Cholesterol removal by peritoneal lavage with phospholipid-HDL apoprotein mixtures in hypercholesterolemic hamsters

Syrian hamsters were rendered hypercholesterolemic by supplementation of their diet with 1% cholesterol and 15% butter. The hamsters were injected intraperitoneally (i.p.) with about 20 mg of phospholipid liposomes containing trace amounts of [3H]cholesteryl linoleyl ether ([ 3H]CLE) alone or combined with 10 mg delipidated high-density lipoprotein (apoHDL). After 2 h the peritoneal cavity was washed repeatedly with up to 15 ml phosphate-buffered saline. 60%-70% of [3H]CLE were retained after i.p. injection without apoHDL, 30-50% in the presence of apoHDL. The amount of free cholesterol recovered in the peritoneal lavage was significantly higher when apoHDL was combined with 18:2 sphingomyelin or dilinoleyl phosphatidylcholine liposomes, when compared to either liposomes or apoHDL alone. It is suggested that supplementation of dialysate with HDL apolipoproteins and phospholipids in patients undergoing continuous peritoneal dialysis could be of use in a cholesterol depletion regimen.     

Guía clínica de diagnóstico y tratamiento del prolactinoma y la hiperprolactinemia

ObjectiveTo provide practical and up to date recommendations for evaluation, differential diagnosis, and treatment of prolactinoma and hyperprolactinemia in various clinical settings.ParticipantsMembers of the Neuroendocrinology Working Group of the Spanish Society of Endocrinology.MethodsRecommendations were formulated according to the Grading of Recommendations, Assessment, Development, and Evaluation system (GRADE) to describe both the strength of recommendations and the quality of evidence. A systematic search was made in Medline (Pubmed) for each subject, and authors’ considerations were added in areas where the literature provided scarce evidence. Finally, recommendations were jointly discussed by the Working Group.ConclusionsThe document provides evidence-based practical and updated recommendations for diagnosis and management of hyperprolactinemia and prolactinoma, including drug-induced hyperprolactinemia, treatment options for prolactinoma (drugs, surgery, and radiotherapy), prolactinoma in pregnancy, adverse effects of dopaminergic agents, and drug-resistant and malignant prolactinomas.     

Enhanced Localization of Genetic Samples through Linkage-Disequilibrium Correction

Characterizing the spatial patterns of genetic diversity in human populations has a wide range of applications, from detecting genetic mutations associated with disease to inferring human history. Current approaches, including the widely used principal-component analysis, are not suited for the analysis of linked markers, and local and long-range linkage disequilibrium (LD) can dramatically reduce the accuracy of spatial localization when unaccounted for. To overcome this, we have introduced an approach that performs spatial localization of individuals on the basis of their genetic data and explicitly models LD among markers by using a multivariate normal distribution. By leveraging external reference panels, we derive closed-form solutions to the optimization procedure to achieve a computationally efficient method that can handle large data sets. We validate the method on empirical data from a large sample of European individuals from the POPRES data set, as well as on a large sample of individuals of Spanish ancestry. First, we show that by modeling LD, we achieve accuracy superior to that of existing methods. Importantly, whereas other methods show decreased performance when dense marker panels are used in the inference, our approach improves in accuracy as more markers become available. Second, we show that accurate localization of genetic data can be achieved with only a part of the genome, and this could potentially enable the spatial localization of admixed samples that have a fraction of their genome originating from a given continent. Finally, we demonstrate that our approach is resistant to distortions resulting from long-range LD regions; such distortions can dramatically bias the results when unaccounted for.     

YopP-Expressing Variant of Y. pestis Activates a Potent Innate Immune Response Affording Cross-Protection against Yersiniosis and Tularemia

Plague, initiated by Yersinia pestis infection, is a rapidly progressing disease with a high mortality rate if not quickly treated. The existence of antibiotic-resistant Y. pestis strains emphasizes the need for the development of novel countermeasures against plague. We previously reported the generation of a recombinant Y. pestis strain (Kim53ΔJ+P) that over-expresses Y. enterocolitica YopP. When this strain was administered subcutaneously to mice, it elicited a fast and effective protective immune response in models of bubonic, pneumonic and septicemic plague. In the present study, we further characterized the immune response induced by the Kim53ΔJ+P recombinant strain. Using a panel of mouse strains defective in specific immune functions, we observed the induction of a prompt protective innate immune response that was interferon-γ dependent. Moreover, inoculation of mice with Y. pestis Kim53ΔJ+P elicited a rapid protective response against secondary infection by other bacterial pathogens, including the enteropathogen Y. enterocolitica and the respiratory pathogen Francisella tularensis. Thus, the development of new therapies to enhance the innate immune response may provide an initial critical delay in disease progression following the exposure to highly virulent bacterial pathogens, extending the time window for successful treatment.     

Hexokinase mediates stomatal closure

Stomata, composed of two guard cells, are the gates whose controlled movement allows the plant to balance the demand for CO₂ for photosynthesis with the loss of water through transpiration. Increased guard‐cell osmolarity leads to the opening of the stomata and decreased osmolarity causes the stomata to close. The role of sugars in the regulation of stomata is not yet clear. In this study, we examined the role of hexokinase (HXK), a sugar‐phosphorylating enzyme involved in sugar‐sensing, in guard cells and its effect on stomatal aperture. We show here that increased expression of HXK in guard cells accelerates stomatal closure. We further show that this closure is induced by sugar and is mediated by abscisic acid. These findings support the existence of a feedback‐inhibition mechanism that is mediated by a product of photosynthesis, namely sucrose. When the rate of sucrose production exceeds the rate at which sucrose is loaded into the phloem, the surplus sucrose is carried toward the stomata by the transpiration stream and stimulates stomatal closure via HXK, thereby preventing the loss of precious water.     

A search for overlapping genetic susceptibility loci between non-Hodgkin lymphoma and autoimmune diseases

Non-Hodgkin lymphoma (NHL) is a hematological malignancy of the immune system, and, as with autoimmune and inflammatory diseases (ADs), is influenced by genetic variation in the major histocompatibility complex (MHC). Persons with a history of specific ADs also have increased risk of NHL. As the coexistence of ADs and NHL could be caused by factors common to both diseases, here we examined whether some of the associated genetic signals are shared. Overlapping risk loci for NHL subytpes and several ADs were explored using data from genome-wide association studies. Several common genomic regions and susceptibility loci were identified, suggesting a potential shared genetic background. Two independent MHC regions showed the main overlap, with several alleles in the human leukocyte antigen (HLA) class II region exhibiting an opposite risk effect for follicular lymphoma and type I diabetes. These results support continued investigation to further elucidate the relationship between lymphoma and autoimmune diseases.     

Money in an Unequal World: Keith Hart and His Memory Bank

Money in an Unequal World: Keith Hart and His Memory Bank. Keith Hart. New York: Texere, 2001. 341 pp.