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1.
Cysteinyl leukotrienes such as LTE4 are produced by mast cells, neutrophils, eosinophils, and macrophages. LTE4 levels have not been reported in systemic mastocytosis, a disorder with a large increase in mast cell numbers. Urinary LTE4 from patients referred for symptoms potentially due to mast cell degranulation or systemic mastocytosis was measured by a commercial cysteinyl leukotriene enzyme immunoassay kit. The diagnosis of systemic mastocytosis was established using current World Health Organization criteria. Compared with a control group of patients with various potential mast cell–related symptoms (e.g., “spells”), patients with systemic mastocytosis had a significant (P = .01) increase in urinary LTE4 excretion, whether expressed as LTE4 ng/g creatinine or as LTE4 ng/24 h. There was a moderate correlation of LTE4 ng/24 h with excretion of N-methyl histamine and serum tryptase but not with urinary 11β-prostaglandin F (11β-PGF) excretion. LTE4 excretion is increased in patients with systemic mastocytosis and potentially contributes to clinical symptoms.  相似文献   

2.
The metabolic transformation of exogenous prostaglandin D2 was investigated in isolated perfused rat lung. Dose-dependent formation (2–150 ng) of 9α,11β-prostaglandin F2, corresponding to about 0.1% of the perfused dose of prostaglandinD2, was observed by specific radioimmunoassay both in the perfusate and in lung tissue after a 5-min perfusion. To investigate the reason for this low conversion ratio, we analyzed the metabolites of tritium-labeled 9α,11β-prostaglandin F2 and prostaglandin D2 by boric acid-impregnated TLC and HPLC. By 5 min after the start of perfusion, 9α,11β-prostaglandin F2 disappeared completely from the perfusate and the major product formed remained unchanged during the remainder of the 30-min perfusion. The major product was separated by TLC and identified as 13,14-dihydro-15-keto-9α,11β-prostaglandin F2 by GC/MS. In contrast, pulmonary breakdown of prostaglandin D2 was slow and two major metabolites in the perfusate increased with time, each representing 56% and 11% of the total radioactivity at the end of the perfusion. The major product (56%) was identified as 13,14-dihydro-15-ketoprostaglandin D2 and the minor one (11%) was tentatively identified as 13,14-dihydro-15-keto-9α,11β-prostaglandin F2 based on the results from radioimmunoassays, TLC, HPLC, and the time course of pulmonary breakdown. These results demonstrate that the metabolism of prostaglandin D2 in rat lung involves at least two pathways, one by 15-hydroxyprostaglandin dehydrogenase and the other by 11-ketoreductase, and that the 9α,11β-prostaglandin F2 formed is rapidly metabolized to 13,14-dihydro-15-keto-9α,11β-prostaglandin F2.  相似文献   

3.
BackgroundSystemic reactions are related to the pathogenesis of Aspirin Exacerbated Respiratory Disease (AERD). With this work we wanted to study the changes in the systemic levels of inflammatory mediators in both baseline and after oral aspirin challenge in patients with and without AERD.MethodsPatients with nasal polyposis and asthma with AERD (n = 20) and without (n = 18) were orally challenged with aspirin in a single-blind placebo controlled study. Serum samples and urine were collected before and 6 h after placebo and aspirin oral challenges. Serum levels of inflammatory mediators were assayed by using the Luminex technology and ELISA. The concentrations of 9-alpha, 11-beta prostaglandin F2, and leukotriene E4 (uLTE4) were measured in urine samples by ELISA. The expression of T-cell surface markers was analyzed in peripheral blood mononuclear cells isolated before and after the challenges.ResultsAERD patients showed significantly higher baseline levels of s-IL-5R-alpha, uLTE4 and percentage of CD4+CD25+CD127pos and CD4+CD45RACD45RO+ but decreased levels of TGF-β1 and number of CD4+CD25+CD127neg cells. Aspirin challenge induced the release of uLTE4, IL-6 and increased the number of CD4+CD45RACD45RO+ memory T-cells only in AERD patients but failed to reduce the levels of sCD40L as observed in non-AERD subjects. Further, IL-8 and sIL-5R-alpha levels directly correlated with the PD20ASA and the effects of aspirin on IL-6 and number of memory T-cells was more pronounced in subjects showing more strong reaction (bronchial and nasal).ConclusionsAERD patients have a differential baseline inflammatory pattern that supports the role inflammation as underlying mechanism of the disease. Systemic response to oral aspirin challenge was related to an increase in serum IL-6 and the number of circulating memory T-cells in AERD patients.  相似文献   

4.
AimTo analyse the possible relationship between the EQD2(α/β=3Gy) at 2 cm3 of the vagina and late toxicity in vaginal-cuff-brachytherapy (VBT) after external-beam-irradiation (EBRT) for postoperative endometrial carcinoma (EC).Materials and methodsFrom 2014 to 2016, 62 postoperative EC patients were treated with EBRT + VBT. The median EBRT dose was 45 Gy (44 Gy–50.4 Gy). VBT involved a single 7 Gy dose. Toxicity was prospectively evaluated using the RTOG score for the rectum and bladder and the objective LENT-SOMA criteria for the vagina. EQD2(α/β = 3Gy) at 2 cm3 of the most exposed part of the vagina was calculated by the sum of the EBRT + VBT dose. Statistics: Boxplot, Student’s t and Chi-square tests and ROC curves.ResultsMean follow-up: 39.2 months (15–68). Late toxicity: bladder:0 patient; rectum:2 patients-G1; Vagina: 26 patients-17G1, 9G2; median EQD2(α/β=3Gy) at 2 cm3 in G0-G1 patients was 70.4 Gy(SD2.36), being 72.5 Gy(SD2.94) for G2p. The boxplot suggested a cut-point identifying the absence of G2: 100 % of G2p received >68 Gy, ROC curves showed an area under the curve of 0.72 (sensitivity of 1 and specificity of 0.15).ConclusionsDoses >68 Gy EQD2(α/β=3Gy) at 2 cm3 to the most exposed area of the vagina were associated with late G2 vaginal toxicity in postoperative EC patients treated with EBRT + VBT suggesting a very good dose limit to eliminate the risk of G2 late toxicity. The specificity obtained indicates the need for prospective analyses.  相似文献   

5.
The present study demonstrates the anti-tumor effects of combined supplementations of dietary fish oil (Maxepa) and 1α,25-dihydroxyvitamin D3 (vitamin D3) on 7,12-dimethylbenz(α)anthracene (DMBA)-induced rat mammary carcinogenesis. Female Sprague–Dawley rats at 50 days of age were treated with 7,12-dimethylbenz(α)anthracene (DMBA; 0.5 mg/100 g body weight) by a single tail vein injection in an oil emulsion. Both fish oil (rich in EPA and DHA) and vitamin D3 were administered orally at a dose of 0.5 ml/day/rat and 0.3 μg/100 μL propylene glycol twice a week respectively and continued to 35 weeks after DMBA administration. Fish oil in combination with vitamin D3 resulted in a significant reduction in incidence, multiplicity and volume of mammary tumors. These supplementation also inhibited DMBA-induced mammary 7-methylguanine DNA adducts formation, which was measured by HPLC-fluorescence assay (at four sequential time points; ANOVA, F = 42.56, P < 0.0001). Immunohistochemical analysis revealed that the effect of fish oil and vitamin D3 occurred through suppression of cell proliferation (BrdU-LI: P < 0.0001). Fish oil and vitamin D3 together also reduced the mRNA expression of iNOS (84%, P < 0.05). In view of their natural availability, non-toxicity and acceptability; combined supplementation of fish oil and vitamin D3 might be effective for chemoprevention of mammary carcinogenesis.  相似文献   

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Microalbuminuria is a predictor of adverse outcome in hypertension. We evaluated in vivo platelet activation, by urinary 11-dehydrothromboxane (TX)B2 and plasma P-selectin, in hypertensives with or without microalbuminuria, and its possible association with oxidative stress, by urinary 8-iso-prostaglandin (PG)F and endothelial dysfunction. Sixty essential hypertensive patients, with (n = 30) or without (n = 30) microalbuminuria, and 30 controls were studied. Endothelial function was assessed by nitric oxide products, intercellular adhesion molecule (ICAM)-1, and asymmetric dimethylarginine (ADMA) levels. Urinary 11-dehydro-TXB2 excretion was higher in microalbuminuric (median 805 pg/mg creatinine) compared to nonmicroalbuminuric patients or controls (414 and 291 pg/mg, respectively; P < 0.0001). Plasma P-selectin was significantly higher in patients with microalbuminuria (median 136 ng/ml) as compared to those without microalbuminuria or controls (85 and 65 ng/ml; P < 0.0001). Urinary 8-iso-PGF excretion was also enhanced in microalbuminuric (median 279 pg/mg creatinine) compared to nonmicroalbuminuric patients or controls (157 and 146 pg/mg, respectively; P < 0.0001). A significant impairment in endothelial function was found in microalbuminuric patients, with decreased nitric oxide and increased ICAM-1 and ADMA levels. Multivariate regression analysis showed that urinary 8-iso-PGF excretion (beta = 0.49; P < 0.0001) and microalbuminuria (beta = 0.36; P < 0.001) were independently related to 11-dehydro-TXB2 in hypertensives. Vitamin E supplementation (900 mg daily for 1 month) in 10 hypertensives with microalbuminuria was associated with normalization in median 11-dehydro-TXB2 and 8-iso-PGF. We conclude that lipid peroxidation is a major determinant of persistent platelet activation in hypertensive patients with microalbuminuria.  相似文献   

9.
AimTo compare the radiotherapy technique used in a randomised trial with VMAT and an in-house technique for prostate cancer.BackgroundTechniques are evolving with volumetric modulated arc therapy (VMAT) commonly used. The CHHiP trial used a 3 PTV forward planned IMRT technique (FP_CH). Our centre has adopted a simpler two PTV technique with locally calculated margins.Materials and methods25 patients treated with FP_CH to 60 Gy in 20 fractions were re-planned with VMAT (VMAT_CH) and a two PTV protocol (VMAT_60/52 and VMAT_60/48). Target coverage, conformity index (CI), homogeneity index (HI), monitor units (MU) and dose to the rectum, bladder, hips and penile bulb were compared.ResultsPTV coverage was high for all techniques. VMAT_CH plans had better CI than FP_CH (p   0.05). VMAT_60/52/48 plans had better CI than VMAT_CH. FP_CH had better HI and fewer MU than VMAT (p   0.05). More favourable rectum doses were found for VMAT _CH than FP_CH (V48.6, V52.8, V57, p   0.05) with less difference for bladder (p   0.05). Comparing VMAT_CH to VMAT_60/52/48 showed little differences for the bladder and rectum but VMAT_CH had larger penile bulb doses (V40.8, V48.6, mean, D2, p   0.05). Femoral head doses (V40.8) were similarly low for all techniques (p = ≥ 0.05).ConclusionVMAT produced more conformal plans with smaller rectum doses compared to FP_CH albeit worse HI and more MU. VMAT_60/52 and VMAT_60/48 plans had similar rectal and bladder doses to VMAT_CH but better CI and penile bulb doses which may reduce toxicity.  相似文献   

10.
AimsRecently, we demonstrated that peripheral antinociception induced by δ opioid receptor is dependent of Ca2 +-activated Cl? channels (CaCCs). Because opioid and cannabinoid receptors share some common mechanisms of action, our objective was to identify a possible relationship between CaCCs and the endocannabinoid system.Main methodsTo induce hyperalgesia, rat paws were treated with intraplantar prostaglandin E2 (PGE2, 2 μg). Nociceptive thresholds to pressure (grams) were measured using an algesimetric apparatus 3 h following injection. Probabilities were calculated using ANOVA/Bonferroni's test, and values that were less than 5% were considered to be statistically significant.Key findingsAdministration of the cannabinoid agonist CB1 anandamide (12.5, 25 and 50 μg/paw) and the cannabinoid agonist CB2 PEA (5, 10 and 20 μg/paw) decreased the PGE2-induced hyperalgesia in a dose-dependent manner. The possibility of the higher doses of anandamide (50 μg) and PEA (20 μg) having a central or systemic effect was excluded because the administration of the drug into the contralateral paw did not elicit antinociception in the right paw. As expected, the antinociceptive effects induced by anandamide and PEA were blocked by the CB1 and CB2 receptor antagonists AM251 and AM630, respectively. The peripheral antinociception was induced by anandamide but not PEA and was dose-dependently inhibited by the CaCC blocker niflumic acid (8, 16 and 32 μg).SignificanceThese results provide the first evidence for the involvement of CaCCs in the peripheral antinociception induced by activation of the CB1 cannabinoid receptor.  相似文献   

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Six cycloartane-type triterpene glycosides were isolated from Astragalus icmadophilus along with two known cycloartane-type glycosides, five known oleanane-type triterpene glycosides and one known flavonol glycoside. The structures of the six compounds were established as 3-O-[α-L-arabinopyranosyl-(1  2)-O-3-acetoxy-α-L-arabinopyranosyl]-6-O-β-D-glucopyranosyl-3β,6α,16β,24(S),25-pentahydroxycycloartane, 3-O-[α-L-rhamnopyranosyl-(1  2)-O-α-L-arabinopyranosyl-(1  2)-O-β-D-xylopyranosyl]-6-O-β-D-glucopyranosyl-3β,6α,16β,24(S),25-pentahydroxy cycloartane, 3-O-[α-L-arabinopyranosyl-(1  2)-O-3,4-diacetoxy-α-L-arabinopyranosyl]-6-O-β-D-glucopyranosyl-3β,6α,16β,24(S),25-pentahydroxycycloartane, 3-O-[α-L-arabinopyranosyl-(1  2)-O-3-acetoxy-α-L-arabinopyranosyl]-6-O-β-D-glucopyranosyl-3β,6α,16β,25-tetrahydroxy-20(R),24(S)-epoxycycloartane, 3-O-[α-L-arabinopyranosyl-(1  2)-O-β-D-xylopyranosyl]-6-O-β-D-glucopyranosyl-3β,6α,16β,24α-tetrahydroxy-20(R),25-epoxycycloartane, 3-O-[α-L-rhamnopyranosyl-(1  2)-O-α-L-arabinopyranosyl-(1  2)-O-β-D-xylopyranosyl]-6-O-β-D-glucopyranosyl-3β,6α,16β,24α-tetrahydroxy-20(R),25-epoxycycloartane by the extensive use of 1D- and 2D-NMR experiments along with ESIMS and HRMS analysis.The first four compounds are cyclocanthogenin and cycloastragenol glycosides, whereas the last two are based on cyclocephalogenin as aglycone, more unusual in the plant kingdom, so far reported only from Astragalus spp.  相似文献   

12.
Two new dammarane saponins, 2α,3β,12β-trihydroxydammar-20(22),24-diene-3-O-[β-d-glucopyranoxyl(1→2)-β-d-6″-O-acetylglucopyranoside (1, namely damulin C) and 2α,3β,12β-trihydroxydammar-20(21),24-diene-3-O-[β-d-glucopyranoxyl(1→2)-β-d-6″-O-acetylglucopyranoside (2, namely damulin D), were isolated from the ethanol extract of Gynostemma pentaphyllum, which had been heat processed by steaming at 125 °C. The NMR spectroscopic data of the novel saponins were completely assigned by using a combination of 2D NMR experiments including 1H–1H COSY, HSQC, and HMBC. Their cytotoxic activities of human liver adenocarcinoma HepG2 cells were evaluated in vitro. They showed cytotoxicities against HepG2 cell line with IC50 of 40 ± 0.7 and 38 ± 0.5 μg/ml, respectively.  相似文献   

13.
PurposeTo verify lung stereotactic body radiotherapy (SBRT) plans using a secondary treatment planning system (TPS) as an independent method of verification and to define tolerance levels (TLs) in lung SBRT between the primary and secondary TPSs.MethodsA total of 147 lung SBRT plans calculated using X-ray voxel Monte Carlo (XVMC) were exported from iPlan to Eclipse in DICOM format. Dose distributions were recalculated using the Acuros XB (AXB) and the anisotropic analytical algorithm (AAA), while maintaining monitor units (MUs) and the beam arrangement. Dose to isocenter and dose-volumetric parameters, such as D2, D50, D95 and D98, were evaluated for each patient. The TLs of all parameters between XVMC and AXB (TLAXB) and between XVMC and AAA (TLAAA) were calculated as the mean ± 1.96 standard deviations.ResultsAXB values agreed with XVMC values within 3.5% for all dosimetric parameters in all patients. By contrast, AAA sometimes calculated a 10% higher dose in PTV D95 and D98 than XVMC. The TLAXB and TLAAA of the dose to isocenter were −0.3 ± 1.4% and 0.6 ± 2.9%, respectively. Those of D95 were 1.3 ± 1.8% and 1.7 ± 3.6%, respectively.ConclusionsThis study quantitatively demonstrated that the dosimetric performance of AXB is almost equal to that of XVMC, compared with that of AAA. Therefore, AXB is a more appropriate algorithm for an independent verification method for XVMC.  相似文献   

14.
A series of 3-arylnortrop-2-enes and 3α-arylmethoxy-3β-arylnortropanes were synthesized and evaluated for binding affinity at monoamine transporters. The 3-(3,4-dichlorophenyl)nortrop-2-ene (6e) exhibited high affinity for the SERT (Ki = 0.3 nM). The 3α-arylmethoxy-3β-arylnortropanes were generally SERT selective with the 3α-(3.4-dichlorophenylmethoxy)-3βphenylnortrop-2-ene (7c) possessing subnanomolar potency (Ki = 0.061 nM). However, 3α-(3,4-dichlorophenylmethoxy)-3β-phenylnortrop-2-ene (7b) exhibited high affinity at all three transporters [(DAT Ki = 22 nM), (SERT Ki = 6 nM) and (NET Ki = 101 nM)].  相似文献   

15.
16 triterpenoid saponins including two new compounds were isolated from the seeds of A esculus sylvatica W. Bartram. The two new saponins were assigned as 3-O-[β-D-glucopyranosyl-(1  2)]-α-L-arabinofuranosyl-(1  3)-β-D-glucuronopyranosyl-21,22-O-ditigloyl-3β,16α,21β,22α,24,28 hexahydroxyolean-12-ene (aesculioside S1, 1) and 3-O-[β-D-glucopyranosyl-(1  2)]-α-L-arabinofuranosyl-(1  3)-β-D-glucuronopyranosyl-21-O-tigloyl-22-O-angeloyl 3β,16α,21β,22α,24,28-hexahydroxyolean-12-ene (aesculioside S2, 2). Aesculioside S1 and S2 displayed moderate cytotoxicity against human non-small cell lung cancer cells (A549) and prostate cancer cells (PC3) (GI50 ranged from 8.7 to 18.2 μM). The structural analysis of the saponins isolated from Aesculus supports the taxonomic placement of A. sylvatica under the section Pavia of Aesculus genus.  相似文献   

16.
This study examined the usefulness of radiotelemetry for estrous detection in buffalo heifers and the impact of prostaglandin F (PGF) administration during the early or late luteal phase on estrous behavior and ovulatory follicle variables. Induction of estrus with PGF at a random stage of the estrous cycle was followed by the arbitrary division of heifers into groups receiving a second dose of PGF during either the early (n = 33) or late (n = 17) luteal phase (6–9 or 11–14 days after estrus, respectively) for the induction of synchronized estrus. The electronic detection of synchronized estrus by radiotelemetry was confirmed using ultrasonography every 6 h until ovulation. Radiotelemetry was 90% efficient and 100% accurate for estrous detection. Intervals between the PGF dose and the beginning of synchronized estrus (40.7 ± 10.9 vs. 56.7 ± 12.8 h) or ovulation (70.0 ± 11.3 vs. 85.6 ± 12.5 h) were shorter (P < 0.05) for heifers receiving PGF during the early luteal phase. PGF administration during the early or late luteal phase produced similar (P > 0.05) results for the duration of estrus, the intervals from the beginning or end of estrus to ovulation, the number and duration of mounts per estrus, the duration of mounts, the diameter of the ovulatory follicle and the luteal profile on day 5 after estrus. In conclusion, radiotelemetry was a suitable tool for the efficient and accurate detection of estrus in buffalo heifers. Treatment with PGF during the early luteal phase had a shorter interval to synchronized estrus and ovulation; however, estrous behavior, ovulatory follicle dynamics and subsequent luteal activity were similar following PGF administration during the early or late luteal phase.  相似文献   

17.
BackgroundThe delay of dermal burn wound healing caused by vascular disorders is a critical problem for many diabetic patients. Thymosin β4 (Tβ4), identified by subtractive cloning of endothelial cells on plastic versus basement membrane substrates, has been found to promote angiogenesis and dermal wound repair in rats, aged mice, and db/db diabetic mice. However, previous studies involving the role of Tβ4 in wound repair were limited to mechanical damage and dermal impairment. Thus, this study aimed to evaluate the improvement of healing of burn wounds by Tβ4 in relation to advanced glycation end products (AGE), which are pathological factors in diabetes.MethodsWe adapted a dermal burn wound in vivo model in which the dorsal skin of db/db mice was exposed for 10 s to 100 °C heated water to produce a deep second-degree burn 10 mm in diameter. Five mg/kg of Tβ4 was then injected intradermally near the burn wound twice a week for 2 weeks.ResultsAfter treatment, Tβ4 improved wound healing markers such as wound closure, granulation, and vascularization. Interestingly, Tβ4 reduced levels of receptor of AGE (RAGE) during the wound healing period.Conclusions4 exerts effects to remedy burn wounds via downregulation of RAGE.General significanceOur results suggest the potential importance of Tβ4 as a new therapy for impaired burn wound healing that is associated with diabetes.  相似文献   

18.
The effects of estrus synchronization with prostaglandin F (PGF) and Controlled Internal Drug Release Device (CIDR) on ensuing antral follicular development were documented and compared to natural estrous cycles of non-seasonal tropical goats. Two to six follicular waves were observed, with the three-follicular wave pattern being most frequently observed (58%), followed by four follicular waves (31.6%) per estrous cycle. There were no significant differences (p > 0.05) between the PGF- or CIDR-synchronized and natural estrous cycles nor between the synchronized and subsequent non-synchronized cycles in terms of the time of ovulation, the duration of inter-ovulatory intervals, daily numbers of antral follicles ≥3 mm in diameter, and the number of follicular waves per cycle in the goats of the present study.  相似文献   

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Two new oleanane-type triterpene saponins, identified as 16α-hydroxy-22-O-angeloyl-23-formyl-28,31-dihydroxymethylene-olean-12-ene-3β-O-{β-d-galactopyranosyl-(1  2)[β-d-xylopyranosyl-(1  2)-α-l-arabinopyranosyl(1  3)]-β-d-glucopyranosiduronic acid} (oleiferasaponin B1, 1) and 22-O-hydrocinnamoyl-23-formyl-28-dihydroxymethylene-olean-12-ene-3β-O-{β-d-glucopyranosyl-(1  2)[β-d-xylopyranosyl-(1  2)-α-l-arabinopyranosyl(1  3)]-β-d-glucopyranosiduronic acid} (oleiferasaponin B2, 2), were isolated from the seed cake of Camellia oleifera Abel. Their structures were established by extensive 1D- and 2D-NMR experiments along with TOF-MS analysis and acid hydrolysis. The cytotoxicity of the isolated compounds was evaluated in four human carcinoma cell lines: A 549, SK-OV-3, SK-MEL-2 and HCT15. Both compounds 1 and 2 exhibited significantly cytotoxic activity with IC50 values of 18.5 μM (A549), 11.3 μM (SK-OV-3), 13.9 μM (SK-MEL-2) and 1.6 μM (HCT15) for 1 and IC50 values of 8.4 μM (A549), 6.3 μM (SK-OV-3), 9.2 μM (SK-MEL-2) and 0.8 μM (HCT15) for 2. In addition, compound 2 showed more effective cytotoxic activity than compound 1.  相似文献   

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