The MiniWiD-Coater. III. Effect of Application Temperature on the Dissolution Profile of Sustained-Release Theophylline Pellets Coated with Eudragit Rs 30 D

Theophylline pellets were coated with Eudragit RS 30 D in a miniature fluid-bed pan coater called MiniWiD developed recently. The dispersions were plasticized with varying amounts of triethyl citrate (TEC), dibutyl phthalate (DBP), and polyethylene glycol 6000 (PEG) and applied at different temperatures ranging from 25 to 45 °C. Theophylline release was tested by dissolution using the USP Apparatus 2 (paddle) in 0.1 N hydrochloric acid under sink conditions over 6 hours.

At a coating level of 4 % (0.7 mg/cm²) sustained-release profiles were obtained from dispersions plasticized with TEC or DBP. By reducing the amount of plasticizer from 20 to 10%, films with higher permeabilities were obtained. This effect was compensated by tempering the pellets at 50 deg;C for 24 hours. The coating temperature had little effect on the dissolution profiles of TEC-plasticized films and no effect on films with DBP.

Coatings plasticized with 20% PEG were applied at temperatures ranging from 25 to 45 °C. These films required a coating level of about 18 % (3.3 mg/cm²) to provide comparable sustained-release properties. In contrast to DBP and TEC, a strong influence of the coating temperature on the release rates was observed in which higher temperatures led to slower release rates. This behavior can be explained by the minimum film-forming temperature (MFT). Since PEG does not lower the MFT of Eudragit RS 30 D, the application of these films below the MFT of 45 °C is associated with a lower degree of film formation.     

Refinements in validity generalization methods: Implications for the situational specificity hypothesis.

Using a large database, this study examined 3 refinements of validity generalization procedures: (1) a more accurate procedure for correcting the residual standard deviation (SD) for range restriction to estimate SDp, (2) use of r? instead of study-observed rs in the formula for sampling error variance, and (3) removal of non-Pearson rs. The 1st procedure does not affect the amount of variance accounted for by artifacts. The addition of the 2nd and 3rd procedures increased the mean percentage of validity variance accounted for by artifacts from 70 to 82%, a 17% increase. The cumulative addition of all 3 procedures decreased the mean SDp estimate from .150 to .106, a 29% decrease. Six additional variance-producing artifacts were identified that could not be corrected for. In light of these it was concluded that the obtained estimates of mean SDp and mean validity variance accounted for were consistent with the hypothesis that the true mean SDp value is close to zero. These findings provide further evidence against the situational specificity hypothesis. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Diarrhea in young children associated with Escherichia coli non-O157 organisms that produce Shiga-like toxin

The aim of this study was to evaluate the way in which short-term protection declines and is eventually lost in preconditioning and to determine the efficacy of a second preconditioning at various reperfusion intervals. Male rabbits were divided into six groups. Forty-five minutes (sustained) ischemia followed by 120 minutes reperfusion was applied 60, 65, 70, 75, and 80 minutes after a 5 minute preconditioning (groups A, B, C, D, and E) and in a control group (F) after no preconditioning. The infarct to risk ratio (I/R) was 38.3 +/- 3.5% in group A, 46.0 +/- 7.8% in B, 61.6 +/- 9.7% in C, 68.1 +/- 4.2% in D, 64.5 +/- 7.8% in E, and 61.0 +/- 7.7% in F. Group A had a smaller I/R compared with groups C, D, E, and F (p < 0.05). In another series, groups G, H, and I were exposed to two 5-minute preconditioning stimuli, separated, respectively, by 45, 60, and 75 minutes of reperfusion; 10 minutes after the last preconditioning, the animals were exposed to 45-minutes ischemia and 120 minutes reperfusion. Groups A and D (with the smaller and higher I/R ratio) were also incorporated into this protocol in order to compare the effect of the additional preconditioning with the single one. The I/R ratio was 25.4 +/- 8.5% in group G, 22.8 +/- 7.0% in group H, and 14.7 +/- 4.0% in group I (p = NS). Group D showed a higher I/R compared with groups G, A, and H (p < 0.01), and group I had a smaller I/R compared with groups A (p < 0.01) and D (p < 0.001). Cardioprotection after a first preconditioning declines gradually and is eventually lost. An additional preconditioning is always effective, and the longer the interval from the first preconditioning, the more potent is the effect.     

Psychoanalytic considerations of right extremist orientation of male adolescents

Giving a case example of an male adolescent with radical right-wing attitudes, the lack of male identification as well as in unresolved dyadic fixation to the mother will be shown. Though the radical right-wing orientation the adolescent tries on the basis of a phallic narcissistic conflict to establish bordes against an unresolved dyadic fixation to his mother.     

Long distance propagation of a polarized neutron beam in zero magnetic field

A beam of fully polarized cold neutrons was transported through a zero magnetic field region of 70 m length without loss of polarization. The purpose of this exercise was twofold: firstly, to demonstrate that the new zero-field neutron spin-echo method will work also for very long neutron flight paths; secondly, to prove in the most direct way that the neutron free-flight region of the ILL neutron-antineutron oscillation experiment was indeed sufficiently field-free (“quasifree condition”) by using the neutrons themselves as a magnetometer. To this purpose the residual magnetic field integrals in the long “zero-field” region were measured with a conventional neutron spin-echo method. The overall spin precession angle of the neutrons during their flight through the long zero-field region was found to be less than 2°.     

Critical care medicine

A postmortem case of HTLV-I associated myelopathy (HAM)/tropical spastic paraparesis (TSP) with a history of remission and exacerbation of neurological signs and symptoms, resembling those of multiple sclerosis is reported. MRI analysis revealed lesions in the periventricular white matter in addition to atrophy of the thoracic spinal cord, characteristic of HAM/TSP. The cerebral periventricular areas consisted of ill-defined paucity of myelin sheaths with astrocytic gliosis and hyaline thickening of blood vessels. The poorly demarcated white matter lesions found in both brain and spinal cord were different from plaques found in multiple sclerosis. It is suggested that, in some cases of HAM/TSP, inflammatory lesions that destroy myelin can involve not only the spinal cord but also the cerebral periventricular white matter.     

Chromosomal and genomic organization of Ty1-copia-like retrotransposon sequences in the genus Avena

Regulation of ligand-mediated signal transduction through transmembrane tyrosine kinase growth factor receptors involves phosphorylation of tyrosine residues in the intracellular domain of the receptor. The insulin-like growth factor-I (IGF-I) receptor contains three tyrosine residues in the carboxy-terminal domain at positions 1250, 1251, and 1316. Of these, only the tyrosine at position 1316 is conserved in the homologous position of the insulin receptor. Mutational analysis was used to study the role of these tyrosines in specific outcomes of IGF-I-mediated signal transduction. Mutations in the human IGF-I receptor were either replacement of tyrosines 1250 and 1251 with phenylalanine and histidine (yyFH), respectively, or replacement of the conserved distal tyrosine (position 1316) with phenylalanine (yCF). The yyFH mutation results in an IGF-I receptor with the amino acids found in the homologous position of the human insulin receptor. Cells overexpressing mutated IGF-I receptors were compared with cells expressing only endogenous IGF-I receptors or overexpressing wild-type IGF-I receptors. The ability of yyFH mutant IGF-I receptors to autophosphorylate the beta-subunit or phosphorylate insulin receptor substrate-1 was not significantly different from wild-type type IGF-I receptors. However, one or both of the proximal tyrosine residues (positions 1250 and 1251) in the carboxy-terminus of the IGF-I receptor are essential for IGF-I-stimulation of mitogenic and tumorigenic pathways. IGF-I-induced mitogenesis, measured as thymidine incorporation and cellular proliferation, was abrogated in cells overexpressing mutant IGF-I receptors with replacement of the proximal double tyrosines (positions 1250 and 1251). Fibroblasts expressing this mutant IGF-I receptor formed fewer tumors than the negative control cells, whereas cells expressing wild-type IGF-I receptors formed large tumors in all recipient mice injected. Conversely, cells expressing mutant IGF-I receptors with only the conserved distal tyrosine (position 1316) replaced had slightly reduced IGF-I-stimulated beta-subunit autophosphorylation, thymidine incorporation, and cellular proliferation when compared with cells expressing wild-type receptors. Phosphorylation of insulin receptor substrate-1 by the yCF mutant receptors was not impaired. Despite the ability of these mutant receptors to stimulate mitogenic growth, fibroblasts expressing this mutant receptor were also incapable of forming tumors in recipient nude mice. The distal tyrosine (position 1316) of the IGF-I receptor is crucial for tumor formation but is not essential for IGF-I stimulated mitogenesis. Thus, the tyrosine moieties in the carboxy-terminus of the IGF-I receptor participate in the signal transduction pathways that affect the mitogenic and tumorigenic potentials of cells expressing mutant IGF-I receptors.     

Intracavitary afterloading therapy as a new technique of boost irradiation in anal canal carcinoma

PURPOSE: There are different techniques of boost irradiation in the treatment of patients with anal carcinoma. A new system of applicators is presented, which can be used for an intracavitary afterloading therapy. MATERIAL AND METHODS: Three different applicators are available, the first with a central catheter (K1), a second with 5 semicircular fixed catheters (K2) and an eccentric shield, a third with 8 circular fixed catheters and a central shield (K3). RESULTS: The adequate choice of applicator and catheters takes into consideration the individual localisation and extension of anal carcinoma in planning therapy. Thus, in circular growing tumors, an irradiation of the whole circumference of the anal canal is possible. In non-circular growing tumors, the dose applied in the non-affected part of the anal canal can be reduced to a quarter of the dose applied at the tumor. CONCLUSION: The new system of intracavitary afterloading therapy is a good alternative to previous techniques of boost irradiation in the treatment of anal carcinoma. By means of this technique, irradiation can be highly individualized, the tumor better included and non-affected sections of the anal canal saved.     

Kinetic model for water/oil absorption of mesquite gum (Prosopis juliflora) and gum arabic (Acacia senegal)

The water and oil uptake of mesquite and arabic gums in powdered form was studied at temperatures of 23, 35 and 45°C. A previously proposed equation to predict osmotic equilibrium was tested using the experimental data with both gums and a good statistical fit was obtained. Mesquite gum showed the highest water and oil absorption at all temperatures studied. Temperature dependence of the reciprocal of the S₁ and WL_∞ were determined using an Arrhenius equation. The activation energy for water and oil absorption for gum arabic was 21.98 and 39.57 kJ mol⁻¹, compared to that of mesquite gum having values of 15.79 and 46.16 kJ mol⁻¹, respectively. A second order kinetic model was obtained for water and oil absorption for both gums.