Marketing approval of mogamulizumab: A triumph for glyco-engineering

Therapeutic properties of antibodies strongly depend on the composition of their glycans. Most of the currently approved antibodies are produced in mammalian cell lines, which yield mixtures of different glycoforms that are close to those of humans, but not fully identical. Glyco-engineering is being developed as a method to control the composition of carbohydrates and to enhance the pharmacological properties of mAbs. The recent approval in Japan of mogamulizumab (POTELIGEO^®), the first glyco-engineered antibody to reach the market, is a landmark in the field of therapeutic antibodies. Mogamulizumab is a humanized mAb derived from Kyowa Hakko Kirin’s POTELLIGENT^® technology, which produces antibodies with enhanced antibody-dependent cell-mediated cytotoxicity (ADCC) activity. The approval was granted April 30, 2012 by the Japanese Ministry of Health, Labour and Welfare for patients with relapsed or refractory CCR4-positive adult T-cell leukemia-lymphoma.     

Aggregation of biopharmaceuticals in human plasma and human serum

Analytical methods based on light microscopy, 90° light-scattering and surface plasmon resonance (SPR) allowed the characterization of aggregation that can occur when antibodies are mixed with human plasma. Light microscopy showed that aggregates formed when human plasma was mixed with 5% dextrose solutions of Herceptin^® (trastuzumab) or Avastin^® (bevacizumab) but not Remicade^® (infliximab). The aggregates in the plasma-Herceptin^®-5% dextrose solution were globular, size range 0.5–9 μm, with a mean diameter of 4 μm. The aggregates in the plasma-Avastin^®-5% dextrose samples had a mean size of 2 μm. No aggregation was observed when 0.9% NaCl solutions of Herceptin^®, Avastin^® and Remicade^® were mixed with human plasma. 90° light-scattering measurements showed that aggregates were still present 2.5 h after mixing Herceptin^® or Avastin^® with 5% dextrose-plasma solution. A SPR method was utilized to qualitatively describe the extent of interactions of surface-bound antibodies with undiluted human serum. Increased binding was observed in the case of Erbitux^® (cetuximab), whereas no binding was measured for Humira^® (adalimumab). The binding of sera components to 13 monoclonal antibodies was measured and correlated with known serum binding properties of the antibodies. The data presented in this paper provide analytical methods to study the intrinsic and buffer-dependent aggregation tendencies of therapeutic proteins when mixed with human plasma and serum.     

Utilisation du système Take-set® pour le radiomarquage des médicaments radiopharmaceutiques : exemple de la préparation du pentétréotide marqué à l’indium 111 (Octreoscan®)

The quality of indium 111 radiolabelled pentetreotide preparation (Octreoscan^®, Covidien) depends on several factors among which the use of a special transfer needle (Sterican^®) especially conceived to avoid the metal impurities introduction into the reactionnal medium during labelling. This device, usually provided by the supplier, can exceptionally present defects (twisted needle, folded bevel...) preventing its use for the preparation. In order to manage this risk, we propose in the present technical note an alternative labelling method, based on an adaptation of the original one and using another transfer device, the Take-set^SWAN® system, which permits to obtain high quality Octreoscan^® preparations that meet the product approval specifications.     

Influence of an Acrylic Polymer Blend on the Physical Stability of Film-Coated Theophylline Pellets

The purpose of this study was to investigate the physical stability of a coating system consisting of a blend of two sustained release acrylic polymers and its influence on the drug release rate of theophylline from coated pellets. The properties of both free films and theophylline pellets coated with the polymer blend were investigated, and the miscibility was determined via differential scanning calorimetry. Eudragit^® RS 30 D was plasticized by the addition of Eudragit^® NE 30 D, and the predicted glass transition temperature (T _g) of the blend was similar to the experimental values. Sprayed films composed of a blend of Eudragit^® NE 30 D/Eudragit^® RS 30 D (1:1) showed a water vapor permeability six times greater than films containing only Eudragit^® NE 30 D. The presence of quaternary ammonium functional groups from the RS 30 D polymer increased the swellability of the films. The films prepared from the blend exhibited stable permeability values when stored for 1 month at both 25°C and 40°C, while the films which were composed of only Eudragit^® NE 30 D showed a statistically significant decrease in this parameter when stored under the same conditions. Eudragit^® NE 30 D/Eudragit^® RS 30 D (1:1)-sprayed films decreased in elongation from 180% to 40% after storage at 40°C for 1 month, while those stored at 25°C showed no change in elongation. In coated pellets, the addition of Eudragit^® RS 30 D to the Eudragit^® NE 30 D increased the theophylline release rate, and the pellets were stable when stored at 25°C for a period of up to 3 months due to maintenance of the physico-mechanical properties of the film. Pellets stored at 40°C exhibited a decrease in drug release rate over time as a result of changes in film physico-mechanical properties which were attributed to further coalescence and densification of the polymer. When the storage temperature was above the T _g of the composite, instabilities in both drug release rate and physical properties were evident. Stabilization in drug release rate from coated pellets could be correlated with the physico-mechanical stability of the film formulation when stored at temperatures below the T _g of the polymer.     

An analysis of the bacterial community in a membrane bioreactor fed with photo-Fenton pre-treated toxic water

A photo-Fenton-membrane bioreactor (MBR) coupled system is an innovative tool for the treatment of wastewater containing high quantities of contaminants. In this paper, wastewater with 200 mg l^?1 of dissolved organic carbon (DOC) of a selected mixture of five commercial pesticides: Vydate^®, Metomur^®, Couraze^®, Ditimur-40^®, and Scala^® was treated by combining photo-Fenton and MBR. The effect of photo-treated pollutants on MBR operation was investigated by studying the population changes that occurred with time in the activated sludge of the biological system. Pre-treatment with photo-Fenton was carried out (only up to 34% of mineralization of DOC) and, after MBR treatment, 98% of biodegradation efficiency was obtained. During the biological treatment, little changes in the activated sludge population were detected by DGGE analysis, maintaining acceptable biodegradation efficiency, which points out the robustness of the MBR treatment versus changes in feed composition.     

Self-Nanoemulsifying Drug Delivery System of Nifedipine: Impact of Hydrophilic–Lipophilic Balance and Molecular Structure of Mixed Surfactants

A simple but novel mixed surfactant system was designed to fabricate a self-nanoemulsifying drug delivery system (SNEDDS) based on hydrophilic–lipophilic balance (HLB) value. The impacts of HLB and molecular structure of surfactants on the formation of SNEDDS were investigated. After screening various oils and surfactants, nifedipine (NDP)-loaded liquid SNEDDS was formulated with Imwitor^® 742 as oil and Tween^®/Span^® or Cremophor^®/Span^® as mixed surfactant. Droplet size of the emulsions obtained after dispersing SNEDDS containing Tween^®/Span^® in aqueous medium was independent of the HLB of a mixed surfactant. The use of the Cremophor^®/Span^® blend gave nanosized emulsion at higher HLB. The structure of the surfactant was found to influence the emulsion droplet size. Solid SNEDDS was then prepared by adsorbing NDP-loaded liquid SNEDDS comprising Cremophor^® RH40/Span^® 80 onto Aerosil^® 200 or Aerosil^® R972 as inert solid carrier. Solid SNEDDS formulations using higher amounts (30–50% w/w) of Aerosil^® 200 exhibited good flow properties with smooth surface and preserved the self-emulsifying properties of liquid SNEDDS. Differential scanning calorimetry and X-ray diffraction studies of solid SNEDDS revealed the transformation of the crystalline structure of NDP due to its molecular dispersion state. In vitro dissolution study demonstrated higher dissolution of NDP from solid SNEDDS compared with NDP powder.     

Study of support materials for sol-gel immobilized lipase

Abstract

A variety of support materials for sol-gel immobilized lipase were considered based on their ability to provide superior sol-gel adhesion, load protein, and synthesize methyl oleate. A standard approach was developed to formulate the supported lipase sol-gels and to allow comparison of the resulting hybrid materials. These supported sol-gels are proposed as an alternative immobilization regime to overcome some challenges associated with enzymatic biodiesel production such as enzyme stability and cost. The support materials considered were 6–12 mesh silica gel, Celite^® R633, Celite^® R632, Celite^® R647, anion-exchange resin AG3-X4, and Quartzel^® felt. Each support material exhibited unique properties that would be beneficial for this application including: Quartzel^® felt had the highest initial sol-gel capacity (62.5 mL/g) and sol-gel adhesion (1100 mg sol-gel/g material); silica gel had the most uniform coating of deposited sol-gel; the anion-exchange resin AG3-X4 supported sol-gel had the highest protein loading (1060 μg lipase/g) and reaction rate [1.25 mM/(min g-material)]; the Celite^® support series were the most thermally stable and had the lowest water content; and the Celite^® R632 supported lipase sol-gels had the highest 6 h biodiesel conversion per gram of supported material (68%) and enzymatic activity [9.4 mmol/(min g-lipase)]. The supported sol-gels with the highest enzymatic properties (conversion, activity, and reaction rate) were those supported on Celite^® R632, anion-exchange resin AG3-X4, and Quartzel^®. These supported sol-gels had superior performance in comparison with the unsupported sol-gels. Based on this study, the lipase sol-gel support material with the most potential for biodiesel production is Celite^® R632.     

Development of Leptospira in vitro potency assays: EU/industry experience and perspectives

Nobivac^® Lepto (MSD Animal Health) is a non-adjuvanted canine leptospirosis vaccine containing inactivated whole cells of Leptospira interrogans serogroup Canicola serovar Portlandvere and L. interrogans serogroup Icterohaemorrhagiae serovar Copenhageni. The current standard in vivo potency test is a hamster challenge test associated with major drawbacks such as animal suffering and poor reproducibility. Here, the quantification of antigenic mass by ELISA as a new in vitro potency test is described, supporting the 3Rs concept (replacement, reduction, and refinement of animal tests) and in accordance with European Pharmacopoeia Monograph 0447 (Canine Leptospirosis Vaccine [Inactivated]). The two corresponding sandwich ELISAs are based on monoclonal antibodies specific for immunodominant leptospiral lipopolysaccharide epitopes. Protection in passive immunization experiments demonstrate that these monoclonal antibodies recognize key protective antigens in currently licensed human and veterinary whole cell Leptospira vaccines. The high precision and robustness renders the two ELISAs much more reliable correlates of potency in dogs than the hamster potency test. The recent approval of these assays for a new canine leptospirosis vaccine is an important contribution to the 3Rs in quality control testing of Leptospira vaccines.     

Deceased tissue donor serology and molecular testing for HIV,hepatitis B and hepatitis C viruses: a lack of cadaveric validated tests

Vital to patient safety is the accurate assessment and minimization of risk for human immunodeficiency virus (HIV), Hepatitis C (HCV), and Hepatitis B (HBV) virus transmission by deceased donor organ and tissue transplantation. The pathogens are tested by serological kits based on enzyme-linked immunosorbent assay (ELISA), chemiluminescence (CLIA) and eletrochemiluminescence (ECLIA) immunoassays. Organ transplantation is a highly successful life-saving treatment in Brazil, but the Brazilian Health Surveillance Agency currently mandates that all deceased organ donors are screened for HIV, HCV and HBV following living donor policies. In this review, six ELISA (Wama^®, Bio-Rad^®, Biomerieux^®, DiaSorin^®, Acon Biotech^® and Biokit^®), three CLIA (Abbott^®, Siemens^®, Diasorin^®) and one ECLIA (Roche^®) were utilized for evaluating the effectiveness of those serological tests for deceased donors in Brazil according to manufacturer’s guidelines. NAT for HIV, HCV and HBV can assist with detection of pre-seroconversion for those infections, and only Cobas^® TaqScreen MPX^® test, the Tigris System^® Procleix Ultrio Assay^® and the Bio-Manguinhos^® HIV/HCV/HBV NAT are commercially available. Between all the tests, only the manufacturer Abbott^® and Cobas^® TaqScreen MPX^® test are currently validated for cadaver samples.     

Improvements of Liver MR Imaging Clinical Protocols to Simultaneously Quantify Steatosis and Iron Overload

Purpose

Fat accumulation and iron overload are important cofactors in chronic liver disease. Clinical quantifications of fat fraction and iron are currently assessed using MRI protocols. The purpose is to improve these measurements to simultaneously provide iron and fat maps from a single acquisition.

Non-fucosylated therapeutic antibodies: the next generation of therapeutic antibodies

Therapeutic antibody IgG1 has two N-linked oligosaccharide chains bound to the Fc region. The oligosaccharides are of the complex biantennary type, composed of a trimannosyl core structure with the presence or absence of core fucose, bisecting N-acetylglucosamine (GlcNAc), galactose, and terminal sialic acid, which gives rise to structural heterogeneity. Both human serum IgG and therapeutic antibodies are well known to be heavily fucosylated. Recently, antibody-dependent cellular cytotoxicity (ADCC), a lytic attack on antibody-targeted cells, has been found to be one of the critical effector functions responsible for the clinical efficacy of therapeutic antibodies such as anti-CD20 IgG1 rituximab (Rituxan^®) and anti-Her2/neu IgG1 trastuzumab (Herceptin^®). ADCC is triggered upon the binding of lymphocyte receptors (FcγRs) to the antibody Fc region. The activity is dependent on the amount of fucose attached to the innermost GlcNAc of N-linked Fc oligosaccharide via an α-1,6-linkage, and is dramatically enhanced by a reduction in fucose. Non-fucosylated therapeutic antibodies show more potent efficacy than their fucosylated counterparts both in vitro and in vivo, and are not likely to be immunogenic because their carbohydrate structures are a normal component of natural human serum IgG. Thus, the application of non-fucosylated antibodies is expected to be a powerful and elegant approach to the design of the next generation therapeutic antibodies with improved efficacy. In this review, we discuss the importance of the oligosaccharides attached to the Fc region of therapeutic antibodies, especially regarding the inhibitory effect of fucosylated therapeutic antibodies on the efficacy of non-fucosylated counterparts in one medical agent. The impact of completely non-fucosylated therapeutic antibodies on therapeutic fields will be also discussed.     

Biomechanical properties of bovine tendon xenografts treated with a modern processing method

Xenograft tendons have been used in few human studies, with variable results. With the advent of novel tissue processing techniques, which may mitigate against an immune-mediated rejection response without adversely affecting mechanical properties, there may now be a clinical role for xenograft tendons, particularly in knee ligament reconstruction. We hypothesize that ‘BioCleanse®’ processed bovine extensor digitorum medialis (EDM) tendons exhibit favorable time-zero pre-implantation biomechanical characteristics when compared to both unprocessed bovine EDM tendons and BioCleanse® processed human cadaveric allograft tibialis anterior tendons.In this in vitro case controlled laboratory study, three groups of tendons underwent a 5-stage static loading test protocol: 15 BioCleanse^® bovine (BCB), 15 fresh frozen unprocessed bovine (FFB), and 12 BioCleanse^® human allograft (BCA) tendons. Cross-sectional area of the grafts was measured using an alginate molding technique, and tendons were mounted within an Instron^® 5565 Materials Testing System using cryogenic clamps.BCB tendons displayed a higher ultimate tensile stress (p<0.05), with equivalent ultimate failure load, creep, and modulus of elasticity when compared to the FFB tendons (p>0.05). BCB tendons had an equivalent cross-sectional area to the BCA tendons (p>0.05) whilst exhibiting a greater failure load, ultimate tensile stress, less creep and a higher modulus of elasticity (p<0.05).The BioCleanse^® process did not adversely affect the time-zero biomechanical properties of bovine xenograft EDM tendons. BioCleanse^® processed bovine xenograft EDM tendons exhibited superior biomechanical characteristics when compared with BioCleanse^® processed allograft tibialis anterior tendons. These findings support further investigation of xenograft tendons in orthopedic soft tissue reconstructive surgery.     

Physicomechanical Characterization and Optimization of EDTA–mPEG and Avicel®–EDTA–mPEG In Situ Melt Dispersion Mini-Pellets

The purpose of this study was to develop a physicomechanically customizable oral metal chelatory in situ hot melt dispersion mini-pellet entity which could be utilized within a binary drug delivery system. Avicel^® RC/CL type R-591 was included within the in situ hot melt dispersion mini-pellet formulations to determine the physicomechanical effect this compound would have on the mini-pellet formulations. The physicomechanical properties of the hot melt in situ mini-pellet formulations were mathematically fitting to regression curves. Physicomechanical adjustment of the in situ hot melt dispersion mini-pellet formulations could be mathematically predicted with the derived regression curve equations. The addition of Avicel^® RC/CL type R-591 increased the physicomechanical properties such as matrix hardness and increased total disintegration of the in situ hot melt dispersion mini-pellet formulations. The utilization of a physicomechanically customizable oral metal chelatory in situ hot melt dispersion mini-pellet entity within a binary drug delivery system would to achieve a synergistically enhance the activity of a drug-carrying entity or a permeation enhancing entity within a single drug delivery unit. The experimental results indicated that weights of the pellets that achieved optimal hardness ranged between 35 and 45 mg. The melt–dispersion formulations disintegrated within shorter time periods and maintained higher ethylenediaminetetraacetic acid (EDTA) concentrations whereas melt–dispersion formulations which included Avicel^® had superior physicomechanical properties. Disintegration times ranged between 1,000 s for melt–dispersions containing EDTA and methyloxy polyethylene glycol 2000 (mPEG) only, to >6,000 s for melt–dispersions comprising EDTA, mPEG, and Avicel^®.     

Cytotoxicity testing of burn wound dressings: first results

Topical antimicrobial therapy represents an essential part of burn wound care. In order to prevent and treat burn wound infection dressings with antimicrobial properties are applied directly on the wound surface. Not only the infection control but also promotion of healing is very important in burn wound management. It is well known, that a dressing in bactericidal concentration might also delay wound healing. This study was aimed to evaluate the potential toxic effect of topical antimicrobial agents on murine and human dermal cells. For toxicity testing the method by Vittekova et al. was used to evaluate potential toxic effects of 16 agents and 6 control samples on two in vitro cultured cell systems [3T3 cells and dermal fibroblasts] during the first 24 h. Following the 24 h cell culture with the tested agents the live cell counts were evaluated. According to results obtained on both cell systems, the tested samples were divided into three groups—nontoxic, semi-toxic and toxic. Nontoxic samples included Acetic acid 1%, Acticoat^®, Dermacyn^®, Framykoin^®, Silverlon^®, gauze, acellular human allodermis and acellular porcine xenodermis. Semi-toxic group included Algivon^®Plus, Aquacel^®Ag, Betadine^®, Nitrofurazone, Octenisept^®, Suprasorb^® A and a porcine dermal scaffold Xeno-Impl. Finally, the toxic group included Algivon^®, Dermazin^®, Ialugen^®Plus, Prontoderm^®, Suprasorb^® A Ag and 20% SDS. As the preliminary results of this study have shown, our findings may serve as a potential guide to selection of the most appropriate topical antimicrobial dressings for treatmet of burns. However before they can be translated into clinical practice recommendations, more research on antimicrobial dressings cytotoxicity testing will be necessary.     

CFD analysis of the Ahmed Glaucoma Valve and design of an alternative device

Computational fluid dynamics (CFD) modelling based on a commercial package, FLUENT, has been used in the present study. The primary aim of this study is to develop a novel implant by employing CFD techniques. Firstly, CFD analyses on the best design commercially available, which is the Ahmed Glaucoma Valve (AGV^®), are accomplished. In the light of the results, the new design focus is selected as the valve. The new design is analysed using GAMBIT and FLUENT software. CFD analyses of the new design and the AGV^® are compared and the strengths of the new design are revealed. The results are also compared with the experimental studies AGV^® in the literature. It is deduced that the proposed model shows a nonlinear pressure drop response, which is quite similar to that of AGV^®. The optimum combination would be a flow rate of 2.5 μl/min and a pressure drop of 1054.58 Pa for the proposed model.     

Comparison of SurePath® and ThinPrep® liquid‐based cervical cytology using positive predictive value,atypical predictive value and total predictive value as performance indicators

P. K. Wright, J. Marshall and M. Desai Comparison of SurePath ^® and ThinPrep ^® liquid‐based cervical cytology using positive predictive value, atypical predictive value and total predictive value as performance indicators Objective: Two liquid‐based cytology (LBC) systems are in widespread use in the UK: ThinPrep^® and SurePath^®. A number of studies have now compared LBC with conventional cytology in cervical screening. However, to date, we are aware of no studies that have compared ThinPrep^® with SurePath^® LBC. As the selection and use of specific diagnostic systems in a laboratory has significant clinical and economic implications, there is a clear need to compare directly existing LBC technology. The objective of this study was to compare ThinPrep^® with SurePath^® LBC in a single cytology laboratory using performance indicators. Methods: Data were collected for all cervical cytology samples processed at Manchester Cytology Centre over a 1‐year period. ThinPrep^® LBC was compared with SurePath^® LBC using positive predictive value (PPV), atypical predictive value (APV) and total predictive value (TPV), reflecting outcome of cervical intraepithelial neoplasia (CIN) grade 2 or worse for high‐grade dyskaryosis (PPV), low‐grade dyskaryosis or borderline (atypical) cytology (APV) and all (total) abnormal cytology (TPV). Results: 2287 (out of 56 467) (ThinPrep^®) and 586 (out of 22 824) (SurePath^®) samples showed borderline or worse cytology after exclusion criteria. PPV, APV and TPV were within acceptable ranges for both ThinPrep^® and SurePath^®. Conclusions: ThinPrep^® and SurePath^® were equivalent based on three performance indicators. We suggest that APV and TPV should be used as an adjunct to PPV and other methods of quality assurance for cervical screening.     

Validation of an automated method for compounding monoclonal antibody patient doses

Automation robots have recently come to the market as an alternative for manual compounding of drugs for intravenous administration. Our aim was to assess whether robotic compounding can be performed with monoclonal antibodies (mAbs) without influencing the aggregation state of the proteins. Three frequently used mAbs were studied: infliximab (Remicade^®, Janssen Biotech) and trastuzumab (Herceptin^®, Roche) in lyophilised form, and bevacizumab (Avastin^®, Roche) as a liquid formulation stored at 2°C to 8°C. The effects of different procedures to prepare the patient doses on antibody aggregation were evaluated. Remicade^® and Herceptin^® were reconstituted both manually and by a robotic arm (i.v.STATION^®, Health Robotics). Additionally, the influence of vigorous shaking during reconstitution was investigated. The effects of rapid aspiration and dispensing on antibody aggregation were investigated for all three mAbs. Aggregation state was assessed by UV-Vis absorbance, 90° light scatter, fluorescence spectroscopy, Nile red fluorescence microscopy, and field flow fractionation without cross and focus flow. Robotic reconstituted samples showed similar findings compared with manual reconstitution if performed exactly according to the summary of product characteristics (SPC). Vials that were vigorously shaken showed a significant increase in aggregates. Similarly, rapid aspiration/dispense cycles resulted in a strong increase in the number and sizes of aggregates for all three mAbs; this result was observed after just one rapid aspiration/dispense cycle. Our study showed that robotic compounding of mAbs is feasible if the robot is exactly programmed according to the SPC, indicating that robotic compounding can be used to achieve reproducible high-quality compounding for delicate formulations.     

RGTA<Superscript>®</Superscript> or ReGeneraTing Agents mimic heparan sulfate in regenerative medicine: from concept to curing patients

The importance of extracellular matrix (ECM) integrity in maintaining normal tissue function is highlighted by numerous pathologies and situations of acute and chronic injury associated with dysregulation or destruction of ECM components. Heparan sulfate (HS) is a key component of the ECM, where it fulfils important functions associated with tissue homeostasis. Its degradation following tissue injury disrupts this delicate equilibrium and may impair the wound healing process. ReGeneraTing Agents (RGTA^®s) are polysaccharides specifically designed to replace degraded HS in injured tissues. The unique properties of RGTA^® (resistance to degradation, binding and protection of ECM structural and signaling proteins, like HS) permit the reconstruction of the ECM, restoring both structural and biochemical functions to this essential substrate, and facilitating the processes of tissue repair and regeneration. Here, we review 25 years of research surrounding this HS mimic, supporting the mode of action, pre-clinical studies and therapeutic efficacy of RGTA^® in the clinic, and discuss the potential of RGTA^® in new branches of regenerative medicine.     

Can Kelp Extract (KELPAK®) be Useful in Seaweed Mariculture?

The addition of low concentrations of commercial kelp extract (Ecklonia maxima: Kelpak^®) in addition to fertiliser has proven to be beneficial in agriculture. It triggers rooting in field crops, increases yields and has other useful effects, such as parasite reduction. Its efficacy has been attributed to the fact that Kelpak^® is produced by a cold process, and is a high auxin/low cytokinin product. The aim of this study was to investigate if seaweeds (which do not have a root system) grown in culture systems, would benefit from the addition of Kelpak^® or a combination of Kelpak^® and fertilizer. A preliminary laboratory experiment was carried out by growing excised 15 mm tips of the red alga Gracilaria gracilis in culture dishes containing Provasoli Enriched Seawater medium to which various concentrations of Kelpak^® were added. Gracilaria tips in some of the Kelpak^® treatments (1:2500; 1:1000; 1:500) grew significantly better than the control. Further experiments were carried out on a pilot commercial scale at Jacobsbaai Sea Products Ltd. on the South African west coast. Ulva lactuca was grown in effluent from fish (turbot) culture, with additions of 1:5000, 1:2500 and 1:500 concentrations of Kelpak^® once a week. The intermediate Kelpak^® concentration (1:2500) produced the highest growth of Ulva in the turbot water, while the highest Kelpak^® concentration (1:500) inhibited Ulva growth. In another Ulva experiment, various combinations of aquaculture effluent water, commercial fertiliser and Kelpak^® at 1:2500 were used. Best growth of Ulva was obtained in turbot water containing both fertiliser and Kelpak^®. The results suggest that Kelpak^® could be useful in commercial seaweed mariculture operations.     

EPs® 7630-solution – an effective therapeutic option in acute and exacerbating bronchitis

Acute bronchitis is one of the most common diagnoses in ambulatory care medicine. Although the benefit of antibiotics for acute bronchitis, which is mostly virally induced, is disputed, they are often prescribed. A therapeutic option for respiratory tract infections that do not fall within the strict indication range for antibiotic administration is the liquid herbal drug preparation from the roots of Pelargonium sidoides, EPs^® 7630 (Umckaloabo^®), which has been tested against placebo in double-blind clinical trials. EPs^® 7630 has both antibacterial and immuno-modulating properties. The efficacy and tolerability of EPs^® 7630 was investigated in a prospective, open, multicentric outcomes study with 205 patients suffering from acute bronchitis or acute exacerbation of chronic bronchitis. The main outcome measure was the change in the total score of five symptoms typical for bronchitis (cough, expectoration, wheezing/whistling on expiration, chest pain during coughing, and dyspnoea), which were each rated using a 5-point scale (from 0=not present to 4=extremely pronounced). Further symptoms (hoarseness, headache, aching limbs and fatigue) were assessed using a four-point scale (from 0=not present to 3=very pronounced). The total score of the typical bronchitis symptoms amounted to 6.1±2.8 points on average at the start of treatment and decreased by 3.3±3.8 points to 2.8±2.6 points by the final examination on day 7. About 60.5% of the patients assessed their health condition at the end of the study as much improved or free from symptoms. The onset of action appeared after two days on average. Adverse events occurred in a total of 16 patients. There were no serious adverse events. Altogether, 78% of the patients were satisfied or very satisfied with the treatment.