Effects of Environmental Temperature and Compression Energy on Polymorphic Transformation During Tabletting

The effects of temperature on the polymorphic transformation and the compression of chlorpropamlde forms A and C during tabletting were investigated by X-ray diffractometry. The X-ray diffraction profiles of the sample powders deagglomerated after compression were recorded to calculate the degree of polymorphic transformation. A single punch eccentric tabletting machine equipped with two load cells (upper and lower punches) and with a noncontact displacement transducer was used to measure the compression stress, energy and distance between punches. A heater and a liquid nitrogen pool were mounted on the die of the tabletting machine, and the die temperature was controlled with a thermocontroller. Two types of compression methods, multi-tabletting at room temperature and single tabletting at 0-45°C, were used in the present study. In the first method, the stable form A or metastable form C was loaded in to the die and the sample was compressed with a compression stress of 196 MPa. Compression was repeated from 1 to 30 times. The results for forms A and C suggested that both forms were mutually transformed, and that the content of forms A and C reached equilibrium above 100 J/g of compression energy after more than 10-times compression. After 30-times compression, the content of A, C, and the noncrystalline solid form were almost constant at about 45%, 25% and 30%, respectively. The compression energy was estimated to be 500-600 J/g. In the second method, single tabletting at 0° and 45°C, the amount of form C transformed from form A at 45°C was about two times larger than that at 0°C at the same compression energy. The amount of form A transformed from form C at 45°C was almost the same as that transformed at 0°C. This suggests that the mechanochemical stability of form A was affected by compression temperature, while that of form C was independent of temperature. The crushing strength (CS) of from A tablet was about two times higher than that of form C even at the same porosity. The relationships between log (CS) of form A tablets compressed at 0 or 45°C and porosity showed straight lines with the same slope, but the slope for form C tablets compressed at 45°C was smaller than that for those compression at 0°C. From these results it appears that the transformation mechanism of forms A and C during compression was as follows: Form A or C was converted to a noncrystalline solid by mechanical energy, and then the solid was transformed into form A or C. The transformation of every form was affected by the environmental temperature.     

A far-infrared spectroscopic study of low temperature soft phonon mode in Tris-Sarcosine Calcium Chloride(TSCC)

Temperature dependences of the soft phonon frequency and the damping constant in Tris-Sarcosine Calcium Chloride (TSCC) single crystal have been investigated between 5K and 100K by using a Fourier-transform far-infrared spectrometer. It has been observed that the soft phonon frequency decreases gradually and the damping constant increases as the transition temperature is approached from below The damping constant varies from 7cm^-1 a 90K to less than 0.5cm^-1 at 5K. It has been found that the damping constant is approximately proportional to temperature below about 60K.     

Sound-velocity measurements for HFC-134a and HFC-152a with a spherical resonator

A spherical acoustic resonator was developed for measuring sound velocities in the gaseous phase and ideal-gas specific heats for new refrigerants. The radius of the spherical resonator, being about 5 cm, was determined by measuring sound velocities in gaseous argon at temperatures from 273 to 348 K and pressures up to 240 kPa. The measurements of 23 sound velocities in gaseous HFC-134a (1,1,1,2-tetrafluoroethane) at temperatures of 273 and 298 K and pressures from 10 to 250 kPa agree well with the measurements of Goodwin and Moldover. In addition, 92 sound velocities in gaseous HFC-152a (1,1-difluoroethane) with an accuracy of ±0.01% were measured at temperatures from 273 to 348 K and pressures up to 250 kPa. The ideal-gas specific heats as well as the second acoustic virial coefficients have been obtained for both these important alternative refrigerants. The second virial coefficients for HFC-152a derived from the present sound velocity measurements agree extremely well with the reported second virial coefficient values obtained with a Burnett apparatus.Paper dedicated to Professor Joseph Kestin.     

Flexural properties of moldings of rigid polyurethane made by reaction injection molding

Flexural properties of moldings made by Reaction Injection Molding (RIM), which are structural foams consisting of high density skin and low density core, were investigated by three-point bending tests. Two failure modes were observed in bending tests of the moldings made by RIM, and they are classified as follows according to the density ratio of skin layer to core layer: the opposite side of the skin layer to which load was subjected failed by tensile stress: and the same side of the skin layer to which load was subjected failed by compressive stress, causing wrinkling or buckling. Then the conventional composite beam theory was applied to the former failure mode and Hoff s buckling theory to the latter, and equations were derived to predict the flexural properties of the structural foams, which involved buckling from the flexural properties of solid construction. In addition, it has been shown that there exists a density distribution that maximizes the flexural strength of the moldings made by RIM with a given overall density. The results obtained here should be useful to the optimum structural design of moldings made by RIM.     

Thieno[2,3-d]pyrimidine-3-acetic acids. A new class of nonpeptide endothelin receptor antagonists

On the basis of structural information for the cyclic hexapeptide endothelin (ET) receptor antagonist, TAK-044, a series of thieno[2,3-d]pyrimidine-2,4-dione derivatives bearing a carboxyl group and aromatic rings that were important for receptor binding were designed, synthesized, and evaluated for ET receptor binding affinities and inhibitory activities against ET-induced vasoconstriction. Optimization of each substituent in the thieno[2,3-d]pyrimidine ring led to the discovery of a novel and potent nonpeptide ET receptor antagonist, 6-(4-methoxymethoxyphenyl)-5-methylsulfonylaminomethyl-1-(2- methylthiobenzyl)-2,4-dioxo-1,2,3,4-tetrahydrothieno[2,3-d]p yrimidine-3- acetic acid (32 g), which binded to human ETA and ETB receptor subtypes with affinities (IC50) of 7.6 and 100 nM, respectively. Compound 32 g effectively antagonized ET-induced vasoconstriction and the inhibitory effect mediated by the ETB receptor was more potent than that of bosentan, while the inhibitory effect mediated by the ETA receptor was slightly less potent than that of bosentan.     

Patterns of expression for the mRNA corresponding to the four isoforms of phospholipase Cbeta in mouse brain

Ligand binding to neurotransmitter and hormone receptors which couple to the Gq subclass of GTP-binding protein leads to the activation of phospholipase Cbeta (PLCbeta) which hydrolyses phosphatidyl-inositol 4,5-bisphosphate, yielding a pair of second messengers, diacylglycerol and inositol 1,4,5-trisphosphate (IP3). The expression of PLCbeta1-4 mRNAs was comparatively examined by in situ hybridization in the mouse brain. In adults, PLCbeta1 mRNA was expressed predominantly in the telencephalon, including the cerebral cortex, hippocampus, amygdala, lateral septum and olfactory bulb, with little expression in most thalamic nuclei. PLCbeta2 mRNA was distributed in the white matter, suggesting its expression in non-neuronal cells, most likely oligodendrocytes. PLCbeta3 mRNA was specifically expressed in cerebellar Purkinje cells. The highest levels of PLCbeta4 mRNA were detected in Purkinje cells. High levels of PLCbeta4 mRNA were also found in the thalamus and medial septum, whereas weak signals were detected in most telencephalic regions, thus showing an expression pattern almost reciprocal to that of PLCbeta1 mRNA. During development, such characteristic regional expression of PLCbeta1 and PLCbeta4 were observed starting in late foetal stages, while specific expression of PLCbeta2 and PLCbeta3 appeared in early postnatal stages. We conclude that despite the existence of four PLCbeta isoforms, only one or two of them is expressed in individual neurons and glial cells. The distinct expression of PLCbetas provides a molecular basis for analysing the nature of the specific signal transduction pathway leading to the production of diacylglycerol and IP3 in distinct cell types and in different regions of the brain.     

A flexible random allocation program for multi-institutional clinical trials

This paper describes a flexible random allocation program that assigns treatments to patients according to their prognostic factors in multi-institutional clinical trials. The source lists are available in the appendix of this paper. This program is based on Pocock and Simon's minimization method and Zelen's method for institution balancing. The numbers of institutions, treatments, and prognostic factors can be set arbitrarily. The maximum number of institutions, treatments, or prognostic factors that can be accommodated by the program is limited only by the size of the main memory. For example, an IBM-PC with a 640KB main memory can run a program of 1500 institutions, 4 treatments and 20 prognostic factors.     

Extrathymic differentiation of resident T cells in the joints of mice with collagen-induced arthritis

Murine collagen-induced arthritis (CIA) is known as a T cell-mediated autoimmune disease, although autoantibodies are also suspected to be associated with the onset of the disease. To determine the origin of such T cells in the joints of mice with CIA, their phenotypic properties as well as those of T cells in other immune organs were examined in DBA/1 mice. Since a significant number of mononuclear cells (MNC) was also yielded by the joints of normal DBA/1 mice, the properties of these T cells were examined in parallel. When CIA was induced by an intradermal injection of type II collagen at the base of the tail, the numbers of MNC yielded by the regional lymph nodes and the foot joints were doubled. Interestingly, regardless of the onset of CIA, the joints were always comprised of unique T cell populations, including IL-2(R)alpha- beta+ T cells, gammadelta T cells, CD8alpha+ beta- cells, and CD44+ L-selectin- cells. All these properties coincide with those of extrathymic T cells in liver and intestine. In the case of gammadelta T cells in joints, Vgamma and Vdelta usages were unique and different from those in the other organs. More importantly, Vgamma and Vdelta usages in gammadelta T cells in the joints of normal mice and in those of mice with CIA were essentially the same. Taken together with the expression of recombination-activating gene-1 and -2 mRNAs by MNC in mice with CIA, these findings raise the possibility that the joints have their own resident T cells that are extrathymically generated in situ.     

Theoretical and measured characteristics of metal(CoSi2)-insulator(CaF2) resonant tunnelingtransistors and the influence of parasitic elements

We report on the theoretical and measured characteristics of triple-barrier metal (CoSi₂)-insulator(CaF₂) (M-I) resonant tunneling transistors (RTT) grown on an n-Si(111) substrate, and the influence of their parasitic elements on the measured characteristics. First, we analyze theoretical characteristics of an M-I RTT, and then show fabrication process and current-voltage (I-V) characteristics obtained at 77 K, in which several degradations are observed: large resonance voltage, low peak-to-valley (P-V) ratios at negative differential resistance (NDR), and reverse base current. Analysis, taking several parasitic elements (e.g., base resistance, substrate resistance and leakage currents connected to the intrinsic transistor) into account, explains observed characteristics well. Finally, we show the first transistor action with large P-V ratios at 300 K, which is achieved by reducing collector-emitter leakage currents     

A case of carcinomatous peritonitis for which combination therapy of 5-FU, leucovorin and cisplatin was effective

This case report describes a case of carcinomatous peritonitis which showed a good response to the combination therapy of 5-FU, leucovorin and cisplatin. A 55-year-old man was admitted with complaints of meteorism due to ascites fluid. Ascitic examination showed a high concentration of CEA and CA19-9, and adenocarcinoma cells. Laboratory and radiological examination did not reveal the origin of the carcinoma, and laparotomy suggested an appendiceal origin. The combination chemotherapy with 5-FU, leucovorin and cisplatin was conducted for a total of 11 courses for 2 years with good QOL until his death. This therapy was suggested to be useful for inoperable carcinomatous peritonitis.