Production of interleukin-12 by monocytes and interferon-gamma by natural killer cells in allergic patients during rush immunotherapy.

BACKGROUND: Allergen specific immunotherapy modifies the immunologic response to allergen exposure; however, the role of cells composing the innate immune system, such as monocytes and natural killer (NK) cells, in this mechanism is still unclear. OBJECTIVE: To examine the effect of rush immunotherapy (RIT) on early allergen-induced cytokine production by peripheral blood mononuclear cells from treated cat- and birch-allergic patients. METHODS: Twelve allergic patients received RIT, and another 4 served as controls. Blood samples were taken before the start and after 3 days, 1 week, 3 weeks, and 3 months of RIT. Allergen-induced production of interleukin-12 (IL-12) by monocytes and interferon-gamma (IFN-gamma) by NK cells was evaluated by means of flow cytometry. RESULTS: Before the start of RIT, allergic patients had significantly lower numbers of IL-12+ monocytes compared with healthy subjects (P = .01). The percentage of IL-12+ monocytes increased after 3 months of RIT (P = .003). In the allergic control group, the proportion of IL-12+ monocytes evaluated after 3 months was not different from baseline and was significantly lower compared with that in the RIT group (P = .005). Before treatment, the percentage of IFN-gamma+ NK cells was lower in allergic patients than in healthy subjects (P = .04). The percentage of IFN-gamma+ NK cells increased after 3 weeks (P = .03) and 3 months (P = .01) of RIT. CONCLUSIONS: Restoration of the cytokine imbalance by immunotherapy is not only restricted to the cells of the adaptive immune system but also concerns cells composing the innate immune system.     

Targeting of endoplasmic reticulum-associated proteins to axons and dendrites in rotavirus-infected neurons

To analyze sorting and compartmentalization of molecules in neuronal endomembranes, the distribution of endogenous proteins associated with the endoplasmic reticulum (ER), intermediate compartment, the Golgi apparatus in cultures of dorsal root ganglion (DRG), and hippocampal neurons was compared with that of newly synthesized ER-associated rotavirus proteins. The endogenous ER-retained immunoglobulin heavy chain binding protein, protein disulfide isomerase, and a peptide containing the KDEL amino acid sequence appeared in the soma and dendrites up to their first branching, but not in axons. However, two other endogenous ER-associated proteins, calreticulin and calnexin, occurred in axons as well as in the somatodendritic domains. The ER-associated rotavirus proteins, VP7 and NSP4, were widely distributed in cell bodies and dendrites. The former appeared also in axons and its localization partially overlapped with that of calreticulin and calnexin. One intermediate compartment protein, ER-Golgi-intermediate compartment-protein-53 (ERGIC-53), extended beyond the first division of the dendrites and did not, as the small guanosine 5′-triphosphate (GTP)-binding protein rab2, appear in axons. The location of rab2 to small vesicles was distinct from that of rotavirus VP7. Cis/medial Golgi cistern proteins were restricted to the cell bodies and proximal dendrites. This study emphasizes the marked heterogeneity in the targeting to axons and dendrites of proteins associated with ER and intermediate compartments. Therefore, the composition of axonal ER-retained molecules differs from that in the soma and this variation may reflect differences in functions between the ER compartments. Viral proteins are useful reporters for such heterogeneities and rotavirus VP7 may be a tool to reveal sorting signals for targeting of vesicular proteins to axons via a nonclassical Golgi-independent mechanism. Such signals may also determine viral targeting to different regions of the brain.     

Characterization of flow emerging from a stenosis using MRI

MRI ultra-fast imaging techniques are used to characterize flow emerging from streamlined and abrupt stenoses inside cylindrical channels. Reattachment lengths of the shear boundary to the channel wall are measured using rotating ultra-fast imaging sequence (RUFIS) in-flow imaging. Velocity profiles of flow are created using velocity (sine and cosine)-encoded RUFIS sequences. The sine-encoded images permit one to identify reverse flow (i.e., eddies) that arise within the region of flow reattachment. The ratios of peak velocities (downstreamhpstream of the stenosis) derived from the cosine-encoded images are used to identify the transition from the laminar to the turbulent regimen. Based on these experiments, the transition from the laminar to turbulent regimen occurs at a stenotic Reynolds Number of 350, whereas fully developed turbulence occurs at a stenotic Reynolds Number of 2600. These results are compared with the results from invasive studies.     

Changes in common carotid artery intima-media thickness over 1 year in patients on peritoneal dialysis.

BACKGROUND: Accelerated atherosclerosis and vascular calcifications increase cardiovascular morbidity and mortality in patients on dialysis. Common carotid artery (CCA) intima-media thickness (IMT) is considered useful for imaging atherosclerosis non-invasively. Since chronic inflammation may accelerate atherosclerosis in end-stage renal disease patients, the aim of this 1 year study was to assess changes in CCA-IMT in stable peritoneal dialysis (PD) patients, and to search for possible associations between these changes and selected cytokines, acute phase proteins and other risk factors of atherosclerosis. METHODS: Of the original cohort of 61 stable patients on PD-28 female, 33 male; mean age 50.4+/-13.6 years; dialyse for a median of 17.5 months at inclusion (range 1-96 months)-47 patients survived the 1 year period on PD. CCA-IMT was assessed at baseline and after 12 months. Pro-inflammatory cytokines (IL-6, TNFalpha), acute phase proteins (CRP, fibrinogen), calcium-phosphate balance and lipid profile were assessed at baseline and after 6 and 12 months. Anthropometric parameters (age, weight, BMI, waist-to-hip ratio) were measured at baseline. RESULTS: The mean CCA-IMT at baseline, 0.66+/- 0.19 mm, increased by a mean of 0.098+/-0.17 to 0.76+/-0.21 mm (P<0.001) in 1 year. In 14 patients (29.8%) at least one plaque was found in the CCAs examined. At the end of follow-up: 28 patients (59.6%) had increases in CCA-IMT (from 0.63+/-0.2 to 0.83+/- 0.21 mm; P = 0.03), and 19 (40.4%) remained stable or even showed slight, but non-significant, decreases of CCA-IMT (from 0.72+/-0.17 to 0.66+/-0.17 mm, P = NS). The 'progressors' had significantly higher initial BMI (P<0.05), and mean concentrations of calcium (P = 0.005), IL-6 (P = 0.05), TNFalpha (P = 0.05), CRP (P = 0.005) and lower HDL-cholesterol than 'non-progressors'. In univariate analysis, DeltaCCA-IMT correlated positively with age (R = 0.32, P = 0.03), BMI (R = 0.29, P = 0.05) and mean concentrations of CRP (R = 0.37, P = 0.01), TNFalpha (0.52, P = 0.0002), but inversely with HDL-cholesterol (R = -0.37, P = 0.01). In multiple regression analysis, however, only age appeared to be independently associated with increase in CCA-IMT (beta = 0.37, P<0.01; R(2) for the model 0.14). CONCLUSIONS: Our results suggest a possible role of non-specific inflammation in the progression of atherosclerosis in patients treated with PD, in addition to age.     

The Links between Cardiovascular Diseases and Alzheimer's Disease

The root cause of non-inherited Alzheimer’s disease (AD) remains unknown despite hundreds of research studies performed to attempt to solve this problem. Since proper prophylaxis remains the best strategy, many scientists have studied the risk factors that may affect AD development. There is robust evidence supporting the hypothesis that cardiovascular diseases (CVD) may contribute to AD progression, as the diseases often coexist. Therefore, a lack of well-defined diagnostic criteria makes studying the relationship between AD and CVD complicated. Additionally, inflammation accompanies the pathogenesis of AD and CVD, and is not only a consequence but also implicated as a significant contributor to the course of the diseases. Of note, АроЕε4 is found to be one of the major risk factors affecting both the cardiovascular and nervous systems. According to genome wide association and epidemiological studies, numerous common risk factors have been associated with the development of AD-related pathology. Furthermore, the risk of developing AD and CVDs appears to be increased by a wide range of conditions and lifestyle factors: hypertension, dyslipidemia, hypercholesterolemia, hyperhomocysteinemia, gut/oral microbiota, physical activity, and diet. This review summarizes the literature and provides possible mechanistic links between CVDs and AD.     

Micronutrients in Multiple Pregnancies—The Knowns and Unknowns: A Systematic Review

Maternal diet and nutritional status are of key importance with regard to the short- and long-term health outcomes of both the mother and the fetus. Multiple pregnancies are a special phenomenon in the context of nutrition. The presence of more than one fetus may lead to increased metabolic requirements and a faster depletion of maternal macro- and micro- nutrient reserves than in a singleton pregnancy. The aim of this systematic review was to gather available knowledge on the supply and needs of mothers with multiple pregnancies in terms of micronutrients and the epidemiology of deficiencies in that population. It was constructed in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses Statement (PRISMA). The authors conducted a systematic literature search with the use of three databases: PubMed/MEDLINE, Scopus and Embase. The last search was run on the 18 October 2020 and identified 1379 articles. Finally, 12 articles and 1 series of publications met the inclusion criteria. Based on the retrieved studies, it may be concluded that women with multiple pregnancies might be at risk of vitamin D and iron deficiencies. With regard to other microelements, the evidence is either inconsistent, scarce or absent. Further in-depth prospective and population studies are necessary to determine if nutritional recommendations addressed to pregnant women require adjustments in cases of multiple gestations.