Pharmacy in transition: A work sampling study of community pharmacists using smartphone technology

Introduction

The nature of community pharmacy is changing, shifting from the preparation and distribution of medicines to the provision of cognitive pharmaceutical services (CPS); however, often the provision of traditional services leaves little time for innovative services. This study investigated the time community pharmacists spend on the tasks and activities of daily practice and to what extent they are able to implement CPS-related services in daily practice.

The effect of pressurized carbon dioxide as a temporary plasticizer and foaming agent on the hot stage extrusion process and extrudate properties of solid dispersions of itraconazole with PVP-VA 64.

The aim of the current research project was to explore the possibilities of combining pressurized carbon dioxide with hot stage extrusion during manufacturing of solid dispersions of itraconazole and polyvinylpyrrolidone-co-vinyl acetate 64 (PVP-VA 64) and to evaluate the ability of the pressurized gas to act as a temporary plasticizer as well as to produce a foamed extrudate. Pressurized carbon dioxide was injected into a Leistritz Micro 18 intermeshing co-rotating twin-screw melt extruder using an ISCO 260D syringe pump. The physicochemical characteristics of the extrudates with and without injection of carbon dioxide were evaluated with reference to the morphology of the solid dispersion and dissolution behaviour and particle properties. Carbon dioxide acted as plasticizer for itraconazole/PVP-VA 64, reducing the processing temperature during the hot stage extrusion process. Amorphous dispersions were obtained and the solid dispersion was not influenced by the carbon dioxide. Release of itraconazole from the solid dispersion could be controlled as a function of processing temperature and pressure. The macroscopic morphology changed to a foam-like structure due to expansion of the carbon dioxide at the extrusion die. This resulted in increased specific surface area, porosity, hygroscopicity and improved milling efficiency.     

Coping with mild inflammatory catamenial acne

BACKGROUND: Acne is a multifactorial disease exhibiting distinct clinical presentations. Among them, the catamenial type is a matter of concern for young women. Some oral contraceptives may help without, however, clearing the skin condition. AIM: The present open study aimed at evaluating the effect of overnight applications of a paste made of petrolatum,15% zinc oxide and 0.25% miconazole nitrate. METHOD: The split-face trial was conducted in 35 women. A non-medicated cream was used as control. Clinical evaluations and biometrological assessments on cyanoacrylate follicular biopsies were performed monthly for 3 months. Comedometry and the density in autofluorescent follicular casts were used as analytical parameters. In addition, the five most severe cases at inclusion were tested at the completion of the study for follicular bacterial viability using dual flow cytometry. RESULTS: Compared with baseline and to the control hemi-face, the medicated paste brought significant improvement of acne. The number of papules and their redness were reduced beginning with the first treatment phase. A reduction in the follicular fluorescence was yielded beginning with the second treatment phase. The ratios between injured and dead bacteria, on the one hand, and live bacteria, on the other hand were significantly increased at completion of the study. CONCLUSION: A miconazole paste applied for 1 week at the end of the ovarian cycle has a beneficial effect on catamenial acne.     

The role of mast cells and histamine in leukocyte-endothelium interactions in four rat strains

 The objective of the present study was to determine the role of mast cells and histamine in leukocyte-endothelium interactions in mesenteric venules of four rat strains: Brown Norway, Lewis, Sprague-Dawley and Wistar. Intravital microscopy showed that the mast cell stabilizer cromoglycate (5 mg/kg i.v. just before exteriorization of the mesentery) did not affect the baseline level and velocity of leukocyte rolling in any of the four strains. This finding is in agreement with the observation that cromoglycate pretreatment only slightly influenced mast cell degranulation in all strains except the Brown Norway. After mast cell stabilization, only in Sprague-Dawley did topical administration of histamine (10^–4 M) result in a significant increase in the level of leukocyte rolling and a decrease in the rolling velocity compared with the time control. Histamine induced leukocyte adhesion only in the Brown Norway strain. In conclusion, the hypothesis presented in other studies, that degranulation of mast cells, and more specifically the release of histamine, is of major importance for the induction of leukocyte-endothelium interactions in rat mesenteric venules is not generally applicable; the present study shows a clear strain dependency. Received: 18 July 1997 / Received after revision: 17 November 1997 / Accepted: 13 March 1998     

Valproic acid induced encephalopathy--19 new cases in Germany from 1994 to 2003--a side effect associated to VPA-therapy not only in young children.

Valproic acid (VPA) is a broad-spectrum antiepileptic drug and is usually well-tolerated. Rare serious complications may occur in some patients, including haemorrhagic pancreatitis, bone marrow suppression, VPA-induced hepatotoxicity and VPA-induced encephalopathy. The typical signs of VPA-induced encephalopathy are impaired consciousness, sometimes marked EEG background slowing, increased seizure frequency, with or without hyperammonemia. There is still no proof of causative effect of VPA in patients with encephalopathy, but only of an association with an assumed causal relation. We report 19 patients with VPA-associated encephalopathy in Germany from the years 1994 to 2003, none of whom had been published previously.     

Retrograde flush following topical cooling is superior to preserve the non-heart-beating donor lung

Objective: The use of non-heart-beating donors (NHBD) has been propagated as an alternative to overcome the scarcity of pulmonary grafts. Formation of microthrombi after circulatory arrest, however, is a major concern for the development of reperfusion injury. We looked at the effect and the best route of pulmonary flush following topical cooling in NHBD. Methods: Non-heparinized pigs were sacrificed by ventricular fibrillation and divided into three groups (n = 6 per group). After 1 h of in situ warm ischaemia and 2.5 h of topical cooling, lungs in group I were retrieved unflushed (NF). In group II, lungs were explanted following an anterograde flush (AF) through the pulmonary artery with 50 ml/kg Perfadex^® (6 °C). Finally, in group III, lungs were retrieved after an identical but retrograde flush (RF) via the left atrium. Flush effluent was sampled at intervals to measure haemoglobin concentration. Performance of the left lung was assessed during 60 min in our ex vivo reperfusion model. Wet-to-dry weight ratio (W/D) of both lungs was calculated as an index of pulmonary oedema. IL-1ß and TNF- protein levels in bronchial lavage fluid from both lungs were compared between groups. Results: Haemoglobin concentration (g/dl) was higher in the first effluent in RF versus AF (3.4 ± 1.1 vs 0.6 ± 0.1; p < 0.05). Pulmonary vascular resistance (dynes × s × cm⁻⁵) was 975 ± 85 RF versus 1567 ± 98 AF and 1576 ± 88 NF at 60 min of reperfusion (p < 0.001). Oxygenation (mmHg) and compliance (ml/cmH₂O) were higher (491 ± 44 vs 472 ± 61 and 430 ± 33 NS, 22 ± 3 vs 19 ± 3 and 14 ± 1 NS, respectively) and plateau airway pressure (cmH₂O) was lower (11 ± 1 vs 13 ± 1 and 13 ± 1 NS) after RF versus AF and NF, respectively. No differences in cytokine levels or in W/D ratios were observed between groups after reperfusion. Histology demonstrated microthrombi more often present after AF and NF compared to RF. Conclusion: Retrograde flush of the lung following topical cooling in the NHBD results in a better washout of residual blood and microthrombi and subsequent reduced pulmonary vascular resistance upon reperfusion.     

Effect of Food on the Pharmacokinetics of a New Hydroxypropyl-β-Cyclodextrin Formulation of Itraconazole

Study Objective . To compare the pharmacokinetics of a single 100-mg oral dose of itraconazole administered as 10 ml of a 10-mg/ml itraconazole solution in hydroxypropyl-β-cyclodextrin under fasting versus postprandial conditions. Design . Open-label, two-way, randomized, crossover study. Setting . Janssen Research Foundation, Belgium. Patients . Twelve healthy volunteers. Interventions . Blood samples were obtained for pharmacokinetic analyses immediately before dosing and at regular intervals up to 96 hours after each dose. Blood and urine samples were obtained for hematologic, biochemical, and urinary safety analyses at baseline and at the end of the study. Measurements and Main Results . The mean peak plasma concentrations of both itraconazole and its active metabolite hydroxy-itraconazole were significantly higher under fasting conditions than under postprandial conditions. The mean times to peak concentration for both the parent compound and its metabolite were significantly shorter under fasting than under nonfasting conditions. The mean areas under the curve (AUC_0–∞ and AUC_{0–24 hrs}) were also significantly higher under fasting than under postprandial conditions. Conclusions . Our findings suggest that the higher bioavailability of this new formulation of itraconazole may be of benefit in seriously ill patients who are not able to ingest adequate quantities of food. The fact that the solution was also well tolerated and was not associated with clinically significant changes in any laboratory value further underscores the potential utility of this dosing form.     

Molecular genetic analysis of familial early-onset Alzheimer's disease linked to chromosome 14q24.3

Genetic linkage studies have indicated that chromosome 14q24.3harbours a major locus for early-onset (onset age <65 years)Alzheimer's disease (AD3). Positional cloning efforts have identifieda novel gene S182 or presenilin 1 as the AD3 gene. We have mappedS182 in the AD3 candidate region between D14S277 and D14S284defined by genetic linkage studies in the two chromosome 14linked, early-onset AD families AD/A and AD/B. We have shownthat S182 is expressed in lymphoblasts and have determined thecomplete cDNA in both brain and lymphoblasts by RT-PCR sequencing.S182 is alternatively spliced in both brain and lymphoblastswithin a putative phosphorylation site located 5' in the codingregion. We identified two novel mutations, Ile143Thr and Gly384Alalocated in, respectively, the second transmembrane domain andin the sixth hydrophilic loop of the putative transmembranestructure of S182. As families AD/A and AD/B have a very similarAD phenotype our observation of two mutations in functionallydifferent domains suggest that onset age and severity of ADmay not be very helpful predictors of the location of putativeS182 mutations.     

Differential expression of FIZZ1 and Ym1 in alternatively versus classically activated macrophages

Alternatively activated macrophages (aaMphi) display molecular and biological characteristics that differ from those of classically activated macrophages (caMphi). Recently, we described an experimental model of murine trypanosomosis in which the early stage of infection of mice with a Trypanosoma brucei brucei variant is characterized by the development of caMphi, whereas in the late and chronic stages of infection, aaMphi develop. In the present study, we used suppression subtractive hybridization (SSH) to identify genes that are expressed differentially in aaMphi versus caMphi elicited during infection with this T. b. brucei variant. We show that FIZZ1 and Ym1 are induced strongly in in vivo- and in vitro-elicited aaMphi as compared with caMphi. Furthermore, we demonstrate that the in vivo induction of FIZZ1 and Ym1 in macrophages depends on IL-4 and that in vitro, IFN-gamma antagonizes the effect of IL-4 on the expression of FIZZ1 and Ym1. Collectively, these results open perspectives for new insights into the functional properties of aaMphi and establish FIZZ1 and Ym1 as markers for aaMphi.