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1.
Malar J ; 18(1): 232, 2019 Jul 11.
Article in English | MEDLINE | ID: mdl-31296238

ABSTRACT

BACKGROUND: In a background of renewed calls for malaria eradication, several endemic countries in sub-Saharan Africa are contemplating malaria elimination nationally or sub-nationally. In Mozambique, a strategy to eliminate malaria in the south is underway in the context of low endemicity levels and cross-border initiatives to eliminate malaria in South Africa and Eswatini. In this context, a demonstration project aiming to interrupt malaria transmission through mass antimalarial drug administrations and intensified vector control programmes accompanied by community engagement and standard case management was implemented in the Magude District. To ensure the necessary uptake of these interventions, formative qualitative research explored the perceptions, beliefs, attitudes, and practices related to malaria, its prevention and control. The current article describes the results of this study. METHODS: Seventeen focus group discussions were conducted between September and October of 2015 with the community leaders (6), adult men (5), women of reproductive age (5), and traditional healers (1) in Magude prior to the implementation of the project interventions. Respondents discussed perceptions around malaria symptoms, causes, preventions, and treatments. RESULTS: Knowledge of malaria was linked to awareness of its clinical presentation, and on-going vector control programmes. Perceptions of malaria aetiology were fragmented but related mainly to mosquito-mediated transmission. Reported preventive measures mostly involved mosquito control although participants were aware of the protective limitations of vector control tools. Awareness of asymptomatic carriers and the risk of outdoor malaria transmission were varied. Fever and malaria-like symptoms triggered immediate care-seeking community at health facilities. The identified barriers to malaria treatment included fear/mistrust in Western medicine, distance to health facilities, and lack of transportation. CONCLUSIONS: Several constraints and opportunities will potentially influence malaria elimination in Magude. Malaria awareness, trust in health institutions, and the demand for chemoprophylaxis could facilitate new interventions, such as mass drug administration. A lack of awareness of asymptomatic carriers, inadequate understanding of residual transmission, and barriers to care seeking could jeopardize uptake. Hence, elimination campaigns require strong community engagement and grassroots mobilization.


Subject(s)
Health Knowledge, Attitudes, Practice , Malaria/psychology , Adult , Aged , Aged, 80 and over , Female , Humans , Interviews as Topic , Malaria/prevention & control , Male , Middle Aged , Mozambique , Qualitative Research , Young Adult
2.
J Adv Vet Anim Res ; 11(1): 65-70, 2024 Mar.
Article in English | MEDLINE | ID: mdl-38680799

ABSTRACT

Objective: This study aims to determine the seroprevalence of African swine fever (ASF) in pigs for slaughter in Leyte, Philippines. It underpins the concept that recovered and infected pigs from ASF are likely sent for slaughter to avoid perceived economic losses. Materials and Methods: A cross-sectional study was conducted from March to June 2023 in eight abattoirs, each representing both a city and a municipality in Leyte province. A total of 218 blood samples from 78 farms were examined for ASF virus (ASFV) (VP72) antibodies using a blocking enzyme-linked immunosorbent assay (ELISA) method. Descriptive and seroprevalence analyses were performed. Results: ASF antibodies were detected in pigs for slaughter from abattoirs in Baybay and Ormoc cities, showing a seroprevalence of 3.57% (1/28 pigs) and 2.27% (1/44 pigs), respectively. An apparent absence of ASF antibodies was observed among pigs for slaughter in Isabel, Villaba, Abuyog, Kananga, Dulag, and Macarthur. The farm-level seroprevalence was 2.56% (95% CI: 0.71%-8.88%), while the pig-level seroprevalence was 0.91% (95% CI: 0.25%-3.27%). Conclusion: Detecting ASF antibodies among pigs for slaughter implies exposure to the virus from the farm of origin. This means that, on some farms, ASF remains unreported or undiagnosed. Active surveillance is needed for early case detection and rapid response to control the spread of ASF in the country.

3.
J Parasit Dis ; 48(1): 53-58, 2024 Mar.
Article in English | MEDLINE | ID: mdl-38440763

ABSTRACT

The periodicity of parasite egg excretion refers to variations in the number of eggs produced across time, with significant implications in optimizing diagnostic procedures and conducting the Fecal Egg Count Reduction Test (FECRT). Here, we explore whether Ascaridia galli egg excretion varies across time under Philippine conditions, thus informing the best time to collect fecal samples during flock health examination. A time-course analysis was performed in chickens (N = 12) experimentally infected with A. galli, isolated from a naturally infected Philippine native chicken. We examined the fecal egg per gram (EPG) count at 3-h intervals for 3 days, starting from 5:00-6:00 h AM to the following day at 1:00-2:00 h AM. Our results showed a consistent daily egg excretion pattern with a peak EPG count in the morning that abruptly declined in the afternoon and lowest in the evening. The EPG counts correlated with the amount of excreta produced, suggesting that A. galli fecundity corresponds to the timing of host defecation. Our results imply that the best time to collect fecal samples for A. galli diagnosis and FECRT in Philippine conditions should be from sunrise until late morning when parasite EPG count and host excreta production are at their highest.

4.
J Foot Ankle Surg ; 51(3): 373-4, 2012.
Article in English | MEDLINE | ID: mdl-22197281

ABSTRACT

Musculoskeletal injury as a result of seizure activity is not uncommon, posterior shoulder dislocation being a well-described example. In this report, we describe what we believe to be the first published case of bilateral talar avulsion fractures secondary to seizure.


Subject(s)
Foot Injuries/etiology , Fractures, Bone/etiology , Seizures/complications , Talus/injuries , Female , Foot Injuries/diagnosis , Fractures, Bone/diagnosis , Humans , Middle Aged , Talus/diagnostic imaging , Tomography, X-Ray Computed
5.
J Parasit Dis ; 46(4): 1021-1027, 2022 Dec.
Article in English | MEDLINE | ID: mdl-36457774

ABSTRACT

Toxocara canis is a parasitic gastrointestinal nematode of dogs causing toxocariasis in humans, a neglected tropical disease. This study examined the burden of T. canis infection in dogs and egg contamination in school playgrounds and public parks in Baybay City, Leyte, Philippines. Fecalysis and egg detection in soils were performed to determine the parasite prevalence in dogs and the environment. In addition, pet owner's survey and GIS mapping were employed to identify the risk factors of infection and map the parasite distribution. Fecalysis revealed a T. canis prevalence of 64.44% (95% CI: 48.78-78.13) at the barangay level and 17.96% (95% CI: 14.12-21.80) at the animal level. Rural areas showed a much higher T. canis prevalence than urban. Factors associated with high T. canis infection included dog's age, specifically puppy (2-8 mo) relative to young (> 8-24 mo) [Adjusted Odds Ratio (AOR): 2.282; 95% CI: 1.137-4.579; p = 0.020] and adult (> 24 mo) (AOR: 3.542; 95% CI: 1.714-7.319; p = 0.001), access to dirty water (AOR: 2.749; 95% CI: 1.575-4.798; p < 0.001), and non-deworming (AOR: 2.961; 95%: CI 1.009-8.684; p = 0.048). Furthermore, we observed high Toxocara egg contamination in school playgrounds and public parks, with a prevalence of 51.11% (95% CI: 35.77-66.3) at the barangay level and 15.45% (95% CI: 10.67-20.23) in soil samples. This epidemiological study is the first in the central Philippines to report a high burden of T. canis infection in dogs and the environment, thus providing crucial data that will help understand the epidemiology of toxocariasis. Supplementary Information: The online version contains supplementary material available at 10.1007/s12639-022-01525-y.

6.
EBioMedicine ; 83: 104198, 2022 Sep.
Article in English | MEDLINE | ID: mdl-35961203

ABSTRACT

BACKGROUND: Artemisinins (ART) are the key component of the frontline antimalarial treatment, but their impact on Plasmodium falciparum sexual conversion rates in natural malaria infections remains unknown. This is an important knowledge gap because sexual conversion rates determine the relative parasite investment between maintaining infection in the same human host and transmission to mosquitoes. METHODS: The primary outcome of this study was to assess the impact of ART-based treatment on sexual conversion rates by comparing the relative transcript levels of pfap2-g and other sexual ring biomarkers (SRBs) before and after treatment. We analysed samples from previously existing cohorts in Vietnam, Burkina Faso and Mozambique (in total, n=109) collected before treatment and at 12 h intervals after treatment. As a secondary objective, we investigated factors that may influence the effect of treatment on sexual conversion rates. FINDINGS: In the majority of infections from the African cohorts, but not from Vietnam, we observed increased expression of pfap2-g and other SRBs after treatment. Estimated parasite age at the time of treatment was negatively correlated with the increase in pfap2-g transcript levels, suggesting that younger parasites are less susceptible to stimulation of sexual conversion. INTERPRETATION: We observed enhanced expression of SRBs after ART-based treatment in many patients, which suggests that in natural malaria infections sexual conversion rates can be altered by treatment. ART-based treatment reduces the potential of a treated individual to transmit the disease, but we hypothesise that under some circumstances this reduction may be attenuated by ART-enhanced sexual conversion. FUNDING: Spanish Agencia Estatal de Investigación (AEI), European Regional Development Fund (ERDF, European Union), Belgium Development Cooperation (DGD), Canadian University Health Network (UHN), TransGlobalHealth-Erasmus Mundus (European Union).


Subject(s)
Antimalarials , Artemisinins , Malaria, Falciparum , Malaria , Animals , Antimalarials/therapeutic use , Artemisinins/pharmacology , Artemisinins/therapeutic use , Canada , Humans , Malaria/parasitology , Malaria, Falciparum/drug therapy , Malaria, Falciparum/epidemiology , Plasmodium falciparum
7.
Methods Mol Biol ; 2369: 165-185, 2021.
Article in English | MEDLINE | ID: mdl-34313989

ABSTRACT

In Plasmodium falciparum, the parasite responsible for the most severe forms of human malaria, many fundamental processes are controlled at the transcriptional level. Studies on diverse aspects of basic parasite biology as well as molecular epidemiology studies often rely on the ability to accurately measure transcript levels, but this is complicated by the cyclic expression patterns of the majority of malaria parasite genes. Here, we provide a complete workflow to measure transcript levels in P. falciparum intraerythrocytic blood stages, overcoming the confounding factors that are commonly encountered. The method described covers all the steps from synchronization of parasite cultures to reverse transcriptase quantitative PCR (RT-qPCR) analysis.


Subject(s)
Plasmodium falciparum , Humans , Malaria, Falciparum , Plasmodium falciparum/genetics , Reverse Transcriptase Polymerase Chain Reaction
8.
Elife ; 92020 10 21.
Article in English | MEDLINE | ID: mdl-33084568

ABSTRACT

Malaria transmission is dependent on the formation of gametocytes in the human blood. The sexual conversion rate, the proportion of asexual parasites that convert into gametocytes at each multiplication cycle, is variable and reflects the relative parasite investment between transmission and maintaining the infection. The impact of environmental factors such as drugs on sexual conversion rates is not well understood. We developed a robust assay using gametocyte-reporter parasite lines to accurately measure the impact of drugs on sexual conversion rates, independently from their gametocytocidal activity. We found that exposure to subcurative doses of the frontline antimalarial drug dihydroartemisinin (DHA) at the trophozoite stage resulted in a ~ fourfold increase in sexual conversion. In contrast, no increase was observed when ring stages were exposed or in cultures in which sexual conversion was stimulated by choline depletion. Our results reveal a complex relationship between antimalarial drugs and sexual conversion, with potential public health implications.


Subject(s)
Antimalarials/pharmacology , Artemisinins/pharmacology , Plasmodium falciparum/drug effects , Trophozoites/drug effects
9.
Vet Parasitol Reg Stud Reports ; 15: 100261, 2019 01.
Article in English | MEDLINE | ID: mdl-30929938

ABSTRACT

Fasciolosis remains an important parasitic disease of ruminants in Southeast Asia. We investigated the prevalence and spatial distribution of Fasciola spp. in carabao (Bubalus bubalis) and snail intermediate hosts (IHs) in Baybay, Leyte, Philippines. Using one-stage cluster sampling, we examined 335 fecal samples of carabaos from 138 herds for Fasciola spp. eggs, and in parallel collected IH snail data in the area. Risk factor analyses were performed and GIS maps were created for Fasciola spp. prevalence and IH snail distribution. The prevalence of Fasciola spp. in animal and herd level was 63.58% and 86.96%, respectively. Risk factor analyses showed that increasing age and drinking from irrigation water were highly associated with Fasciola infection in carabaos. Inversely, access to wallowing ponds seemed to be a significant protective factor. Lymnaeid snail presence was higher in areas with intensive networks of irrigated water system and rivers, land elevation above sea level, and moderate vegetation. Our epidemiologic data suggest a high endemicity of Fasciola spp. in Baybay, Leyte and present essential factors to consider in implementing control measures.


Subject(s)
Animal Distribution , Buffaloes/parasitology , Fasciola/isolation & purification , Fascioliasis/veterinary , Snails/parasitology , Spatial Analysis , Animals , Cross-Sectional Studies , Fascioliasis/epidemiology , Fascioliasis/transmission , Feces/parasitology , Geographic Information Systems , Philippines/epidemiology , Prevalence , Risk Factors , Water/parasitology
10.
Sci Rep ; 9(1): 14595, 2019 10 10.
Article in English | MEDLINE | ID: mdl-31601834

ABSTRACT

Transmission of malaria parasites from humans to mosquito vectors requires that some asexual parasites differentiate into sexual forms termed gametocytes. The balance between proliferation in the same host and conversion into transmission forms can be altered by the conditions of the environment. The ability to accurately measure the rate of sexual conversion under different conditions is essential for research addressing the mechanisms underlying sexual conversion, and to assess the impact of environmental factors. Here we describe new Plasmodium falciparum transgenic lines with genome-integrated constructs in which a fluorescent reporter is expressed under the control of the promoter of the gexp02 gene. Using these parasite lines, we developed a sexual conversion assay that shortens considerably the time needed for an accurate determination of sexual conversion rates, and dispenses the need to add chemicals to inhibit parasite replication. Furthermore, we demonstrate that gexp02 is expressed specifically in sexual parasites, with expression starting as early as the sexual ring stage, which makes it a candidate marker for circulating sexual rings in epidemiological studies.


Subject(s)
Genetic Techniques , Plasmodium falciparum/genetics , Promoter Regions, Genetic , CRISPR-Cas Systems , Erythrocytes/parasitology , Fluorescent Dyes , Genes, Reporter , Humans , Protozoan Proteins/genetics , Transgenes
11.
J Bone Joint Surg Br ; 89(6): 742-5, 2007 Jun.
Article in English | MEDLINE | ID: mdl-17613497

ABSTRACT

We describe three cases of fracture of the titanium JRI-Furlong hydroxyapatite-ceramic (HAC)-coated femoral component. We have examined previous case reports of failure of this stem and conclude that fracture may occur in two places, namely at the neck-shoulder junction and at the conical-distal cylindrical junction. These breakages are the result of fatigue in a metallurgically-proven normal femoral component. All the cases of failure of the femoral component have occurred in patients with a body mass index of more than 25 in whom a small component, either size 9 or 10, had been used. In patients with a body mass index above normal size 9 components should be avoided and the femoral canal should be reamed sufficiently to accept a large femoral component to ensure that there is adequate metaphyseal fixation.


Subject(s)
Arthroplasty, Replacement, Hip , Ceramics , Durapatite , Hip Prosthesis , Postoperative Complications/etiology , Prosthesis Failure , Aged , Body Mass Index , Equipment Failure Analysis , Female , Humans , Male , Middle Aged , Postoperative Complications/diagnostic imaging , Prosthesis Design , Radiography , Titanium
12.
Int J Vet Sci Med ; 5(1): 30-34, 2017 Jun.
Article in English | MEDLINE | ID: mdl-30255045

ABSTRACT

Haemonchus contortus is one of the prevalent and pathogenic ruminant parasites that has grown resistance to common anthelmintic treatment. This study evaluated the anthelmintic potential of Moringa oleifera seed ethanolic and aqueous extracts against H. contortus eggs and infective stage larvae (L3s). The efficacy of five extract concentrations (0.95, 1.95, 3.9, 7.8, and 15.6 mg/mL) were tested through egg hatch assay and larval motility test. Phytochemical tests were conducted to detect the different plant secondary metabolites in the extracts. In the ovicidal assay, the ethanolic and aqueous extracts showed 95.89% and 81.72% egg hatch inhibition at 15.6 mg/mL, respectively. The ovicidal activity of 15.6 mg/mL ethanolic extract was comparable with that of albendazole (p > 0.05). The LC50 against the eggs was recorded at 2.91 and 3.83 mg/mL for ethanolic and aqueous extracts, respectively. In the larvicidal assay, the ethanolic and aqueous extracts exhibited 56.94% and 92.50% efficacy at 7.8 mg/mL, respectively. The larvicidal activity of 7.8 mg/mL aqueous extract was similar statistically with that of ivermectin (p > 0.05). The LC50 against L3s was recorded at 6.96 and 4.12 mg/mL for ethanolic and aqueous extracts, respectively. The secondary metabolites detected were tannins in ethanolic extract and saponins in aqueous extract. Both extracts inhibited larvae formation inside the eggs and rendered the L3s immobile. Therefore, M. oleifera seed extracts contained plant bioactive compounds with anthelmintic property against the eggs and L3s of H. contortus.

13.
Vet World ; 9(7): 728-34, 2016 Jul.
Article in English | MEDLINE | ID: mdl-27536034

ABSTRACT

AIM: Gastrointestinal parasitism is a serious constraint affecting goat production in the Philippines. This study aimed to determine the prevalence and associated risk factors of gastrointestinal nematode infection in goat-populated barangays of Baybay City, Leyte. MATERIALS AND METHODS: A total of 81 households or farms were interviewed, and 450 goats were sampled for fecalysis. Fecal egg count along with egg morphological identification and coproculture for third stage larvae identification were conducted. Descriptive statistics and logistic regression analyses were carried out to determine the farm- and animal-level prevalence and risk factors. RESULTS: Fecalysis revealed the presence of strongyle and Trichuris spp. with a farm-level prevalence of 100% and 4.94%, respectively; and animal-level prevalence of 96.22% and 4.44%, respectively. The identified strongyle genera per barangay were Haemonchus spp. (34.79%), Trichostrongylus spp. (33.29%), Oesophagostomum spp. (24.21%), Cooperia spp. (6.93%), and Chabertia spp. (0.79%). Goats older than 12 months were four times more likely to present high strongyle burden when compared to goats <6 months. With each month increase in goat's age, the odds of acquiring strongyle infection also increased by 1.07 times. Animals kept in goat house with cemented flooring have lower odds of acquiring strongyle (odds ratio=0.12). Goats raised for leisure purposes and fed with carabao grass (Paspalum conjugatum) were 8.12 and 5.52 times more likely to acquire Trichuris, respectively. CONCLUSION: Most of the backyard goat raisers in Baybay City, Leyte, do not practice sound helminth control measures as shown by the high prevalence of gastrointestinal nematodes. The most relevant risk factors for gastrointestinal nematode infection were the age of the goat, type of goat house's flooring, purpose of raising goats, and feeding practices.

14.
Biochim Biophys Acta ; 1461(1): 27-46, 1999 Nov 09.
Article in English | MEDLINE | ID: mdl-10556486

ABSTRACT

Formation of liposome/polynucleotide complexes (lipoplexes) involves electrostatic interactions, which induce changes in liposome structure. The ability of these complexes to transfer DNA into cells is dependent on the physicochemical attributes of the complexes, therefore characterization of binding-induced changes in liposomes is critical for the development of lipid-based DNA delivery systems. To clarify the apparent lack of correlation between membrane fusion and in vitro transfection previously observed, we performed a multi-step lipid mixing assay to model the sequential steps involved in transfection. The roles of anion charge density, charge ratio and presence of salt on lipid mixing and liposome aggregation were investigated. The resonance-energy transfer method was used to monitor lipid mixing as cationic liposomes (DODAC/DOPE and DODAC/DOPC; 1:1 mole ratio) were combined with plasmid, oligonucleotides or Na(2)HPO(4). Cryo-transmission electron microscopy was performed to assess morphology. As plasmid or oligonucleotide concentration increased, lipid mixing and aggregation increased, but with Na(2)HPO(4) only aggregation occurred. NaCl (150 mM) reduced the extent of lipid mixing. Transfection studies suggest that the presence of salt during complexation had minimal effects on in vitro transfection. These data give new information about the effects of polynucleotide binding to cationic liposomes, illustrating the complicated nature of anion induced changes in liposome morphology and membrane behavior.


Subject(s)
Liposomes/chemistry , Plasmids/chemistry , Polynucleotides/chemistry , Transfection , 4-Chloro-7-nitrobenzofurazan , Animals , Cations , Cryoelectron Microscopy , Fluorescent Dyes , Liposomes/ultrastructure , Mice , Models, Molecular , Molecular Structure , Particle Size , Sodium Chloride , Structure-Activity Relationship , Tumor Cells, Cultured
15.
Genetics ; 149(1): 217-31, 1998 May.
Article in English | MEDLINE | ID: mdl-9584098

ABSTRACT

We have used an enhancer-trap approach to begin characterizing the function of the Drosophila endocrine system during larval development. Five hundred and ten different lethal PZ element insertions were screened to identify those in which a reporter gene within the P element showed strong expression in part or all of the ring gland, the major site of production and release of developmental hormones, and which had a mutant phenotype consistent with an endocrine defect. Nine strong candidate genes were identified in this screen, and eight of these are expressed in the lateral cells of the ring gland that produce ecdysteroid molting hormone (EC). We have confirmed that the genes detected by these enhancer traps are expressed in patterns similar to those detected by the reporter gene. Two of the genes encode proteins, protein kinase A and calmodulin, that have previously been implicated in the signaling pathway leading to EC synthesis and release in other insects. A third gene product, the translational elongation factor EF-1alpha F1, could play a role in the translational regulation of EC production. The screen also identified the genes couch potato and tramtrack, previously known from their roles in peripheral nervous system development, as being expressed in the ring gland. One enhancer trap revealed expression of the gene encoding the C subunit of vacuolar ATPase (V-ATPase) in the medial cells of the ring gland, which produce the juvenile hormone that controls progression through developmental stages. This could reveal a function of V-ATPase in the response of this part of the ring gland to adenotropic neuropeptides. However, the gene identified by this enhancer trap is ubiquitously expressed, suggesting that the enhancer trap is detecting only a subset of its control elements. The results show that the enhancer trap approach can be a productive way of exploring tissue-specific genetic functions in Drosophila.


Subject(s)
Drosophila melanogaster/genetics , Endocrine Glands/chemistry , Amino Acid Sequence , Animals , Genes, Reporter , Genetic Techniques , In Situ Hybridization , Molecular Sequence Data , Phenotype , Promoter Regions, Genetic , Sequence Alignment , Signal Transduction/genetics , Transposases/genetics , beta-Galactosidase/genetics
16.
AIDS ; 9(7): 701-7, 1995 Jul.
Article in English | MEDLINE | ID: mdl-7546414

ABSTRACT

OBJECTIVE: To improve the pharmacokinetics and lymphoid tissues targeting of 2',3'-dideoxyinosine (ddI) by encapsulation in liposomes. METHODS: The pharmacokinetics and tissue distribution of free and liposome-encapsulated ddI were determined in C57BL/6 mice following intravenous and subcutaneous administration of a single bolus dose (3 mg ddI/kg). RESULTS: Intravenous administration of liposome-encapsulated ddI greatly reduced the systemic clearance of the anti-HIV agent. The elimination plasma half-life of ddI incorporated in 112 and 83 nm liposomes was 46 and 14 times higher than that of the free drug, respectively. The tissue distribution profile of liposomal lipids clearly showed that the use of liposomes allows efficient targeting of lymph nodes and macrophage-rich tissues (spleen and liver) for at least 24 h following intravenous injection. In contrast, the accumulation of liposomes in these tissues was much lower following subcutaneous administration. CONCLUSION: Incorporation of ddI in liposomes greatly improved the pharmacokinetics of the anti-HIV agent after intravenous injection. The use of liposomes could represent a convenient approach to targeting lymphoid tissues. Strategies aimed at improving drug retention within liposomes should further enhance and prolong drug delivery to lymphoid organs.


Subject(s)
Antiviral Agents/administration & dosage , Didanosine/administration & dosage , Lymphoid Tissue/drug effects , Animals , Antiviral Agents/pharmacokinetics , Didanosine/pharmacokinetics , Drug Carriers , HIV/drug effects , Injections, Intravenous , Injections, Subcutaneous , Liposomes , Lymphoid Tissue/virology , Mice , Mice, Inbred C57BL , Tissue Distribution
17.
AIDS ; 8(11): 1545-53, 1994 Nov.
Article in English | MEDLINE | ID: mdl-7848591

ABSTRACT

OBJECTIVE: To evaluate the effect of liposome encapsulation on the in vitro antiviral efficacy, intracellular uptake and in vivo pharmacokinetics of 2',3'-dideoxyinosine (ddl). METHODS: The accumulation of free and liposome-encapsulated ddl was determined in murine monocyte-macrophage RAW 264.7 cells and human premonocytoid U937 cells. The antiviral efficacy was evaluated in U937 cells infected with HIVIIIB. Tissue distribution and pharmacokinetics of free and liposomal ddl were determined in female Sprague-Dawley rats following the administration of a single intravenous bolus dose (3 mg ddl/kg). RESULTS: The entrapment of ddl in liposomes results in a lower drug accumulation in both U937 and RAW 264.7 cells. A lower antiviral efficacy against HIVIIIB replication in U937 cells was observed on encapsulation of ddl in liposomes. Improved pharmacokinetics were observed on entrapment of ddl in liposomes. Higher drug levels were found in plasma for the liposomal formulation. The systemic clearance of the liposomal drug was 120 times lower than that of free drug. Liposome encapsulation of ddl greatly enhanced the drug accumulation in organs of the reticuloendothelial system. CONCLUSION: The encapsulation of ddl in liposomes modified the tissue distribution and plasma pharmacokinetics of the antiviral agent resulting in a marked improvement of drug biodisponibility. The antiviral efficacy of liposomal ddl was lower than that of free drug in HIVIIIB-infected U937 cells.


Subject(s)
Didanosine/administration & dosage , HIV/drug effects , 1,2-Dipalmitoylphosphatidylcholine , Analysis of Variance , Animals , Biological Transport , Cell Line , Cell Survival/drug effects , Didanosine/pharmacokinetics , Didanosine/pharmacology , Drug Carriers , Enzyme-Linked Immunosorbent Assay , Female , HIV/metabolism , HIV Core Protein p24/analysis , Humans , Kinetics , Liposomes , Lymphoma, Large B-Cell, Diffuse , Macrophages , Male , Mice , Monocytes , Phosphatidylcholines , Phosphatidylglycerols , Rats , Rats, Sprague-Dawley , Time Factors
18.
Soc Sci Med ; 47(10): 1611-7, 1998 Nov.
Article in English | MEDLINE | ID: mdl-9823056

ABSTRACT

This study examined the relationships of nurse burnout, intention to quit, and meaningfulness of work as assessed on a staff survey with patient satisfaction with nursing care, physician care, information provided and coordination of care, and outcomes of the hospital stay assessed post-discharge. Sixteen inpatient units from two hospital sites formed the data base and included 605 patients and 711 nurses. Patients' perceptions of the quality of each of the four care dimensions corresponded to the relationships nurses had with their work. Patients on units where nurses found their work meaningful were more satisfied with all aspects of their hospital stay. Patients who stayed on units where nursing staff felt more exhausted or more frequently expressed the intention to quit were less satisfied with the various components of their care. Although nurse cynicism was reflected in lower patient satisfaction with interactions with nursing staff, the correlations between cynicism and other aspects of care fell below statistical significance. No significant correlations were found between nurse professional efficacy and any of the patient satisfaction components measured. The implications of the relationship between patient satisfaction and nurses' perception of their work is discussed.


Subject(s)
Burnout, Professional , Nursing Staff, Hospital/psychology , Patient Satisfaction , Adolescent , Adult , Aged , Aged, 80 and over , Canada , Child , Female , Hospitalization , Humans , Male , Middle Aged , Nurse-Patient Relations
19.
J Pharm Sci ; 89(5): 652-63, 2000 May.
Article in English | MEDLINE | ID: mdl-10756331

ABSTRACT

We evaluated the use of poly(ethylene glycol) (PEG)-modified lipids to control the surface properties of a lipid-based gene transfer system. The lipid-DNA particles (LDPs) used form spontaneously when plasmid DNA is added to mixed detergent lipid micelles consisting of the non-ionic detergent n-octyl-D-glucopyranoside, the cationic lipid dioleyldimethylammonium chloride (DODAC), the zwitterionic lipid 1,2-dioleoyl-sn-glycero-3-phosphoethanolamine (DOPE), and selected PEG-modified phosphatidylethanolamines. The inclusion of DODAC is required to form the hydrophobic lipid-DNA complex. DOPE is included to facilitate dissociation of DNA from the cationic lipid and the PEG-modified lipids are added in an effort to stabilize the surface attributes of the resulting lipid-DNA particles. We used PEG-lipids that varied in acyl chain composition because of recent results demonstrating acyl chain dependent transfer of PEG-lipids from lipid vesicles, providing the potential to allow a transformation of the surface properties due to loss of surface grafted PEG. The addition of PEG-modified lipids does not interfere in LDP formation and its presence favors formation of smaller particles (75 nm in contrast to 130 nm in the absence of the PEG-modified lipid). PEG-lipid incorporation causes a concentration dependent reduction in LDP-mediated transfection of B16/BL6 melanoma cells, a result that can be partially attributed to a reduction in particle binding to cells. However, significant LDP binding to B16/BL6 cells was still observed under conditions where LDP transfection activity was reduced by more than 85%. The potential for PEG to interfere with LDP processing following cell binding is discussed.


Subject(s)
DNA/administration & dosage , Genetic Vectors , Lipids/chemistry , Polyethylene Glycols/chemistry , Transfection/methods , Animals , DNA/chemistry , Genetic Therapy/methods , Lipids/administration & dosage , Melanoma, Experimental , Mice , Particle Size , Surface Properties , Tumor Cells, Cultured
20.
Methods Mol Med ; 25: 255-304, 2000.
Article in English | MEDLINE | ID: mdl-21318851

ABSTRACT

The overall goal of gene therapy is to cure or stabilize a disease process that results from the production of a mutant protein (for example, the chloride channel protein important in cystic fibrosis) or overproduction of a normal protein (such as the products of certain oncogenes). We can achieve this goal by replacing the defective gene or by reducing the overexpression of the target gene using an antisense strategy, thus reducing the production of the diseasepromoting protein (1,2). For either method, it is critical to transfer DNA into target cells in a concentration high enough to be effective in modifying the disease. DNA must be delivered to the desired cell population in an intact state, whereby it can be efficiently transcribed and ultimately translated. The method of gene transfer must be highly efficient and nontoxic, and the delivery system must be relatively easy to prepare and administer (3). There is a great deal of optimism surrounding the development of gene therapy as an effective strategy for management of many different human diseases. The active agent used to procure gene therapy is likely to consist of oligonucleotides, ribozymes, or a DNA sequence that can be transcribed into a message capable of eliciting a therapeutic response. Unlike conventional small-molecule therapeutics however, gene therapy requires the use of a carrier system to deliver the active agent directly into the target cell population.

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