Materials Research With Neutrons at NIST.

The NIST Materials Science and Engineering Laboratory works with industry, standards bodies, universities, and other government laboratories to improve the nation's measurements and standards infrastructure for materials. An increasingly important component of this effort is carried out at the NIST Center for Neutron Research (NCNR), at present the most productive center of its kind in the United States. This article gives a brief historical account of the growth and activities of the Center with examples of its work in major materials research areas and describes the key role the Center can expect to play in future developments.

Electric nerve stimulation: analysis of two clinical cases of failed nerve electrolocation by using sheathed needles.

The aim of this work was to explain the reasons of two unsuccessful blocks of sciatic nerve even if anaesthetic solution was injected through insulated needle on elicited twitch. The clinical cases were two outpatients undergoing diagnostic arthroscopy of knee under anaesthetic block of sciatic and femoral nerves. In both patients, the muscular twitch appeared when the ischiatic bone was kept in unexpected touch with needle tip. In spite of the attempt to locate correctly the needle (the touch with bone means that the nerve is not in front of the needle tip), the injection of anaesthetic solution was unsuccessful. In clinical environment, when electroinsulated needles gathered total amount of administered current on the needle tip, it was not possible to elicit a twitch just at the moment of touch of the needle with the bone. Referred events disagree with some experimental works performed out of clinical environment, which found that total amount of administered current through an insulated needle gathers always in front of the tip. Our clinical observations seems to confirm an electrolocation mistake called "electrical shadow". The ability of sheathed needles to work as occasional capacitor due to the alternation of two conductor layers (needle shaft and tissue) and of a dielectric (coating material) can explain some missing electrolocations, as the appearance of electric fields within dielectric needle sheathing.

Structural characterization of terflavoxate.

Data are reported on the structural characterization of 3-methyl-4-oxo-2-phenyl-4H-1-benzopyran-8-carboxylic acid 1,1-dimethyl-2-(N-piperidinyl)ethyl ester hydrochloride (terflavoxate-HCl, Rec 15/2053, CAS 86433-39-8), a new antispasmodic for the lower urinary tract. UV, IR, NMR and MS spectra fully confirmed the structure. The X-ray crystal structure determination revealed that the molecular structure consists of a rigid platform, formed by the chromone system, with two arms, the phenyl group at C(2) and the ester chain at C(8). The ester chain conformation generates a small hollow where two oxygen atoms face.

Heparan sulfate endoglycosidase and metastatic potential in murine fibrosarcoma and melanoma.

Several fibroblast and melanoma cell lines were studied with respect to their ability to degrade heparan sulfate (HS). The optimum pH for HS degradation by HS endoglycosidase (heparanase) for all cell lines is about 5.6, but the activity of the enzyme is still present at physiological pH. The gel permeation analysis of degradation products revealed that heparanase cuts HS in fragments about one-seventh of their original size. Since the optimum pH of HS endoglycosidase activity and the terminal molecular weight of degraded HS are the same in both cell lines, it is likely that fibrosarcoma and melanoma heparanases are identical enzymes. Cell extracts and intact cells of metastatic sublines degrade HS faster than do their nonmetastatic counterparts. The degradative activity of intact cells parallels those of cell extracts, but at a much lower level; moreover, conditioned media do not appreciably degrade HS, suggesting that heparanase is scarcely released into the medium; thus, considering the differences in degradative activity between cell extracts and intact cells or conditioned medium and the occurrence of cell lysis in a tumor in vivo, we suggest that the measure of degradative activity of intact cells in vitro is not indicative of a relationship to metastasis. The total cellular content of lytic enzymes could represent the real metastatic potential of proliferating cells, but it is also necessary to find an in vitro model better representing the behavior of neoplastic cells in vivo.

[Indolin-2,3-dione-3,N-alkylamino- and 3,N-piperazinoacetylhydrazones, new substances with anti-ulcer and antisecretory activity]. / Indolin-2,3-dione-3,N-alchilamino- e 3,N-piperazinoacetidrazoni, nuove sostanze ad attività antiulcerogena ed antisecretiva.

New indolin-2,3-dione-3,N-alkylamino- and 3,N-piperazinoacetylhydrazones were synthesized and the gastric antisecretory activity was tested. Most of the active products were selected to evaluate the inhibition of peptic ulcer induced by phenylbutazone or by stress (restraint and cold).

Involvement of chondroitin sulphate in preventing adhesive cellular interactions.

Glycosaminoglycans isolated from native non-adhesive surfaces of both endothelial and mesothelial origin and from endothelial cells cultured in vitro were analyzed by electrophoresis and characterized by chemical and enzymatic breakdown. All the surfaces examined expose in vivo chondroitin 6-sulphate as the main glycosaminoglycan. Under in vitro culture, the exposure of chondroitin sulphate is reduced. Paper chromatography of hydrolysis products upon degradation by chondroitinase AC shows equal amounts of both 6- and 4-sulphated disaccharides. At the same time, the surfaces lose their non-adhesiveness to leukocytes. The addition of fibroblast growth factor to endothelial monolayers restores both non-adhesiveness to leukocytes and exposure of chondroitin sulphate. These results seem to indicate that the exposure of chondroitin sulphate is important in preventing cellular adhesion.

Glycosaminoglycan changes involved in polymorphonuclear leukocyte activation in vitro.

The changes of cell coat and endocellular glycosaminoglycans associated with adhesion of polymorphonuclear leukocytes to tissue culture dishes were studied by electrophoresis on cellulose acetate. Polymorphonuclear leukocytes are coated by chondroitin 4 sulphate, while undersulphated chondroitin 4 sulphate and heparan sulphate are present in the cytoplasm. Upon adhesion polymorphonuclear leukocytes shed into the culture medium chondroitin 4 sulphate and concomitantly hyaluronic acid and heparan sulphate are exposed at the cell surface and shed into the culture medium. The role of these compounds in polymorphonuclear leukocyte physiology is discussed.

[Anesthesia and post-operative intensive care in 55 patients with heart valve disease at high surgical risk. Technics and analysis of results]. / Trattamento anestesiologico e rianimatorio di 55 pazienti affetti da cardiopatie valvolari ad alto rischio operatorio. Nostra politica ed analisi dei risultati.

Anaesthetic and Postoperative intensive Care techniques employed in 55 successive high risk surgical patients with valvular heart disease are discussed. Whereas an anaesthetic standard procedure is well established. Postoperative cardio-respiratory therapy in ICU is singularly decided on the basis of the physiological signs measured. The cardio-respiratory monitoring system at work is explained in details and a special bedside estimation of pulmonary circulation morphology is outlined. In our opinion an individualized treatment causes the post-operative recovery time to be sharply reduced. The myocardial protection during ischemic cardiac arrest has a crucial influence on the early mortality: among patients treated with Breitschneider II cardioplegic solution the early mortality is 10,8% at the lower level of the mortality range exhibited by other outstanding surgical teams.

Binding of the basement-membrane glycoprotein laminin to glycosaminoglycans. An affinity-chromatography study.

The binding of the basement-membrane glycoprotein laminin to glycosaminoglycans (aggregating and non-aggregating subsets of heparan sulphates and dermatan sulphates, as well as heparin, chondroitin sulphates and hyaluronic acid) was studied by affinity chromatography. Partially periodate-oxidized chains of glycosaminoglycans were coupled to adipic acid dihydrazide-substituted agarose. Co-polymeric glycosaminoglycans reveal high affinity for laminin, whereas hyaluronic acid does not. Competitive-release experiments indicate that glycosaminoglycans share a common binding site on the laminin molecule.

Involvement of glycosaminoglycans in detachment of early myeloid precursors from bone-marrow stromal cells.

Fibroblast-like cells were obtained by in vitro cultivation of needle aspirations of human bone-marrow. These cells show a unique composition of coat-associated glycosaminoglycans: 10% chondroitin 4-sulfate, 30% hyaluronic acid and 60% heparan sulfate which were resolved and characterized by electrophoresis, nitrous acid treatment and enzymatic degradation. Chondroitin 4-sulfate is the only glycosaminoglycan detectable on the surface of mature granulocytes, whereas the immature cells do not seem to possess surface glycosaminoglycans. Immature hemopoietic cells can adhere on to marrow-derived fibroblast cells, whereas mature granulocytes cannot. Treatment with mucopolysaccharidases of both mature leukocytes and marrow stromal cells can interfere in these adhesive relationships, suggesting a role of glycosaminoglycans in regulating short-range interactions during hematopoiesis.

Synthesis and antimycotic activity of alpha-aryl-beta,N-imidazolylalkyl benzyl ethers.

A new series of alpha-aryl-beta,N-imidazolylalkyl benzyl ethers was synthesized and tested for antimycotic and antimicrobial activity. Most of the compounds was highly active in vitro against fungi and gram-positive bacteria. The alpha,4-phenylthiophenyl-beta,N-imidazolylethyl benzyl ether (7) and the alpha,4-biphenyl-beta,N-imidazolylethyl benzyl ether (17) showed higher antifungal activity than 1-[2,4,dichloro-beta-(2,4-dichlorobenzyloxy)phenethyl]imidazole (miconazole) against Candida albicans. None of the compounds was more active than miconazole against Trichophyton mentagrophytes. The most interesting compounds of the series were assayed in vivo, but their activity was inconstant and always lower than that of miconazole.

New alpha-aryl-beta,N-imidzolylethyl benzyl and naphthylmethyl ethers with antimycotic and antibacterial activity.

A new series of alpha-aryl-beta,N-imidazolylethyl benzyl and naphthylmethyl ethers was synthesized and tested for antimycotic and antimicrobial activity. All compounds showed antifungal activity; most of them were also active against gram-positive bacteria, whereas no activity was detected against gram-negative bacteria. Structure-activity relationships are discussed. The alpha-(2,4-dichlorophenyl)-beta,N-imidazolylethyl 4-phenylthiobenzyl ether nitrate (8), which showed good skin tolerability and in vivo antimycotic activity comparable with or better than 1-[2,4-dichloro-beta-(2,4-dichlorobenzyloxy)phenethyl]imidazole (miconazole) and 1-(alpha-(o-chlorophenyl)benzhydryl]imidazole (clotrimazole), was selected for further researches.