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101.
Whole-cell current clamp, single-channel recordings and 86Rb+ flux techniques have been used to show that 8-(N,N-diethyl-amino)octyl-3,4,5-trimethoxybenzoate (TMB-8) inhibits ATP-sensitive K+ channels in HIT-T15 beta-cells. TMB-8 inhibition is observed when KATP channels are activated by ATP depletion or by the K+ channel opener, diazoxide. 相似文献
102.
High-Temperature Short-Time Heat Inactivation of HIV and Other Viruses in Human Blood Plasma 总被引:4,自引:0,他引:4
Stanley E. Charm Steven Landau Bolanle Williams Bernard Horowitz Alfred M. Prince and Donna Pascual 《Vox sanguinis》1992,62(1):12-20
An ultra-short-time heating system was used to process blood plasma spiked with various viruses (HIV, vesicular stomatitis virus, encephalomyocarditis virus). Virus reduction and recovery of plasma proteins were measured at various temperatures from 65 to 85 degrees C. Processing at 77 degrees C and 0.006 s resulted in a high level of virus kill, including greater than or equal to 4.4 log10 HIV, while maintaining protein structure and activity essentially intact. 相似文献
103.
Adrenocortical carcinoma in surgically treated patients: a retrospective study on 156 cases by the French Association of Endocrine Surgery. 总被引:4,自引:0,他引:4
BACKGROUND. Because of the rarity of adrenocortical carcinoma, survival rates and prognosis for patients who have undergone operation are not well known. The purpose of the French Association of Endocrine Surgery was to evaluate these factors in all patients treated during a 12-year period by its members. METHODS. One hundred fifty-six patients (95 women, 61 men) with a mean age of 47 years were included. Functional symptoms were found in 52% of patients, and hormonal studies revealed secreting tumors in 62% of cases. Ninety-four percent of the patients underwent resection of the adrenal tumor, and 20% of them had extensive resection because of invasive cancers. Complete resection was achieved in 127 patients (81%) and incomplete resection in 29 patients. Mean tumor weight was 714 gm (range, 12 to 4750 gm), and the mean diameter was 12 cm (range, 3 to 30 cm). The results of the tumor staging were stage I, eight patients (5%); stage II (local disease), 75 patients (48%); stage III (locoregional disease), 39 patients (25%); and stage IV (metastases), 34 patients (22%). RESULTS. The 5-year actuarial survival rates were 34% overall, 42% in curative group, 53% in local cancer group, 24% in regional disease group, and 27% in the reoperated group. One-year actuarial survival rate of the palliative group was 9% (median survival, 6 months). Multivariate analysis showed that better prognosis occurred in patients younger than 35 years of age (p = 0.01) and in patients with androgen-secreting tumors, precursor-secreting tumors, or nonsecreting tumors (p = 0.003). Mitotane improved the survival rate only in patients with metastases who received it after operation (vs non-mitotane-treated patients [p < 0.05]). CONCLUSIONS. In this study age, extent of disease, aspect of the surgical resection, and type of hormonal secretion influenced survival. 相似文献
104.
G. Toffoli I. Robieux D. Fantin M. Gigante S. Frustaci G. L. Nicolosi M. De Cicco & M. Boiocchi 《British journal of clinical pharmacology》1997,44(3):255-260
Aims In an attempt to reverse multidrug resistance, in a recent trial of verapamil in association with doxorubicin, we used escalating doses of continuous intravenous (i.v.) verapamil under close haemodynamic monitoring. We report the pharmacokinetics of escalating doses of verapamil.
Methods We studied nine patients [
seven males, two females; median age 46 years (range, 31–57)] with advanced adenocarcinoma of the colon and normal renal, hepatic, and cardiac functions. After a loading dose (0.15 mg kg−1 followed by 12 h continuous i.v. infusion at 0.20 mg kg−1 h−1 ), the infusion rate (ko) of verapamil was increased every 24 h (0.25, 0.30, 0.35, and 0.40 mg kg−1 h−1 ). The highest rate was maintained for 48 h. Doxorubicin was given as a continuous i.v. infusion from 12 to 108 h (n=4) or 60 to 108 h (n=5). Blood samples and urine collections were taken every 12 h. Verapamil and nor-verapamil were assayed by high performance liquid chromatography. We calculated systemic clearance of verapamil (CL=ko/Css ) and renal clearance (CLr) of verapamil and nor-verapamil. The Cssvs rate relationship was fitted to a Michaelis-Menten equation: Css=ko(Km+Css )/(V Vm ).
Results CL was dose-dependent and in all nine patients a significant reduction in CL was observed over the dose range (mean CL±s.d. were 0.51±0.31, 0.38±0.16, 0.32±0.18, and 0.27±0.11 l h−1 kg−1, respectively, at 0.25, 0.30, 0.35, and 0.40 mg kg−1 h−1; P=0.0001). Css increased more than proportionally to the dose rate and the Cssvs rate relationship was best defined by a Michaelis-Menten equation (Km=730 μg l−1; V Vm=0.55 mg kg−1 h−1 ), (r=0.994; P=0.006). CLr of verapamil and nor-verapamil was not saturable but the contribution to the elimination was only 2 to 4% of the dose.
Conclusions These findings suggest a non-linear, capacity-limited metabolic clearance of high-dose verapamil. Using escalating infusion rates, high verapamil concentrations (1500–2500 ng ml−1 ) were achieved without major toxicity. Saturable clearance may cause higher bioavailability and slower elimination of verapamil after acute oral overdoses. 相似文献
105.
Mnica De la Fuente Juan Jos Garrido Rosa María Arahuetes Angel Hernanz 《Journal of neuroimmunology》1993,42(1)
The neuropeptides neurotensin and neuromedin N (from 10−12 M to 10−9 M) have been showed in this study to stimulate significantly in vitro several steps of the phagocytic process: adherence to substrate, chemotaxis, ingestion of inert particles (latex beads) and production of superoxide anion measured by nitroblue tetrazolium reduction in resting peritoneal macrophages from BALB/c mice. A dose-response relationship was observed, with a maximal stimulation of the phagocytic process at 10−11 M. The two neuropeptides induced no change of intracellular cyclic AMP in murine macrophages. Moreover, adherence and chemotaxis decreased significantly in the presence of EGTA (1 mM), a chelator of extracellular Ca2+, or ryanodine (0.5 mM), a blocker of a Ca2+-gated channel from the endoplasmic reticulum, in both controls and samples with the addition of neurotensin or neuromedin N. These results suggest that there is no relation between the cAMP messenger system and the phagocytic process stimulation in murine peritoneal macrophages by neurotensin or neuromedin N. In addition, the results observed with EGTA and ryanodine could indicate that these two neuropeptides produce their effects through an increase of intracellular Ca2+ concentration. 相似文献
106.
R 75251, a new inhibitor of steroid biosynthesis 总被引:1,自引:0,他引:1
J Bruynseels R De Coster P Van Rooy W Wouters M C Coene E Snoeck A Raeymaekers E Freyne G Sanz G Vanden Bussche 《The Prostate》1990,16(4):345-357
R 75251, a new imidazole derivative, inhibited the conversion of androgens to estrogens, of progestins to androstenedione and testosterone, and of 11-deoxycorticosterone to corticosterone in human placenta microsomes, subcellular fraction of rat testis, bovine adrenocortical mitochondria, in cultured rat granulosa, testicular and adrenal cells, respectively. In vitro, no effect on cholesterol synthesis and cholesterol side-chain cleavage was found at concentrations up to 10 microM. In rat granulosa cells, no effect on progesterone production was detected. In vitro, no effect on steroid radioligand binding was observed. In male volunteers, a single dose of 300 mg of R 75251 significantly lowered plasma testosterone and estradiol for 24 hours and increased plasma concentration of 17 alpha-hydroxyprogesterone and progesterone. As compared with ketoconazole high dose (600 mg b.i.d), R 75251 (300 mg b.i.d) was at least as efficacious as inhibitor of testosterone synthesis when studied during ACTH stimulation. In contrast to ketoconazole, R 75251 did not significantly affect circulating adrenal androgen levels in male volunteers. Precursors of gluco- and mineralocorticoids such as 11-deoxycortisol and 11-deoxycorticosterone accumulated more than after ketoconazole administration. The data show that the cytochrome P450-dependent aromatase, 17-hydroxylase/17,20-lyase, and 11-hydroxylase are the target enzymes for R 75251. 相似文献
107.
Synergistic antiproliferative activity of quercetin and cisplatin on ovarian cancer cell growth 总被引:1,自引:0,他引:1
G Scambia F O Ranelletti P Benedetti Panici G Bonanno R De Vincenzo M Piantelli S Mancuso 《Anti-cancer drugs》1990,1(1):45-48
It has been demonstrated that the flavonoid quercetin (3,3',4',5-7-pentahydroxyflavone) (Q) inhibits the growth of several cancer cell lines and that the antiproliferative activity of this substance is mediated by a so-called type II estrogen binding site (type II EBS). We investigated the effects of quercetin and cisplatin (CDDP) alone and in combination on the proliferation of the ovarian cancer cell line OVCA 433. Both drugs exhibited a dose-related growth inhibition in a range of concentrations between 0.01 and 2.5 microM and 0.01 and 2.5 micrograms/ml for Q and CDDP respectively. The combination of the two drugs resulted in a synergistic antiproliferative activity. Two other flavonoids tested, i.e., rutin (3-rhamnosylglucoside of quercetin) and hesperidin [7-b rutinoside of hesperetin (3'-5-3-hydroxy-4-methoxyflavone)] were ineffective both alone and in combination with CDDP. Since both rutin and hesperidin do not bind to type II EBS it can be hypothesized that Q synergizes with CDDP by acting through an interaction with these binding sites. 相似文献
108.
The morphological changes produced in the thyroid glands of albino rats following radiation with a 904 nm infrared laser were studied. Two different levels of radiation were applied: 46.8 J/cm2 and 140.4 J/cm2. Evaluation of the changes in the densities of the epithelial, colloidal and follicular volumes and of the activation index revealed that the laser beam produced changes in the thyroid parenchyma. It was observed that there was a direct relationship between the severity of the lesion and the radiation energy applied. 相似文献
109.
R De Schrijver 《The Journal of nutrition》1990,120(12):1624-1632
In two feeding experiments immature (180 g) and mature rats (370 g) were fed a semi-purified diet containing 20% of a protein source (casein, wheat gluten, soybean or potato protein) for 4 wk. Food supply was restricted to 15 g daily. As compared to casein, plant proteins induced significantly lower concentrations of plasma total cholesterol and high density lipoprotein (HDL) cholesterol. The plasma cholesterol increase associated with aging was not prevented by consumption of casein, soybean or potato protein, but wheat gluten seemed to be effective. Lecithin-cholesterol acyltransferase (LCAT) activity was not significantly different in rats of the same age fed different plant proteins, whereas the esterification rate was lower in rats fed casein. With aging the LCAT activity generally decreased. As compared to the casein groups, the rats fed plant proteins showed higher excretion of fecal neutral and acidic steroids. Among the groups fed plant proteins, the fecal output of steroids was variable. Significantly negative correlations were found between fecal total sterol excretion and plasma total cholesterol or HDL cholesterol, respectively. Plant proteins showed a faster migration rate in the stomach, whereas their migration and absorption were slower in the first half of the small intestine. A relation between nonabsorbed nitrogen-containing substances and sterol excretion was hypothesized. 相似文献
110.
P J Bernard P M Som M L Urken W Lawson H F Biller 《Otolaryngology--head and neck surgery》1988,99(5):489-493
Although acute thyroiditis often has a distinctive clinical presentation, this relatively uncommon entity can occasionally be confused with other inflammatory processes. In general, the earlier the diagnosis of acute thyroiditis is established, the lower is the frequency and severity of its attendant complications. Computed tomography (CT) is an extremely useful modality in establishing the diagnosis early because it can evaluate iodine content of the thyroid gland and provides more accurate mapping than ultrasound and nuclear medicine techniques. Three patients with acute thyroiditis--two with suppuration--are presented and the CT findings and clinical aspects of this disease are reviewed. 相似文献