White-light toxicity, resulting from systemically administered 5-aminolevulinic acid, under normal operating conditions

This study has investigated damage to the intraperitoneal organs of the rat after systemic (intraperitoneal and intravenous) administration of low doses of 5-aminolevulinic acid (ALA) and illumination with a standard white-light operating-room (o.r.) lamp. The study has been done within the framework of a larger study in which the possibility of using ALA for localization of small-volume macroscopically non-visible peritoneal metastasis of ovarian tumors is being investigated. Fluorescence diagnostics are done in addition to the standard staging and localization procedures, either through a laparoscope or during laparotomy. In these circumstances, fluorescence diagnostics involve some risk of photosensitization of critical organs since a broad-band (o.r.) light source is used during the surgical procedures for illumination of the operating area. The drug dose and the time interval between administration of ALA and illumination are varied and normal tissues are examined both macroscopically and microscopically for damage. A relationship is demonstrated between the maximum tolerable dose (MTD) of ALA (defined as the dose that does not cause any tissue damage) and the time interval between administration and illumination. The white light that is used for illumination of the operating area is sufficient to induce damage to the peritoneal organs at relatively low ALA doses. The MDTs for 2, 6 and 16 h intervals are found to be respectively 1, 10 and 100 mg kg-1. The results are similar for both intraperitoneal and intravenous administration

Reovirus mutant jin-3 exhibits lytic and immune-stimulatory effects in preclinical human prostate cancer models

Treatment of castration-resistant prostate cancer remains a challenging clinical problem. Despite the promising effects of immunotherapy in other solid cancers, prostate cancer has remained largely unresponsive. Oncolytic viruses represent a promising therapeutic avenue, as oncolytic virus treatment combines tumour cell lysis with activation of the immune system and mounting of effective anti-tumour responses. Mammalian Orthoreoviruses are non-pathogenic human viruses with a preference of lytic replication in human tumour cells. In this study, we evaluated the oncolytic efficacy of the bioselected oncolytic reovirus mutant jin-3 in multiple human prostate cancer models. The jin-3 reovirus displayed efficient infection, replication, and anti-cancer responses in 2D and 3D prostate cancer models, as well as in ex vivo cultured human tumour slices. In addition, the jin-3 reovirus markedly reduced the viability and growth of human cancer cell lines and patient-derived xenografts. The infection induced the expression of mediators of immunogenic cell death, interferon-stimulated genes, and inflammatory cytokines. Taken together, our data demonstrate that the reovirus mutant jin-3 displays tumour tropism, and induces potent oncolytic and immunomodulatory responses in human prostate cancer models. Therefore, jin-3 reovirus represents an attractive candidate for further development as oncolytic agent for treatment of patients with aggressive localised or advanced prostate cancer.Experimental cancer immunology and therap

Development of a tomato/root knot nematode bioassay to screen beneficial microbes

In common with other root knot nematodes Meloidogyne hapla is a serious plant pest. A rapid screening system for candidate microbes that benefit plant growth is a first step to developing screening bioassays in other plant–nematode systems. Cultures of M. hapla established on tomatoes were used to define the nematode damage function, and required bioassay duration for this plant-pest system, followed by scale-up to a glasshouse level. The quantities of Meloidogyne inoculum were chosen such that they would cause minor, moderate or severe plant damage; hence the degree of protection afforded by the microbes in bioassays could be readily evaluated. An inoculation rate of 3542 eggs/plant caused a significant reduction in shoot weight (30%) and an increase in root galling in excess of 50%. Percentage of root gall and root gall index were good indicators of nematode impact and provide a relatively quick method of assessment

Plant parasitic nematode survival and detection to inform biosecurity risk assessment

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Home assessment of peak inspiratory flow through the Turbohaler in asthmatic patients.

BACKGROUND: The efficacy of dry powder inhalers depends on the patient's inspiratory flow. Drug delivery from the Turbohaler (Turbuhaler in some countries), a multidose powder inhaler, is optimal at flows of > 40 l/min. The aim of this study was to investigate the peak inspiratory flow that can be generated by asthmatic patients through the budesonide Turbohaler (PIFTBH) during maintenance treatment at home. METHODS: Thirty asthmatic patients, consecutively recruited from the outpatient clinic, inhaled their maintenance dose of 800 (n = 16) or 1600 micrograms/day (n = 14) for two months or one month, respectively. The Turbohaler was connected to a modified Vitalograph Compact installed at home to obtain printed PIFTBH values for all inhalations. Peak expiratory flow (PEF) was measured twice daily. RESULTS: Flows were remarkably constant with individual mean PIFTBH values ranging from 55 l/min to 95 l/min. Only 13 of the 5248 PIFTBH recordings taken at home (three patients) were < 40 l/min and all were > 30 l/min. Weekly mean morning PEF values ranged from 114 l/min to 733 l/min. PIFTBH values could not be accurately predicted from lung function parameters in individual patients. CONCLUSIONS: In a group of stable asthmatic patients inspiratory flow rates rarely fell below the 40 l/min needed to operate a Turbohaler

The value of sentinel plants for risk assessment and surveillance to support biosecurity

Effective surveillance for early detection of invasive alien species in natural ecosystems, or on valued plants found in modified areas, could prevent potentially devastating and costly impacts (whether environmental, economic or cultural) of new invasions on the invaded country. Surveillance technologies are often constrained by a range of factors. Determining which species present a significant risk before they reach the border is an effective strategy to minimize the possibility of invasion and/or the impact of invasion. Surveillance of sentinel plants provides an important tool to strengthen biosecurity programs assisting with i) detecting and identifying insect pests, nematodes and plant diseases that could potentially invade uncolonized countries, and ii) developing pest risk analysis profiles to eliminate or mitigate the risk of arrival. This review examines some of the challenges and opportunities provided by sentinel plant research and discusses the factors that could affect the success of their use for biosecurity risk assessment and surveillance in the New Zealand context

Defining the biosecurity risk posed by transported soil: Effects of storage time and environmental exposure on survival of soil biota

Soil frequently occurs as a contaminant on numerous sea, land and air transport pathways. It can carry unwanted invasive species, is widely recognized as a biosecurity risk, and is usually strictly regulated by biosecurity authorities. However, little is known about relative risk levels between pathways, thus authorities have limited capability to identify and target the riskiest soil pathways for management. We conducted a an experiment to test the hypotheses that biosecurity risks from soil organisms will increase both with declining transport duration and with increasing protection from environmental extremes. Soil was collected from two sites, a native forest remnant and an orchard, and stored on, in and under sea containers, or in cupboards, and assayed after 0, 3, 6 and 12 months for bacteria, fungi, nematodes and seeds. Results showed that viability of Pseudomonas spp., bacteria, nematodes and plants declined over 12 months, irrespective of soil source. Also, mortality of most biota was higher when exposed to sunlight, moisture and desiccation than when protected. However, bacterial and fungal numbers were higher in exposed environments, possibly due to ongoing colonization of exposed soil by airborne propagules. The results were consistent with our observations of organisms in soil intercepted from airports and sea ports, and indicated there is potential to rank risks from transported soils based partly on transport duration and environmental exposure. This would help authorities to optimally allocate management resources according to pathway-specific risks

Defining the biosecurity risk posed by transported soil: Effects of storage time and environmental exposure on survival of soil biota

Soil frequently occurs as a contaminant on numerous sea, land and air transport pathways. It can carry unwanted invasive species, is widely recognized as a biosecurity risk, and is usually strictly regulated by biosecurity authorities. However, little is known about relative risk levels between pathways, thus authorities have limited capability to identify and target the riskiest soil pathways for management. We conducted a an experiment to test the hypotheses that biosecurity risks from soil organisms will increase both with declining transport duration and with increasing protection from environmental extremes. Soil was collected from two sites, a native forest remnant and an orchard, and stored on, in and under sea containers, or in cupboards, and assayed after 0, 3, 6 and 12 months for bacteria, fungi, nematodes and seeds. Results showed that viability of Pseudomonas spp., bacteria, nematodes and plants declined over 12 months, irrespective of soil source. Also, mortality of most biota was higher when exposed to sunlight, moisture and desiccation than when protected. However, bacterial and fungal numbers were higher in exposed environments, possibly due to ongoing colonization of exposed soil by airborne propagules. The results were consistent with our observations of organisms in soil intercepted from airports and sea ports, and indicated there is potential to rank risks from transported soils based partly on transport duration and environmental exposure. This would help authorities to optimally allocate management resources according to pathway-specific risks

Defining the biosecurity risk posed by soil found on sea freight

Soil associated with sea freight (shipping containers, flat racks and used machinery) arriving at New Zealand seaports was sampled for bacteria, fungi, nematodes, macro-invertebrates and plant seeds. Pseudomonads were selectively isolated, as several significant plant pathogens fall within this bacterial group. The mean and median sample weight collected from sea freight was found to be 417.3 and 152.7 g, respectively, with most recovered soil (73%) collected from the underside of shipping containers and flat rack containers. Likewise, for used machinery, most recovered soil (75%) was found under the machinery. Flat rack containers had significantly higher soil contamination compared to shipping containers and used machinery, but generally the counts and incidence of taxa were significantly lower compared to these other freight types. Viable bacteria, fungi, nematodes, seeds and arthropods were associated with the soil, with both counts g-1 and prevalence in samples varying with taxa, freight type, and location on the freight. Various regulated biosecurity organisms were recovered from the samples, including Aphelenchoides besseyi (rice white tip nematode), and seeds from genera such as Brachiaria, Cortaderia, Digitaria, Eragrostis and Sonchus. There were also live arthropod taxa that were not recorded as being present in New Zealand. No known plant pathogenic pseudomonads were identified through sequencing of the 16S ribosomal RNA gene. Shipping containers were found to be an important introduction pathway for exotic species, and therefore require careful monitoring and management. Comparisons of the incidence and mean number of organisms associated with soil on sea freight compared to a previous study with soil on footwear, generally showed that incidence and counts of many taxa were lower on sea freight, indicating that biosecurity risk can vary with pathway. However, prioritising one soil pathway over another according to the risks they present, and differentially allocating resources is problematic because the relative risk is dynamic, dictated by factors such as new pests or diseases entering the respective pathways