Human macrophages limit oxidation products in low density lipoprotein

This study tested the hypothesis that human macrophages have the ability to modify oxidation products in LDL and oxidized LDL (oxLDL) via a cellular antioxidant defence system. While many studies have focused on macrophage LDL oxidation in atherosclerosis development, less attention has been given to the cellular antioxidant capacity of these cells. Compared to cell-free controls (6.2 ± 0.7 nmol/mg LDL), macrophages reduced TBARS to 4.42 ± 0.4 nmol/mg LDL after 24 h incubation with LDL (P = 0.022). After 2 h incubation with oxLDL, TBARS were 3.69 ± 0.5 nmol/mg LDL in cell-free media, and 2.48 ± 0.9 nmol/mg LDL in the presence of macrophages (P = 0.034). A reduction of lipid peroxides in LDL (33.7 ± 6.6 nmol/mg LDL) was found in the presence of cells after 24 h compared to cell-free incubation (105.0 ± 14.1 nmol/mg LDL) (P = 0.005). The levels of lipid peroxides in oxLDL were 137.9 ± 59.9 nmol/mg LDL and in cell-free media 242 ± 60.0 nmol/mg LDL (P = 0.012). Similar results were obtained for hydrogen peroxide. Reactive oxygen species were detected in LDL, acetylated LDL, and oxLDL by isoluminol-enhanced chemiluminescence (CL). Interestingly, oxLDL alone gives a high CL signal. Macrophages reduced the CL response in oxLDL by 45% (P = 0.0016). The increased levels of glutathione in oxLDL-treated macrophages were accompanied by enhanced catalase and glutathione peroxidase activities. Our results suggest that macrophages respond to oxidative stress by endogenous antioxidant activity, which is sufficient to decrease reactive oxygen species both in LDL and oxLDL. This may suggest that the antioxidant activity is insufficient during atherosclerosis development. Thus, macrophages may play a dual role in atherogenesis, i.e. both by promoting and limiting LDL-oxidation. © 2005 Hultén et al; licensee BioMed Central Ltd

Axion-like-particle search with high-intensity lasers

We study ALP-photon-conversion within strong inhomogeneous electromagnetic fields as provided by contemporary high-intensity laser systems. We observe that probe photons traversing the focal spot of a superposition of Gaussian beams of a single high-intensity laser at fundamental and frequency-doubled mode can experience a frequency shift due to their intermittent propagation as axion-like-particles. This process is strongly peaked for resonant masses on the order of the involved laser frequencies. Purely laser-based experiments in optical setups are sensitive to ALPs in the $\mathrm{eV}$ mass range and can thus complement ALP searches at dipole magnets.Comment: 25 pages, 2 figure

Higher-order nonlinear electron-acoustic solitary excitations in partially degenerate quantum electron-ion plasmas

Propagation of dressed solitary excitations are studied in a partially degenerate quantum plasma in the framework of quantum-hydrodynamics (QHD) model using multiple scales technique. The evolution equation together with a linear inhomogeneous differential equation is solved using Kodama-Taniuti renormalizing technique. It is shown that the type of solitary excitations (bright or dark) is defined by two critical plasma parameter values.Comment: To appear in Indian Journal of Physic

Polymorphisms in the Mn-SOD and EC-SOD Genes and Their Relationship to Diabetic Neuropathy in Type 1 Diabetes Mellitus

BACKGROUND: Oxidative stress, resulting in a marked increase in the level of oxygen free radicals (OFR), has been implicated in the etiology of diabetic neuropathy (DN). Antioxidant enzymes may protect against the rapid onset and progression of DN, by reducing the excess of OFR and peroxide. Mutations and polymorphisms in the genes encoding such enzymes may therefore result in predisposition to DN. We investigated the role of genes encoding two antioxidant enzymes, mitochondrial (Mn-SOD) and extracellular (EC-SOD) superoxide dismutase, in DN pathogenesis in a Russian population. We studied Ala(-9)Val and Ile58Thr polymorphisms of the Mn-SOD gene and Arg213Gly dimorphism of the EC-SOD gene in type 1 diabetic patients with (n = 82) and without DN (n = 84). RESULTS: We developed and used a new polymerase chain reaction (PCR) assays for rapid detection of polymorphisms. These assays involved the use of mismatch PCR primers to create restriction sites in the amplified product only in presence of the polymorphic base. The PCR product was than digested with BshTI, Eco32I or Eco52I to detect Ala(-9)Val, Ile58Thr or Arg213Gly polymorphic site respectively. The frequencies of the Ala allele (50.6% vs. 68.5%, p < 0.002) and the Ala/Ala genotype (17.1% vs. 39.3%, p < 0.005) of the Mn-SOD gene were significantly lower in DN patients than in diabetic subjects without DN. In contrast, the Val allele (49.4% vs. 31.5%, p < 0.002) and the Val/Val genotype (15.9% vs. 2.4%, p < 0.01) were significantly more frequent in the DN patients than in the control group. CONCLUSIONS: Ala(-9)Val substitution in the Mn-SOD gene was associated with DN in a Russian populatio

Food allergy knowledge, attitudes and beliefs: Focus groups of parents, physicians and the general public

<p>Abstract</p> <p>Background</p> <p>Food allergy prevalence is increasing in US children. Presently, the primary means of preventing potentially fatal reactions are avoidance of allergens, prompt recognition of food allergy reactions, and knowledge about food allergy reaction treatments. Focus groups were held as a preliminary step in the development of validated survey instruments to assess food allergy knowledge, attitudes, and beliefs of parents, physicians, and the general public.</p> <p>Methods</p> <p>Eight focus groups were conducted between January and July of 2006 in the Chicago area with parents of children with food allergy (3 groups), physicians (3 groups), and the general public (2 groups). A constant comparative method was used to identify the emerging themes which were then grouped into key domains of food allergy knowledge, attitudes, and beliefs.</p> <p>Results</p> <p>Parents of children with food allergy had solid fundamental knowledge but had concerns about primary care physicians' knowledge of food allergy, diagnostic approaches, and treatment practices. The considerable impact of children's food allergies on familial quality of life was articulated. Physicians had good basic knowledge of food allergy but differed in their approach to diagnosis and advice about starting solids and breastfeeding. The general public had wide variation in knowledge about food allergy with many misconceptions of key concepts related to prevalence, definition, and triggers of food allergy.</p> <p>Conclusion</p> <p>Appreciable food allergy knowledge gaps exist, especially among physicians and the general public. The quality of life for children with food allergy and their families is significantly affected.</p

Two Notch Ligands, Dll1 and Jag1, Are Differently Restricted in Their Range of Action to Control Neurogenesis in the Mammalian Spinal Cord

Notch signalling regulates neuronal differentiation in the vertebrate nervous system. In addition to a widespread function in maintaining neural progenitors, Notch signalling has also been involved in specific neuronal fate decisions. These functions are likely mediated by distinct Notch ligands, which show restricted expression patterns in the developing nervous system. Two ligands, in particular, are expressed in non-overlapping complementary domains of the embryonic spinal cord, with Jag1 being restricted to the V1 and dI6 progenitor domains, while Dll1 is expressed in the remaining domains. However, the specific contribution of different ligands to regulate neurogenesis in vertebrate embryos is still poorly understood.In this work, we investigated the role of Jag1 and Dll1 during spinal cord neurogenesis, using conditional knockout mice where the two genes are deleted in the neuroepithelium, singly or in combination. Our analysis showed that Jag1 deletion leads to a modest increase in V1 interneurons, while dI6 neurogenesis was unaltered. This mild Jag1 phenotype contrasts with the strong neurogenic phenotype detected in Dll1 mutants and led us to hypothesize that neighbouring Dll1-expressing cells signal to V1 and dI6 progenitors and restore neurogenesis in the absence of Jag1. Analysis of double Dll1;Jag1 mutant embryos revealed a stronger increase in V1-derived interneurons and overproduction of dI6 interneurons. In the presence of a functional Dll1 allele, V1 neurogenesis is restored to the levels detected in single Jag1 mutants, while dI6 neurogenesis returns to normal, thereby confirming that Dll1-mediated signalling compensates for Jag1 deletion in V1 and dI6 domains.Our results reveal that Dll1 and Jag1 are functionally equivalent in controlling the rate of neurogenesis within their expression domains. However, Jag1 can only activate Notch signalling within the V1 and dI6 domains, whereas Dll1 can signal to neural progenitors both inside and outside its domains of expression

IGF-1 Induction by Acylated Steryl β-Glucosides Found in a Pre-Germinated Brown Rice Diet Reduces Oxidative Stress in Streptozotocin-Induced Diabetes

BACKGROUND: The pathology of diabetic neuropathy involves oxidative stress on pancreatic β-cells, and is related to decreased levels of Insulin-like growth factor 1 (IGF-1). Acylated steryl β-glucoside (PR-ASG) found in pre-germiated brown rice is a bioactive substance exhibiting properties that enhance activity of homocysteine-thiolactonase (HTase), reducing oxidative stress in diabetic neuropathy. The biological importance of PR-ASG in pancreatic β-cells remains unknown. Here we examined the effects of PR-ASG on IGF-1 and glucose metabolism in β-cells exposed to oxidative stress. METHODOLOGY/PRINCIPAL FINDINGS: In the present study, a pre-germinated brown rice (PR)-diet was tested in streptozotocin (STZ)-induced diabetic rats. Compared with diabetic rats fed control diets, the PR-diet fed rats showed an improvement of serum metabolic and neurophysiological parameters. In addition, IGF-1 levels were found to be increased in the serum, liver, and pancreas of diabetic rats fed the PR-diet. The increased IGF-1 level in the pancreas led us to hypothesize that PR-ASG is protective for islet β-cells against the extensive injury of advanced or severe diabetes. Thus we examined PR-ASG to determine whether it showed anti-apoptotic, pro-proliferative effects on the insulin-secreting β-cells line, INS-1; and additionally, whether PR-ASG stimulated IGF-1 autocrine secretion/IGF-1-dependent glucose metabolism. We have demonstrated for the first time that PR-ASG increases IGF-1 production and secretion from pancreatic β-cells. CONCLUSION/SIGNIFICANCE: These findings suggest that PR-ASG may affect pancreatic β-cells through the activation of an IGF-1-dependent mechanism in the diabetic condition. Thus, intake of pre-germinated brown rice may have a beneficial effect in the treatment of diabetes, in particular diabetic neuropathy

Adolescents' experiences of being food-hypersensitive: a qualitative study

<p>Abstract</p> <p>Background</p> <p>Experiencing or being at risk of adverse reactions to certain food items is a common health issue, especially among children and adolescents. Research has shown that living with the risk of food reactions and always having to take measures to avoid certain food in one's diet has a negative impact on quality of life. The aim of this study was to illuminate adolescents' experiences of being food hypersensitive.</p> <p>Methods</p> <p>Three focus group interviews and six individual interviews were carried out with all together 17 adolescents, 14–18 years of age, who had exclusion diets at school due to food hypersensitivity. The interviews were taped and transcribed verbatim and a qualitative content analysis was carried out.</p> <p>Results</p> <p>Five categories with subcategories, and one pervading theme, emerged. The categories were: <it>Perceiving oneself as being particular</it>, <it>Feeling constrained</it>, <it>Experiencing others' ignorance</it>, <it>Keeping control</it>, and <it>Feeling it's okay</it>. A pervading theme was conceptualised as <it>Striving to normalise the experience of being food-hypersensitive</it>. The adolescents regarded themselves as competent and courageous, but also described how they avoided the extra attention it implied to ask for special food considerations taken into account. Their self-conceptions were probably essential for their management of and attitude toward the hypersensitivity condition. They felt deprived, and those at risk of severe food reactions experienced insecurity and fear. Feelings of being disregarded were expressed, as well as facing unreliability and a lack of understanding from others. The continual work of constant vigilance and decision-making was described as time-consuming and frustrating. However, the adolescents also experienced considerate and supportive surroundings and were at pains to tone down the negative experiences and consequences of being food-hypersensitive.</p> <p>Conclusion</p> <p>Food avoidance by itself, and not only the somatic food reactions, brings about consequences with significant impacts on adolescents' lives. The findings from this study have implications for all of those who deal with adolescents who are food-hypersensitive, and not only health professionals. A deeper insight into adolescents' experiences gives an understanding which can improve the care-givers' efforts.</p

Efficiency of Organelle Capture by Microtubules as a Function of Centrosome Nucleation Capacity: General Theory and the Special Case of Polyspermia

Transport of organelles along microtubules is essential for the cell metabolism and morphogenesis. The presented analysis derives the probability that an organelle of a given size comes in contact with the microtubule aster. The question is asked how this measure of functionality of the microtubule aster is controlled by the centrosome. A quantitative model is developed to address this question. It is shown that for the given set of cellular parameters, such as size and total tubulin content, a centrosome nucleation capacity exists that maximizes the probability of the organelle capture. The developed general model is then applied to the capture of the female pronucleus by microtubules assembled on the sperm centrosome, following physiologically polyspermic fertilization. This application highlights an unintuitive reflection of nonlinearity of the nucleated polymerization of the cellular pool of tubulin. The prediction that the sperm centrosome should lower its nucleation capacity in the face of the competition from the other sperm is a stark illustration of the new optimality principle. Overall, the model calls attention to the capabilities of the centrosomal pathway of regulation of the transport-related functionality of the microtubule cytoskeleton. It establishes a quantitative and conceptual framework that can guide experiment design and interpretation

Carbonic anhydrase IX in oligodendroglial brain tumors

Background Carbonic anhydrase IX is a hypoxia-induced enzyme that has many biologically important functions, including its role in cell adhesion and invasion. Methods This study was set out to investigate the role of CA IX in a series of 86 oligodendroglial brain tumors (71 primary and 15 recurrent; 48 pure oligodendrogliomas and 40 mixed oligoastrocytomas). Results 80% of the tumors showed CA IX expression by immunohistochemistry. Tumors with moderate or strong CA IX expression had decreased level of cell proliferation compared to weak or no CA IX expression (median 2.9 vs. 5.8, p = 0.015). CA IX correlated with two antioxidative enzymes, manganese superoxide dismutase (MnSOD) and regulatory gammaglutamylcysteine synthetase (GLCL-R): CA IX expression was significantly higher in MnSOD-positive tumors (p = 0.008) and decreased in GLCL-R-positive tumors (p = 0.044). In Cox multivariate analysis CA IX expression, patient age and histological component (pure oligodendroglioma vs. mixed oligoastrocytoma) showed independent prognostic values (p = 0.009, p = 0.003 and p = 0.022, respectively), CA IX positivity predicting poorer outcome. Conclusion CA IX was proved to be an independent prognostic indicator in oligodendroglial brain tumors, and it also correlates reversely with cell proliferation. It may have a role in the biology of oligodendrogliomas, and most interestingly, as it is mainly expressed in tumor tissue, CA IX could serve as a target molecule for anticancer treatments.BioMed Central Open acces