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61.
62.
Urinary pharmacokinetics of betalains following consumption of red beet juice in healthy humans. 总被引:1,自引:0,他引:1
Thomas Frank Florian Conrad Stintzing Reinhold Carle Irmgard Bitsch Daniela Quaas Gabriele Strass Roland Bitsch Michael Netzel 《Pharmacological research》2005,52(4):290-297
The aim of the present pilot study was to characterise the renal elimination of betalains after consumption of red beet juice (RBJ). Six healthy, non-smoking female volunteers were given a single oral dose of either 500 mL of a commercial RBJ containing 362.7 mg of betalains and 500 mL of tap water, respectively, in a sequential manner. Urine was collected in intervals up to 24 h post-dose. Renal excretion of betalains was determined spectrophotometrically and quantified as betanin-equivalents. In addition, the identity of individual compounds was confirmed by HPLC coupled with diode-array detection and positive ion electrospray mass spectrometry, respectively. The amount (mean+/-S.D.) of intact betalains (betanin and isobetanin) recovered in urine was 1001+/-273 microg corresponding to 0.28+/-0.08% of the administered dose. Maximum excretion rates were observed after a median tmax,R of 3.0 h (range 2.5-8.0 h) amounting to 91.7+/-30.1 microg/h. The terminal elimination rate constant (lambdaz) and the corresponding half-life were 0.097+/-0.021 h(-1) and 7.43+/-1.47 h, respectively. Using the lambdaz estimates obtained the expected total betalain amount excreted in urine was 1228+/-291 microg. Based on the results obtained it is assumed that either the bioavailability of the betalains is low or that renal clearance is a minor route of systemic elimination for these compounds. The urinary excretion rates of unmetabolised betalains were fast and appeared to be monoexponential suggesting a one-compartment model. In order to get a more complete picture of the pharmacokinetics and health-promoting properties of red beet betalains, quantitative data on betalain bioavailability should include measurements of unchanged compounds and their corresponding metabolites in plasma, urine and bile. 相似文献
63.
Jan M Schwenkenbecher Chris Fr?hlich Florian Gehre Lionel F Schnur Gabriele Sch?nian 《Infection, genetics and evolution》2004,4(2):99-105
Sixteen polymorphic microsatellite markers were developed for phylogenetic analysis of Leishmania tropica. The phylogenetic tests done demonstrated that they do provide a powerful tool for epidemiological studies. They were also tested for their ability to differentiate strains of other species of Leishmania, confirming that microsatellite markers developed for one leishmanial species cannot generally be used for other leishmanial species. In addition to length variation, a high degree of allelic heterozygosity was seen among the strains investigated, suggestive of sexual recombination within the species L. tropica. 相似文献
64.
Markus Grube Henriette Meyer Zu Schwabedissen Katrin Draber Damaris Pr?ger Klaus-Uwe M?ritz Knud Linnemann Christoph Fusch Gabriele Jedlitschky Heyo K Kroemer 《Drug metabolism and disposition》2005,33(1):31-37
L-carnitine is assumed to play an important role in fetal development, and there is evidence that carnitine is transported across the placenta. The protein involved in this transfer, however, has not been identified on a molecular level. We therefore characterized localization and function of the carnitine transporter OCTN2 in human placenta. Significant expression of OCTN2 mRNA was detected in human placenta applying real-time polymerase chain reaction technology. Confocal immunofluorescence microscopy using an antibody directed against the carboxy terminus of OCTN2 protein revealed that it is predominantly expressed in the apical membrane of syncytiotrophoblasts. This was confirmed by the costaining of organic anion-transporting polypeptide B and MRP2, which are known to be expressed mainly in the basal and apical syncytiotrophoblasts membrane, respectively. To further support this finding, we performed transport studies using basal and apical placenta membrane vesicles. We could demonstrate that the carnitine uptake into the apical vesicles was about eight times higher compared with the basal ones. Moreover, this uptake was sodium- and pH-dependent with an apparent K(m) value of 21 muM and inhibited by verapamil, which is in line with published data for recombinant OCTN2. Finally, experiments using trophoblasts in cell culture revealed that expression of OCTN2 paralleled human choriogonadotropin production and thus is modulated by cellular differentiation. In summary, we show expression and function of OCTN2 in human placenta. Moreover, several lines of evidence indicate that OCTN2 is localized in the apical membrane of syncytiotrophoblasts, thereby suggesting a major role in the uptake of carnitine during fetal development. 相似文献
65.
Matthias Kirsch Patrick Weigel Thomas Pinzer Rona S Carroll Peter McL Black Hans-Konrad Schackert Gabriele Schackert 《Clinical cancer research》2005,11(3):1259-1267
PURPOSE: Cerebral metastases represent the most common type of brain tumors. This study investigated the effects of endogenous endostatin on hematogenous cerebral melanoma metastases. EXPERIMENTAL DESIGN: Murine K1735 melanoma cells were transfected with the mouse endostatin cDNA. Experimental tumors were induced either by s.c. injection, intracerebral implantation, or via injection into the internal carotid artery to simulate hematogenous metastatic spread. The effects of endostatin expression on tumor incidence, growth pattern, and vascularity were analyzed. RESULTS: In vitro secretion of endostatin by 2.5 x 10(5) cells within 24 hours was 0.12 +/- 0.03 ng, 4.35 +/- 0.4, and 1.18 +/- 0.7 ng/mL for wild type and two endostatin-transfected K1735 clones termed K1735-endo/2 and K1735-endo/8, respectively. Tumor inhibition in vivo correlated with endogenous endostatin production. Within 25 days, growth of s.c. K1735-endo/2 tumors was <20% compared with wild-type controls. Following intracerebral implantation the average survival time of mice was 27.8 +/- 2.6 versus 13.3 +/- 3.7 days in the K1735-endo/2 versus the wild-type group, respectively. Intracarotid injection of 1 x 10(5) wild-type cells killed the mice within 24 +/- 1.8 days. In contrast, endostatin expression prevented macroscopic metastatic tumor growth in 11 of 12 mice, although viable microscopic tumor pockets were detectable in all animals. CONCLUSION: Endostatin inhibits tumor progression of multiple cerebral metastases in vivo. Hematogenous micrometastases are more efficiently suppressed than tumors resulting from high focal cell numbers which may be due to a higher angiogenic signaling exerted by massive cell deposits. Endostatin may prevent solid tumor growth more effectively by inhibition of early angiogenesis. 相似文献
66.
Gabriele Grassi Rossella Farra Dr Paolo Caliceti Gianfranco Guarnieri Stefano Salmaso Mario Carenza Mario Grassi 《American Journal of Drug Delivery》2005,3(4):239-251
Thermo-sensitive polymers are appealing materials for several therapeutic applications, such as in regenerative medicine and in situ drug release. These macromolecules are characterized by the ability to undergo swelling/deswelling processes during temperature change-induced phase transitions. Swelling and shrinking temperatures depend on the specific physicochemical properties, namely salt concentration or pH, of the thermo-sensitive gels as well as the incubation environment. An understanding of the mechanisms underlying the gel-swelling equilibrium and kinetics is necessary for the selection of an appropriate gel in relation to the specific pharmaceutical application. Thermo-sensitive polymers used in medicine include polyacrylamides, polyvinyls, polyethers, polysaccharides, and polyphosphazenes. A few of them have been successfully used as 3-dimentional supports for cell cultivation, allowing for the production of scaffolds with excellent biologic properties for application in regenerative medicine. Stem cells that can undergo specific differentiation under the appropriate stimulation have also been cultivated. The ability of drug/polymer solutions to turn into gels at physiologic temperature has been exploited for local drug delivery. The prolonged in situ presence and slow drug release enhances the therapeutic performance of antibiotics used in urogenital pathologies, anti-inflammatory agents, and anticancer drugs. The reduced toxicity as well as lower fluctuations in peak-to-trough drug concentrations make these systems superior to traditional gels. Thermo-sensitive hydrogels have also been demonstrated to be interesting formulations for the delivery of biotechnological drugs. Proteins and oligonucleotides can be loaded under mild conditions, stabilized, and released at a controlled rate. Finally, thermo-reversible polymers have been investigated for protein conjugation to enhance the physicochemical, biologic, immunologic, and pharmacokinetic properties of biotechnological products. 相似文献
67.
Domenico Acanfora Maria Nolano Chiara Acanfora Camillo Colella Vincenzo Provitera Giuseppe Caporaso Gabriele Rosario Rodolico Alessandro Santo Bortone Gennaro Galasso Gerardo Casucci 《Viruses》2022,14(5)
Long-COVID-19 refers to the signs and symptoms that continue or develop after the “acute COVID-19” phase. These patients have an increased risk of multiorgan dysfunction, readmission, and mortality. In Long-COVID-19 patients, it is possible to detect a persistent increase in D-Dimer, NT-ProBNP, and autonomic nervous system dysfunction. To verify the dysautonomia hypothesis in Long-COVID-19 patients, we studied heart rate variability using 12-lead 24-h ECG monitoring in 30 Long-COVID-19 patients and 20 No-COVID patients. Power spectral analysis of heart rate variability was lower in Long-COVID-19 patients both for total power (7.46 ± 0.5 vs. 8.08 ± 0.6; p < 0.0001; Cohens-d = 1.12) and for the VLF (6.84 ± 0.8 vs. 7.66 ± 0.6; p < 0.0001; Cohens-d = 1.16) and HF (4.65 ± 0.9 vs. 5.33 ± 0.9; p = 0.015; Cohens-d = 0.76) components. The LF/HF ratio was significantly higher in Long-COVID-19 patients (1.46 ± 0.27 vs. 1.23 ± 0.13; p = 0.001; Cohens-d = 1.09). On multivariable analysis, Long-COVID-19 is significantly correlated with D-dimer (standardized β-coefficient = 0.259), NT-ProBNP (standardized β-coefficient = 0.281), HF component of spectral analysis (standardized β-coefficient = 0.696), and LF/HF ratio (standardized β-coefficient = 0.820). Dysautonomia may explain the persistent symptoms in Long COVID-19 patients. The persistence of a procoagulative state and an elevated myocardial strain could explain vagal impairment in these patients. In Long-COVID-19 patients, impaired vagal activity, persistent increases of NT-ProBNP, and a prothrombotic state require careful monitoring and appropriate intervention. 相似文献
68.
Cis-diaminechloro-[2-(diethylamino) ethyl 4-amino-benzoate, N4]-chloride platinum (II) monohydrochloride monohydrate (DPR) is a monofunctional Pt triamine complex synthesized starting from cisplatin and procaine hydrochloride, characterized by a good antitumor activity coupled with low toxic effects and able to impair prenatal development of mice but at doses outside or just in the upper range of therapeutic doses. In the present paper the transplacental passage of DPR-derived Pt was investigated in CD1 mice on days 9, 13, 16 and 18 of pregnancy, 24 h after ip administration of 21 mg/kg DPR. For comparison, groups of mice were treated with an equivalent Pt-containing dose of cisplatin (10.7 mg/kg). Similarly to cisplatin, small amounts of Pt were detected in fetuses on day 9. From day 13 of gestation the concentration of DPR- and cisplatin-derived Pt increased up to the highest fetal concentrations detected on day 16. On day 18 the concentration of Pt decreased. Most importantly, on days 13–18 of pregnancy cisplatin-derived Pt was always significantly higher than that assayed after DPR administration. In addition, on day 13 of pregnancy Pt exposure of fetuses was significantly higher when dams were treated with cisplatin (AUC0.5–24= 3.40 vs. 4.95 g·h/g). Finally, it is worth noting that serum decay of Pt after DPR or cisplatin administration in adult female mice was similar with AUC0.13–2h s of 7.5 and 6.6 g·h/ml, respectively. When we determined the concentration of Pt into the main organs of fetuses from dams treated with either DPR or cisplatin on day 18 of gestation, we observed a different organ distribution. In fact, while the concentration of DPR-derived Pt was greater in the heart (1.08±0.30 vs. 0.78±0.35 g/g, p <0.10), an opposite situation was found in the kidney (0.51±0.20 vs. 0.69±0.22 g/g, p <0.05). In conclusion, our data show that DPR may pass through the placenta with an efficiency significantly lower than that of cisplatin. This finding may represent one of the possible causes of the lower embryotoxic/teratogenic effect of DPR as compared to cisplatin. 相似文献
69.
Most of the copper sulfide synthetic approaches developed until now are still facing issues in their procedure, such as long synthesis duration, high energetic consumption, and high implementation costs. This publication reports a facile and sustainable approach for synthesizing copper sulfides on a large scale. In particular, an industrial by-product of sulfur waste was used as a sulfurizing agent for copper sulfide synthesis in a water medium. The reaction was performed in the hydrothermal environment by following a novel proposed mechanism of copper sulfide formation. The investigation of morphological and optical properties revealed that the target products obtained by using waste possess the resembling properties as the ones synthesized from the most conventional sulfurizing agent. Since the determined band gap of synthesis products varied from 1.72 to 1.81 eV, the photocatalytic properties, triggered under visible light irradiation, were also investigated by degrading the methylene blue as a model pollutant. Importantly, the degradation efficiency of the copper sulfide synthesized from sulfur waste was equivalent to a sample obtained from a reference sulfurizing agent since the value for both samples was 96% in 180 min. This very simple synthetic approach opens up a new way for large-scale sustainable production of visible-light-driven photocatalysts for water purification from organic pollutants. 相似文献
70.
Unusual association of endometrial cancer and multiple myeloma 总被引:1,自引:1,他引:0
Buda G Orciuolo E Galimberti S Petrini M Maggini V Barale R Rossi AM 《Gynecologic oncology》2008,110(2):265-266