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Novel approach to estimate quality of binary random powder mixtures: samples of constant volume. I: Derivation of equation.

An equation of the quality of binary random mixtures that applies to powder samples of constant bulk volume was derived from the binomial distribution. In contrast to the Stange-Poole equation for samples of constant mass, this approach can also be used for constituents with large differences in particle size and in bulk density. The validity of this equation was verified with tablets directly compressed from mixtures composed of equal mass proportions of sucrose [volume-weighted/volume-number mean diameter (dv), 504 microns] as the coarse ingredient (A) and of a microcrystalline cellulose (Avicel PH 101)-talc mixture (dv, 60 microns) as the fine constituent (B). Because of the difference in the bulk densities of A and B, the equation estimated a coefficient of the random content variation, which for A was double that for B. The content variations found with the tablets were in excellent agreement with the calculated values and reflected the differences predicted from theory. The Stange-Poole equation yielded identical values of the content variations of A and B, which is in contrast to the experimental results.

Chemistry, Pharmaceutical↗

Novel approach to estimate quality of binary random powder mixtures: samples of constant volume. II: Applications of equation to optimize tableting conditions.

In a companion communication, an equation (eq 1) of the homogeneity of binary random mixtures, which applies to constituents differing in particle size and in bulk density, was derived. The present paper demonstrates the practical applications of this equation in optimizing tableting conditions with respect to a high dose uniformity. Tablets of 50:50 (w/w) mixtures of coarse sucrose and of fine microcrystalline cellulose (Avicel PH 101)-talc vehicle were produced on a single-punch machine. Without a spin feeder, the tablets showed variations in content uniformity that were significantly higher than those estimated from eq 1. Correlation analysis between the individual mass and the content of the constituents of the tablets revealed this difference to be due to nonuniformity of the die filling and not due to incomplete mixing. Accordingly, the use of a spin feeder allowed production of tablets with higher dose uniformity, which conformed well with the theoretical optimum predicted with eq 1. Further variation of the processing conditions cannot improve the quality (i.e., varying the tableting speed resulted in equal or in poorer uniformity of dose content).

Algorithms↗

Novel approach to estimate quality of binary random powder mixtures: samples of constant volume. III: Range of validity of equation.

The validity of an equation developed to determine the quality of binary random mixtures (eq 1) was evaluated with tablets prepared from random mixtures of a coarse constituent A (sucrose) and fine constituent B [microcrystalline cellulose (Avicel PH 101)-talc] with the A:B ratios (w/w) varying from 10:90 to 80:20. With all A:B ratios, superior agreement was established between the random content variations determined with eq 1 and the content variations found in the tablets. The 80:20 ratio, however, was just at the boundary, and random quality was achieved with the 50-mg tablets but not with the 200-mg tablets because of segregation. From percolation theory, this result is a consequence of the small proportion by volume (bv) of B that is almost equal to the precolation threshold (Pcb) of B of 0.3. With bv less than Pcb, the fine constituent B does not form a coherent lattice, and eq 1 is no longer valid. To estimate the volume proportions av and bv from the mass proportions a and b, two methods were established. Method 1 assumed the bulk densities of A and B to be representative and was used when av was higher than the percolation threshold (Pca) of A of 0.3 (a, 0.5). Method 2 used the true particle density of A and was valid with av values of less than 0.1 (a, 0.3), in which case the particles of A were dispersed as individuals in the matrix of B.

Chemistry, Pharmaceutical↗

Survival after conservative (palliative) management of pleural malignant mesothelioma.

BACKGROUND AND OBJECTIVES: Malignant mesothelioma is a lethal disease. Aggressive multimodality treatment protocols are reportedly associated with improved survival, but the apparent survival benefits may simply reflect patient selection and the variable natural history of this malignancy. Before embarking on our own protocol of experimental treatment for mesothelioma, we sought to identify important prognostic factors and document the survival of patients treated conservatively (with palliative intent only) in our region. METHODS: We performed a retrospective review of all patients with a diagnosis of malignant mesothelioma seen at our center between 1987 and 1999. Since curative intent treatment had not been given, we assumed that measured survival would largely reflect the natural history of the malignancy. RESULTS: There were 101 patients (80 males and 21 females). Mean age was 65 +/- 9.2 years. Symptoms of disease were present for a median time of 5 months before the diagnosis was established. The most common presenting symptoms were dyspnea (46 patients), chest pain (30 patients), and weight loss (22 patients). Sixty-eight patients (68%) had a history of asbestos exposure. Mesothelioma subtypes included epithelial (43 patients), sarcomatous (26 patients), mixed (19 patients), desmoplastic (4 patients), and unspecified (9 patients). All 101 patients were treated with palliative intent. Talc pleurodesis was performed in 70 patients. At the time of analysis, 90 patients had died and 11 remained alive. Median survival was 213 (95% CI 137-289) days. Survival for the three major histological subtypes was significantly different (log rank, P = 0.0016). Histological subtype (epithelial favorable) was the only significant independent prognostic factor (Cox proportional hazard regression, P = 0.0009). CONCLUSIONS: Patients with epithelial mesothelioma survive longer than those with other histological subtypes. Conservatively managed patients with pleural malignant mesothelioma have a median survival of approximately 7 months. These data from conservatively treated patients can serve as baseline information for future studies of experimental treatments.

Adult↗

Biobased contents of biodegradable poly(epsilon-caprolactone) composites polymerized and directly molded using aluminium triflate from caprolactone with cellulose and inorganic filler.

Poly(epsilon-caprolactone) (PCL) composite samples were prepared by polymerization and direct molding. The starting compound was epsilon-caprolactone monomer liquid combined with cellulose and inorganic fillers, using aluminium triflate as a catalyst at 80 degrees C, for 6 or 24 h. Cylinder-shaped PCL composite samples with a homogeneously dispersed cellulose filler were prepared with (-)M(n) = 4 600 ((-)M(w)/(-)M(n) = 2.9). The mechanical properties of the PCL composite samples were studied using compression test methods. The strength of a PCL composite with 50 wt.-% cellulose filler (10.8 MPa) was found to be lower than the PCL sample without fillers (19.2 MPa). The biobased content of the PCL composite with 50 wt.-% cellulose filler (51.67%) measured using accelerated mass spectrometry (AMS) was slightly higher than the carbon ratio of cellulose in the starting powder samples (41.3 mol-%). The biobased content of the polymer composite powders by AMS was found not to be affected by the presence of inorganic fillers, such as talc. The rate and extent of biodegradation, caused by Amano Lipase PS, of the PCL composite sample with cellulose filler (40% degradation in 4 d) was the same as that of a PCL sample without the cellulose filler.

Biodegradation, Environmental↗

Chemometric evaluation of time-of-flight secondary ion mass spectrometry data of minerals in the frame of future in situ analyses of cometary material by COSIMA onboard ROSETTA.

Chemometric data evaluation methods for time-of-flight secondary ion mass spectrometry (TOF-SIMS) have been tested for the characterization and classification of minerals. Potential applications of these methods include the expected data from cometary material to be measured by the COSIMA instrument onboard the ESA mission ROSETTA in the year 2014. Samples of the minerals serpentine, enstatite, olivine, and talc have been used as proxies for minerals existing in extraterrestrial matter. High mass resolution TOF-SIMS data allow the selection of peaks from inorganic ions relevant for minerals. Multivariate cluster analysis of peak intensity data by principal components analysis and the new method CORICO showed a good separation of the mineral classes. Classification by k nearest-neighbor classification (KNN) or binary decision trees (CART method) results in more than 90% correct class assignments in a leave-one-out cross validation.

Journal Article↗

Transfection of human mesothelial cells mediated by different asbestos fiber types.

Several different asbestos fiber types mediate transfection of human mesothelial cells by exogenous DNA. We have employed the human MeT-5A mesothelial cell line, which allows the use of DNA replication as an assay for entry of DNA when plasmids bearing the SV40 origin of replication are used for transfection. We find that Canadian chrysotile, Calidria chrysotile, amosite, and crocidolite are each capable of introducing plasmid pSVod DNA into MeT-5A cells followed by subsequent replication of a fraction of the plasmid DNA. A significant fraction of the input plasmid DNA associated with the cells in the presence of asbestos is fragmented, and this fragmentation is particularly evident with crocidolite. Each of the fiber types is highly cytotoxic for the MeT-5A cells, and these cells actively accumulate the added fibers from the surrounding environment as visualized by phase-contrast microscopy. MeT-5A cells were transfected at higher efficiency with calcium phosphate than were several other primate cell lines. Calcium phosphate, however, did not induce fragmentation of the input plasmid DNA. Compared with several different mineral agents, including glass fibers, kaolin, and talc, Calidria chrysotile fibers were most effective at mediating transfection of the MeT-5A cells. Results provide a mechanism by which transfection can contribute to mutagenicity of asbestos fibers and indicate that this mechanism can operate in human mesothelial cells.

Asbestos↗

Computational Studies on Interaction between Air Bubbles and Hydrophobic Mineral Particles Covered by Nonpolar Oil.

Computations based on the extended DLVO theory are carried out on the potential energies of interactions between air bubbles and talc particles covered by nonpolar oil. It is shown that the major role of nonpolar oil in this system is to greatly increase the depth of the primary energy valley, giving rise to a much stronger bubble-particle aggregate that can support greater aggregate-rupture force fields from turbulent flows. Also, due to nonpolar oil involvement, the energy barrier between bubbles and mineral particles sharply collapses down and further separates, indicative of a greater probability of attachment of mineral particles to air bubbles. A linear relationship is found between the primary energy valley and the contact angles of oil or bubbles, and thus a simple and approximate formula is presented to evaluate the depth of the primary energy valley. In addition, it is found that the primary energy valley and the energy barrier are directly proportional to the effective particle radius, but the barrier location is independent of the effective particle radius. Copyright 1999 Academic Press.

Journal Article↗

Conformational Changes of Bovine Serum Albumin Induced by Adsorption on Different Clay Surfaces: FTIR Analysis.

Interactions between proteins and clays perturb biological activity in ecosystems, particularly soil extracellular enzyme activity. The pH dependence of hydrophobic, hydrophilic, and electrostatic interactions on the adsorption of bovine serum albumin (BSA) is studied. BSA secondary structures and hydration are revealed from computation of the Amide I and II FTIR absorption profiles. The influence of ionization of Asp, Glu, and His side chains on the adsorption processes is deduced from correlation between p(2)H dependent carboxylic/carboxylate ratio and Amide band profiles. We quantify p(2)H dependent internal and external structural unfolding for BSA adsorbed on montmorillonite, which is an electronegative phyllosilicate. Adsorption on talc, a hydrophobic surface, is less denaturing. The results emphasize the importance of electrostatic interactions in both adsorption processes. In the first case, charged side chains directly influence BSA adsorption that generate the structural transition. In the second case, the forces that attract hydrophobic side chains toward the protein-clay interface are large enough to distort peripheral amphiphilic helical domains. The resulting local unfolding displaces enough internal ionized side chains to prevent them from establishing salt bridges as for BSA native structure in solution. On montmorillonite, a particular feature is a higher protonation of the Asp and Glu side chains of the adsorbed BSA than in solution, which decreases coulombic repulsion. Copyright 2000 Academic Press.

Journal Article↗

Formation of Layered Single- and Double-Metal Hydroxide Precipitates at the Mineral/Water Interface: A Multiple-Scattering XAFS Analysis.

Spectroscopic and microscopic studies have shown that Ni and Co sorption by clay minerals may proceed via formation of surface precipitates. Several studies employing X-ray absorption fine structure (XAFS) spectroscopy suggested the formation of turbostratic, alpha-type metal hydroxides, of layered double hydroxides (LDH) with Al-for-metal substitution, and of 1:1 or 2:1 phyllosilicates. Distinction of these phases is difficult because they have low crystallinity and/or a small mass compared to the sorbents, and because they have similar metal-metal distances in their hydroxide layers/sheets. Distinction of these phases is crucial, however, because they have substantially differing solubilities. In this paper we show that an XAFS beat pattern at about 8 Å(-1) can be used as a fingerprint to unequivocally distinguish LDH from the alpha-type hydroxides and phyllosilicates. Full multiple-scattering simulations and experimental spectra of model compounds indicate that the beat pattern is due to focused multiple scattering at Me/Al ratios between 1 and 4 (Me=Ni, Co). By applying the fingerprint method to new and to already published XAFS data on Ni and Co surface precipitates, we found that LDH preferentially forms in the presence of the Al-containing sorbents pyrophyllite, illite, kaolinite, gibbsite, and alumina above pH 7.0. However, alpha-type metal hydroxides form in the presence of the Al-free sorbents talc, silica, and rutile, and in the presence of the Al-containing clay minerals montmorillonite and vermiculite. We believe that the high permanent charge of these latter minerals prevents or retards the release of Al. When Al is available, the formation of LDH seems to be thermodynamically and/or kinetically favored over the formation of alpha-type hydroxides. Copyright 2000 Academic Press.

Journal Article↗

Foveal avascular zone in macular branch retinal vein occlusion.

The mean area of the foveal avascular zone (FAZ) in normal subjects was reported as 0.231 mm2 to 0.405 mm2, using fluorescein angiography. The FAZ enlarges in vaso-occlusive diseases, especially diabetic retinopathy, sickle cell retinopathy, talc retinopathy and branch retinal vein occlusion. In the present study the FAZ of 20 patients affected by macular branch retinal vein occlusion (MBRVO) was compared with the FAZ of 41 control subjects. The FAZ mean area was 0.56 +/- 0.34 mm2 SD in the MBRVO group, while 0.26 +/- 0.07 mm2 SD in the control group, with a statistically significant difference (p < 0.001). The FAZ mean perimeter was 4.77 +/- 1.90 mm SD in the MBRVO group, and 2.36 +/- 0.32 mm SD in the control group, with a statistically significant difference (p < 0.001). Taking into account the MBRVO group, a statistical correlation was found between visual acuity impairment and FAZ enlargement (p = 0.02), but not between visual acuity impairment and macular edema (p = 0.41). In 14 cases (70%) secondary avascular microzones located in the macular sector correspondent to MBRVO were also evident. MBRVO causes an irregular enlargement of the FAZ which seems to represent the most important feature related to visual acuity impairment.

Aged↗

Thoracoscopic surgery in the elderly population.

BACKGROUND: We review our experience in video-assisted thoracoscopic surgery (VATS) on patients over 75 years of age from a single institution. METHODS: From September 1992 to November 1995, 22 patients (13 males and 9 females with mean age of 78.1 years) underwent the following procedures: pleural biopsies with or without drainage and decortication (5), drainage of empyema (2), wedge lung biopsy (3), bullectomy and talc insufflation (1), major lung resections (5), mediastinal biopsy (1), pericardiectomy (3), and thymectomy (2). Pulmonary function tests of the entire group showed the mean forced expiratory volume in 1 s (FEV1) to be 1.46 1 (range 0.63-2.11) and forced vital capacity (FVC) to be 2.04 (range 0.98-3.55) 1. RESULTS: There was no mortality. Morbidity included prolonged chest drainage over 7 days in two patients (9.1%), one of whom was discharged with a drainage bag. Particularly of note was the lack of postoperative pulmonary complications. CONCLUSIONS: We conclude that VATS in the elderly population is safe. Age alone should not be a contraindication for major lung or mediastinal surgery.

Aged↗

Port-site recurrence following video-assisted thoracoscopic surgery.

Video-assisted thoracoscopic surgery (VATS) is an established modality in the management of pleural diseases. We report a case of port-site recurrence following management of malignant pleural effusion in an elderly patient with extensive pleural metastasis from adenocarcinoma of the lung. Although her shortness of breath was relieved following VAT decortication and talc insufflation, at 3 months she was found to have a 2.5-cm subcutaneous nodule at the camera port site which on biopsy was confirmed to be metastatic in nature. Even though the nodule was asymptomatic and the patient prognosis was not affected, it is important that both the surgeon and future patients should be aware of this potential complication.

Adenocarcinoma↗

Hypersensitivity and cross-reactivity to cisplatin and analogues.

We report on a 49-year-old woman with relapsing ovarian cancer who developed a hypersensitivity reaction (HSR) to carboplatin and, subsequently, to cisplatin. This patient was known to be allergic to Co-Amoxiclav and talc, both giving rise to a transient macular skin rash, but had no other history of atopy. Similar cases, including some of life-threatening severity, have been reported in the literature. These severe reactions may prevent a small population of young patients from receiving effective therapy with cisplatin or its analogues, treatment known to be associated with a significant improvement in survival in germ-cell tumours, ovarian cancer and osteogenic sarcoma.

Carboplatin↗

Increase in TCR gamma delta T lymphocytes in synovia from rheumatoid arthritis patients with active synovitis.

To determine the relative presence of TCR gamma delta+ and TCR alpha beta+ T cells in synovial tissue from patients with various types of inflammatory synovitis and in tissues from patients with a number of chronic T cell-mediated conditions, we stained frozen tissue sections with monoclonal antibodies in indirect immunofluorescence assays. In tissues obtained from patients with chronic T cell-mediated granulomatous conditions (Wegener's granulomatosis, lymphomatoid granulomatosis, granuloma annulare, Langerhans' cells granulomatosis, pigmented villonodular synovitis, Takayasu's arteritis, and talc granulomatosis), the T cells present were predominantly TCR alpha beta+, without an increased presence of TCR gamma delta+ cells. In contrast, 6 of 14 (43%) synovia from patients with rheumatoid arthritis (RA) showed increased TCR gamma delta+ T cells (3-10 cells/hpf). The RA synovia with increased TCR gamma delta+ cells present had an increased tissue inflammation score compared to RA synovia with few TCR gamma delta+ cells [18.6 +/- 5.8 versus 11.6 +/- 4.2 (mean +/- SE), P less than 0.05]. In contrast, synovia from patients with osteoarthritis, systemic lupus erythematosus, and trauma did not show an increased presence of TCR gamma delta+ T cells. Thus, in cellular inflammatory infiltrates the presence of increased TCR gamma delta cells is not a component of noninfectious granulomatous inflammation but is found in approximately 40% of RA synovia with high levels of inflammation.

Adult↗

Asbestos-mediated transfection of mammalian cell cultures.

The capacity of asbestos to mediate transfection was tested in a rapid and relatively simple system: picornavirus RNAs and mammalian cells in vitro. Thirteen asbestos samples, including amosite, anthophyllite, chrysotile, and crocidolite, 4 picornaviruses (poliovirus 1 and 2, echovirus 7, and encephalomyocarditis virus), and 4 cell lines (CLI, chimpanzee liver; KB, human carcinoma; eta, monkey kidney; NIH 3T3, mouse embryo) were tested. The results showed that all asbestos samples mediated transfection and that all cell lines were transfectible by viral RNA with asbestos. Transfection was much greater with asbestos added to the viral RNA inoculum than to the cells before or after the RNA. Transfection was directly proportional to asbestos concentration. Initiation of transfection events was rapid, with half becoming irreversible by washing 2 min postinoculation. DNA in the inoculum strongly interfered with asbestos-mediated transfection by the RNA but was ineffective when added, with or without asbestos, to the cells before or after the inoculum. Asbestos compared with six classical "insoluble" facilitators (bentonite, calcium phosphate, chromic oxide, ferric oxide, kaolin, talc) was of intermediate rank in transfection mediation. It is hypothesized that the prominence of asbestos in carcinogenesis is due to a combination of properties, including transfection mediation as well as chromosome mutagenicity, fiber dimensions, biological durability, hydrocarbon transport, and prevalence.

Adsorption↗

A comparative analysis of macrophage activation in C57B1/6 mice treated with inflammatory compounds or bearing Lewis lung carcinoma.

The different percentages of acid hydrolases released by peritoneal macrophages obtained from C57B1/6 mice injected i.m. with talc, carrageenan or 3LL cells, and also the demonstration that hydrolase secretion from in vitro macrophage monolayers of tumor-bearing mice undergoes a further increase when zymosan is added to the culture, strongly suggest the possibility that more than one membrane surface receptor is involved in the triggering of lysosomal enzyme release. Furthermore, there is evidence from the reported results that, besides immune complexes, neoplastic cells or their metabolic product(s) could act as inducers of the lysosomal enzyme secretion by macrophages.

Acetylglucosaminidase↗

Characterization of the physicochemical properties of KR-31378.

KR-31378 is a new drug candidate intended for the use in the prevention of ischemia-reperfusion damage. The objective of this preformulation study was to determine the physicochemical properties of KR-31378. The n-octanol to water partition coefficients of KR-31378 were 0.0504 at pH 3 and 0.8874 at pH 10. Accelerated stability of KR-31378 in solution and solid state was studied at 5, 40, 60 degrees C. The stability testing indicated that the t90 for the drug in solid was estimated to be 2 years and 128.6 days at 25 degrees C, while that in aqueous solution was 68.6 days at 25 degrees C. The KR-31378 was also found to be unstable under the relative humidity of 76%, probably because of the hygroscopic nature of the drug. In order to study compatibility of KR-31378 with typical excipients, potential change in differential scanning calorimetry spectrum was studied in 1:1 binary mixtures of KR-31378 and Aerosil, Avicel, Eudragit, lactose, PEG, talc, CMC, PVP, starch. As a result, CMC, PVP, and starch were found to be incompatible with KR-31378, indicating the addition of these excipients may complicate the manufacturing of the formulation for the drug. Particle size distribution of KR-31378 powder was in the size range of 9-93 microm with the mean particle size of 37.9 microm. The flowability of KR-31378 was apparently inadequate, indicating the granulation may be necessary for the processing of the drug to solid dosage forms. Crystallization of the drug with a number of organic solvents did not lead a crystalline polymorphism. In addition, dissolution of the drug from the powder was adequately rapid at 37 degrees C in water.

Chemical Phenomena↗