142 research outputs found
Interaction of Liposomal Drug Delivery Systems with Cells and Tissues: Microscopic Studies
Liposomes , as drug carriers, can be administered into the body by several routes e.g. intravenously, intraperitoneally, intramuscularly, intratracheally and topically among others. Radiolabelled markers are suitable to monitor the distribution and elimination of liposomes, but the tissue deposition of intact liposomes, the mode and sites of drug release from the liposomes and liposome-cell interactions cannot be investigated morphologically. Microscopic techniques could provide information regarding the intact state of liposomes and possibly the dynamics of liposomes in tissues provided that they can be identified with certainty in vivo. This is a formidable problem and in spite of several attempts, there is still a lot of work and new ideas needed to overcome this problem.
This paper gives a detailed review of liposome markers used in light and electron microscopy. The use of markers or the technique involved in the identification of liposomes in cells or t issues is discussed.
The feasibility of using colloidal iron, a new electron dense marker, as a marker for intravenously injected liposomes was investigated in mice. Intact multilamellar vesicles containing colloidal iron were identified in the liver, spleen and lung of mice injected with liposomes. The liver and the spleen are organs for the storage of iron containing proteins (ferritin, hemosiderin), therefore studying the disposition of colloidal iron from the liposomes was not possible. However, in organs not containing iron, e.g. lung, the presence of colloidal iron can easily be recognized. The colloidal iron marker may be suitable to label liposomes targeted to the brain , heart or certain tumors
On the role of bacterial metalloproteases in COVID-19 associated cytokine storm
The cytokine release syndrome or cytokine storm, which is the hyper-induction of inflammatory responses has a central role in the mortality rate of COVID-19 and some other viral infections. Interleukin-6 (IL-6) is a key player in the development of cytokine storms. Shedding of interleukin-6 receptor (IL-6RΞ±) results in the accumulation of soluble interleukin-6 receptors (sIL-6R). Only relatively few cells express membrane-bound IL-6RΞ±. However, sIL-6R can act on potentially all cells and organs through the ubiquitously expressed gp130, the coreceptor of IL-6RΞ±. Through this, so-called trans-signaling, IL-6βsIL-6R is a powerful factor in the development of cytokine storms and multiorgan involvement. Some bacteria (e.g., Serratia marcescens, Staphylococcus aureus, Pseudomonas aeruginosa, Listeria monocytogenes), commonly considered to cause co-infections during viral pneumonia, can directly induce the shedding of membrane receptors, including IL-6RΞ±, or enhance endogenous shedding mechanisms causing the increase of sIL-6R level. Here we hypothesise that bacteria promoting shedding and increase the sIL-6R level can be an important contributing factor for the development of cytokine storms. Therefore, inhibition of IL-6RΞ± shedding by drastically reducing the number of relevant bacteria may be a critical element in reducing the chance of a cytokine storm. Validation of this hypothesis can support the consideration of the prophylactic use of antibiotics more widely and at an earlier stage of infection to decrease the mortality rate of COVID-19
Cross-sectional relationship between physical fitness components and functional performance in older persons living in long-term care facilities
BACKGROUND: The age-related deterioration of physiological capacities such as muscle strength and balance is associated with increased dependence. Understanding the contribution of physical fitness components to functional performance facilitates the development of adequate exercise interventions aiming at preservation of function and independence of older people. The aim of the study was to investigate the relationship between physical fitness components and functional performance in older people living in long-term care facilities. METHODS: Design cross-sectional study Subjects 226 persons living in long-term care facilities (mean age: 81.6 Β± 5.6). Outcome measures Physical fitness and functional performance were measured by performance-based tests. RESULTS: Knee and elbow extension strength were significantly higher in men (difference = 44.5 and 50.0 N, respectively), whereas women were more flexible (difference sit & reach test = 7.2 cm). Functional performance was not significantly different between the genders. In men, motor coordination (eye-hand coordination) and measures of strength were the main contributors to functional performance, whereas in women flexibility (sit and reach test) and motor coordination (tandem stance and eye-hand coordination) played a major role. CONCLUSION: The results of this study show that besides muscle strength, fitness components such as coordination and flexibility are associated with functional performance of older people living in long-term care facilities. This suggests that men and women living in long-term care facilities, differ considerably concerning the fitness factors contributing to functional performance. Women and men may, therefore, need exercise programs emphasizing different fitness aspects in order to improve functional performance
Osteo-cise: Strong Bones for Life: protocol for a community-based randomised controlled trial of a multi-modal exercise and osteoporosis education program for older adults at risk of falls and fractures
Background : Osteoporosis affects over 220 million people worldwide, and currently there is no \u27cure\u27 for the disease. Thus, there is a need to develop evidence-based, safe and acceptable prevention strategies at the population level that target multiple risk factors for fragility fractures to reduce the health and economic burden of the condition. Methods : The \u27Osteo-cise: Strong Bones for Life\u27 study will investigate the effectiveness and feasibility of a multi-component targeted exercise, osteoporosis education/awareness and behavioural change program for improving bone health and muscle function, and reducing falls risk in community-dwelling older adults at an increased risk of fracture. Men and women aged 60 years or above will participate in an 18-month randomised controlled trial comprising a 12-month structured and supervised community-based program and a 6-month \u27research to practise\u27 translational phase. Participants will be randomly assigned to either the \u27Osteo-cise\u27 intervention or a self-management control group. The intervention will comprise a multi-modal exercise program incorporating high velocity progressive resistance training, moderate impact weight-bearing exercise and high challenging balance exercises performed three times weekly at local community-based fitness centres. A behavioural change program will be used to enhance exercise adoption and adherence to the program. Community-based osteoporosis education seminars will be conducted to improve participant knowledge and understanding of the risk factors and preventative measures for osteoporosis, falls and fractures. The primary outcomes measures, to be collected at baseline, 6, 12, and 18 months, will include DXA-derived hip and spine bone mineral density measurements and functional muscle power (timed stair-climb test). Secondary outcomes measures include: MRI-assessed distal femur and proximal tibia trabecular bone micro-architecture, lower limb and back maximal muscle strength, balance and function (four square step test, functional reach test, timed up-and-go test and 30-second sit-to-stand), falls incidence and health-related quality of life. Cost-effectiveness will also be assessed. Discussion : The findings from the Osteo-cise: Strong Bones for Life study will provide new information on the efficacy of a targeted multi-modal community-based exercise program incorporating high velocity resistance training, together with an osteoporosis education and behavioural change program for improving multiple risk factors for falls and fracture in older adults at risk of fragility fracture.<br /
Ageing, Muscle Power and Physical Function: A Systematic Review and Implications for Pragmatic Training Interventions.
BACKGROUND: The physiological impairments most strongly associated with functional performance in older people are logically the most efficient therapeutic targets for exercise training interventions aimed at improving function and maintaining independence in later life. OBJECTIVES: The objectives of this review were to (1) systematically review the relationship between muscle power and functional performance in older people; (2) systematically review the effect of power training (PT) interventions on functional performance in older people; and (3) identify components of successful PT interventions relevant to pragmatic trials by scoping the literature. METHODS: Our approach involved three stages. First, we systematically reviewed evidence on the relationship between muscle power, muscle strength and functional performance and, second, we systematically reviewed PT intervention studies that included both muscle power and at least one index of functional performance as outcome measures. Finally, taking a strong pragmatic perspective, we conducted a scoping review of the PT evidence to identify the successful components of training interventions needed to provide a minimally effective training dose to improve physical function. RESULTS: Evidence from 44 studies revealed a positive association between muscle power and indices of physical function, and that muscle power is a marginally superior predictor of functional performance than muscle strength. Nine studies revealed maximal angular velocity of movement, an important component of muscle power, to be positively associated with functional performance and a better predictor of functional performance than muscle strength. We identified 31 PT studies, characterised by small sample sizes and incomplete reporting of interventions, resulting in less than one-in-five studies judged as having a low risk of bias. Thirteen studies compared traditional resistance training with PT, with ten studies reporting the superiority of PT for either muscle power or functional performance. Further studies demonstrated the efficacy of various methods of resistance and functional task PT on muscle power and functional performance, including low-load PT and low-volume interventions. CONCLUSIONS: Maximal intended movement velocity, low training load, simple training methods, low-volume training and low-frequency training were revealed as components offering potential for the development of a pragmatic intervention. Additionally, the research area is dominated by short-term interventions producing short-term gains with little consideration of the long-term maintenance of functional performance. We believe the area would benefit from larger and higher-quality studies and consideration of optimal long-term strategies to develop and maintain muscle power and physical function over years rather than weeks
Comparative Genomic Hybridization (CGH) Reveals a Neo-X Chromosome and Biased Gene Movement in Stalk-Eyed Flies (Genus Teleopsis)
Chromosomal location has a significant effect on the evolutionary dynamics of genes involved in sexual dimorphism, impacting both the pattern of sex-specific gene expression and the rate of duplication and protein evolution for these genes. For nearly all non-model organisms, however, knowledge of chromosomal gene content is minimal and difficult to obtain on a genomic scale. In this study, we utilized Comparative Genomic Hybridization (CGH), using probes designed from EST sequence, to identify genes located on the X chromosome of four species in the stalk-eyed fly genus Teleopsis. Analysis of log2 ratio values of female-to-male hybridization intensities from the CGH microarrays for over 3,400 genes reveals a strongly bimodal distribution that clearly differentiates autosomal from X-linked genes for all four species. Genotyping of 33 and linkage mapping of 28 of these genes in Teleopsis dalmanni indicate the CGH results correctly identified chromosomal location in all cases. Syntenic comparison with Drosophila indicates that 90% of the X-linked genes in Teleopsis are homologous to genes located on chromosome 2L in Drosophila melanogaster, suggesting the formation of a nearly complete neo-X chromosome from Muller element B in the dipteran lineage leading to Teleopsis. Analysis of gene movement both relative to Drosophila and within Teleopsis indicates that gene movement is significantly associated with 1) rates of protein evolution, 2) the pattern of gene duplication, and 3) the evolution of eyespan sexual dimorphism. Overall, this study reveals that diopsids are a critical group for understanding the evolution of sex chromosomes within Diptera. In addition, we demonstrate that CGH is a useful technique for identifying chromosomal sex-linkage and should be applicable to other organisms with EST or partial genomic information
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Conformation and self-association of peptide amphiphiles based on the KTTKS collagen sequence
Studying peptide amphiphiles (PAs), we investigate
the influence of alkyl chain length on the aggregation behavior of the collagen-derived peptide KTTKS with applications ranging from antiwrinkle cosmetic creams to potential uses in regenerative medicine. We have studied synthetic peptides amphiphiles C14β KTTKS (myristoyl Lys-Thr-Thr-Lys-Ser) and C18βKTTKS(stearoyl-Lys-Thr Thr-Lys-Ser) to investigate in detail their physicochemical properties. It is presumed that the hydrophobic chain in these self-assembling peptide amphiphiles enhances peptide permeation across the skin compared to KTTKS alone.
Subsequently CnβKTTKS should act as a prodrug and release the peptide by enzymatic cleavage. Our results should be useful in the further development of molecules with collagen-stimulating activity
The application of strength and power related field tests in older adults: criteria, current status and a future perspective
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