Pharmacokinetics and chemotherapeutic efficacy of adriamycin encapsulated in immunoliposomes against avian myeloblastosis virus infection

Immunoliposomes were prepared using rabbit anti-AMV gp80 IgG for the targeted chemotherapy of avian myeloblastosis virus infection. Adriamycin was encapsulated into immunoliposomes and used for in vivo studies. Comparative pharmacokinetics of free drug, drug encapsulated in free liposomes and of drug encapsulated in immunoliposomes in the virus-infected cells revealed that (i) the drug encapsulated in liposomes was cleared from the plasma slowly, and (ii) the drug encapsulated in immunoliposomes accumulated in the target tissue, the bone marrow, 5- and 8.5-fold more than the drug encapsulated in free liposomes and free drug, respectively. The drug encapsulated in immunoliposomes inactivated the virus and exhibited more chemotherapeutic efficacy as compared to controls when injected up to 24 h post-infection. However, when injected 48 h post-infection the drug encapsulated in immunoliposomes did not offer any protection against the virus infection. There is no detectable antibody response against immunoliposomes in the infected animals.

Examining effectiveness of an immigrant labor market integration intervention. The role of acculturation, discrimination, self-efficacy, outcome expectances, action and coping planning.

The designing of effective intervention tools to improve immigrants’ labor market integration remains an important topic in contemporary Western societies. This study examines whether and how a new intervention tool, Working Life Certificate (WLC), helps unemployed immigrants to find employment and strengthen their belief of their vocational skills. The study is based on quantitative longitudinal survey data from 174 unemployed immigrants of various origins who participated in the pilot phase of WLC examinations in 2009. Surveys were administered in three waves: before the test, right after it, and three months later. Although it is often argued that the unemployment among immigrants is due either to their lack of skills and cultural differences or to discrimination in recruitment, scholars within social psychology of behavior change argue that the best way of helping people to achieve their goals (e.g. finding employment) is to build up their sense of self-efficacy, alter their outcome expectances in a more positive direction or to help them to construct more detailed action and coping plans. This study aims to shed light on the role of these concepts in immigrants’ labor market integration. The results support the theories of behavior change moderately. Having positive expectances regarding the outcomes of various job search behaviors was found to predict employment in the future. Together with action and coping planning it also predicted increase in job search behavior. The intervention, WLC, was able to affect participants’ self-efficacy, but contrary to expectations, self-efficacy was found not to be related to either job search behavior or future labor market status. Also, perceived discrimination did not explain problems in finding employment, but hints of subtle or structural discrimination were found. Adoption of Finnish work culture together with strong family culture was found to predict future employment. Hence, in this thesis I argue that awarding people diplomas should be preferred in immigrant integration training as it strengthens people’s sense of self-efficacy. Instead of teaching new information, more attention should be directed at changing people’s outcome expectances in a more positive direction and helping them to construct detailed plans on how to achieve their goals.

The Biocontrol Agent Phlebiopsis gigantea: Efficacy and Impacts on the Stump Bacterial Biota and Conifer tree Defences

Phlebiopsis gigantea has been for a long time known as a strong competitor against Heterobasidion annosum and intensively applied as a biological control agent on stump surfaces of Picea abies in Fennoscandia. However, the mechanism underlying its antagonistic activity is still unknown. A primary concern is the possible impact of P. gigantea treatment on resident non-target microbial biota of conifer stumps. Additional risk factor is the potential of P. gigantea to acquire a necrotrophic habit through adaptation to living wood tissues. This study focused on the differential screening of several P. gigantea isolates from diverse geographical sources as well as the use of breeding approach to enhance the biocontrol efficacy against H. annosum infection. The results showed a significant positive correlation between growth rate in wood and high biocontrol efficacy. Furthermore, with aid of breeding approach, several progeny strains were obtained that had better growth rate and control efficacy than parental isolates. To address the issue of the potential of P. gigantea to acquire necrotrophic capability, a combination of histochemical, molecular and transcript profiling (454 sequencing) were used to investigate the interactions between these two fungi and ten year old P. sylvestris seedlings. The results revealed that both P. gigantea and H. annosum provoked strong necrotic lesions, but after prolonged incubation, P. gigantea lesions shrank and ceased to expand further. Tree seedlings pre-treated with P. gigantea further restricted H. annosum-induced necrosis and had elevated transcript levels of genes important for lignification, cell death regulation and jasmonic acid signalling. These suggest that induced localized resistance is a contributory factor for the biocontrol efficacy of P.gigantea, and it has a comparatively limited necrotrophic capability than H. annosum. Finally, to investigate the potential impact of P. gigantea on the stump bacterial biota, 16S rDNA isolated from tissue samples from stumps of P. abies after 1-, 6- and 13-year post treatment was sequenced using bar-coded 454 Titanium pyrosequencing. Proteobacteria were found to be the most abundant at the initial stages of stump decay but were selectively replaced by Acidobacteria at advanced stages of the decay. Moreover, P. gigantea treatment significantly decreased the bacterial richness at initial decay stage in the stumps. Over time, the bacterial community in the stumps gradually recovered and the negative effects of P. gigantea was attenuated.

Syntheses, Transfection Efficacy and Cell Toxicity Properties of Novel Cholesterol-based Gemini Lipids having Hydroxyethyl Head group

We have synthesized five new cholesterol based gemini cationic lipids possessing hydroxyethyl (-CH2CH2OH) function on each head group, which differ in the length of the polymethylene spacer chain. These gemini lipids are important for gene delivery processes as they possess pre-optimized molecular features, e. g., cholesterol backbone, ether linkage and a variable spacer chain between both the headgroups of the gemini lipids. Cationic liposomes were prepared from each of these lipids individually and as a mixture of individual cationic gemini lipid and 1,2-dioleoyl phosphatidylethanolamine (DOPE). Each gemini lipid based formulation induced better transfection activity than that of their monomeric counterpart. One such gemini lipid with a -(CH2)(12)-spacer, HG-12, showed dramatic increase in the mean fluorescence intensity due to the expression of green-fluorescence protein (GFP) in the presence of 10% FBS compared to the conditions where there was no serum. Other gemini lipids retained their gene transfection efficiency without any marked decrease in the presence of serum. The only exception was seen with the gemini with a -(CH2)(3)-spacer, HG-3, which on gene transfection in the presence of 10% FBS lost similar to 70% of its transfection efficiency. Overall the gemini lipid with a -(CH2)(5)-spacer, HG-5, showed the highest transfection activity at N/P (lipid/DNA) ratio of 0.5 and lipid : DOPE molar ratio of 2. Upon comparison of the relevant parameters, e. g., %-transfected cells, the amount of DNA transfected to each cell and %-cell viability all together against Lipofectamine 2000, one of the best commercial transfecting agents, the optimized lipid formulation based on DOPE/HG-5 was found to be comparable. In terms of its ability to induce gene-transfer in the presence of serum and shelf-life DOPE/HG-5 liposome was found to be superior to its commercial counterpart. Confocal imaging analysis confirmed that in the presence of 10% serum using a Lipid : DOPE of 1 : 4 and N/P charge ratio of 0.75 with 1.2 mu g DNA per well, HG-5 is better than Lipofectamine 2000.

Formulation of nanotized curcumin and demonstration of its antimalarial efficacy

Aim: The present study was conducted to overcome the disadvantages associated with the poor water solubility and low bioavailability of curcumin by synthesizing nanotized curcumin and demonstrating its efficacy in treating malaria. Materials and methods: Nanotized curcumin was prepared by a modified emulsion-diffusion-evaporation method and was characterized by means of transmission electron microscopy, atomic force microscopy, dynamic light scattering, Zetasizer, Fourier transform infrared spectroscopy, and differential thermal analysis. The novelty of the prepared nanoformulation lies in the fact that it was devoid of any polymeric matrices used in conventional carriers. The antimalarial efficacy of the prepared nanotized curcumin was then checked both in vitro and in vivo. Results: The nanopreparation was found to be non-toxic and had a particle size distribution of 20-50 nm along with improved aqueous dispersibility and an entrapment efficiency of 45%. Nanotized curcumin (half maximal inhibitory concentration IC50]: 0.5 mu M) was also found to be ten-fold more effective for growth inhibition of Plasmodium falciparum in vitro as compared to its native counterpart (IC50: 5 mu M). Oral bioavailability of nanotized curcumin was found to be superior to that of its native counterpart. Moreover, when Plasmodium berghei-infected mice were orally treated with nanotized curcumin, it prolonged their survival by more than 2 months with complete clearance of parasites in comparison to the untreated animals, which survived for 8 days only. Conclusion: Nanotized curcumin holds a considerable promise in therapeutics as demonstrated here for treating malaria as a test system.

Comparative Efficacy of Diquat for Control of Two Members of the Hydrocharitaceae: Elodea and Hydrilla

The submersed plants hydrilla (Hydrilla verticillata (L.f.) Royle) and elodea (Elodea canadensis Rich.) are both members of the Hydrocharitaceae family and cause problems in waterways throughout the world. Diquat (6,7-dihydrodipyrido[1,2-α:2’,1’-c]pyrazinediium dibromide) is a contact herbicide used to control nuisance submersed and floating aquatic macrophytes. There is no readily available information in the literature on the control of elodea under various diquat concentration and exposure times (CET) and other than a study by Van et. al 1987, little on hydrilla. Since CET relationships are critical in controlling submersed plants in areas influenced by water exchange, this study was designed to evaluate the efficacy of diquat on hydrilla and elodea under various CET scenarios. (PDF has 3 pages.)

Influence of Foliar Exposure, Adjuvants, and Rain-free Period on the Efficacy of Glyphosate for Torpedograss Control

The proportion of torpedograss tissue exposed to glyphosate at application rates of 0.28, 0.56, 1.12, 2.24, and 4.48 kg/ha affected control as measured by regrowth. The effect of tissue exposure was more pronounced as application rate decreased. This study suggests that higher rates of glyphosate need to be used during higher water levels, when less torpedograss tissue is exposed to herbicide spray and lower rates may be used during periods of low water levels. Addition of the water conditioning agent Quest (R) (0.25% v/v) to glyphosate spray mixtures diminished the influence of simulated rain events following glyphosate application. Twelve other adjuvants did not influence the effect of simulated rain events.

Influence of water temperature on the efficacy of diquat and endothall versus curlyleaf pondweed

determine the impact of water temperature on the efficacy of the contact herbicides diquat (6,7-dihydrodipyrido [1,2- α:2’,1’-c] pyrazinediium ion) and endothall (7-oxabicyclo [2.2.1] heptane-2,3-dicarboxylic acid) for control of the exotic nuisance species curlyleaf pondweed (Potamogeton crispus L.) across a range of water temperatures.

Fish Habitat Utilization Patterns and Evaluation of the Efficacy of Marine Protected Areas in Hawaii: Integration of NOAA Digital Benthic Habitat Mapping and Coral Reef Ecological Studies

Over the past four decades, the state of Hawaii has developed a system of eleven Marine Life Conservation Districts (MLCDs) to conserve and replenish marine resources around the state. Initially established to provide opportunities for public interaction with the marine environment, these MLCDs vary in size, habitat quality, and management regimes, providing an excellent opportunity to test hypotheses concerning marine protected area (MPA) design and function using multiple discreet sampling units. NOAA/NOS/NCCOS/Center for Coastal Monitoring and Assessment’s Biogeography Team developed digital benthic habitat maps for all MLCD and adjacent habitats. These maps were used to evaluate the efficacy of existing MLCDs for biodiversity conservation and fisheries replenishment, using a spatially explicit stratified random sampling design. Coupling the distribution of habitats and species habitat affinities using GIS technology elucidates species habitat utilization patterns at scales that are commensurate with ecosystem processes and is useful in defining essential fish habitat and biologically relevant boundaries for MPAs. Analysis of benthic cover validated the a priori classification of habitat types and provided justification for using these habitat strata to conduct stratified random sampling and analyses of fish habitat utilization patterns. Results showed that the abundance and distribution of species and assemblages exhibited strong correlations with habitat types. Fish assemblages in the colonized and uncolonized hardbottom habitats were found to be most similar among all of the habitat types. Much of the macroalgae habitat sampled was macroalgae growing on hard substrate, and as a result showed similarities with the other hardbottom assemblages. The fish assemblages in the sand habitats were highly variable but distinct from the other habitat types. Management regime also played an important role in the abundance and distribution of fish assemblages. MLCDs had higher values for most fish assemblage characteristics (e.g. biomass, size, diversity) compared with adjacent fished areas and Fisheries Management Areas (FMAs) across all habitat types. In addition, apex predators and other targeted resources species were more abundant and larger in the MLCDs, illustrating the effectiveness of these closures in conserving fish populations. Habitat complexity, quality, size and level of protection from fishing were important determinates of MLCD effectiveness with respect to their associated fish assemblages. (PDF contains 217 pages)

Efficacy and safety of autologous platelet rich plasma for the treatment of vascular ulcers in primary care: Phase III study

Background: Vascular ulcers are commonly seen in daily practice at all levels of care and have great impact at personal, professional and social levels with a high cost in terms of human and material resources. Given that the application of autologous platelet rich plasma has been shown to decrease healing times in various different studies in the hospital setting, we considered that it would be interesting to assess the efficacy and feasibility of this treatment in primary care. The objectives of this study are to assess the potential efficacy and safety of autologous platelet rich plasma for the treatment of venous ulcers compared to the conventional treatment (moist wound care) in primary care patients with chronic venous insufficiency (C, clinical class, E, aetiology, A, anatomy and P, pathophysiology classification C6). Design: We will conduct a phase III, open-label, parallel-group, multicentre, randomized study. The subjects will be 150 patients aged between 40 and 100 years of age with an at least 2-month history of a vascular venous ulcer assigned to ten primary care centres. For the treatment with autologous platelet rich plasma, all the following tasks will be performed in the primary care setting: blood collection, centrifugation, separation of platelet rich plasma, activation of coagulation adding calcium chloride and application of the PRP topically after gelification. The control group will receive standard moist wound care. The outcome variables to be measured at baseline, and at weeks 5 and 9 later include: reduction in the ulcer area, Chronic Venous Insufficiency Quality of Life Questionnaire score, and percentage of patients who require wound care only once a week. Discussion: The results of this study will be useful to improve the protocol for using platelet rich plasma in chronic vascular ulcers and to favour wider use of this treatment in primary care.

Increased antiparkinson efficacy of the combined administration of VEGF- and GDNF-loaded nanospheres in a partial lesion model of Parkinson's disease

Current research efforts are focused on the application of growth factors, such as glial cell line-derived neurotrophic factor (GDNF) and vascular endothelial growth factor (VEGF), as neuroregenerative approaches that will prevent the neurodegenerative process in Parkinson's disease. Continuing a previous work published by our research group, and with the aim to overcome different limitations related to growth factor administration, VEGF and GDNF were encapsulated in poly(lactic-co-glycolic acid) nanospheres (NS). This strategy facilitates the combined administration of the VEGF and GDNF into the brain of 6-hydroxydopamine (6-OHDA) partially lesioned rats, resulting in a continuous and simultaneous drug release. The NS particle size was about 200 nm and the simultaneous addition of VEGF NS and GDNF NS resulted in significant protection of the PC-12 cell line against 6-OHDA in vitro. Once the poly(lactic-co-glycolic acid) NS were implanted into the striatum of 6-OHDA partially lesioned rats, the amphetamine rotation behavior test was carried out over 10 weeks, in order to check for in vivo efficacy. The results showed that VEGF NS and GDNF NS significantly decreased the number of amphetamine-induced rotations at the end of the study. In addition, tyrosine hydroxylase immunohistochemical analysis in the striatum and the external substantia nigra confirmed a significant enhancement of neurons in the VEGF NS and GDNF NS treatment group. The synergistic effect of VEGF NS and GDNF NS allows for a reduction of the dose by half, and may be a valuable neurogenerative/neuroreparative approach for treating Parkinson's disease.

Efficacy of a cognitive and behavioural psychotherapy applied by primary care psychologists in patients with mixed anxiety-depressive disorder: a research protocol

Background: In contrast with the recommendations of clinical practice guidelines, the most common treatment for anxiety and depressive disorders in primary care is pharmacological. The aim of this study is to assess the efficacy of a cognitive-behavioural psychological intervention, delivered by primary care psychologists in patients with mixed anxiety-depressive disorder compared to usual care. Methods/Design: This is an open-label, multicentre, randomized, and controlled study with two parallel groups. A random sample of 246 patients will be recruited with mild-to-moderate mixed anxiety-depressive disorder, from the target population on the lists of 41 primary care doctors. Patients will be randomly assigned to the intervention group, who will receive standardised cognitive-behavioural therapy delivered by psychologists together with usual care, or to a control group, who will receive usual care alone. The cognitive-behavioural therapy intervention is composed of eight individual 60-minute face-to face sessions conducted in eight consecutive weeks. A follow-up session will be conducted over the telephone, for reinforcement or referral as appropriate, 6 months after the intervention, as required. The primary outcome variable will be the change in scores on the Short Form-36 General Health Survey. We will also measure the change in the frequency and intensity of anxiety symptoms (State-Trait Anxiety Inventory) and depression (Beck Depression Inventory) at baseline, and 3, 6 and 12 months later. Additionally, we will collect information on the use of drugs and health care services. Discussion: The aim of this study is to assess the efficacy of a primary care-based cognitive-behavioural psychological intervention in patients with mixed anxiety-depressive disorder. The international scientific evidence has demonstrated the need for psychologists in primary care. However, given the differences between health policies and health services, it is important to test the effect of these psychological interventions in our geographical setting.