Microcrystalline Preparation Research Articles

Intrathecal busulfan treatment of human neoplastic meningitis in athymic nude rats.

The current study was designed to evaluate the toxicity and activity of Spartaject Busulfan, a microcrystalline preparation of busulfan, following its intrathecal administration into a nude rat model of human neoplastic meningitis. Animals were treated through permanent indwelling subarachnoid catheters. Human glioma D-456 MG growing in the subarachnoid space was treated with 8.1 micromol of intrathecal Spartaject Busulfan. Single-dose therapy was also subsequently compared with 4 doses of 8.1 and 2.0 micromol busulfan, respectively, against D-456 MG neoplastic meningitis. Additional experiments evaluated a saline control versus 8.1 micromol x 1, 6.2 micromol x 4 and 4.1 micromol x 4, respectively, against D-456 MG. A single dose of 8.1 micromol of intrathecal Spartaject Busulfan resulted in an increase in median survival of 61.7% compared with the saline control. In experiment 2, all busulfan treatments showed increases in median survival of 142.8% (8.1 micromol x 1), 52.3% (2.0 micromol x 4), and 23% (8.1 micromol x 4) (p < 0.001 for all groups) compared with the saline control. These results suggest that a narrow therapeutic dose range for both toxicity and activity has been defined for intrathecal busulfan in the treatment of human neoplastic meningitis in athymic nude rats. Although busulfan has only limited activity against solid tumors, the high doses achievable in the CSF following intrathecal administration coupled with the steep dose-response relationships of alkylating agents, provide rationale for further evaluation of this agent.

Preparation and Characterization of Microcrystalline and Epitactially Grown Emitter Layers for Silicon Solar Cells

AbstractWe have deposited thin B- and P-doped Si layers by electron cyclotron resonance CVD on c- Si (4 Ωcm, CZ) and on quartz glass substrates at T=325°C. Films grown on quartz glass are of microcrystalline nature with crystalline volume fractions of about 70 % and a resistivity ranging from 0.01 - 10 (Ωcm)−1 depending on doping concentration. The doping efficiency is close to unity with the carrier mobility being independent of doping concentration for both B- and Pdoping. Films grown on c-Si, on the other hand, exhibit perfect homoepitaxial morphology when the gas phase doping concentration exceeds 1000 ppm and 5000 ppm for P- and B-doping, respectively. The quality of the films is tested by preparing thin film emitter solar cells. We find efficiencies above 11 % for cells without ARC. The result are compared to cells with diffused emitters, otherwise prepared with the same technological steps.

The crystal structure and changes of (NH4)1.4[Cu(NH3)2]0.3Br2 composition

Abstract The crystal stucture of (NH4)1.4[Cu(NH3)2]0.3 · Br2 is composed from a NH4Br structure where part of NH4 + ions was replaced with NH3 groups. The Cu atoms statistically occupy the centre of a cubic unit cell, with Br− ions in its apexes resulting in the creation of linear [H3N–Cu–NH3]2+ units. The statistical weight of the cationic units is 0.13(1). The Cu–N and Cu–Br− bond distances are 2.0293(4) (2 ×) and 2.8699(5) (4 ×) Å, respectively. Microcrystalline preparations having the composition of (NH4)2(1 − x)[Cu(NH3)2] x Br2 (x = 0.0 to 0.92) show continuous logarithmic normal x vs. density dependence. The formula for calculation of x from density (Dm ) of crystalline and microcrystalline preparations was derived.

金属線への気相成長ダイヤモンドの微結晶コーディング

Fine-grained diamond coating was obtained on W, Mo or Ti wire substrates by the microwave plasma CVD method from a gas mixture of the CO-H2 system. The effects of CVD parameters on a uniform coating of polycrystalline diamond were investigated under the constant conditions of reaction time (5 h) and CO concentration (5 vol%), using the wire substrates mounted horizontally on a pyrophyllite susceptor. Homogeneous and fine-grained diamond film was prepared on the whole surface of W wire substrate with the wire height of 2 mm from the susceptor, which was placed parallel to the irradiation direction of microwave power (750-1100 W). Deposition conditions under higher microwave power, lower pressure and lower wire height were found to be suited for preparation of microcrystalline and uniform coating of diamond. Plasma density and substrate temperature are considered to have great influences on the nucleation of diamond.

Electron crystallography of membrane phospholipids

Membrane phospholipids are notoriously difficult to crystallize to sample sizes suitable for collection of single crystal X-ray intensity data, accounting for the relatively few crystal structures which have been reported to date. At the 24th Annual EMSA meeting, Parsons and Nyburg suggested that the enhanced scattering of electrons by matter be exploited to obtain single crystal electron diffraction patterns from the more readily available microcrystalline preparations, an example of which was shown in a subsequent paper. For almost 20 years ve have investigated the utility of such intensity data forab initiocrystal structure analysis.

ホウ素ドープ微結晶化Ｓｉ：Ｈ膜の評価

Preparation and structure of B-doped microcrystalline hydrogenated silicon (Si : H) films produced by a glow-discharge decomposition method were studied at a low substrate temperature (120°C). The microcrystallization was confirmed to occur at 2% of SiH4 gas diluted by H2 and 200 W of the rf power of glow discharge. The Raman specta of Si : H films showed that the structure of microcrystals had a tensile stress. The tensile stress increased with increasing in SiH2 concentration in Si : H films. It was considered that divalent silicon atoms existed as defects in the Si : H films. Analysis of B in Si : H films by a secondary ion mass spectrometer (SIMS) showed that the concentration of B doped in microcrystalline Si : H films was lower than that in amorphous films.

Chemistry and Solid State Physics of Microcrystalline Silicon

AbstractVarious methods for the preparation of microcrystalline (nanocrystalline) silicon are summarized and compared with respect to the possibility of the control of the materials quality and scaling of the deposition process to large area applications. It is shown that the deposition of a pure microcrystalline material is achieved under conditions close to partial chemical equilibrium. The mechanism of the crystallization during the growth will be briefly discussed.The second part of the paper deals with the physical properties of pure microcrystalline silicon which is free of any amorphous phase detectable by X-ray diffraction, i.e. less than about 1 vol%. Several aspects of electric conductivity, optical absorption and Raman scattering which have been frequently misinterpreted in the literature will be reviewed.

5-Methoxypsoralen (Bergapten) for photochemotherapy: Bioavailability, phototoxicity, and clinical efficacy in psoriasis of a new drug preparation

In a previous study we evaluated a microcrystalline preparation of 5-methoxypsoralen (5-MOP; Bergapten) for its photochemotherapeutic properties. Preliminary data indicated that the clinical efficacy of 5-MOP is comparable to that of 8-methoxypsoralen. 5-MOP appeared as a promising alternative photosensitizer for the management of psoriasis because of the almost complete lack of phototoxic and drug intolerance reactions that are frequently encountered in patients undergoing 8-MOP photochemotherapy. With a new liquid preparation of 5-MOP we have now extended our earlier investigation on a larger clinical scale and have correlated the clinical response with the bioavailability of the drug. Serum level determinations showed an absorption rate of only approximately 25% that of 8-MOP. When administered in the same dosage as 8-MOP, 5-MOP turned out to be significantly less effective; however, by doubling the oral dosage, comparable results in terms of clearing of psoriasis were obtained. Also with this high-dose 5-MOP regimen, no drug intolerance was noted and other side effects, such as severe erythema, pruritus, and nausea, occurred only rarely. We propose 5-MOP as a valuable alternative for photochemotherapy (PUVA) of PUVA-responsive diseases.

Quantitative Crystal Structure Analysis In The Electron Microscope

Electron crystallography is a term which has emerged in the past few years to describe the quantitative structure analysis of microcrystalline preparations in the electron microscope. The field represents the confluence of two techniques, i.e. the ultramicroscopic capabilities of the electron microscope coupled with analytical techniques long in use by X-ray crystallographers. In the area of organic materials, the most visible success of the technique to date has been in the structure analysis of thin protein microcrystals typically to ca20 Å resolution but sometimes out to e.g. 7 Å and, in this field, there has been considerable effort by an increasing number of laboratories.Although the electron crystallography of small organic molecules and linear polymers has a much longer history than the application to globular proteins, one cannot cite an overwhelming enthusiasm for this technique, despite its promise as a probe for molecules which are not easily crystallized to sample sizes useful for single crystal X-ray diffraction measurements.

Studies of pharmacokinetics and therapeutic effects of glucocorticoids entrapped in liposomes after intraarticular application in healthy rabbits and in rabbits with antigen-induced arthritis.

Dexamethasone palmitate (DMP) entrapped in liposomes of defined sizes was administered intraarticularly in healthy rabbits and in rabbits with antigen-induced arthritis. The pharmacokinetics and therapeutic effect of liposomal DMP were measured and compared with corresponding experiments using microcrystalline triamcinolone acetonide (TAC). The small DMP liposomes (diameter 160 nm) showed a greater decrease in joint circumference than the 3-times-higher dose of microcrystalline TAC. Moreover, about 98% of administered TAC had already disappeared from the joint 6 h after injection, whereas about 36% of liposomal DMP was still measured in synovial fluid and synovium at the same time. Increasing the vesicle diameter from 160 to 750 nm (large liposomes) improved the retention of DMP by a factor of 2.6 within 48 h after injection in healthy rabbits. In addition, none of the liposomal glucocorticoid preparations ever suppressed the endogenous plasma cortisol level, which is in contrast to the suppression measured after administration of the microcrystalline preparation.

Prolonged Release Extradural Morphine

Abstract The effects of extradural administration of a microcrystalline preparation of morphine (Duromorph) were studied in 5 patients with postoperative or malignant pain. As assessed by pain scores on a visual analogue scale, the effects of the analgesic were extremely variable; the best results were obtained in patients with postoperative pain. Two patients with chronic pain due to malignant disease developed slow respiratory rates. The plasma concentration of morphine usually followed a biphasic pattern; an initial peak between 0.5 and 1.5 hours was succeeded by a second, large peak between 6 and 12 hours. There was little or no apparent relation between the plasma concentration of morphine and the relief of pain, suggesting that Duromorph may have a local effect on the spinal cord.

Investigation of absorption, metabolism kinetics and dna-binding of intratracheally administered benzo[ A]-pyrene in the isolated, perfused rat lung : A comparative study between microcrystalline and particulate adsorbed benzo[ A]pyrene

Benzo[a]pyrene (B[a]P) adsorbed onto urban air particles (UAP) or in microcrystalline form (MCr) was administered intratracheally to the isolated perfused lung in doses of 100 and 1.5 micrograms. The appearance rate constant calculated for B[a]P release to the perfusate buffer was significantly lower for B[a]P administered adsorbed onto UAP (0.007 +/- 0.002 min-1) compared to the microcrystalline preparation (0.051 +/- 0.030 min-1). A classical two-compartmental model fitted well to the elimination of B[a]P from the perfusate buffer, after administration in solution to the buffer reservoir; C = 24 e-0.05t + 14 e-0.01t (pmol/ml). The concentration of polar metabolites in the perfusion buffer, at the end of experiments was approx. 9-fold higher for lungs administered the microcrystalline preparation compared to UAP at 1.5 microgram doses. At the 100 microgram dose level, the difference between preparations was only 2-fold, the data indicating that enzyme saturation might be important at the high dose level. With regard to the metabolite pattern, adsorption of B[a]P onto urban air particles caused a relative increase in the formation of B[a]P-9,10-dihydrodiol, whereas the relative formation rate for phenols was decreased. The absolute levels of B[a]P metabolites covalently bound to DNA was significantly higher in lungs given the MCr preparation compared to the UAP. When calculated as the amount metabolites bound, in relation to the total amount polar metabolites at the end of perfusion, however, the UAP preparation was significantly more efficient to enhance the production of DNA binding metabolites; 2.62 +/- 0.59 X 10(-5) vs. 1.33 +/- 0.21 X 10(-5) (pmol covalently DNA-bound metabolites/mg DNA/pmol metabolites formed). The results indicate that urban air particles may exert a cocarcinogenic effect with polynuclear aromatic hydrocarbons by increasing the pulmonary residence time for the carcinogenic hydrocarbon and/or alter the metabolite pattern in a way that enhances the covalent binding of metabolites to DNA.

Electron crystal structure analysis of small organic molecules

AbstractElectron crystallography of small organic molecules, i.e., electron diffraction crystal structure analysis, has been long recognized to possess definite advantages over neutron and x‐ray diffraction techniques for the investigation of microcrystalline preparations. Quantitative application of the technique to real structural problems, on the other hand, had been hindered initially by an inadequate theoretical model. Yet, as demonstrated in this review of the methodology, the adequate recognition of limiting factors due to n‐beam dynamical scattering and crystal deformation permits design of optimal diffraction experiments which yield intensity data suitable for ab initio structure analysis. Representative crystallographic analyses discussed here underscore the utility of this technique as a probe of organic molecular structure at atomic resolution.

The crystallization of outer membrane proteins from Escherichia coli. Studies on lamB and ompA gene products.

The outer membrane protein LambB from Escherichia coli has been crystallized from detergent-containing solutions. Several different crystal habits can be obtained under the same ionic and precipitant conditions by altering the detergent head group composition of the protein-detergent mixed micelle or by adding polar organic compounds. Two crystal forms have been partially characterized as P1 and C2221, the former diffracting to beyond 4 A resolution and the latter to 6 A. The detergents used were beta-octyl glucoside, octyl tetraoxyethylene, and octyl polyoxyethylene (polydisperse) either alone or as mixtures. In some experiments, the addition of small nonionic amphiphiles having n-butyl alkyl tails significantly influenced crystallization. The experiments suggest that the detergent region of the mixed micelle plays a critical role in crystal formation. Using the methods developed here for LamB and also for matrix porin (Garavito, R. M., Jenkins, J. A., Jansonius, J. N., Karlsson, R., and Rosenbusch, J. P. (1983) J. Mol. Biol. 164, 313-327), an additional protein from the outer membrane, OmpA, has been obtained as a microcrystalline preparation.

Intra-articular Corticosteroids

Local corticosteroid injections are a relatively safe and effective adjunct in managing rheumatoid arthritis, other connective tissue arthropathies, and soft tissue rheumatism. Rheumatoid synovitis may be suppressed for three months or longer using relatively insoluble microcrystalline preparations. No convincing evidence exists, however, that joint erosive changes are retarded, and steroid injections should be considered ancillary to rest, physical therapy, nonsteroidal anti-inflammatory agents, and disease modifying antirheumatic drugs. The few controlled studies in hip and knee osteoarthritis have demonstrated only modest, fleeting beneficial effects. Nonetheless, clinical experience suggests that intra-articular steroids often ameliorate acute exacerbations of knee osteoarthritis associated with significant effusions, symptomatic involvement of interphalangeal and other nonweight-bearing articulations, synovial cysts, and lumbar facet arthropathy. Judicious use of intrasynovial injections seldom produces significant adverse effects. Iatrogenic infectious arthritis follows one in 14,000-50,000 injections. Rapid acceleration of cartilage attrition is observed rarely. The concept of "corticosteroid arthropathy" is based largely on subprimate animal studies and several anecdotal case reports; limited investigation of primate (monkey) models has shown no significant long-term deleterious effect on cartilage.

Clinical and pharmacological observations on a new oral preparation of theophylline

AbstractA single-blind, crossover study was carried out in 11 patients with reversible airway obstruction to assess the clinical response related to plasma concentrations achieved with an oral microcrystalline preparation of theophylline (‘Nuelin”). There were 9 males and 2 females, with a mean age of 51 years (range 19 to 68 years). Eight of them had chronic obstructive bronchitis (2 with emphysema) and 3 had bronchial asthma. The mean duration of disease was 14 years (range 3 to 30 years). Three of the patients were smokers. Patients were included only if they had a reversible condition shown by an improvement of 20% or more in the forced expiratory volume in 1 second (FEV.,) or peak expiratory flow rate (PEFR) after 2 to 3 puffs (aerosol) of isoproterenol or rimiterol.Plasma concentrations were measured both after a single dose and during a dosing interval at steady-state. When these tablets were given 250 mg at 6-hourly intervals for 6 days, minimum plasma theophylline concentrations in 8 patients ave...

Pharmacology, Toxicity, and Therapeutic Usefulness of Amphotericin B

The polyene antibiotic, amphotericin B, has been used clinically for nearly ten years, and during this time, it has played a paramount role in the treatment of systemic fungal diseases. Recently reported studies not only have confirmed the early favorable reports but have served to define more clearly the degree of effectiveness of the drug in treatment of specific fungal infections. In addition, certain aspects of the pharmacological and toxic properties of the drug have been explained. Drug Preparations Amphotericin B is available in two types of preparations, one which forms a microcrystalline suspension and the other which forms a colloidal suspension in water. Microcrystalline Preparation.— This material is marketed in two forms. The first is for topical application and includes 3% amphotericin B in appropriate vehicles to form a lotion, cream, or ointment. It has been used for topical application in superficial Candida infections. 1 The second, or oral

Effective use of griseofulvin.

Confirmation of the increased gastrointestinal absorption of microcrystalline griseofulvin is provided. Serum levels of griseofulvin after administration of the microcrystalline preparation can again be doubled by administration of the dose after a fatty meal. Proper utilization of this pharmacologic knowledge is essential to the effective therapeutic management of human cutaneous fungus disease.