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1.
Nat Geosci ; 16(3): 238-243, 2023.
Article in English | MEDLINE | ID: mdl-36920161

ABSTRACT

Ice streams flowing into Ross Ice Shelf are presently responsible for around 10% of the mass flux from West Antarctica, with the noteworthy exception of Kamb Ice Stream, which stagnated in the late 1800s. The subsequent reduction in ice supply led to grounding-line retreat at the coastal margin where Kamb transitions into the floating Ross Ice Shelf. Grounding-line migration is linked to broader changes in ice-sheet mass balance and sea level, but our understanding of related ice, ocean and seafloor interactions is limited by the difficulty in accessing these remote regions. Here we report in situ observations from an underwater vehicle deployed at Kamb that show how fine-scale variability in ice and ocean structure combine to influence a diversity of ice-ocean interactions. We found a stratified water column within a tenth of a degree of freezing at the ice base and mapped basal crevasses with supercooled water and active marine ice formation. At the seafloor, we interpret parallel ridges as crevasse impressions left as the ice lifted off during grounding-line retreat. These observations from a recently ungrounded sub-shelf environment illuminate both the geomorphological signatures of past grounding-line retreat and the fine-scale sensitivity of ongoing ice-ocean interactions to ice topography.

2.
Nature ; 614(7948): 471-478, 2023 02.
Article in English | MEDLINE | ID: mdl-36792738

ABSTRACT

Thwaites Glacier represents 15% of the ice discharge from the West Antarctic Ice Sheet and influences a wider catchment1-3. Because it is grounded below sea level4,5, Thwaites Glacier is thought to be susceptible to runaway retreat triggered at the grounding line (GL) at which the glacier reaches the ocean6,7. Recent ice-flow acceleration2,8 and retreat of the ice front8-10 and GL11,12 indicate that ice loss will continue. The relative impacts of mechanisms underlying recent retreat are however uncertain. Here we show sustained GL retreat from at least 2011 to 2020 and resolve mechanisms of ice-shelf melt at the submetre scale. Our conclusions are based on observations of the Thwaites Eastern Ice Shelf (TEIS) from an underwater vehicle, extending from the GL to 3 km oceanward and from the ice-ocean interface to the sea floor. These observations show a rough ice base above a sea floor sloping upward towards the GL and an ocean cavity in which the warmest water exceeds 2 °C above freezing. Data closest to the ice base show that enhanced melting occurs along sloped surfaces that initiate near the GL and evolve into steep-sided terraces. This pronounced melting along steep ice faces, including in crevasses, produces stratification that suppresses melt along flat interfaces. These data imply that slope-dependent melting sculpts the ice base and acts as an important response to ocean warming.

4.
Soc Sci Med ; 276: 113741, 2021 05.
Article in English | MEDLINE | ID: mdl-33640157

ABSTRACT

BACKGROUND: In the United States, Black Americans are suffering from a significantly disproportionate incidence of COVID-19. Going beyond mere epidemiological tallying, the potential for racial-justice interventions, including reparations payments, to ameliorate these disparities has not been adequately explored. METHODS: We compared the COVID-19 time-varying Rt curves of relatively disparate polities in terms of social equity (South Korea vs. Louisiana). Next, we considered a range of reproductive ratios to back-calculate the transmission rates ßi→j for 4 cells of the simplified next-generation matrix (from which R0 is calculated for structured models) for the outbreak in Louisiana. Lastly, we considered the potential structural effects monetary payments as reparations for Black American descendants of persons enslaved in the U.S. would have had on pre-intervention ßi→j and consequently R0. RESULTS: Once their respective epidemics begin to propagate, Louisiana displays Rt values with an absolute difference of 1.3-2.5 compared to South Korea. It also takes Louisiana more than twice as long to bring Rt below 1. Reasoning through the consequences of increased equity via matrix transmission models, we demonstrate how the benefits of a successful reparations program (reflected in the ratio ßb→b/ßw→w) could reduce R0 by 31-68%. DISCUSSION: While there are compelling moral and historical arguments for racial-injustice interventions such as reparations, our study considers potential health benefits in the form of reduced SARS-CoV-2 transmission risk. A restitutive program targeted towards Black individuals would not only decrease COVID-19 risk for recipients of the wealth redistribution; the mitigating effects would also be distributed across racial groups, benefiting the population at large.


Subject(s)
Black or African American , COVID-19 , Humans , Louisiana , Republic of Korea , SARS-CoV-2 , United States/epidemiology
5.
Eur Rev Med Pharmacol Sci ; 25(24): 7643-7653, 2021 Dec.
Article in English | MEDLINE | ID: mdl-34982426

ABSTRACT

OBJECTIVE: Trastuzumab is an HER-2 targeted humanized monoclonal antibody that significantly improves metastatic and non-metastatic breast cancer therapeutic outcomes. This study compares trastuzumab outcomes between two age cohorts in the Kuwait Cancer Control Centre (KCCC). PATIENTS AND METHODS: In a prospective comparative observational study, 93 HER-2 positive breast cancer patients undergoing different chemotherapy protocols + trastuzumab between April 2016 and April 2019 were included and divided into two cohorts based on their age (<60 and ≥60 years old). The individual decline in the LVEF from the baseline was calculated and compared between the two age cohorts. Logistic regression analysis was applied to investigate the association between age, comorbidities, BMI, anthracycline treatment, and baseline LVEF value, and trastuzumab-induced cardiotoxicity after adjustments made for the disease stage. RESULTS: The median baseline LVEF was 65% in both age cohorts (IQR 8% and 9% for older and younger patients, respectively). Whereas the median LVEF post-trastuzumab treatment was 51% and 55% in older and younger patients, respectively (IQR 8%; p-value = 0.22), even though older patients had significantly lower exposure to anthracyclines compared to younger patients (60% and 84.1%, respectively; p-value <0.001). 86.7% and 55.6% of older and younger patients, respectively, developed ≥10% decline in their LVEF from the baseline. Statistically, age was the only factor that significantly correlated with developing ≥10% decline in the LVEF (OR 4; p-value <0.012). CONCLUSIONS: Breast cancer patients aged 60 years and above in Kuwait were at a 4-fold higher risk of developing ≥10% decline in their LVEF from the baseline value compared to younger patients during trastuzumab treatment. Previous exposure to anthracyclines and comorbidities were not associated with a significantly increased cardiotoxicity risk in this study.


Subject(s)
Antineoplastic Agents, Immunological/adverse effects , Breast Neoplasms/drug therapy , Cardiotoxicity/etiology , Trastuzumab/adverse effects , Adult , Age Factors , Aged , Aged, 80 and over , Breast Neoplasms/physiopathology , Cardiotoxicity/physiopathology , Female , Humans , Middle Aged , Prospective Studies , Stroke Volume/drug effects , Ventricular Function, Left/drug effects , Young Adult
6.
Biomater Biosyst ; 4: 100030, 2021 Dec.
Article in English | MEDLINE | ID: mdl-36824570

ABSTRACT

Collagen type II is the major constituent of cartilage tissue. Yet, cartilage engineering approaches are primarily based on collagen type I devices that are associated with suboptimal functional therapeutic outcomes. Herein, we briefly describe cartilage's development and cellular and extracellular composition and organisation. We also provide an overview of collagen type II biosynthesis and purification protocols from tissues of terrestrial and marine species and recombinant systems. We then advocate the use of collagen type II as a building block in cartilage engineering approaches, based on safety, efficiency and efficacy data that have been derived over the years from numerous in vitro and in vivo studies.

7.
medRxiv ; 2020 Jun 05.
Article in English | MEDLINE | ID: mdl-32577701

ABSTRACT

Background In the United States, Black Americans are suffering from significantly disproportionate incidence and mortality rates of COVID-19. The potential for racial-justice interventions, including reparations payments, to ameliorate these disparities has not been adequately explored. Methods We compared the COVID-19 time-varying R t curves of relatively disparate polities in terms of social equity (South Korea vs. Louisiana). Next, we considered a range of reproductive ratios to back-calculate the transmission rates ß i→j for 4 cells of the simplified next-generation matrix (from which R 0 is calculated for structured models) for the outbreak in Louisiana. Lastly, we modeled the effect that monetary payments as reparations for Black American descendants of persons enslaved in the U.S. would have had on pre-intervention ß i→j . Results Once their respective epidemics begin to propagate, Louisiana displays R t values with an absolute difference of 1.3 to 2.5 compared to South Korea. It also takes Louisiana more than twice as long to bring R t below 1. We estimate that increased equity in transmission consistent with the benefits of a successful reparations program (reflected in the ratio ß b→b / ß w→w ) could reduce R 0 by 31 to 68%. Discussion While there are compelling moral and historical arguments for racial injustice interventions such as reparations, our study describes potential health benefits in the form of reduced SARS-CoV-2 transmission risk. As we demonstrate, a restitutive program targeted towards Black individuals would not only decrease COVID-19 risk for recipients of the wealth redistribution; the mitigating effects would be distributed across racial groups, benefitting the population at large.

8.
J Invest Surg ; 31(3): 185-191, 2018 Jun.
Article in English | MEDLINE | ID: mdl-28594257

ABSTRACT

BACKGROUND: The frequency of laparoscopic approaches increased in hernia surgery over the past years. After mesh placement in IPOM position, the real extent of the meshes configurational changes after termination of pneumoperitoneum is still largely unknown. To prevent a later mesh folding it might be useful to place the mesh while it is kept under tension. Conventionally used meshes may lose their Effective Porosity under these conditions due to poor elastic properties. The aim of this study was to evaluate a newly developed elastic thermoplastic polyurethane (TPU) containing mesh that retains its Effective Porosity under mechanical strain in IPOM position in a porcine model. It was visualized under pneumoperitoneum using MRI in comparison to polyvinylidenefluoride (PVDF) meshes with similar structure. METHODS: In each of ten minipigs, a mesh (TPU containing or native PVDF, 10 × 20 cm) was randomly placed in IPOM position at the center of the abdominal wall. After 8 weeks, six pigs underwent MRI evaluation with and without pneumoperitoneum to assess the visibility and elasticity of the mesh. Finally, pigs were euthanized and abdominal walls were explanted for histological and immunohistochemical assessment. The degree of adhesion formation was documented. RESULTS: Laparoscopic implantation of elastic TPU meshes in IPOM position was feasible and safe in a minipig model. Mesh position could be precisely visualized and assessed with and without pneumoperitoneum using MRI after 8 weeks. Elastic TPU meshes showed a significantly higher surface increase under pneumoperitoneum in comparison to PVDF. Immunohistochemically, the amount of CD45-positive cells was significantly lower and the Collagen I/III ratio was significantly higher in TPU meshes after 8 weeks. There were no differences regarding adhesion formation between study groups. CONCLUSIONS: The TPU mesh preserves its elastic properties in IPOM position in a porcine model after 8 weeks. Immunohistochemistry indicates superior biocompatibility regarding CD45-positive cells and Collagen I/III ratio in comparison to PVDF meshes with a similar structure.


Subject(s)
Abdominal Wall/surgery , Hernia, Abdominal/surgery , Laparoscopy/methods , Polyurethanes/chemistry , Surgical Mesh , Animals , Elasticity , Female , Magnetic Resonance Imaging , Materials Testing/methods , Models, Animal , Pneumoperitoneum, Artificial , Porosity , Prostheses and Implants , Stress, Mechanical , Swine , Swine, Miniature
9.
Biomed Mater ; 10(6): 065005, 2015 Nov 06.
Article in English | MEDLINE | ID: mdl-26541078

ABSTRACT

Collagen type I, in various physical forms, is widely used in tissue engineering and regenerative medicine. To control the mechanical properties and biodegradability of collagen-based devices, exogenous cross-links are introduced into the 3D supramolecular structure. However, potent cross-linking methods are associated with cytotoxicity, whilst mild cross-linking methods are associated with suboptimal mechanical resilience. Herein, we assessed the influence of resilin, a super-elastic and highly stretchable protein found within structures in arthropods where energy storage and long-range elasticity are needed, on the biophysical and biological properties of mildly cross-linked extruded collagen fibres. The addition of resilin-like protein in the 4-arm poly(ethylene glycol) ether tetrasuccinimidyl glutarate cross-linked collagen fibres resulted in a significant increase of stress and strain at break values and a significant decrease of modulus values. The addition of resilin-like protein did not compromise cell metabolic activity and DNA concentration. All groups are supported parallel to the longitudinal fibre axis cell orientation. Herein we provide evidence that the addition of resilin-like protein in mildly cross-linked collagen fibres improves their biomechanical properties, without jeopardising their biological properties.


Subject(s)
Biocompatible Materials/chemical synthesis , Cell Survival/drug effects , Fibrillar Collagens/chemistry , Fibrillar Collagens/toxicity , Insect Proteins/chemistry , Insect Proteins/toxicity , Biocompatible Materials/toxicity , Cells, Cultured , DNA Damage/physiology , Elastic Modulus , Fibrillar Collagens/ultrastructure , Fibroblasts/drug effects , Fibroblasts/physiology , Humans , Insect Proteins/ultrastructure , Materials Testing , Nanocomposites/chemistry , Nanocomposites/toxicity , Nanocomposites/ultrastructure , Stress, Mechanical , Tensile Strength
10.
J Clin Pharm Ther ; 40(5): 539-544, 2015 Oct.
Article in English | MEDLINE | ID: mdl-26111223

ABSTRACT

WHAT IS KNOWN AND OBJECTIVES: Obstetrics services are a high-throughput and high-risk environment poised for pharmacist involvement, but determining how to ideally allocate services is difficult. There is recent interest in the development of tools for service prioritization, but none are specifically targeted to obstetrics. Therefore, the aim of this study was (i) to conduct a practice audit surveying the demographics of patients attending obstetrics wards at a high-capacity maternity hospital; and (ii) to evaluate a triage tool developed to prioritize pharmacy services. METHODS: A retrospective case review of women discharged after birth admissions was undertaken at a hospital in National Health Service (NHS) Scotland during June 2014. Demographic and admission data were collected, as well as pharmacist interventions and missed opportunities in patient care on post-natal wards. A pharmacy triage tool was developed and retrospectively applied to each case to ascertain a risk category that would trigger and target pharmacist review. Interventions/opportunities were classified as either clinical (medication related) or administrative (potential for error development). RESULTS AND DISCUSSION: One hundred and seventy-five cases were reviewed with a median age of 29 years old. Eighty-six patients (49·1%) were retrospectively classified with elevated risk using the triage tool. A total of 117 charts (66·9%) were identified with missed opportunities for pharmacist intervention, which was significantly greater among patients classified as higher risk (75·6 vs. 58·4%, P = 0·017). Compared to low-risk patients, patients with a higher-risk classification had lower rates of administrative missed opportunities (55·4 vs. 80·8%, P = 0·015), but numerically higher rates of clinical (26·2 vs. 9·6%, p=NS) and mixed clinical/administrative (18·5 vs. 9·6%, p=NS) missed opportunities, although this failed to reach statistical significance. WHAT IS NEW AND CONCLUSION: Evaluation of a triage tool for obstetric services demonstrated potential for prioritizing higher-risk patients for pharmacist review and addressing opportunities for clinical improvements.

11.
Theriogenology ; 84(4): 600-7, 2015 Sep 01.
Article in English | MEDLINE | ID: mdl-26025241

ABSTRACT

Declines of the southern Rocky Mountain population of boreal toad (Anaxyrus boreas boreas) have led to the establishment of a captive assurance population and reintroduction program, in an attempt to preserve and propagate this geographically isolated population. One of the unique adaptations of this species is its ability to survive in cold environments by undergoing long periods of hibernation. In captivity, hibernation can be avoided altogether, decreasing morbidity caused by compromised immune systems. However, it is not entirely clear how essential hibernation is to reproductive success. In this study, the effects of hibernation versus nonhibernation, and exogenous hormones on oviposition, were examined in boreal toad females in the absence of males. In the summers of 2011 and 2012, 20 females housed at Mississippi State University were treated with a double priming dose of hCG and various ovulatory doses of hCG and LH-releasing hormone analog but denied hibernation. Exogenous hormones, in the absence of hibernation, could not induce oviposition over two breeding seasons (2011-2012). In contrast, during the summer of 2012 and 2013, 17 of 22 females (77%) housed at the Native Aquatic Species Restoration Facility (Alamosa, CO, USA) oviposited after they were treated with two priming doses of hCG (3.7 IU/g each) and a single ovulation dose of hCG (13.5 IU/g) and LH-releasing hormone analog (0.4 µg/g) after hibernation. There was a significant difference in oviposition between females that were hibernated and received hormones (2012, P < 0.05 and 2013, P < 0.01) compared to hibernated control females. In 2013, 12 of 16 remaining Mississippi State University females from the same group used in 2011 and 2012 were hibernated for 1, 3, and 6 months, respectively and then treated with the same hormone regimen administered to females at the Native Aquatic Species Restoration Facility. Together, hibernation and hormone treatments significantly increased oviposition (P < 0.05), with 33% of females ovipositing. These results suggest that (1) hibernation is a key factor influencing oviposition that cannot be exclusively circumvented by exogenous hormones; (2) females do not require the presence of a male to oviposit after hormone treatments; and (3) longer hibernation periods are not beneficial for oviposition. The hormonal induction of oviposition in the absence of males and shorter hibernation periods could have important captive management implications for the boreal toad. Furthermore, the production of viable offspring by IVF where natural mating is limited could become an important tool for genetic management of this boreal toad captive population.


Subject(s)
Bufonidae/physiology , Chorionic Gonadotropin/pharmacology , Gonadotropin-Releasing Hormone/pharmacology , Hibernation/physiology , Oviposition/drug effects , Animals , Female , Oviposition/physiology , Time Factors
12.
Oncogene ; 34(30): 4005-10, 2015 Jul 23.
Article in English | MEDLINE | ID: mdl-25284589

ABSTRACT

Cellular transformation is associated with altered glutamine (Gln) metabolism. Tumor cells utilize Gln in the tricarboxylic acid (TCA) cycle to maintain sufficient pools of biosynthetic precursors to support rapid growth and proliferation. However, Gln metabolism also generates NADPH, and Gln-derived glutamate is used for synthesis of glutathione (GSH). As both NADPH and GSH are antioxidants, Gln may also contribute to redox balance in transformed cells. The Hace1 E3 ligase is a tumor suppressor inactivated in diverse human cancers. Hace1 targets the Rac1 GTPase for degradation at Rac1-dependent NADPH oxidase complexes, blocking superoxide generation by the latter. Consequently, loss of Hace1 increases reactive oxygen species (ROS) levels in vitro and in vivo. Given the link between Hace1 loss and increased ROS, we investigated whether genetic inactivation of Hace1 alters Gln metabolism. We demonstrate that mouse embryonic fibroblasts (MEFs) derived from Hace1(-/-) mice are highly sensitive to Gln withdrawal, leading to enhanced cell death compared with wild-type (wt) MEFs, and Gln depletion or chemical inhibition of Gln uptake blocks soft agar colony formation by Hace1(-/-) MEFs. Hace1(-/-) MEFs exhibit increased Gln uptake and ammonia secretion, and metabolic labeling using (13)C-Gln revealed that Hace1 loss increases incorporation of Gln carbons into the TCA cycle intermediates. Gln starvation markedly increases ROS levels in Hace1(-/-) but not in wt MEFs, and treatment with the antioxidant N-acetyl cysteine or the TCA cycle intermediate oxaloacetate efficiently rescues Gln starvation-induced ROS elevation and cell death in Hace1(-/-) MEFs. Finally, Gln starvation increases superoxide levels in Hace1(-/-) MEFs, and NADPH oxidase inhibitors block the induction of superoxide and cell death by Gln starvation. Together, these results suggest that increased ROS production due to Hace1 loss leads to Gln addiction as a mechanism to cope with increased ROS-induced oxidative stress.


Subject(s)
Glutamine/physiology , Reactive Oxygen Species/metabolism , Tumor Suppressor Proteins/genetics , Ubiquitin-Protein Ligases/genetics , Animals , Apoptosis , Cells, Cultured , Mice, Knockout , Tumor Suppressor Proteins/metabolism , Ubiquitin-Protein Ligases/metabolism
13.
Adv Drug Deliv Rev ; 84: 257-77, 2015 Apr.
Article in English | MEDLINE | ID: mdl-25499820

ABSTRACT

Tendon injuries represent a significant clinical burden on healthcare systems worldwide. As the human population ages and the life expectancy increases, tendon injuries will become more prevalent, especially among young individuals with long life ahead of them. Advancements in engineering, chemistry and biology have made available an array of three-dimensional scaffold-based intervention strategies, natural or synthetic in origin. Further, functionalisation strategies, based on biophysical, biochemical and biological cues, offer control over cellular functions; localisation and sustained release of therapeutics/biologics; and the ability to positively interact with the host to promote repair and regeneration. Herein, we critically discuss current therapies and emerging technologies that aim to transform tendon treatments in the years to come.


Subject(s)
Regeneration/physiology , Tendons/physiology , Tissue Scaffolds/trends , Humans
14.
Int J Clin Pract ; 68(10): 1200-8, 2014 Oct.
Article in English | MEDLINE | ID: mdl-24797899

ABSTRACT

AIM: To describe and compare adherence and persistence with maintenance therapies in patients with asthma or chronic obstructive pulmonary disease (COPD) in the United Kingdom (UK). METHODS: A retrospective prescribing database cohort was obtained from 44 general practitioner surgeries in National Health Service Forth Valley Scotland. Patients with physician-diagnosed asthma or COPD who received maintenance therapy between January 2008 and December 2009 were included. Five classes of therapy were assessed: inhaled corticosteroids, long-acting beta-agonists, combination therapy inhalers, theophyllines and long-acting muscarinic antagonists. Adherence was calculated using the medication possession ratio (MPR) and persistence was determined using Kaplan-Meier survival analysis for the time to discontinuation (TTD) over 1 year. Two step-wise logistic regressions were performed to assess the contribution of diagnosis to adherence/persistence. RESULTS: A total of 13,322 patients were included in the analysis: 10,521 patients with asthma and 2801 patients with COPD. 25.2% of medication episodes for asthma and 45.6% of medication episodes for COPD were classified as having an adequate medication supply (MPR of 80-120%). The overall median TTD was 92 days (IQR, interquartile range: 50-186 days) for patients with asthma and 116 days (IQR: 58-259 days, comparison p < 0.001) for patients with COPD. Patients with COPD were found to be more likely to achieve an MPR of at least 80% (OR: 1.27, 95% CI: 1.15-1.40), but had a similar likelihood of persistence at 1 year to patients with asthma. CONCLUSION: Adherence and persistence with respiratory therapies in the UK is relatively low. There is suggestion that patients with COPD may display more adherent behaviours than patients with asthma.


Subject(s)
Asthma/drug therapy , Medication Adherence , Pulmonary Disease, Chronic Obstructive/drug therapy , Adolescent , Adrenal Cortex Hormones/therapeutic use , Adult , Aged , Aged, 80 and over , Bronchodilator Agents/therapeutic use , Cohort Studies , Female , Humans , Male , Middle Aged , Muscarinic Antagonists/therapeutic use , Retrospective Studies , United Kingdom/epidemiology
15.
Meat Sci ; 96(1): 633-9, 2014 Jan.
Article in English | MEDLINE | ID: mdl-24056406

ABSTRACT

This study investigated effects of high pressure (HP) treatment of pork meat at 150 or 300 MPa for 5 min before manufacturing sausages on the reduction of phosphate levels and compared to sausages manufactured with untreated pork meat (control sausages). Improvement in perceived saltiness, juiciness and overall flavour was observed in sausages manufactured using HP-treated meat at 150 MPa and 0% phosphate, compared to control sausages. Sausages manufactured using meat HP-treated at 150 MPa and 0.25% phosphate (P<0.05) improved hardness of sausages. HP-treated meat at 300 MPa and 0% phosphate decreased juiciness and adhesiveness, while at 0.25% phosphate, adversely affected emulsion stability and sensory attributes. HP treatment did not affect significantly the lightness of the sausages; however, elimination of phosphate reduced (P<0.05) the yellowness, while HP treatment at 150 MPa with 0.25 or 0.5% phosphate increased (P<0.05) redness. HP reatment at 150 MPa has potential for reducing phosphate levels in sausages without significant changes in their functionality and improved acceptability.


Subject(s)
Food Handling/methods , Meat Products/analysis , Phosphates/analysis , Pressure , Animals , Breakfast , Chemical Phenomena , Color , Emulsions/chemistry , Humans , Swine , Taste
16.
J Control Release ; 160(3): 685-91, 2012 Jun 28.
Article in English | MEDLINE | ID: mdl-22516093

ABSTRACT

Amphotericin B (AMB) is used to treat both fungal and leishmanial infections, which are of major significance to human health. Clinical use of free AMB is limited by its nephrotoxicity, whereas liposomal AMB is costly and requires parenteral administration, thus development of novel formulations with enhanced efficacy, minimal toxicity and that can be applied via non-invasive routes is required. In this study we analysed the potential of non-ionic surfactant vesicles (NIV) given by nebulisation to deliver AMB to the lungs, liver and skin. Treatment with AMB-NIV resulted in significantly higher drug levels in the lungs and skin (p<0.05) compared to similar treatment with AMB solution but significantly lower plasma levels (p<0.05). Treatment with AMB-NIV resulted in a significant reduction in fungal lung burdens in a rat model of invasive pulmonary aspergillosis (p<0.05) compared to treatment with the carrier alone. Treatment with AMB-NIV but not AMB solution significantly suppressed Leishmania donovani liver parasite burdens (p<0.05) but could not inhibit the growth of cutaneous Leishmania major lesions. The results of this study indicate that aerosolised NIV enhanced pulmonary and hepatic delivery whilst minimising systemic exposure and toxicity.


Subject(s)
Amphotericin B/administration & dosage , Antifungal Agents/administration & dosage , Drug Carriers/administration & dosage , Leishmaniasis/drug therapy , Pulmonary Aspergillosis/drug therapy , Surface-Active Agents/administration & dosage , Aerosols , Animals , Cricetinae , Disease Models, Animal , Female , Firefly Luciferin/administration & dosage , Leishmaniasis/metabolism , Leishmaniasis/microbiology , Liver/metabolism , Liver/microbiology , Lung/metabolism , Lung/microbiology , Mesocricetus , Mice , Mice, Inbred BALB C , Pulmonary Aspergillosis/metabolism , Pulmonary Aspergillosis/microbiology , Rats , Rats, Sprague-Dawley
17.
Vaccine ; 30(7): 1357-63, 2012 Feb 08.
Article in English | MEDLINE | ID: mdl-22210224

ABSTRACT

Leishmaniasis is a major health problem and it is estimated that 12 million people are currently infected. A vaccine which could cross-protect people against different Leishmania spp. would facilitate control of this disease as more than one species of Leishmania may be present. In this study the ability of a DNA vaccine, using the full gene sequence for L. donovani gamma glutamyl cysteine synthetase (γGCS) incorporated in the pVAX vector (pVAXγGCS), and a protein vaccine, using the corresponding recombinant L. donovani γGCS protein (LdγGCS), to protect against L. major or L. mexicana infection was evaluated. DNA vaccination gave transient protection against L. major and no protection against L. mexicana despite significantly enhancing specific antibody titres in vaccinated infected mice compared to infected controls. Vaccination with the LdγGCS protected against both species but only if the protein was incorporated into non-ionic surfactant vesicles for L. mexicana. The results of this study indicate that a L. donovani γGCS vaccine could be used to vaccinate against more than one Leishmania species but only if the recombinant protein is used.


Subject(s)
Antigens, Protozoan/immunology , Glutamate-Cysteine Ligase/immunology , Leishmania donovani/immunology , Leishmaniasis Vaccines/immunology , Leishmaniasis, Cutaneous/prevention & control , Leishmaniasis, Visceral/prevention & control , Animals , Antibodies, Protozoan/biosynthesis , Antibodies, Protozoan/immunology , Antigens, Protozoan/genetics , Cross Protection , Epitopes , Glutamate-Cysteine Ligase/genetics , Humans , Leishmania major/immunology , Leishmania mexicana/immunology , Leishmaniasis Vaccines/genetics , Leishmaniasis, Cutaneous/immunology , Leishmaniasis, Cutaneous/parasitology , Leishmaniasis, Visceral/immunology , Leishmaniasis, Visceral/parasitology , Mice , Mice, Inbred BALB C , Recombinant Proteins/genetics , Recombinant Proteins/immunology , Vaccination , Vaccines, DNA , Vaccines, Subunit
19.
Syst Parasitol ; 77(3): 233-9, 2010 Nov.
Article in English | MEDLINE | ID: mdl-20960093

ABSTRACT

Wild and cultured winter flounder Pseudopleuronectes americanus (Walbaum) from Passamaquoddy Bay were surveyed for species of Gyrodactylus Nordmann, 1832. Two species were found: G. pleuronecti Cone, 1981 and G. aideni n. sp, both members of Malmberg's 'groenlandicus group'. Although the hard parts in the haptor are very similar in the two species, hamuli of G. aideni are consistently shorter than those of G. pleuronecti. The two species differed by 35 base pairs in the ITS 1, 5.8 and ITS 2 region. A BLAST search identified a variety of species of Gyrodactylus from marine fishes in the Atlantic Ocean as closest matches, indicating the 'groenlandicus group' is part of a major marine lineage within Gyrodactylus (sensu lato) that has successfully radiated among coastal percid, pleuronectid, cottid and anarhichadid fishes. Exposure experiments suggested that winter flounder is the primary host of both species of parasites and that three other pleuronectid species in the bay may potentially serve only as occasional transport hosts.


Subject(s)
Flounder/parasitology , Trematoda/anatomy & histology , Trematoda/classification , Animals , New Brunswick , Trematoda/genetics
20.
J Parasitol ; 96(5): 929-36, 2010 Oct.
Article in English | MEDLINE | ID: mdl-20950100

ABSTRACT

Visceral leishmaniasis presents a serious health threat in many parts of the world. There is, therefore, an urgent need for an approved vaccine for clinical use to protect against infection. In this study, the ability of recombinant Leishmania donovani gamma-glutamyl cysteine synthetase protein (LdγGCS) alone or incorporated into a non-ionic surfactant vesicle (NIV) delivery system to protect against L. donovani infection was evaluated in a BALB/c mouse model. Immunization with LdγGCS alone or LdγGCS-NIV induced specific IgG1 and IgG2a antibodies compared to controls, with LdγGCS-NIV inducing significantly higher titers of both antibody classes (P < 0.05). Both formulations induced similar increases in splenocyte IFN-γ production following ex vivo antigen stimulation with LdγGCS compared with cells from control mice (P < 0.05). Similar levels of protection against infection were induced by LdγGCS alone and LdγGCS-NIV, based on their ability to suppress liver parasite burdens compared to control values (P < 0.01), indicating that using a carrier system did not enhance the protective responses induced by the recombinant protein. The results of this study indicate that LdγGCS may be a useful component in a vaccine against L. donovani.


Subject(s)
Glutamate-Cysteine Ligase/immunology , Leishmania donovani/immunology , Leishmaniasis, Visceral/prevention & control , Recombinant Fusion Proteins/immunology , Adjuvants, Immunologic , Animals , Antibodies, Protozoan/blood , Coated Vesicles/immunology , Cricetinae , Enzyme-Linked Immunosorbent Assay , Female , Glutamate-Cysteine Ligase/genetics , Immunoglobulin G/blood , Interferon-gamma/biosynthesis , Leishmania donovani/genetics , Leishmaniasis, Visceral/immunology , Mesocricetus , Mice , Mice, Inbred BALB C , Protozoan Vaccines/administration & dosage , Protozoan Vaccines/immunology , Recombinant Fusion Proteins/genetics , Spleen/cytology , Spleen/immunology , Th1 Cells/immunology , Th2 Cells/immunology
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