Innate and Acquired Cellular Immunity in Children with Familial Hypercholesterolemia Treated with Simvastatin.

The aim of this cross-sectional study was to assess the influence of simvastatin treatment in children with familial hypercholesterolemia (FH) on parameters of cellular immunity. Twenty-six children with FH were included, of which thirteen were treated with 10 mg simvastatin for at least 26 weeks, and thirteen were age- and sex-matched with a low-cholesterol diet only. Total WBC count and lipid profile were measured. Flow cytometry was used to identify lymphocyte subsets and determine the expression of adhesion molecules (AM) and toll-like receptors (TLRs) on leukocytes. No differences were found in the basic values of peripheral blood count and subpopulations of lymphocytes between groups. The percentage of granulocytes with the expression of AM was higher in those treated with statins. The TLR-2 expression on granulocytes and monocytes showed higher values, whereas the TLR-4 expression was lower on lymphocytes and granulocytes in simvastatin-treated children. Treatment with simvastatin in children with FH is not associated with alterations in the amounts of granulocytes and monocytes. There is no association between statin treatment and the pattern of peripheral blood lymphocyte subpopulations. The role of AM and TLRs needs further investigation, given the effect of statins on the innate immunity may be important for their efficacy and safety during growth.

Transnasal endoscopic skull base surgery in the COVID-19 era: Recommendations for increasing the safety of the method.

Transnasal endoscopic skull base surgery (eSBS) has been adopted in recent years, in great part to replace the extended procedures required by external approaches. Though sometimes perceived as "minimally invasive", eSBS still necessitates extensive manipulations within the nose/paranasal sinuses. Furthermore, exposure of susceptible cerebral structures to light and heat emanated by the telescope should be considered to comprehensively evaluate the safety of the method. While the number of studies specifically targeting eSBS safety still remains scarce, the problem has recently expanded with the SARS-CoV-2 pandemic, which also has implications for the safety of the surgical personnel. It must be stressed that eSBS may directly expose the surgeon to potentially high volumes of virus-contaminated aerosol. Thus, the anxiety of both the patient and the surgeon must be taken into account. Consequently, safety requirements must follow the highest standards. This paper summarizes current knowledge on SARS-CoV-2 biology and the peculiarities of human immunology in respect of the host-virus relationship, taking into account the latest information concerning the SARS-CoV-2 worrisome affinity for the nervous system. Based on this information, a workflow proposal is offered for consideration. This could be useful not only for the duration of the pandemic, but also during the unpredictable timeline involving our coexistence with the virus. Recommendations include technical modifications to the operating theatre, personal protective equipment, standards of testing for SARS-CoV-2 infection, prophylactic pretreatment with interferon, anti-IL6 treatment and, last but not least, psychological support for the patient.

Cardiac Surgery is Associated with Biomarker Evidence of Neuronal Damage.

BACKGROUND: Anesthesia and surgery is commonly associated with central nervous system sequelae and cognitive symptoms, which may be caused by neuronal injury. Neuronal injury can be monitored by plasma concentrations of the neuronal biomarkers tau and neurofilament light protein (NFL). Currently, there are no studies examining whether neuronal injury varies between surgical procedures. OBJECTIVE: Our aim was to investigate if neuronal damage is more frequent after cardiac than after otolaryngeal surgery, as estimated by tau and NFL concentrations in plasma. METHODS: Blood samples were drawn before, during, and after surgery and concentrations of tau, NFL, Aß40, and Aß42 were measured in 25 patients undergoing cardiac surgery (9 off-pump and 16 on-pump) and 26 patients undergoing otolaryngeal surgery. RESULTS: Tau increased during surgery (1752%, p = 0.0001) and NFL rose seven days post-surgery (1090%, p < 0.0001) in patients undergoing cardiac surgery; even more in patients on-pump than off-pump. No changes were observed in patients undergoing otolaryngeal surgery and only minor fluctuations were observed for Aß40 and Aß42. CONCLUSION: Cardiac surgery is associated with neuronal injury, which is aggravated by extracorporeal circulation. Analyses of NFL and tau in blood may guide development of surgical procedures to minimize neuronal damage, and may also be used in longitudinal clinical studies to assess the relationship of surgery with future neurocognitive impairment or dementia.

Association of antioxidants and vitamin D level with inflammation in children with atopic dermatitis.

BACKGROUND: Changing the resources of vitamin D and antioxidant nutrients may affect the course of allergic diseases. The aim of the study was to investigate the association between CoQ10, vitamin D, retinol, and α-tocopherol serum levels and severity of atopic dermatitis (AD) in children. METHODS: Twenty-nine children with AD aged from 1 to 15 years were enrolled into the study. The severity of AD was categorized into mild or moderate (≤50 points in SCORAD - Scoring Atopic Dermatitis index) and severe (>50 SCORAD points). The control group was comprised of 22 children with negative history of allergy aged from 2 to 15. The serum measurements included vitamin D, retinol, α-tocopherol, CoQ10, C-reactive protein (CRP), complete blood count (CBC), and total immunoglobulin E (IgE). RESULTS: Low vitamin D concentration (<20 ng/ml) was observed mainly in patients with severe AD (77.8%), compared to children with mild or moderate AD (25%) or the control group (31.8%). Concentration of retinol was decreased significantly in patients with severe AD (median 1.32 µmol/l), compared to children with mild and moderate AD (median 1.66 µmol/l), but not to the control. Among inflammatory markers, only the group with severe AD demonstrated significantly elevated platelet count (PLT), red blood cell distribution width (RDW), and eosinophil count (EO). Retinol level correlated with PLT (R = -0.7; P = 0.003), white blood count (WBC) (R = -0.54; P = 0.01), total IgE (R = -0.51; P = 0.016), mean platelet volume (MPV) (R = 0.51; P = 0.02), and also with a disease severity index, SCORAD (R = -0.55; P = 0.007), whereas vitamin D level correlated only with MPV (R = 0.61; P = 0.003). No significant changes were found in tocopherol and CoQ10 levels between groups. CONCLUSIONS: Children with AD should be routinely tested for vitamin D deficiency, especially during disease exacerbation. Our results confirmed correlation of serum inflammatory markers with decreased concentration of vitamin A in children with AD. This finding, however, might be an effect of severe stage of disease and not only of inadequate intake of retinol in the diet.

Longitudinal observation of children with enhanced total serum IgE.

BACKGROUND: Long-term studies on the evolution of elevated total IgE (tIgE) concentration are in demand. OBJECTIVE: To investigate the prevalence of allergic diseases and influential factors in children with high tIgE levels during a 5-year period. METHODS: Children with high tIgE levels (>100 IU/mL) were study subjects. After the 5-year follow-up, an interview with the parents, clinical examination, and evaluation of tIgE and specific IgE (sIgE) to selected food and inhalant allergens were performed. RESULTS: The mean tIgE decreased significantly after 5 years in girls and boys regardless of the place of residence. Monosymptomatic patients accounted for most cases throughout the study, with the highest tIgE level at the beginning. After follow-up, the percentage of polysymptomatic patients increased. Their mean tIgE level was significantly higher than in the other groups. After follow-up, 11.7% of participants remained asymptomatic, and another 11.7% reported relief from symptoms. Allergy symptoms persisted in most children with normal tIgE levels. The 2-allergen sensitization was the most common through the study. Only patients sensitized to 4 allergens had unchanged levels of mean tIgE after follow-up and those with the highest mean tIgE level had a newly diagnosed sensitization to at least 1 allergen. A significant decrease of sIgE level was observed for food allergens. The values of sIgE to inhalant allergens even increased after the 5-year follow-up, despite decreased tIgE levels. CONCLUSION: In children with allergy and an elevated concentration of tIgE, the increasing or stable value of tIgE could be a useful parameter for the prediction of the development of polysymptomatic allergy.

T-regulatory cells in severe atopic dermatitis: alterations related to cytokines and other lymphocyte subpopulations.

The changes in lymphocyte subpopulations in atopic dermatitis (AD) concern also T-regulatory cells. We investigated the expression of various surface receptors on CD3(+)CD4(+)CD25(high)FoxP3(+) T-regulatory cells and the activation CD28(+) receptor and the inhibitory CD152(+) receptor on helper/inducer as well as cytotoxic/suppressor T cells. Peripheral blood lymphocytes of 15 AD patients and 20 healthy subjects were analyzed by flow cytometry using monoclonal antibodies. The concentrations of IL-6, IL-10 and TGF-ß were determined in the serum and the supernatant of ConA-stimulated CD4(+) lymphocytes. In AD patients the percentage of CD4(+)CD25(high)FoxP3(+) as well as CD3(+)CD8(+) cells increased, which positively correlated with SCORAD index (r = 0.55, p = 0.03). The concentrations of IL-10 in the CD4(+) lymphocyte culture supernatants and the concentrations of TGF-ß in the sera and the supernatant negatively correlated with the severity of AD (p < 0.01, r = -0.63; p < 0.02, r = -0.64 and p < 0.03, r = -0.58, respectively), whereas the serum concentration of IL-6 correlated positively (p < 0.003, r = 0.71). The regulatory cells expressed more CD62L and CD134 surface markers but less CD95. Reduced expression of the apoptotic CD95 receptor suggests that survival time of these cells is prolonged. Since CD62L and CD134 were upregulated, the enhanced modulatory effect of CD4(+)CD25(high)FoxP3(+) cells seemed to be suggested, which may result in increased co-expression of CD28/CD152 on both CD4(+) and CD8(+) subpopulations.

[Concentration of IL-10, IL-13 and IFN-gamma cytokines in supernatants of microcultured CD4+ and NK cells in patients with non-allergic bronchial asthma]. / Stezenie cytokin IL-10, IL-13 i IFN-gamma w nadsaczach hodowli komórek CD4+ i NK u chorych na niealergiczna astme oskrzelowa.

UNLABELLED: THE AIM OF THIS STUDY was the evaluation of T lymphocytes and NK function in patients with non-allergic asthma. MATERIAL AND METHODS: Three groups: patients with non-allergic asthma (n = 30), patients with non-allergic asthma with concomitant recurrent infections (n = 24) and group of healthy adult volunteers (n = 20) were examined. CD4+ and NK cells were isolated from peripheral blood by magnetic separation method. Cells were cultured and level of cytokine IL-10, IL-13, IFN-gamma in medium were measured. RESULTS: In patients with non-allergic asthma with recurrent infections mean value of IFN-gamma in medium from IL-15 + IL-12 stimulated NK cells was significantly lower compared with control group (p < 0.01). Mean value of IL-10 and IL-13 in medium from Con A stimulated CD4+ cells in patients with non-allergic asthma with recurrent infections were significantly higher than in control group (p < 0.05). CONCLUSIONS: Multitudes of cell and humoral factors interactions overlap dysfunction of immunological system in patients with non-allergic asthma. It causes higher susceptibility to infections factors especially viruses. Viruses give feedback for escalation of infection and worsening of clinical course of disease. Knowing mechanisms of inflammation intensification would let us specific prophylaxis use (specific antinflammatory or immunomodulatory drugs).

Heart rate turbulence in children--age and heart rate relationships.

Heart rate turbulence (HRT) is a chronotropic response of the sinus heart rhythm to ventricular premature beat (VPB). Children show decreasing heart rate together with the maturation of the autonomic nervous system. The aim of the research was to assess the relationship between HRT parameters, age, and heart rate and time domain heart rate variability (HRV) parameters in healthy children. Twenty-four-hour ECG Holter recording was performed on 398 healthy children. The mean RR interval preceding VPB, number of VPBs, and HRT parameters-turbulence onset (TO) and turbulence slope (TS)-were determined. We observed significant correlation among TS and mean RR and age. Children with prepubertal status have lower values of TS compared with those during puberty. According to given quartiles, upper for TO was > or =-0.8%, lower for TS was < or =4.56 ms/RR, 13 patients (3%) obtained abnormal both TO and TS. The correlations between HRT and HRV parameters were observed among the youngest children. Age and heart rate preceding VPB have no effect on HRT onset in children, whereas HRT slope is highly dependent on these variables. Our results support hypothesis that in older children HRT is dependent on autonomic tone and also determined by other intrinsic modulators.

CD80 and CD86 expression on LPS-stimulated monocytes and the effect of CD80 and CD86 blockade on IL-4 and IFN-gamma production in nonatopic bronchial asthma.

CD80 and CD86 seem to play an important role in the allergen-induced secretion of interleukin (IL)-5 and IL-13. Up to now, the expressions of CD80 (B7.1) and CD86 (B7.2) on monocytes and the kinetics of the expression of these molecules on lipopolysaccharide-stimulated monocytes in nonatopic asthma have not been defined. Using monoclonal antibodies, we have compared the expressions of CD80 (B7.1) and CD86 (B7.2) on the monocytes of healthy persons and nonatopic asthmatic patients. We have also assessed the effect of CD80 and CD86 inactivation on IL-4 and interferon (IFN)-gamma production in nonatopic asthmatics and healthy subjects. We found that a low expression of CD80 (1.64 +/- 0.65 vs. 3.53 +/- 1.43%) and a moderate expression of CD86 (41.25 +/- 13.4 vs. 49.46 +/- 11.49%) on the studied monocytes were characteristic for asthma. In nonatopic asthma patients inactivation of CD80 or CD86 blockade significantly reduced IFN-gamma production by T lymphocytes (p < 0.02; p < 0.03). In both the studied groups, anti-CD80 antibodies did not diminish T lymphocyte production of IL-4. However, anti-CD86 antibodies significantly (p < 0.04) reduced the IL-4 concentration in culture supernatants. Our results confirm that both the CD80 and CD86 molecules play an important role in the maintenance and amplification of the inflammatory process. It suggests that in the inflammatory process that occurs in nonatopic bronchial asthma, Th1 as well as Th2 lymphocytes are equally important.

[Blood pressure in neonates born from pregnancies complicated by diabetes]. / Cisnienie tetnicze u noworodków urodzonych z ciaz powiklanych cukrzyca.

INTRODUCTION: Diabetes is one of the most frequent metabolic disorders that may be influenced by and occur during pregnancy. Hypertension is frequently associated with a diabetes and, as well as diabetes, is considered to be one of the risk factors of the cardiovascular and the renal disease. Diabetes during a pregnancy may predispose fetus, and therefore neonate, to develop several metabolic abnormalities. Abnormalities observed after delivery are primarily due to disregulated glucose homeostasis and are considered as indices of pregnant glycemic status. MATERIALS AND METHODS: 44 neonates (28 boys and 16 girls) from pregnancies complicated by the diabetes (12 from pregnancy in course of insulin dependent diabetes mellitus diagnosed before the conception) were included into the study. During first day of life all newborns have blood pressure evaluated (Korotkoff's method; automated measurements using Vital Signs Dinamap Plus (Criticon Inc., USA)). After each blood pressure measurement the capillary blood glucose evaluation was performed (GlucoStix, Bayer GmbH, Germany). RESULTS: We found statistically significant differences between IDDM and GDM neonates in blood glucose concentration at 1/2 and 2 hours after delivery. In all measurements the mean results of systolic blood pressure were higher in IDDM than GDM group, however the difference did not reach significance level. When comparing mean arterial blood pressure significant difference was observed at 18 hour after birth. DISCUSSION AND CONCLUSIONS: We did not find significantly higher blood pressure in neonates born from IDDM complicated pregnancies (apart from mean arterial blood pressure in one measurement). Mean values of blood pressure in IDDM group were however higher than in GDM group. It may be a signal of improper tendency of the arterial blood pressure stabilization which may require additional studies.