolysis, all HC adducts were converted to corresponding phenyl purines, which were identified as 7-phenylguanine (7-PhG), 3-phenyladenine (3-PhA) and N(6)-phenyladenine (6-PhA). The yield of 7-PhG amounted to 14?±?5 and 16?±?7?ppm for 2'-deoxyguanosine and 2'-deoxyguanosine-5'-monophosphate, respectively, that of 6-PhA was 500?±?70 and 455?±?75?ppm with 2'-deoxyadenosine and 2'-deoxyadenosine-5'-phosphate, respectively, with only traces of 3-PhA. Reactions with the DNA followed by acidic hydrolysis yielded 26?±?11?ppm (mean ± SD; n?=?9) of 7-PhG as the sole adduct detected. In contrast to the reactions with S-nucleophiles, the reactivity of BO with nucleophilic sites in the DNA is very low and can therefore hardly account for a significant DNA damage caused by benzene.  相似文献   

6.
目的:探讨不同病因的慢性肝病( CLD)患者肝组织中白细胞介素?10( IL?10)的表达及其与肝组织炎症和纤维化的关系。方法收集93例CLD患者及23例正常对照肝组织石蜡标本,免疫组织化学方法检测肝组织中IL?10的表达。结果不同病因的CLD患者肝组织中肝小叶及汇管区IL?10的表达均较正常对照明显增高( P<0.01)。随着肝脏炎症分级( G)的增高,CLD患者肝组织内肝小叶及汇管区IL?10的表达逐渐增强,差异有统计学意义。随着肝脏纤维化程度分期( S)的增高,CLD患者肝组织内肝小叶及汇管区IL?10的表达亦逐渐增高,差异有统计学意义。结论 IL?10可能参与CLD患者肝脏的炎症和纤维化的发生。  相似文献   

7.
1. The presence of specific binding sites and the contractile activity of the novel peptide, endothelin have been investigated in rat trachea. 2. Endothelin (10(-8)-10(-5) M) induced long-lasting contraction of rat tracheal rings superfused with Krebs solution (EC50 5.4 x 10(-6) M). Contractions of the tissue to 10(-6) M endothelin were attenuated in Ca2+-free medium containing 0.1 mM EGTA but unaffected by nicardipine (10(-7) M). 3. After equilibration in Ca2+-free medium (without EGTA) a return to normal Ca2+ concentrations (2.5 mM), 30 min or 60 min following endothelin (10(-6) M), produced a sustained contraction of the tissue. 4. Specific binding sites for endothelin were identified on rat tracheal smooth muscle (KD 1.34 x 10(-10) M, maximal binding 1.2 fmol mm-2). Specific binding sites were also identified on nerve trunks. Endothelin binding was unaffected by co-incubation with nicardipine (10(-7) M) or verapamil (10(-7) M). 5. The discrepancy between the apparent KD for endothelin binding and the EC50 for endothelin-induced contraction suggests that the endothelin binding sites identified in this study may not be associated with the receptors mediating contraction. 6. These results indicate that endothelin binding sites are present on tracheal smooth muscle. The mechanism of endothelin-induced contraction, whilst being dependent on extracellular calcium, does not appear to involve binding to the dihydropyridine- or verapamil-sensitive sites on the voltage-dependent Ca2+ channel. Its long duration of action may be associated with a sustained increase in Ca2+ permeability.  相似文献   

8.
The effects of various divalent cations on the Ca2+-binding sites of calmodulin were observed by 400 MHz 1H-NMR. The first and second Ca ions bound to sites III and IV (stage I), while the third and fourth bound to sites I and II (stage II). Zn2+, Hg2+ and Mn2+ bound to the first and third Ca2+-binding sites, but not to the second and fourth. Zn2+, Hg2+ or Mn2+ could bind to the first Ca2+-binding site by themselves and could bind to the third site only after the conformational change which occurs when two Ca2+ ions bind to first and second sites. Although Mg2+ did not bind to the first, second or fourth Ca2+-binding sites, it did bind to the third site. These results suggest that the order of Ca2+-binding and the order of affinity of the binding sites are not parallel; the first and third Ca2+-binding sites have high Ca2+-affinity, with the third being highest, whereas the second and fourth sites are of lower affinity. Also, we suggest in this study that the first and second sites are exposed on the surface of the protein, while the third and fourth ones are buried in the interior; the latter are exposed by the conformational change accompanying the binding of calcium to the first and second sites. Furthermore, the form of the interface by which calmodulin binds to target enzyme was altered slowly and continuously by the calcium-induced conformational change. The target enzyme was chosen and bound selectively to calmodulin among various enzymes by each interface form.  相似文献   

9.
SUMMARY

Objective: The purpose of this double-blind, randomised, placebo-controlled study was to assess the effects of intramuscular and subcutaneous PDRN in favouring the wound-healing process in donor sites of grafts.

Methods: 26 adult patients of both sexes (15 males and 11 females; mean age: 68.2?±?16.1 years) subjected to skin explants due to plastic surgery were eligible to participate in this double-blind, placebo-controlled study. Patients were randomly allocated into the PDRN group (14 subjects) or the placebo group (12 subjects). PDRN (5625?mg/vial) or placebo were administered by the intramuscular route once daily, associated with a subcutaneous administration of the same dosage form (2 vials every 3 days) for 10 consecutive days.

The primary end point for efficacy was the evolution of wound healing in donor sites, which was evaluated measuring wound surface area and then calculating percentage re-epithelialisation. Secondary end points were local subjective symptoms, such as pain and itching, and objective signs such as perilesional erythema and blisters. Signs and symptoms were quantified through an analogue scale.

Results: At day 7 of the treatment period, the difference in percentage of re-epithelialisation was statistically significant (p?<?0.008) in; favour of the PDRN group. At the end of the observational period, between-group comparison demonstrated that patients treated: with PDRN had a more prompt trophic effect.

No adverse events were reported during the trial.

Conclusions: The findings of our study demonstrated that PDRN is able to modify positively the repair processes in donor sites of autologous skin grafts. This could improve the clinical outcome and decrease the need for additional therapies or hospital stay.  相似文献   

10.
CPU 86017, a derivative of berberine, was administered to rats in which acute and chronic heart failure was induced by left coronary artery ligation for 3 h and 8 weeks, respectively. The rats were divided into the following groups: sham operation, coronary artery ligation (CAL), CAL+ CPU 86017 (80?40 and 20 mg/kg, ig) and CAL+ captopril (60 mg/kg, ig). In the acute model, the systolic parameters of LVSP and LV+dp/dtmax as well as the diastolic parameters of LVEDP and LV‐dp/dtmin improved significantly on pretreatment of CPU 86017 (80 mg/kg). Reductions in elevated serum CPK?LDH?MDA?GOT?GPT?infarcted area and blood viscosity were also significant (P < 0.01). In the chronic model, CPU 86017 (80 mg/kg) preserved the systolic parameters of LVSP and LV+dp/dtmax and the diastolic function of the LVEDP and LV‐dp/dtmin. CPU 86017 completely suppressed elevated plasma ANP and ET‐1, serum and tissue iNOS?NO and MDA, whereas the decreased SOD was improved. CPU 86017 and captopril improved cardiac failure performance and regressed cardiac remodeling in CHF by reducing tissue weight index: lung weight/body weight (BW), right ventricular weight/BW, and left ventricular weight/BW. CPU 86017 exerted beneficial actions in cardiac performance in models of both acute and chronic heart failure, mainly by suppressing ET‐1, iNOS, and oxidative stress in infarcted tissue. Drug Dev Res 63:22–32, 2004. © 2004 Wiley‐Liss, Inc.  相似文献   

11.
X Xu  Q Liu 《Toxicon》2001,39(9):1359-1365
Anticoagulation factor II (ACF II) from the venom of Agkistrodon acutus has been identified as a binding protein to activated bovine coagulation factor X (FXa) by the method of polyacrylamide gel electrophoresis and high performance liquid chromatography. This protein formed a 1:1 complex with FXa in the presence of Ca2+ ions, and the maximal binding of ACF II to FXa occurred at the concentration of Ca2+ ions of about 1mM. The binding of Ca2+ ions to ACF II was analyzed by equilibrium dialysis and two Ca2+-binding sites with different affinities were identified. At pH 8.0, the apparent association constant K1 and K2 values for these sites were (1.1+/-0.3)x10(5) M(-1) and (1.7+/-0.4)x10(4) M(-1) (mean+/-SE, n=4), respectively. It was evident from the observation of Ca2+-induced changes in the intrinsic fluorescence of ACF II that ACF II underwent a conformational change upon binding of Ca2+ ions. The occupation of both Ca2+-binding sites in ACF II requires a concentration of Ca2+ ions of about 1mM, which is equal to the effective concentration of Ca2+ ions required for maximal binding of ACF II to FXa, and for the maximal Ca2+-induced enhancement of emission fluorescence of ACF II. It can be deduced from these results that the occupation of both Ca2+-binding sites in ACF II with Ca2+ ions and subsequent conformational rearrangement should be essential for its recognition of Ca2+-mediated conformational changes of FXa.  相似文献   

12.
The influence of buffer and two different albumin preparations on the albumin-quinidine interaction was investigated. Human serum albumin was prepared by either alcohol fractionation or ultracentrifugation with subsequent gel filtration. The interaction between albumin and quinidine was determined by equilibrium dialysis. It was inhibited by halide ions and consequently different binding parameters were found to be valid for the complex in sodium phosphate and in Krebs-Ringer phosphate buffer. The influence of Ca2+, Mg2+ and SO2?4 in physiological amounts was negligible. The albumin obtained by alcohol fractionation possessed one binding site for quinidine, while the albumin isolated by ultracentrifugation with subsequent gel filtration possessed two binding sites when tested in a Krebs-Ringer phosphate buffer. In sodium phosphate buffer both albumin preparations had two independent binding sites, and showed essentially identical binding parameters.  相似文献   

13.
This study was conducted to investigate the prophylactic effects of lycopene (LC) and ellagic acid (EA) on 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD)-induced testicular and spermatozoal toxicity. These toxicological changes are associated with the oxidative stress and apoptosis in male rats. Forty-eight male rats were allocated to one of six groups of 8 rats each: control, LC, EA, TCDD, TCDD+LC, and TCDD+EA. The control group was treated with 0.5?mL/rat slightly alkaline solution+0.5?mL/rat corn oil every other day. The LC group was treated with 0.5?mL/rat slightly alkaline solution+0.5?mL/rat corn oil containing 10?mg/kg of LC every other day. The EA group received 0.5?mL/rat corn oil+0.5?mL/rat slightly alkaline solution containing 2?mg/kg of EA every other day. The TCDD group received 0.5?mL/rat corn oil containing 100?ng/kg/day of TCDD+0.5?mL/rat slightly alkaline solution. The TCDD+LC group was treated with 0.5?mL/rat TCDD+0.5?mL/rat LC. The TCDD+EA group was treated with 0.5?mL/rat TCDD+0.5?mL/rat EA. All treatments were made by gavage, and the experimental period was maintained during 8 weeks. Sperm motility, concentration, and abnormal sperm rate in epididymal tissue, testicular tissue lipid peroxidation (LPO), antioxidant enzyme activity, histopathological changes, and apoptosis (i.e., Bax and Bcl-2 proteins) were determined. TCDD exposure resulted in significant decreases in sperm motility, concentration, testicular superoxide dismutase activity, germinal cell-layer thickness, Johnsen's testicular score, and significant increases in abnormal sperm rate, testicular malondialdehyde, glutathione levels, Bax-positive staining, and Bax-positive apoptotic cell score, along with some testicular histopathological lesions. TCDD treatment did not affect significantly catalase activity. However, combined treatment with LC or EA, in addition to TCDD, prevented the development of TCDD-induced damages in sperm quality, testicular histology, and LPO. Improvements in testicular apoptosis after the administration of LC and EA to TCDD-treated rats were minimal, but not statistically significant. TCDD-induced lipid peroxidation leads to functional and structural damages, as well as apoptosis, in spermatogenic cells of rats. Both LC and EA protected against the development of these effects.  相似文献   

14.
Abstract: Taenia coli was used to study the property of binding of Cd2+. The Scatchard plots of cadmium uptake showed that two qualitative Cd2+ binding sites (high and low affinity binding sites) exist in taenia coli. Decrease in Ca2+ concentration in the medium did increase the cadmium binding. The Scatchard analysis of Cd2+ binding in taenia coli at 4° indicated a single class of binding sites (only high affinity binding sites). These findings suggest that the greater number of high affinity Cd2+ binding sites in taenia coli may relate to the binding to cell membrane. Further, it was postulated that some of low affinity binding sites in taenia coli may reflect intracellular accumulation, indicating the action on the contractile system.  相似文献   

15.
【摘要】目的 观察甲状腺结节(TN)患者血清甲状腺激素的水平并探讨其与TN良恶性的关系。方法随机抽取TN患者245例,根据甲状腺相关抗体水平及术后病理结果分为结节性甲状腺肿组(NG组)、甲状腺腺瘤组(TA 组)和甲状腺癌组(TC组),TC组进一步分为甲状腺相关抗体升高组(TC-Ab +组)和甲状腺相关抗体正常组(TC-Ab - 组)。检测患者术前血清游离T3(FT3)、游离T4(FT4)和促甲状腺激素(TSH)。分析各组患者甲状腺激素水平的差异。结果以NG组、TA组和TC组3组比较时,TC组血清TSH水平高于其他2组(P<0.05)。TC-Ab +组血清FT3水平低于NG组和TC-Ab -组,FT4水平低于NG组,TSH水平明显高于其他各组(P<0.05)。结论部分TC患者出现血清TSH水平升高,其原因可能是由于伴有自身免疫性甲状腺炎并继发了甲状腺功能减退。血清TSH水平升高未必是TC的固有特征。  相似文献   

16.
T. Kubo  Y. Misu 《Neuropharmacology》1981,20(5):521-524
Microinjection of nicotine (0.1 μg) into several sites in the vicinity of the area postrema of the rat elicited hypertension followed by hypotension and bradycardia. The highest sensitivity was found at a site just caudal to the area postrema. Cardiovascular effects produced following injection of nicotine (0.1 μg) into the nicotine-sensitive site were sensitive to hexamethonium (2 μg) but resistant to atropine (2 μg), similarly injected. Intravenous administration of methylatropine (1 mg/kg) descreased the bradycardic response to nicotine but did not affect the blood pressure responses. These data may indicate that there are nicotinic receptors responsible for cardiovascular effects in specific sites surrounding the area postrema.  相似文献   

17.
Tetrahydroaminoacridine (THA; Tacrine) is a potent, non-competitive inhibitor of the neuronal enzyme acetylcholinesterase (AChE) and, consequently, a potent modulator of central cholinergic function. The compound reportedly improves the memory deficits of Alzheimer's dementia. Experiments were run with purified bovine caudate AChE to examine the kinetic properties of THA-AChE interaction within the scheme of multiple binding sites on the enzyme and a proposed "map" of the enzyme surface. The kinetic analyses were also designed to determine whether chemical modification of peripheral anionic sites on AChE may provide insight into mechanism for selective pharmacological alteration of cholinergic function in the brain. The studies demonstrated that THA is a reversible, non-competitive inhibitor with an I50 of 160 +/- 10 nM. THA bound primarily at a hydrophobic area outside of the catalytic sites, and binding of THA enhanced the effect of Ca2+ binding to a separate group of "accelerator" sites. Experiments with Al3+ demonstrated non-competitive inhibitor effects that were additive with THA inhibition and consistent with a model suggesting interaction of THA and Al3+ at the enzyme surface. In vitro enzyme inhibition studies also provide evidence for THA "protection" of the catalytic site against inhibition by the high-affinity phosphorylating agent, DFP (isoflurophate).  相似文献   

18.
Investigations on asymmetries showed that deviations from perfect bilateral symmetry are interpreted as environmental changes inducing developmental instability. Since morphological abnormalities increase with pollution, deformations may be considered indicators of the organism exposition to pollution. Therefore, the onset of asymmetry in otherwise normally symmetrical traits has been used as a measure of some stresses as well. In this context, we studied how marine pollution affects the valve morphological alterations in the mussel Mytilus galloprovincialis. We used 180 specimens (30 per site) from the aquaculture area of Goro (River Po delta, northern Adriatic Sea), translocated, and released within 50?×?50?×?50?cm cages in five sites: two disturbed and one undisturbed near Naples (eastern Tyrrhenian Sea), and one disturbed and one undisturbed near Siracusa (western Ionian Sea). Disturbed sites were stressed by heavy industrialization and heavy tankers traffic of crude and refined oil, and were defined basing on sediment contamination. In particular, by the cone-beam computed tomography we obtained 3D virtual valve surfaces to be analyzed by the geometric morphometric techniques. Specifically, we focused the levels of the shell shape fluctuating asymmetry in relation to the degrees of marine pollution in different sites of the Tyrrhenian Sea. The Mahalanobis distances (interpreted as proxy of the individual shape asymmetry deviation from the mean asymmetry) significantly regressed with the sediment contamination gradient. Indeed, although the left–right differences were normally distributed in each studied site, the individual asymmetry scores (IAS) significantly varied amongst the investigated sites. IAS showed higher values in disturbed areas than those of undisturbed ones in both Tyrrhenian and Ionian Sea. Our results are consistent with past studies on molluscans and other taxa, demonstrating some detrimental effects of chemicals on organisms, although the investigated morphological marker did not discriminate the real disturbance source. Our findings indicate that the mussels act as a prognostic tool for sea pollution levels driving detrimental effects on benthic community.  相似文献   

19.
20.
To assess the genotoxicity of nicotine, its DNA-damaging effect on Caenorhabditis elegans cells was tested with the alkaline single-cell microgel electrophoresis (comet) assay. The degree of DNA migration (a measure of possible DNA single-strand breaks, alkali-labile sites, and incomplete excision repair sites) was expressed as the head DNA%, tail length, and Olive tail moment. Large differences were found between experimental variants: 0, 1, 10, and 100?μM (-)-nicotine. At concentrations of 1 and 10?μM, no damages were detected by the comet assay, and the Olive tail moment and tail length were significantly lower than in the control (P?<?0.001). The highest head DNA% and the lowest tail length and Olive tail moment were observed in the presence of 1?μM of nicotine. At 100?μM of nicotine, a significant increase (P?<?0.001) was observed in Olive tail moment and tail length (up to 2.7- and 3-fold, respectively, compared to the control). The results are consistent with the lowest head DNA% among the three tested variants. This study demonstrated that nicotine treatment had dose-dependent effects on the level of DNA damage. Generally, a high dose of nicotine (100?μM) is genotoxic, while a reasonably low concentration has a protective effect. The possible participation of reactive oxygen species in the DNA-damaging potential of nicotine in C. elegans is discussed.  相似文献   

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