UK PID Patients: Overview of perception on IgRT and infections using short survey.

Immunoglobulin replacement therapy (IgRT) has advanced over the years and is used to treat many patients with primary immunodeficiencies reducing the number of infections and the burden of disease. We investigated the perception of IgRT in two patient groups (UKPIPS and PID UK) and their condition through a short survey. The survey was a multiple-choice short survey consisting of 20 questions completed either online or on paper. Data analysis was performed using SAS analysis software using regression analysis, correlation analysis and t-tests. Statistical significance was considered with p<0.05. 278 surveys were analysed which showed that the majority of participants were satisfied with the immunoglobulin therapy they received (n=225, 80.9%). However, there was a small but significant number of participants (n=19, 6.9%) that still experienced severe and very severe infections despite adequate IgRT. 236 (84.9%) participants reported limitations in daily life due to infections. The dissatisfied participants (n=55, 18.3%) had more non-routine visits to healthcare providers, higher numbers of antibiotic treatments and more days absent from school, work, university or equivalent than the satisfied participants.

Tyrothricin--An underrated agent for the treatment of bacterial skin infections and superficial wounds?

The antimicrobial agent tyrothricin is a representative of the group of antimicrobial peptides (AMP). It is produced by Bacillus brevis and consists of tyrocidines and gramicidins. The compound mixture shows activity against bacteria, fungi and some viruses. A very interesting feature of AMPs is the fact, that even in vitro it is almost impossible to induce resistances. Therefore, this class of molecules is discussed as one group that could serve as next generation antibiotics and overcome the increasing problem of bacterial resistances. In daily practice, the application of tyrothricin containing formulations is relatively limited: It is used in sore throat medications and in agents for the healing of infected superficial and small-area wounds. However, due to the broad spectrum antimicrobial activity and the low risk of resistance development it is worth to consider further fields of application.

A randomized, controlled, double-blind, multi-center trial to evaluate the efficacy and safety of a liquid containing ivy leaves dry extract (EA 575®) vs. placebo in the treatment of adults with acute cough.

This randomized, placebo-controlled, double-blind trial was conducted to assess the efficacy and safety of ivy leaves cough liquid in the treatment of acute cough. A total of 181 adult patients with acute cough were treated with either ivy leaves cough liquid containing EA 575® or with placebo three times a day for one week. The primary efficacy outcome was cough severity (CS) assessed by Visual Analogue Scale (VAS) over the whole treatment period (area-under-the-curve (AUC0-168 h) over 7 days (visit (V)1, V2, V3, V4, and V5). The secondary endpoints were defined as the CS assessed by VAS over the whole observation period (V1 - V6) and by Bronchitis Severity Score (BSS) and Verbal Category Descriptive (VCD) score. The evaluation of the VAS, BSS and VCD score revealed that subjects treated with ivy leaves cough liquid showed statistically significant and clinically relevant reductions in CS, severity of symptoms associated with cough and bronchitis compared to the placebo group. Furthermore, a remarkable early onset of efficacy was observed as significant reductions of cough severity were detected within 48 hours after the first drug intake. At all following visits and even 7 days after the end of treatment (V6) this significant treatment advantage was detected in comparison to placebo. All adverse events (AEs) in this clinical trial were non-serious, mild or of moderate severity and not drug-related. This clinical trial proved consistent superiority of the ivy leaves cough liquid treatment versus placebo and confirmed the EA 575® preparation to be a safe and efficacious option for the treatment of acute cough.

Can pharmaceutical history courses contribute in building future pharmacy leaders? A preliminary study from Erciyes University, Turkey.

This study aimed to investigate the relationship between pharmacy students' opinions on the importance of leadership and their levels of interest in pharmaceutical history. We administered a structured questionnaire to 160 undergraduate students (response rate of 86.3%) who have taken pharmaceutical history courses at the Erciyes University Faculty of Pharmacy in the past three years. We observed that 42.8% of the participants valued leadership as a very important skill that a pharmacist should possess through his/her professional career, of which 54.2% were very interested in pharmaceutical history. There is a statistically significant relationship between participants' opinions on the importance of leadership and their levels of interest in pharmaceutical history. Our findings suggest that the participants valuing leadership as a very important skill are more interested in pharmaceutical history than those valuing leadership as an unimportant skill. This result indicates that pharmaceutical history courses can serve as an effective tool for developing pharmacy students' awareness and attitudes toward professional leadership.

Efficacy and safety of comfrey root extract ointment in the treatment of acute upper or lower back pain: results of a double-blind, randomised, placebo controlled, multicentre trial.

OBJECTIVE: The objective was to show the superiority of comfrey root extract ointment to placebo ointment in patients with acute upper or lower back pain. DESIGN: The study was conducted as a double-blind, multicentre, randomised clinical trial with parallel group design over a period of 5 days (SD 1). The patients (n = 120, mean age 36.9 years) were treated with verum or placebo ointment three times a day, 4 g ointment per application. The trial included four visits. MAIN OUTCOME MEASURES: The primary efficacy variable was the area under the curve (AUC) of the visual analogue scale (VAS) on active standardised movement values at visits 1 to 4. The secondary efficacy variables were back pain at rest using assessment by the patient on VAS, pressure algometry (pain-time curve; AUC over 5 days), global assessment of efficacy by the patient and the investigator, consumption of analgesic medication and functional impairment measured using the Oswestry disability index. RESULTS: There was a significant treatment difference between comfrey extract and placebo regarding the primary variable. In the course of the trial the pain intensity on active standardised movement decreased on average (median) approximately 95.2% in the verum group and 37.8% in the placebo group. CONCLUSIONS: The results of this clinical trial were clear-cut and consistent across all primary and secondary efficacy variables. Comfrey root extract showed a remarkably potent and clinically relevant effect in reducing acute back pain. For the first time a fast-acting effect of the ointment (1 h) was also witnessed.

Anxiolytic effects of a passion flower (Passiflora incarnata L.) extract in the elevated plus maze in mice.

The purpose of this study was to characterize the putative anxiolytic-like activity of an ethanolic extract prepared from passion flower (PF) (Passiflora incarnata L.) using the elevated plus maze (EPM) in mice. The mice were either treated orally with three different concentrations of the PF extract or the positive control diazepam. The number of entries in the open arms was significantly increased after administration of diazepam compared to the control. PF extract showed a significant increase in number of open arm entries at a concentration of 375 mg/kg, whereas no activity was observed in 150 and 600 mg/kg, respectively, indicating an U-shaped dose response curve. In conclusion, using the EPM we were able to detect putative anxiolytic effects of a Passiflora incarnata extract in mice.

Efficacy of a comfrey root (Symphyti offic. radix) extract ointment in the treatment of patients with painful osteoarthritis of the knee: results of a double-blind, randomised, bicenter, placebo-controlled trial.

This randomised, double-blind, bicenter, placebo-controlled clinical trial investigated the effect of a daily application of 6g Kytta-Salbe f (3 x 2 g) over a 3 week period with patients suffering from painful osteoarthritis of the knee. The two hundred and twenty patients examined consisted of 153 women and 67 men of an average age of 57.9 years. On average, the complaints relating to osteoarthritis of the knee had persisted for 6.5 years. Two hundred and twenty patients were included in the Full Analysis Set (FAS) and safety collective, 186 (84.5%) in the Valid Case Analysis Set (VCAS) collective. In the course of the trial, the visual analog scale (VAS) total score (primary target value) in the verum group dropped by 51.6 mm (54.7%) and in the placebo group by 10.1 mm (10.7%). The average difference between the groups of 41.5 mm (95% confidence interval=34.8 to 48.2 mm) or 44.0% is significant (p<0.001). The significance is confirmed through the evaluation of the diary, the VCAS evaluation and the separate assessment of the two centres. This also applies to the separate assessment of the VAS total score following pain at rest and on movement. The WOMAC (Western Ontario and McMaster Universities) total score (secondary target value) also improved similar to the VAS total score. At the end of the trial, a reduction by 60.4 mm (58.0%) was recorded for the verum group and a reduction of 14.7 mm (14.1%) for the placebo group. The average group difference of 45.7 mm (95% confidence interval=37.1 to 54.3 mm) or 43.9% is significant (p<0.001). The difference between the treatment groups increased systematically and significantly, in parallel with the duration of the treatment. Thus, the superiority of the treatment with Kytta-Salbe f over that with the placebo is proven, even by means of the multi-factorial multivariate analysis for repetitive measurements. In respect of the explorative secondary target values SF-36 (quality of life), angle measurement (mobility of the knee), CGI (clinical global impression) and global assessment of efficacy by the physician and the patient, a significant superiority (p<0.001 each) of the verum group over the placebo group was also proven. The results suggest that the comfrey root extract ointment is well suited for the treatment of osteoarthritis of the knee. Pain is reduced, mobility of the knee improved and quality of life increased.

Efficacy of a comfrey root extract ointment in comparison to a diclofenac gel in the treatment of ankle distortions: results of an observer-blind, randomized, multicenter study.

In the treatment of minor blunt injuries several topical drugs are known to have anti-inflammatory and analgesic properties. They represent, however, two fundamentally different major pharmacological therapy approaches: the "chemical-synthetical" and the "phytotherapeutical" approach. The main objective of this trial (CODEC_2004) was to compare the efficacy and tolerability of an ointment of Comfrey extract (Extr. Rad. Symphyti) with that of a Diclofenac gel in the treatment of acute unilateral ankle sprain (distortion). In a single-blind, controlled, randomized, parallel-group, multicenter and confirmatory clinical trial outpatients with acute unilateral ankle sprains (n=164, mean age 29.0 years, 47.6% female) received either a 6 cm long ointment layer of Kytta-Salbe f (Comfrey extract) (n=82) or of Diclofenac gel containing 1.16 g of diclofenac diethylamine salt (n=82) for 7 +/- 1 days, four times a day. Primary variable was the area-under-the-curve (AUC) of the pain reaction to pressure on the injured area measured by a calibrated caliper (tonometer). Secondary variables were the circumference of the joint (swelling; figure-of-eight method), the individual spontaneous pain sensation at rest and at movement according to a Visual Analogue Scale (VAS), the judgment of impaired movements of the injured joint by the method of "neutral-zero", consumption of rescue medication (paracetamol), as well as the global efficacy evaluation and the global assessment of tolerability (both by physician and patient, 4 ranks). In this study the primary variable was also to be validated prospectively. It was confirmatorily shown that Comfrey extract is non-inferior to diclofenac. The 95% confidence interval for the AUC (Comfrey extract minus Diclofenac gel) was 19.01-103.09h*N/cm2 and was completely above the margin of non-inferiority. Moreover, the results of the primary and secondary variables indicate that Comfrey extract may be superior to Diclofenac gel.

Efficacy and tolerance of a comfrey root extract (Extr. Rad. Symphyti) in the treatment of ankle distorsions: results of a multicenter, randomized, placebo-controlled, double-blind study.

Comfrey (Symphytum officinale L.) is a medicinal plant with anti-inflammatory, analgesic and tissue regenerating properties. In a double-blind, multicenter, randomized, placebo-controlled, group comparison study on patients suffering from unilateral acute ankle sprains (n = 142, mean age 31.8 years, 78.9% male), the percutaneous efficacy of an ointment of comfrey extract (Kytta-Salbe f, four treatments per day for 8 days) was confirmed decisively. Compared to placebo, the active treatment was clearly superior regarding the reduction of pain (tonometric measurement, p<0.0001, as the primary efficacy variable) and ankle edema (figure-of-eight method, p = 0.0001). Statistically significant differences between active treatment and placebo could also be shown for ankle mobility (neutral zero method), and global efficacy. Under active treatment, no adverse drug reactions were reported. The good local and global tolerance of the trial medication could also be confirmed. The study results are consistent with the known pre-clinical and clinical data concerning comfrey.

The role of the actin cytoskeleton in plant cell signaling.

The plant actin cytoskeleton provides a dynamic cellular component which is involved in the maintenance of cell shape and structure. It has been demonstrated recently that the actin cytoskeleton and its associated elements provide a key target in many signaling events. In addition to acting as a target, the actin cytoskeleton can also act as a transducer of signal information. In this review we describe some newly discovered aspects of the roles of the actin cytoskeleton in plant cell signaling. In addition to a summary of the roles played by actin-binding proteins, we also briefly review the progress made in understanding how the actin cytoskeleton participates in the self-incompatibility response in pollen tubes. Finally, the emerging importance of the actin cytoskeleton in the perception and responses to stimuli such as gravity, touch and cold stress exposure are discussed. Contents I. Introduction - the actin cytoskeleton 13 II. Actin-binding proteins 14 III. The actin cytoskeleton as a target and mediator of plant cell signaling 20 IV. Summary and conclusion 25 References 25 Acknowledgements 25.

[Two editors in dialog. The example of Justus von Liebig (1803-1873) and Johann Bartholomäus Trommsdorff (1770-1837) and their letters]. / Zwei Zeitschriftenherausgeber im Dialog--dargestellt am Beispiel des Briefwechsels zwischen Justus von Liebig (1803-1873) und Johann Bartholomäus Trommsdorff (1770-1837).

Today, scientists willing to publish results face a wide range of requirements (instructions for authors, peer review procedure). During the 18th and 19th century manuscripts were treated in a less formal way. However, the scientific discussion was vital and implemented intensely via various means, especially by letters. This study analyses the dialog of two distinguished contributors to chemical and pharmaceutical sciences, both experienced journal editors, from January 1828 to February 1837.

The actin cytoskeleton is a target of the self-incompatibility response in Papaver rhoeas.

The integration of signals received by a cell, and their transduction to targets, is essential for all cellular responses. The cytoskeleton has been identified as a major target of signalling cascades in both animal and plant cells. Self-incompatibility (SI) in Papaver rhoeas involves an allele-specific recognition between stigmatic S-proteins and pollen, resulting in the inhibition of incompatible pollen. This highly specific response triggers a Ca(2+)-dependent signalling cascade in incompatible pollen when a stigmatic S-protein interacts with it. It has been demonstrated recently that SI induces dramatic alterations in the organization of the pollen actin cytoskeleton. This implicates the actin cytoskeleton as a key target for the SI-stimulated signals. The cytological alterations to the actin cytoskeleton that are triggered in response to SI are described here and there seem to be several stages that are distinguishable temporally. Evidence was obtained that F-actin depolymerization is also stimulated. The current understanding that the actin cytoskeleton is a target for the signals triggered by the SI response is discussed. It is suggested that these F-actin alterations may be Ca(2+)-mediated and that this could be a mechanism whereby SI-induced tip growth inhibition is achieved. The potential for actin-binding proteins to act as key mediators of this response is discussed and the mechanisms that may be responsible for effecting these changes are described. In particular, the parallels between sustained actin rearrangements during SI and in apoptosis of animal cells are considered.

Actin and actin-binding proteins in higher plants.

The actin cytoskeleton is a complex and dynamic structure that participates in diverse cellular events which contribute to plant morphogenesis and development. Plant actins and associated actin-binding proteins are encoded by large, differentially expressed gene families. The complexity of these gene families is thought to have been conserved to maintain a pool of protein isovariants with unique properties, thus providing a mechanistic basis for the observed diversity of plant actin functions. Plants contain actin-binding proteins which regulate the supramolecular organization and function of the actin cytoskeleton, including monomer-binding proteins (profilin), severing and dynamizing proteins (ADF/cofilin), and side-binding proteins (fimbrin, 135-ABP/villin, 115-ABP). Although significant progress in documenting the biochemical activities of many of these classes of proteins has been made, the precise roles of actin-binding proteins in vivo awaits clarification by detailed mutational analyses.

Chlamydomonas reinhardtii produces a profilin with unusual biochemical properties.

We report the characterization of a profilin orthologue from Chlamydomonas reinhardtii. CrPRF, probably the only profilin isoform, is present in both the cell body and flagella. Examination of vegetative and gametic cells by immunofluorescence microscopy using multiple fixation procedures also revealed enrichment of CrPRF at the anterior of the cell near the base of flagella and near the base of the fertilization tubule in mating type plus gametes. Purified, recombinant CrPRF binds to actin with a Kd value approximately 10(-7) and displaces nuclei in a live cell 'nuclear displacement' assay, consistent with profilin's ability to bind G-actin in vivo. However, when compared with other profilin isoforms, CrPRF has a relatively low affinity for poly-L-proline and for phosphatidylinositol (4,5) bisphosphate micelles. Furthermore, and surprisingly, CrPRF inhibits exchange of adenine nucleotide on G-actin in a manner similar to human ADF or DNase I. Thus, we postulate that a primary role for CrPRF is to sequester actin in Chlamydomonas. The unusual biochemical properties of CrPRF offer a new opportunity to distinguish specific functions for profilin isoforms.

SEPH, a Cdc7p orthologue from Aspergillus nidulans, functions upstream of actin ring formation during cytokinesis.

In the filamentous fungus, Aspergillus nidulans, multiple rounds of nuclear division occur before cytokinesis, allowing an unambiguous identification of genes required specifically for cytokinesis. As in animal cells, both an intact microtubule cytoskeleton and progression through mitosis are required for actin ring formation and contraction. The sepH gene from A. nidulans was discovered in a screen for temperature-sensitive cytokinesis mutants. Sequence analysis showed that SEPH is 42% identical to the serine-threonine kinase Cdc7p from fission yeast. Signalling through the Septation Initiation Network (SIN), which includes Cdc7p and the GTPase Spg1p, is emerging as a primary regulatory pathway used by fission yeast to control cytokinesis. A similar group of proteins comprise the Mitotic Exit Network (MEN) in budding yeast. This is the first direct evidence for the existence of a functional SIN-MEN pathway outside budding and fission yeast. In addition to SEPH, potential homologues were also identified in other fungi and plants but not in animal cells. Deletion of sepH resulted in a viable strain that failed to septate at any temperature. Interestingly, quantitative analysis of the actin cytoskeleton revealed that sepH is required for construction of the actin ring. Therefore, SEPH is distinct from its counterpart in fission yeast, in which SIN components operate downstream of actin ring formation and are necessary for ring contraction and later events of septation. We conclude that A. nidulans has components of a SIN-MEN pathway, one of which, SEPH, is required for early events during cytokinesis.

Fluorescently-labeled fimbrin decorates a dynamic actin filament network in live plant cells.

Recently it has been established, through a detailed biochemical analysis, that recombinant Arabidopsis thaliana fimbrin 1 (AtFim1) is a member of the fimbrin/plastin family of actin filament bundling or cross-linking proteins [D.R. Kovar et al. (2000) Plant J 24:625-636]. To determine whether AtFim1 can function as an F-actin-binding protein in the complex environment of the plant cell cytoplasm, we created a fluorescent protein analog and introduced it by microinjection into live Tradescantia virginiana L. stamen hair cells. AtFim1 derivatized with Oregon Green 488 had biochemical properties similar to unlabeled fimbrin, including the Kd value for binding to plant F-actin and the ability to cross-link filaments into higher-order structures. Fluorescent-fimbrin decorated an array of fine actin filaments in the cortical cytoplasm of stamen hair cells, which were shown with time-course studies to be highly dynamic. These data establish AtFim1 as a bona fide member of the fimbrin/plastin family, and represent the first use of a plant actin-binding protein as a powerful cytological tool for tracking the spatial and temporal redistribution of actin filaments in individual cells.

The characterization of ligand-specific maize (Zea mays) profilin mutants.

Profilins are low-molecular-mass (12-15 kDa) cytosolic proteins that are major regulators of actin assembly in all eukaryotic cells. In general, profilins from evolutionarily diverse organisms share the ability to bind to G-actin, poly-(L-proline) (PLP) and proline-rich proteins, and polyphosphoinositides. However, the functional importance of each of these interactions remains unclear and might differ between organisms. We investigated the importance of profilin's interaction with its various ligands in plant cells by characterizing four maize (Zea mays) profilin 5 (ZmPRO5) mutants that had single amino acid substitutions in the presumed sites of ligand interaction. Comparisons in vitro with wild-type ZmPRO5 showed that these mutations altered ligand association specifically. ZmPRO5-Y6F had a 3-fold increased affinity for PLP, ZmPRO5-Y6Q had a 5-fold decreased affinity for PLP, ZmPRO5-D8A had a 2-fold increased affinity for PtdIns(4,5)P(2) and ZmPRO5-K86A had a 35-fold decreased affinity for G-actin. When the profilins were microinjected into Tradescantia stamen hair cells, ZmPRO5-Y6F increased the rate of nuclear displacement in stamen hairs, whereas ZmPRO5-K86A decreased the rate. Mutants with a decreased affinity for PLP (ZmPRO5-Y6Q) or an enhanced affinity for PtdIns(4,5)P(2) (ZmPRO5-D8A) were not significantly different from wild-type ZmPRO5 in affecting nuclear position. These results indicate that plant profilin's association with G-actin is extremely important and further substantiate the simple model that profilin acts primarily as a G-actin-sequestering protein in plant cells. Furthermore, interaction with proline-rich binding partners might also contribute to regulating profilin's effect on actin assembly in plant cells.

Ferdinand von Mueller in philately.

Ferdinand von Mueller was one of the greatest Australia's nineteenth-century scientists, with an international botanical reputation. The substantial international recognition for his work in the form of numerous titles, awards and honorary memberships of scientific societies did not end at his death. In 1948, a stamp showing his portrait commemorated the discovering and tableting of Australian flora. On the 100th anniversary of Mueller's death in 1996, both the German Mail Office and the Australian Post Office honored him with a stamp.

AtFim1 is an actin filament crosslinking protein from Arabidopsis thaliana.

ATFIM1 is a widely expressed gene in Arabidopsis thaliana that encodes a putative actin filament-crosslinking protein, AtFim1, belonging to the fimbrin/plastin class of actin-binding proteins. In this report we have used bacterially expressed AtFim1 and actin isolated from Zea mays pollen to demonstrate that AtFim1 functions as an actin filament-crosslinking protein. AtFim1 binds pollen actin filaments (F-actin) in a calcium-independent manner, with an average dissociation constant (Kd) of 0.55+/-0.21 microM and with a stoichiometry at saturation of 1:4 (mol AtFim1 : mol actin monomer). AtFim1 also crosslinks pollen F-actin by a calcium-independent mechanism, in contrast to crosslinking of plant actin by human T-plastin, a known calcium-sensitive actin-crosslinking protein. When micro-injected at high concentration into living Tradescantia virginiana stamen hair cells, AtFim1 caused cessation of both cytoplasmic streaming and transvacuolar strand dynamics within 2-4 min. Using the 'nuclear displacement assay' as a measure of the integrity of the actin cytoskeleton in living stamen hair cells, we demonstrated that AtFim1 protects actin filaments in these cells from Z. mays profilin (ZmPRO5)-induced depolymerization, in a dose-dependent manner. The apparent ability of AtFim1 to protect actin filaments in vivo from profilin-mediated depolymerization was confirmed by in vitro sedimentation assays. Our results indicate that AtFim1 is a calcium-independent, actin filament-crosslinking protein that interacts with the actin cytoskeleton in living plant cells.

Technical advance: identification of plant actin-binding proteins by F-actin affinity chromatography.

Proteins that interact with the actin cytoskeleton often modulate the dynamics or organization of the cytoskeleton or use the cytoskeleton to control their localization. In plants, very few actin-binding proteins have been identified and most are thought to modulate cytoskeleton function. To identify actin-binding proteins that are unique to plants, the development of new biochemical procedures will be critical. Affinity columns using actin monomers (globular actin, G-actin) or actin filaments (filamentous actin, F-actin) have been used to identify actin-binding proteins from a wide variety of organisms. Monomeric actin from zucchini (Cucurbita pepo L.) hypocotyl tissue was purified to electrophoretic homogeneity and shown to be native and competent for polymerization to actin filaments. G-actin, F-actin and bovine serum albumin affinity columns were prepared and used to separate samples enriched in either soluble or membrane-associated actin-binding proteins. Extracts of soluble actin-binding proteins yield distinct patterns when eluted from the G-actin and F-actin columns, respectively, leading to the identification of a putative F-actin-binding protein of approximately 40 kDa. When plasma membrane-associated proteins were applied to these columns, two abundant polypeptides eluted selectively from the F-actin column and cross-reacted with antiserum against pea annexins. Additionally, a protein that binds auxin transport inhibitors, the naphthylphthalamic acid binding protein, which has been previously suggested to associate with the actin cytoskeleton, was eluted in a single peak from the F-actin column. These experiments provide a new approach that may help to identify novel actin-binding proteins from plants.