Supplementation with Octacosanol Affects the Level of PCSK9 and Restore Its Physiologic Relation with LDL-C in Patients on Chronic Statin Therapy

Dietary supplementation with sugar cane derivates may modulate low-density lipoprotein cholesterol (LDL-C) and proprotein convertase subtilisin/kexin type 9 (PCSK9) levels. The purpose of this study was to determine if dietary supplement (DS), containing Octacosanol (20 mg) and vitamin K2 (45 µg), could restore the disrupted physiologic relation between LDL-C and serum PCSK9. Double-blind, randomized, placebo-controlled, single-center study including 87 patients on chronic atorvastatin therapy was conducted. Eighty-seven patients were randomized to receive DS (n = 42) or placebo (n = 45), and followed for 13 weeks. Serum PCSK9 levels, lipid parameters and their relationship were the main efficacy endpoints. The absolute levels of PCSK9 and LDL-C were not significantly different from baseline to 13 weeks. However, physiologic correlation between % change of PCSK9 and % change of LDL-C levels was normalized only in the group of patients treated with DS (r = 0.409, p = 0.012). This study shows that DS can restore statin disrupted physiologic positive correlation between PCSK9 and LDL-C. Elevated PCSK9 level is an independent risk factor so controlling its rise by statins may be important in prevention of cardiovascular events.     

Immune tolerance induced by intravenous transfer of immature dendritic cells via up-regulating numbers of suppressive IL-10+ IFN-γ+-producing CD4+ T cells

Dendritic cells (DCs) regulate immunity and immune tolerance in vivo. However, the mechanisms of DC-mediated tolerance have not been fully elucidated. Here, we demonstrate that intravenous (i.v.) transfer of bone marrow-derived DCs pulsed with myelin oligodendrocyte glycoprotein (MOG) peptide blocks the development of experimental autoimmune encephalomyelitis in C57BL/6J mice. i.v. transfer of MOG-pulsed DCs leads to the down-regulation of the production of IL-17A and IFN-γ and up-regulation of IL-10 secretion. The development of regulatory T cells (Tregs) is facilitated via up-regulation of FoxP3 expression and production of IL-10. The number of suppressive CD4⁺IL-10⁺IFN-γ⁺ T cells is also improved. The expression of OX40, CD154, and CD28 is down-regulated, but the expression of CD152, CD80, PD-1, ICOS, and BTLA is up-regulated on CD4⁺ T cells after i.v. transfer of immature DCs. The expression of CCR4, CCR5, and CCR7 on CD4⁺ T cells is also improved. Our results suggest that immature DCs may induce tolerance via facilitating the development of CD4⁺FoxP3⁺ Tregs and suppressive CD4⁺IL-10⁺IFN-γ⁺ T cells in vivo.     

Tolerogenic dendritic cells produced by lentiviral‐mediated CD40‐ and interleukin‐23p19‐specific shRNA can ameliorate experimental autoimmune encephalomyelitis by suppressing T helper type 17 cells

Down‐regulation of soluble or membrane‐bound co‐stimulatory molecules by RNAi in dendritic cells can prevent the activation of immune responses. Therefore, this study was designed to evaluate the therapeutic efficacy of bone marrow‐derived DCs (BMDCs) transduced with lentiviral vectors to permanently expressed shRNA specific for CD40 (CD40LV‐DCs) and/or p19 subunit of interleukin (IL)‐23 (p19LV‐DCs) mRNAs in experimental autoimmune encephalomyelitis (EAE). In‐vitro studies showed that double‐transduced BMDCs (CD40⁺p19LV‐DCs) resemble tolerogenic DCs due to profound down‐regulation of CD40, lower expression of proinflammatory cytokines (IL‐6 and IL‐12), increased IL‐10 production and stronger stimulation of myelin oligodendrocyte glycoprotein (MOG)_35–55‐specific T cells for production of IL‐10 compared with CD40LV‐DCs, p19LV‐DCs and BMDCs transduced with control lentiviral vector (CoLV‐DCs). Moreover, injection of transduced CD40⁺p19LV‐ BMDCs in EAE mice resulted in more reduction in clinical score, significant reduction in IL‐17 or increased production of IL‐10 by mononuclear cells derived from the lymph nodes or spinal cord compared with CoLV‐DCs‐treated EAE mice. In conclusion, simultaneous knock‐down of CD40 and IL‐23 production by BMDCs may represent a promising therapeutic tool for the treatment of IL‐17‐dependent autoimmune diseases, including multiple sclerosis.     

Polysaccharide Biocatalysis: From Synthesizing Carbohydrate Standards to Establishing Characterization Methods

Starch, glycogen, and cellulose are all around us. They are eaten and used on a daily basis but they are not understood completely. Even though these carbohydrates are simple, concerning their repeating unit, they are hard to characterize. In order to try to understand as much as possible about their structure and the relationship between their molecular structure and physical properties, it is very practical to create such polysaccharides, for instance enzymatically, characterize them, and use them as standards for the characterization of natural ones. Therefore, the main objective of this Trend article is to outline different enzymatic routes to such carbohydrates, possibilities for their characterization, and the characterization of natural ones.     

Pituitary cushing''s syndrome and nelson''s syndrome: Diagnostic criteria, surgical therapy, and results

Eight patients with pituitary Cushing's syndrome and 2 with Nelson's syndrome were followed from one to ten years after removal of pituitary adenomas. A detailed assessment of the pituitary-adrenal axis was obtained in all patients when last seen, save the first, who had undergone a complete hypophysectomy ten years previously. Long-term observations have shown sustained endocrine cure in 7 of 8 patients with pituitary Cushing's syndrome. One patient with Nelson's syndrome was also cured. There was no operative morbidity or mortality. There were no instances of diabetes insipidus. The long-term results in this study indicate that patients with pituitary Cushing's syndrome have a better than 90% chance of being cured after transsphenoidal removal of the pituitary (micro) adenomas. Current diagnostic and therapeutic concepts in the management of pituitary Cushing's syndrome are discussed in detail.     

Neuron-binding human monoclonal antibodies support central nervous system neurite extension

Two human IgMs (sHIgM12 and sHIgM42) were identified that supported in vitro central nervous system (CNS) neurite extension equal to the potent neurite stimulatory molecule laminin. Both IgMs bound to multiple cell types in unfixed CNS tissue and to the surface of neurons in culture. Both monoclonal antibodies (mAbs) overrode the inhibitory effect of CNS mouse myelin on granule cell neurite extension. Neither mAb bound to the surface of mature oligodendrocytes or strictly colocalized with myelin proteins. Sialidase treatment eliminated the neuronal surface binding of both mAbs, whereas blocking sphingolipid synthesis with Fumonisin B1 or removing GPI-linked proteins with PIPLC did not. When used as substrates for mixed neuron/glia aggregates, sHIgM12 and sHIgM42 supported robust neurite extension while astrocytes remained in the aggregates. In contrast, laminin supported astrocyte migration and spreading. Human mAbs that support neurite extension are novel factors that may be of use in encouraging axon repair following injury while minimizing glial cell infiltration. Both human mAbs were isolated from individuals with monoclonal gammopathy. Each individual has carried high mAb titers in circulation for years without detriment. sHIgM12 and sHIgM42 are therefore unlikely to be systemically pathogenic.     

Factors of home dream recall: a structural equation model

Previous research has indicated that personality factors such as openness to experience, creativity, visual memory, attitude toward dreams, and sleep behavior is related to home dream recall frequency (DRF). However, a study investigating all areas simultaneously within one sample in order to determine the percentage of variance explained by all variables and to take intercorrelations between the influencing factors into account has not been performed till now. The present study with 444 participants fills this gap. Using several indicators for each of the variables mentioned above, a structural equation model was tested. Although the model fit was satisfying, the four factors which were significantly related to DRF: personality (openness to experience, thin boundaries, absorption), creativity, nocturnal awakenings, and attitude toward dreams, explained only 8.4% of the total variance. As this value is considerably lower than those of studies investigating a single influencing factor and using similar measurement instruments in similar samples, one might speculate about possible expectancy effects in these previous studies, an effect which has been demonstrated for DRF in the laboratory setting. In addition, the small percentage of explained variance of each single factors (<3%) may indicate that other, in this study unmeasured, variables such as sleep duration (state aspect), introspection, and cognitive functioning immediately upon awakening (sleep inertia) show substantial covariance with the interindividual differences in DRF. Future studies should focus on longitudinal aspects in order to differentiate between state versus trait factors (although methodologic issues, e.g. the effect of the measurement technique on DRF itself, have to be clarified) and investigate additional variables which might be associated with DRF (see above).