Modeling in Frequency Domain Used for Assessment of In Vivo Dissolution Profile

Purpose. To present a model-dependent approach for the assessment of the in vivo drug dissolution profile based on in vitrodata for the multiple unit dosage form, as an alternative to the numerical method proposed in the study by Hayashi et al, Pharm. Res. 12:1333–1337 (1995). Methods. The data for aspirin granules administered to healthy subjects obtained in the above mentioned study were re-evaluated. The subject dissolution system was considered to consist of two subsystems connected in series, i.e. the subsystem describing the gastric-emptying process and the subsystem describing the intestinal dissolution process. The frequency response method was used to model the subject dissolution system. Results. The model in vivodissolution profile of aspirin, assessed as the integral of the model weighting function of the subject dissolution system, was in agreement with the in vivo cumulative absorption profile calculated by the Wagner-Nelson method. Conclusions. Comparison of dynamic properties of the subject dissolution system with the subsystem describing the gastric-emptying process yielded quantitative confirmation of the decisive role of the gastric-emptying process in the in vivodrug dissolution after administration in the multi unit dosage form.     

Some indications for the gynaecological use of budesonide (Apulein).

Budesonide-containing Apulein ointment has been used for the treatment of 29 women suffering from vulvitis, pruritus vulvae caused by vaginal discharge, gestational inflamed hemorrhoid, hymenitis, and late postoperative suture inflammation. The ointment rapidly and completely controlled local infiltration and the accompanying subjective complaints. It did not cause local alteration, the consistency of the ointment met the requirements and it did not disturb the patients' making their toilet. According to the author's opinion the product is a potent antiphlogistic which proved to be a valuable adjuvant to target specific treatment of inflammatory processes of the external female genital organs and perianal regions.     

A new modification in temporary stent technique of microvenous anastomosis — An experimental study

Summary A new modification of microvenous anastomosis, which has increased patency rates while simultaneously decreasing the difficulty of the procedure, is presented in this paper. The primary purpose of this study was to compare the classical and the temporary stent techniques of microvenous anastomosis. Because of problems such as mixing and tangling of strings during insertion and tying of the last four sutures while applying the temporary stent technique, we decided to modify the procedure. The silastic tube was removed through an incision (venotomy), distant from the actual suture line. This modified technique and the other above mentioned techniques were carried out on rat femoral veins. The results indicate that this modification has increased patency rates, shortened the time of anastomosis and facilitated the procedure.     

PIP2 hydrolysis underlies agonist-induced inhibition and regulates voltage gating of two-pore domain K+ channels

Two-pore (2-P) domain potassium channels are implicated in the control of the resting membrane potential, hormonal secretion, and the amplitude, frequency and duration of the action potential. These channels are strongly regulated by hormones and neurotransmitters. Little is known, however, about the mechanism underlying their regulation. Here we show that phosphatidylinositol 4,5-bisphosphate (PIP₂) gating underlies several aspects of 2-P channel regulation. Our results demonstrate that all four 2-P channels tested, TASK1, TASK3, TREK1 and TRAAK are activated by PIP₂. We show that mechanical stimulation may promote PIP₂ activation of TRAAK channels. For TREK1, TASK1 and TASK3 channels, PIP₂ hydrolysis underlies inhibition by several agonists. The kinetics of inhibition by the PIP₂ scavenger polylysine, and the inhibition by the phosphatidylinositol 4-kinase inhibitor wortmannin correlated with the level of agonist-induced inhibition. This finding suggests that the strength of channel PIP₂ interactions determines the extent of PLC-induced inhibition. Finally, we show that PIP₂ hydrolysis modulates voltage dependence of TREK1 channels and the unrelated voltage-dependent KCNQ1 channels. Our results suggest that PIP₂ is a common gating molecule for K⁺ channel families despite their distinct structures and physiological properties.     

Lectin-induced increase in clonogenic growth of haematopoietic progenitor cells

Abstract: The galactoside-specific plant lectin, Viscum album agglutinin (VAA-I) increases cellular parameters of natural host defence. It also binds to a variety of haematopoietic cells, including progenitors. We investigated whether VAA-I has a stimulatory effect on haematopoietic progenitor cells. Peripheral blood progenitor cells from 7 healthy volunteers were cultured in a colony assay with VAA-I plus erythropoietin (EPO) and stem cell factor (SCF). At 50 pg/ml VAA-I induced a significant increase in the cytokine-dependent clonogenic growth (52% in median, p<0.05). In another set of experiments purified CD34+ cells were isolated from the bone marrow aspirate of 4 patients with non-metastatic breast cancer using fluorescence-activated cell sorting. Binding to CD34+ cells was demonstrated by using directly fluorescence-conjugated VAA-I. Co-incubation with d -galactose significantly abrogated this effect. CD34+ cells were cultured in the presence of EPO, SCF, interleukin-3, granulocyte/monocyte colony-stimulating factor and granulocyte colony-stimulating factor. VAA-I alone had no measurable effect on the clonogenic growth of the isolated cells. However, at concentrations of 100 and 250 pg/ml VAA-I increased the cytokine-dependent proliferation and differentiation of CD34+ cells by a median of 75 and 85%, respectively. The results show that VAA-I binds to haematopoietic progenitor cells and has a co-stimulatory effect on their proliferation.