1-乙基-6-氟-1,4-二氢-4-氧代-7-(4-芳酰硫代氨甲酰基-1-哌嗪基)-3-喹啉羧酸的合成及抗菌作用

Thirteen new 1-ethyl-6-fluoro-1,4-dihydro-4-oxo-7-(4-aroyl-thiocarbamoyl- 1 piperazinyl)-3-quinoline carboxylic acids were prepared, Their structures were characterized by elemental analysis, IR, HNMR and MS spectra.Preliminary pharmacological tests indicated that some of compounds Ia～m possess strong inhibiting activity against Escherichia coli, Bacillus subtilis and Proteus at concentration of 100 μg/ml.     

Uptake and dissolution of particulate iodipamide ethyl ester in the spleen. A morphologic study

Iodipamide ethyl ester (IDE) is an experimental particulate contrast agent being developed for CT image enhancement of the liver and spleen. IDE particles are phagocytized by the reticuloendothelial cells after an intravenous injection. The uptake and dissolution of IDE particles were studied in the spleen with light and electron microscopy. Two minutes after injection, intra- and extracellular IDE particles were found in the red pulp of the spleen. Highest concentration of IDE was seen in the marginal zone surrounding the white pulp. Particles also were seen elsewhere in the red pulp but only occasionally between the outermost cells of the white pulp. The extracellular particles disappeared within 4 hours postinjection. At one day postinjection, the amount of intracellular IDE particles had begun to decrease. Electron micrographs showed that the intracellular particles dissolved gradually in the phagocytes and caused transient degenerative morphologic changes. At three days postinjection, practically all IDE particles had disappeared from the spleen. Polystyrene latex particles were used as controls. They were phagocytized like the IDE particles, but they did not disappear from the phagocytes. IDE particles caused no morphologic injuries in nonphagocytic cells of the spleen.     

Synthesis of poly[isobutyl (2S,3R)-3-benzyloxyaspartate]

A chiral poly(3-substituted isobutyl D -aspartate) 12 was synthesized by polymerization of the chiral β-lactam 11 derived from D -glyceraldehyde. The new polyamide was characterized by elemental analyses, and infrared, ¹H- and ¹³C nuclear magnetic resonance spectroscopies. The molecular weight was estimated as 543 000 and 230 000 on the basis of viscosimetric measurements and gel-permeation chromatography, respectively. Polyamide 12 is soluble in a variety of organic solvents including chloroform.     

Criteria for evaluating the clinical and practical utility of models used by nurses

Arguably, nursing, like all health care disciplines, is an applied science. Essentially, this refers to the application of theory in order to understand and respond to the health problems of clients. These theories may be drawn (borrowed) from any applied science, or generated inductively from clinical nursing practice. Alternatively, nurses may attempt to apply deductive theory (global theoretical frameworks) known as nursing models. In this paper, all theoretical approaches, irrespective of origin, are referred to as models used by nurses. Thirteen criteria by which clinicians, and others, can evaluate the clinical and practical utility of models used by nurses which are expressed in the form of questions are identified and discussed. The criteria are an extension, both in detail and in number, of those developed by Reynolds and Cormack and subsequently applied by those writers to the Johnson Behavioural System Model of Nursing. The value, or otherwise, of individual models, or of models in general, will not be discussed in this paper. However, the authors propose that if the evaluation criteria described here are applied to existing models, serious deficits will be identified in relation to their clinical and practical utility.     

Micronuclei frequencies in hospital workers occupationally exposed to low levels of ionizing radiation: influence of smoking status and other factors

In the context of a medical surveillance program aimed at preventing cancer risk from exposure to ionizing radiation, we investigated chromosomal damage in peripheral lymphocytes from 37 hospital workers exposed to low levels of ionizing radiation and 37 controls. The micronuleus (MN) assay was used as a biomarker of genetic damage. The influence of confounding factors like smoking status, age and gender was investigated by multiple regression analysis. The results indicated that, overall, MN frequency was higher in exposed workers than in controls, although the difference was not statistically significant. Interestingly, smoking status significantly raised MN frequency among the exposed workers but not among controls. This suggests that smoking can influence chromosomal damage induced in humans by ionizing radiation. Among both exposed workers and controls, MN frequency was found to increase with age. Female gender influenced the increase in MN frequency in the exposed group. Our results suggest that the effect of cigarette smoking should be carefully factored into genetic monitoring studies assessing the risks associated with low level radiation exposure.     

Identification of MEN1 gene mutations in sporadic carcinoid tumors of the lung

Lung carcinoids occur sporadically and rarely in association with multiple endocrine neoplasia type 1 (MEN1). There are no well defined genetic abnormalities known to occur in these tumors. We studied 11 sporadic lung carcinoids for loss of heterozygosity (LOH) at the locus of the MEN1 gene on chromosome 11q13, and for mutations of the MEN1 gene using dideoxy fingerprinting. Additionally, a lung carcinoid from a MEN1 patient was studied. In four of 11 (36%) sporadic tumors, both copies of the MEN1 gene were inactivated. All four tumors showed the presence of a MEN1 gene mutation and loss of the other allele. Observed mutations included a 1 bp insertion, a 1 bp deletion, a 13 bp deletion and a single nucleotide substitution affecting a donor splice site. Each mutation predicts truncation or potentially complete loss of menin. The remaining seven tumors showed neither the presence of a MEN1 gene mutation nor 11q13 LOH. The tumor from the MEN1 patient showed LOH at chromosome 11q13 and a complex germline MEN1 gene mutation. The data implicate the MEN1 gene in the pathogenesis of sporadic lung carcinoids, representing the first defined genetic alteration in these tumors.      

Protein binding of brequinar in the plasma of healthy donors and cancer patients and analysis of the relationship between protein binding and pharmacokinetics in cancer patients

The protein binding of weakly acidic and basic drugs has been shown to be altered in cancer patients. Brequinar is a weakly acidic, low-clearance, and highly protein-bound (>98% bound) antitumor agent. The pharmacokinetic parameters of brequinar are subject to large interpatient variability. This large interpatient variability may be related to brequinar's plasma protein-binding capacity (assuming no change in the intrinsic clearance of the unbound drug). The objectives of this study, therefore, were (a) to characterize brequinar's protein binding in the plasma of healthy donors and cancer patients and (b) to examine the relationships between brequinar's plasma protein binding and its pharmacokinetics in patients. Brequinar protein binding was determined in human serum albumin (HSA) solution, drug-free donor plasma, and brequinar-free, predose plasma samples obtained from a phase I cancer trial. Pharmacokinetic results from this study were used to examine relationships between plasma protein binding and drug disposition. In HSA solution and healthy donor plasma, brequinar's protein binding as determined using spiked samples was concentration-dependent. The unbound brequinar fraction increased by a factor of 3 (from 0.3% to 0.9% free) in 4% HSA solution and by a factor of 4 (from 0.4% to 1.6% free) in donor plasma as the brequinar concentrations increased from 0.1 to 2.3 mM in the HSA solution and from 0.076 to 1.5 mM in the donor plasma. Analysis of brequinar binding characteristics using the binding ratio and Rosenthal binding plots showed that albumin was the primary protein for brequinar binding in human plasma. The addition of various concentrations of ₁-acid glycoprotein to 4% HSA solution did not affect the protein binding of brequinar to HSA. The protein binding determined in the plasma of cancer patients was not quantitatively different, except for variability, from that observed in the plasma of healthy donors. Examination of relationships between the unbound brequinar fraction and pharmacokinetics suggested that plasma protein binding was not a major determinant of brequinar disposition in cancer patients.