5 research outputs found
The bioelectrical impedance vector migration in healthy infants
No full textBackground & aims: Detecting young children with high amount of body fat is important to intervene in the development of obesity. The aim of this study is to gain inside in the bioelectrical impedance vector analysis in healthy infants. Methods: Repeated measurements of whole body reactance and resistance were assessed, using a 50 kHz frequency bioelectrical impedance analysis, in 51 boys and 62 girls during infancy. Bivariate vector analysis, which can be used to determine tissue hydration and soft tissue mass, was conducted. The 95% confidence intervals of the mean vectors for different age groups and the 95%, 75% and 50% tolerance intervals were plotted, using resistance and reactance components standardized by the participant's height. Results: During infancy impedance vectors changed significantly: A vector migration of the Xc/H of 8.50 ohm/m and the R/H of 95.68 ohm/m between the age of two months and eight to twelve months (p = 0.0001) was observed. Bivariate, reference tolerance intervals of the impedance vectors for healthy infants at the age of two months are presented. Conclusion: Our results show a significant impedance vector migration during the first year of life. New reference tolerance intervals for the second month of life were constructed. (C) 2009 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved
Prevalence of visual impairment and severity of diabetic retinopathy in various ethnic groups in the UK
No full textDiabetic Retinopathy (DR) is a leading cause of visual impairment (VI) in the working population. Minor ethnic groups are at increased risk of diabetes. Diabetic Retinopathy In Various Ethnic groups in the United Kingdom (DRIVE UK) is a cross-sectional study to estimate the prevalence of DR, VI and associated risk factors for sight threatening diabetic retinopathy (STDR) in Afro-Caribbeans (AC) and South Asians (SA) compared to Caucasians. People with diabetes in two regions in the United Kingdom who were screened and/or treated for DR from September 2008 to September 2009 were included in this study. VI and severe visual impairment (SVI) were defined as Snellen visual acuity of ≤ 6/18 and ≤ 6/60 respectively. DR was graded according to National Screening Committee (NSC) for diabetes guidelines UK.
There were 57,144 people on the diabetic register, of which retinopathy data was available from 50,285 (88.1%) subjects (type 1 n=3,323, type 2 n=46,962). In type 1 and type 2 diabetes, any DR was detected in 53.1%, 39.5%, diabetic maculopathy in 13.1%, 8.4% and STDR in 9.91%, 4.0% of people respectively. STDR was significantly more prevalent in the SA (10.3%) and AC (11.5%) populations compared to Caucasians (5.5%). Overall VI was significantly higher in the ethnic minority population. A total of 7.5% (95% CI 7.3, 7.8) people with diabetes were not eligible for driving based on their visual acuity, 3.4% (95% CI 3.2, 3.5) were classified as VI and 0.4% (95% CI 0.33, 0.44) as SVI. Risk factors for STDR were found to include longer duration of diabetes and higher mean HbA1c.
This study provides information that could be used to help develop future service frameworks and guidelines for local health bodies responsible for delivery of end userservices. The study also supports the need to explore the role of inflammatory, genetic and epigenetic factors as markers for ethnic differences in DR and potential treatment avenues for diabetic retinopathy
Glaucoma awareness
No full textThis thesis investigates three different aspects of glaucoma awareness
using both quantitative and qualitative methods.
Patient Awareness:
This qualitative study looked at patients perceptions of glaucoma.
Participants (N=28) reported low levels of awareness of glaucoma prior to
their diagnosis and assumed that symptoms were the ‘normal’
deterioration of eyesight. As symptoms have a gradual onset, participants
had learnt to cope with diminishing sight ability. Findings suggested
health promotion a priority to increase public awareness of the existence
and symptoms of glaucoma among those at high risk.
Current public awareness:
This study looked to document public awareness and knowledge of
glaucoma.
The study used health knowledge questionnaires in three different
populations:
1. nationally representative sample of 1009 people
2. telephone Interviews – 500 Isle of Wight, 226 Ealing
3. face-to-face interviews – 300 Ealing
Between 71-93% of those interviewed by telephone had heard of
glaucoma. However, only 23% of those interviewed face-to-face in Ealing
reported having heard of glaucoma. We found a relatively high level of awareness and knowledge of glaucoma in the general UK population but
identified at least one pocket of poor knowledge in a specific subpopulation.
Can we change awareness?
This study investigated whether a public health campaign could increase
awareness and change help-seeking behaviour with respect to ocular
health with residents in Southall, Ealing aged 60+. The health knowledge
questionnaire from the previous study was used to assess the campaign.
The health campaign comprised of four components.
1. Television
2. Local Press
3. Local Radio
4. Places of worship
The results showed a significant increase in the number of people who
had heard of Glaucoma rising from 22% to 53%. Before the intervention
most people had heard about glaucoma from their GP, friend or relative.
After intervention the majority (69%) had heard of glaucoma from the
radio.
This study showed a significant increase in awareness from using
different kinds of media and showed radio to be the most effective in the target community. Although the campaign raised awareness it did not
show a change in help seeking behaviour
Determinism and organization. Foundations and limits of Claude Bernard’s program
No full textComo lo afirma el autor de este perspicazlibro: el presente de una ciencia no solamente se define por su éxito y su proyección, también hacen parte de su imagen más completa -aunque precisamente por eso jamás acabada- los problemas y polémicas de dicha ciencia; asuntos que la mantienen activa, creativa y avanzando.
Este libro se constituye en una franca imagen del presente de una ciencia como la Biología. Magistralmente Gustavo Caponi examina, a la luz de los problemas y tensiones actuales de la Filosofía de la Biología, la historia del programa de la Fisiología Experimental conformado en el siglo XIX por el médico y biólogo francés Claude Bernard. Así, el objeto de este libro es al menos doble: por un lado, examinar con detalle y ofrecer claridad de los presupuestos y consecuencias epistemológicas de la Fisiología Experimental de Claude Bernard; por otro, valerse de las discusiones históricas de la Biología para traer nuevas respuestas y precisiones al actual debate presente en la Filosofía de la Biología.The present of a science is not only defined by its success and projection; the problems and controversies that keep it moving forward are also part of its complete image. This book constitutes a frank image of the present of Biology. The author examines, in light of the current problems of the philosophy of biology, the history of the program of experimental physiology elaborated in the 19th century by the French scientist Claude Bernard
Towards the optimization of tumor targeting radiolabeled peptides for molecular imaging and therapy
No full textRadiopharmaceuticals based on regulatory peptides have become an indispensable tool in nuclear medicine for the diagnosis (molecular imaging) and radionuclide therapy of cancer. The specificity of these radiopeptides towards G-protein-coupled receptors (GPCR), which are overexpressed by various cancer cells and their favorable pharmacological properties make them ideal vectors for the targeted delivery of radioactivity to tumors and metastases. However, there are still challenges to be met in order to develop peptide-based radiopharmaceuticals with ideal properties in terms of imaging quality and therapeutic efficacy where therapeutic radionuclides are employed.
A potential drawback of several radiolabeled peptides under investigation is represented by a rapid washout of radioactivity after receptor-mediated internalization into tumor cells. In certain cases, the washout of radioactivity from cells occurs at a rate comparable to that required for accumulation in cancerous tissues. This not only renders the initial efforts of targeted delivery in part futile but also results in an imaging quality and therapeutic efficiency lower than achievable. To address this issue, novel strategies are needed to improve the cellular retention of the radioactivity. A possible approach may include the employment of multi-targeting radioconjugates made of different moieties specific for extra- and intracellular targets. Towards this goal, we investigated the combination of tumor targeting peptides with an additional moiety specific for an intracellular target and radiolabeled the conjugate with the 99mTc-tricarbonyl core as a reporter probe for single-photon emission computed tomography (SPECT). We envisioned that enabling interactions of radioconjugates with intracellular targets after receptor-mediated uptake by endocytosis would result in the trapping of radioactivity in tumors.
Specifically, we combined a modified binding sequence of the peptide bombesin, [Nle14]BBS(7-14), for extracellular targeting of the tumor-associated gastrin releasing peptide receptor (GRP-r) with a triphenylphosphonium group for intracellular targeting of the organelle mitochondria or with the peptide shepherdin, an inhibitor of the cytosolic chaperon heat-shock protein 90 (Hsp90). The conjugates were assembled by the "Click-to-Chelate" approach, an efficient synthetic strategy for the preparation of bifunctional 99mTc-labeled radiopharmaceuticals. The radioconjugates were evaluated in vitro using GRP-r-overexpressing PC-3 cells. Our investigations revealed that the additional moiety for intracellular targeting did not impact the tumor-targeting capability of the bombesin-derived conjugates but neither did it result in an improved cellular retention of the radioactivity. Drawing from our experience and considering recent literature data, we conclude that endosomal entrapment or lysosomal degradation of the bifunctional radiopeptide conjugates is likely to impede with intracellular interactions and thus, responsible for the observed unaltered cellular efflux of radioactivity. Future studies will be directed towards the combination of bifunctional radiopeptide conjugates with drug delivery systems designed to facilitate endosomal escape.
A different approach for the optimization of peptidic radiotracers includes the improvement of their metabolic stability since most of them exhibit a very short biological half-life due to rapid degradation by endogenous peptidases. Enhancement of the stability of radiopeptides results in a prolonged circulation time in the blood and, as a consequence, an improved tumor uptake in vivo. A number of different strategies have been reported for the stabilization of regulatory peptides, however, with varying degree of success in providing peptidomimetics with retained affinity to the corresponding GPCR. In an effort to probe a novel peptide backbone modification methodology, the use of 1,4-disubstituted 1,2,3-triazoles as metabolically stable trans amide bond isosters was investigated. The systematic replacement of amide bonds within the binding sequence of the tumor-affine peptide bombesin, [Nle14]BBS(7-14), by triazoles provided a series of 177Lu-labeled peptidomimetics with both retained affinity towards GRP-r and an increased stability in blood serum. In vivo evaluation of a lead compound in xenografted mice showed that the enhanced stability of the radiopeptidomimetic resulted in a doubling of the uptake of radioactivity in tumors. The described amide-to-triazole substitution methodology is currently being applied to other tumor targeting peptides of medicinal interest.
The specificity and affinity of radiopeptides towards different receptor subtypes is another aspect to consider for optimizations. Inhomogeneous expression of receptor subtypes by tumors may influence the efficiency of a radiotracer. For example, intratumoral administration of radiolabeled substance P (SP) led to significant differences in the clinical response of patients suffering from gliomas despite proven expression of its target, the neurokinin-1 receptor (NK1R). In an effort to identify factors that may be responsible for the varying therapeutic outcome observed, several SP conjugates were evaluated in vitro using four established glioma cell lines differing in their level of RNA expression of the full length and truncated receptor isoforms. Cell binding and internalization of SP-conjugates were only observed with cell lines exhibiting high expression of RNA of the full-length NK1R. Pre-therapeutic screening for NK1R isoforms may therefore be advisable for the selection of glioma patients for NK1R-targeted radionuclide therapy
