Elevated concentrations of TNF-alpha are related to low serum magnesium levels in obese subjects.

The aim of this study was to determine the relationship between serum magnesium and TNF-alpha levels in obese subjects. A cross-sectional population based study that included 192 non-diabetic, non-hypertensive subjects allocated in three categories of body mass index (BMI) <25; > or =25 to <30 kg/m2; and > or =30 kg/m2. Elevation of TNF-alpha levels was defined by serum levels > or =3.5 pg/mL, and low serum magnesium by levels < or = 0.74 mmol/L. Multivariate odds ratios (OR) adjusted by age, HOMA-IR index, and glucose tolerance status are presented. Obese subjects exhibited higher serum concentration of TNF-alpha (p = 0.002) and lower serum magnesium levels (p < 0.0001) than lean and overweight subjects. Ninety-one (47.4%) subjects showed elevated levels of TNF-alpha, of them 7 (10.9%), 31 (48.4%), and 43 (67.2%) in the groups with BMI <25, > or = 25 to < 0, and > or =0 kg/m2, respectively. Multivariate OR between low serum magnesium and TNF-alpha levels in obese subjects was of 1.8, Cl95% 1.2-9.1, P = 0.001, whereas in the lean and overweight individuals of 1.1, Cl95% 0.7-8.7, P = 0.12, and 1.3, Cl95% 0.9-10.8, P = 0.09, respectively. These data shows that low serum magnesium levels and elevated TNF-alpha are related in the obese subjects. It will be necessary to conduct more studies in order to add new data on this issue.     

Susceptibilities of plasma antioxidants and erythrocyte constituents to low levels of ozone

To evaluate the susceptibilities of human blood constituents to the low levels of ozone used in ozonated autohemotherapy (40 microgO3/ml), we quantified plasma antioxidants and erythrocyte constituents after rapid mixing of human whole blood with ozone at 20, 40, 60, and 100 microg/ml blood. Ascorbic acid, uric acid, and alpha-tocopherol in plasma decreased as ozone increased, but bilirubin was unaffected. The content of thiobarbituric acid-reactive substances in plasma was increased by ozone. However, the content of thiobarbituric acid-reactive substances and alpha-tocopherol in the erythrocyte membrane was not significantly affected. No significant changes occurred in the content of methemoglobin, cytoskeleton proteins or erythrocyte enzymes such as Na+/K+-ATPase, acetylcholinesterase, catalase, glutathione peroxidase, glutathione reductase, and superoxide dismutase at all the ozone levels tested. A decrease in reduced glutathione in erythrocytes was the only significant change caused by the ozone level used for autohemotherapy. It may be one of the chemical events responsible for the beneficial effects of ozonated autohemotherapy.     

Clinical significance of low cytomegalovirus DNA levels in human plasma

The clinical significance of the detection of low copy numbers of cytomegalovirus (CMV) DNA in immune-suppressed patients remains unclear. In this study, we compared the artus CMV Rotor-Gene PCR, utilizing an automated nucleic acid extraction and assay setup (the artus CMV protocol), with the COBAS Amplicor CMV Monitor test (our reference protocol). We then analyzed the results of all CMV PCR tests ordered following the implementation of the artus CMV protocol at our institution and followed 91 adult patients with positive test results. The artus CMV protocol had a linear range extending from 2.0 to 7.0 log(10) copies/ml and had a lower limit of 95% detection of 57 copies/ml. With archived plasma samples, this protocol demonstrated 100% sensitivity and 94% specificity for the detection of CMV DNA. Following implementation of the artus CMV protocol, 320 of 1,403 (22.8%) plasma samples tested positive (compared with 323/3,579 [9.0%] samples in the preceding 6 months), and 227 (16.2%) samples had copy numbers of <400/ml. Ninety-one adult patients had at least one positive test. The data were analyzed using a threshold of 200 copies/ml, and in 22 episodes, the viral load increased from <200 copies/ml to ≥ 200 copies/ml on sequential tests. In 21 of these 22 episodes, either the viral load continued to increase or antiviral treatment was initiated in response to the repeat value. In summary, we evaluate the performance characteristics of a protocol utilizing the artus CMV PCR and identify clinically meaningful changes in CMV DNA copy numbers even when they are initially detected at a low level.     

Tocopherols and tocotrienols plasma levels are associated with cognitive impairment

Vitamin E includes 8 natural compounds (4 tocopherols, 4 tocotrienols) with potential neuroprotective activity. α-Tocopherol has mainly been investigated in relation to cognitive impairment. We examined the relation of all plasma vitamin E forms and markers of vitamin E damage (α-tocopherylquinone, 5-nitro-γ-tocopherol) to mild cognitive impairment (MCI) and Alzheimer's disease (AD). Within the AddNeuroMed-Project, plasma tocopherols, tocotrienols, α-tocopherylquinone, and 5-nitro-γ-tocopherol were assessed in 168 AD cases, 166 MCI, and 187 cognitively normal (CN) people. Compared with cognitively normal subjects, AD and MCI had lower levels of total tocopherols, total tocotrienols, and total vitamin E. In multivariable-polytomous-logistic regression analysis, both MCI and AD cases had 85% lower odds to be in the highest tertile of total tocopherols and total vitamin E, and they were, respectively, 92% and 94% less likely to be in the highest tertile of total tocotrienols than the lowest tertile. Further, both disorders were associated with increased vitamin E damage. Low plasma tocopherols and tocotrienols levels are associated with increased odds of MCI and AD.     

Mucosal plasma cells are required to protect the upper airway and brain from infection

1. Download : Download high-res image (312KB)
2. Download : Download full-size image

     

The haematology ofTrypanosoma congolense infection in cattle II. Macrophage structure and function in the bone marrow of Boran cattle

Macrophages (Mø) in smears and sections of sternal bone marrow (BM) derived by weekly sequential biopsies from five adult Boran cattle re-challenged withTrypanosoma congolense were studied by light and transmission electron microscopy (TEM). Cells of the mononuclear phagocyte system including monoblasts, promonocytes, monocytes and Mø increased several-fold in the sinusoids and haemopoietic compartment (HC) of the BM during infection. Mø activation occurred with significant increases (p<0.001) in Mø size and numbers of organelles including mitochondria, lysosomes and rough endoplasmic reticulum. Light microscopic examination of the BM smears showed that 25.8% of 1200 Mø examined phagocytosed many non-mitotic haemopoietic cells of the erythroid and granulocytic series as well as mature erythrocytes and thrombocytes but seldom lymphocytes from day 29 postinfection (dpi), when the first peak of parasitaemia occurred, until and termination of the experiment on 98 dpi. Some of the Mø with phagocytosed cells (10.4%) had cells from more than one lineage. TEM confirmed cytophagia and showed that the process begins with cell to Mø attraction characterised by development of microvilli at the surface of contact by the target cell and of envoloping pseudopodia by the Mø. This was followed by target cell to Mø adhesion and finally phagocytosis. The cells being phagocytosed and those freshly engulfed appeared morphologically normal. TEM showed that the activated Mø in the BM Many Mø were heavily laden with haemosiderin in the chronic phase of the infection (78 and 98 dpi). TEM showed that the activated Mø in the BM developed extensive contacts through reciprocal blunt microvilli with the haemopoietic cells. Macrophages were absent from the sinusoids of the BM prior to infection but became numerous during infection, and were adhered to sinusoidal endothelial cells by reciprocal blunt microvilli. These Mø phagocytosed blood cells (erythrocytes, neutrophils, thrombocytes), and free trypanosomes which, though present in the arterioles of the BM, were never seen in the sinusoids and HC of the BM. This study indicates that the Mø plays very vital roles in regulating and executing the events in the BM duringT. congolense infection of cattle.     

The haematology ofTrypanosoma congolense infection in cattle I. Sequential cytomorphological changes in the blood and bone marrow of Boran cattle

Five adult Boran cattle (Bos indicus), infected with a clone ofTrypanosoma congolense IL13-E3 three years earlier and treated, were re-challenged with the same clone. Changes in the peripheral blood were monitored twice weekly, and events in the bone marrow (BM) were assessed by weekly biopsies of the sternal BM, until day 98 postinfection (dpi) when the three surviving animals were treated with diminazene aceturate. One animal died on 57 dpi whereas another was treated on 63 dpi when the packed cell volume was 15%. The infected animals developed anaemia, leucopenia and thrombocytopenia during the first peak of parasitaemia which persisted until the experiment was terminated. Three phases of BM response were demonstrated on light microscopic examination of BM smears. The first, the preparasitaemic phase represented by samples taken on 15 dpi, was an immunological response with slight but significant increases in lymphoblasts, lymphocytes, plasma cells and macrophages (Mø) whereas erythroid and granulocytic cells were unchanged. The second, the early parasitaemic or acute phase (21–57 dpi) associated with the development of anaemia, leucopenia and thrombocytopenia, was characterised by intensification of the immunological response, and an early but transient granulocytic hyperplasia. The third, the late parasitaemic or chronic phase (63–98 dpi) associated with persisting pancytopenia, was characterised by erythroid, megakaryocytic and Mø hyperplasia, dyserythropoiesis, granulocyte hypoplasia and return of lymphoid cell counts to preinfection numbers. Transmission electron microscopy confirmed these findings and showed that intact trypanosomes were not observed in the sinusoids and haemopoiesic compartment of the BM. This study demonstrates thatT. congolense infection the various blood cell lineages depending on the stage of infection. This suggests a fine control mechanism, presumably cytokine-mediated. Erythropoiesis, thrombopoiesis and monocytopoiesis were generally upregulated, whereas granulopoiesis was downregulated. However, haemopoiesis was generally ineffective as numbers of circulating blood cells remained below preinfection levels throughout the period of the study.     

Human immunodeficiency virus infection and levels of Dehydroepiandrosterone sulfate in plasma among Indians

The shift in cytokine profile during human immunodeficiency virus (HIV) disease progression is influenced by dehydroepiandrosterone sulfate (DHEAS) level. Radioimmunoassay was used to measure plasma DHEAS for 30 treatment-na?ve HIV-infected and 30 uninfected individuals. There was a significant negative correlation of viral load with DHEAS level (P<0.05). Further studies of the use of DHEAS levels for monitoring HIV patients economically are warranted.     

The poor prognostic value of low to moderate levels of sperm surface-bound antibodies.

The clinical significance of antisperm antibodies for fertility remains controversial. In this study, we determined whether the presence, isotype, region and/or amount of sperm-bound antibody was of any predictive value for future fertility in 534 men using Cox's proportional hazards model. Significant correlations between the presence of antibodies and semen parameters were recorded, such as sperm mucus penetration and sperm motility. However, low (less than 10%) negative binding and moderate (less than 50%) binding had no significant effect on the probability of conception or the time to conception. This study confirms in-vitro data suggesting that sperm function is not impaired unless the degree of antibody binding to spermatozoa is very high.     

Relationship between plasma corticosterone levels and levels of aggressiveness in mice.

The relationship between individual differences in circulating levels of corticosterone and individual differences in aggressiveness was studied in mice. Resting (baseline) levels of plasma corticosterone were inversely correlated with several measures of aggressiveness. On the other hand, no correlations were found between aggressiveness displayed in an encounter and the plasma corticosterone responses to that encounter. These findings are consistent with data from studies using experimental manipulations of hormonal states, such as glandular removal and hormone replacement therapy, and suggest that baseline levels of pituitary-adrenal activity are important in the determination of individual differences in aggressiveness.     

Germline rare variants of lectin pathway genes predispose to asymptomatic SARS-CoV-2 infection in elderly individuals

PurposeEmerging evidence suggest that infection-dependent hyperactivation of complement system (CS) may worsen COVID-19 outcome. We investigated the role of predicted high impact rare variants — referred as qualifying variants (QVs) — of CS genes in predisposing asymptomatic COVID-19 in elderly individuals, known to be more susceptible to severe disease.MethodsExploiting exome sequencing data and 56 CS genes, we performed a gene-based collapsing test between 164 asymptomatic subjects (aged ≥60 years) and 56,885 European individuals from the Genome Aggregation Database. We replicated this test comparing the same asymptomatic individuals with 147 hospitalized patients with COVID-19.ResultsWe found an enrichment of QVs in 3 genes (MASP1, COLEC11, and COLEC10), which belong to the lectin pathway, in the asymptomatic cohort. Analyses of complement activity in serum showed decreased activity of lectin pathway in asymptomatic individuals with QVs. Finally, we found allelic variants associated with asymptomatic COVID-19 phenotype and with a decreased expression of MASP1, COLEC11, and COLEC10 in lung tissue.ConclusionThis study suggests that genetic rare variants can protect from severe COVID-19 by mitigating the activity of lectin pathway and prothrombin. The genetic data obtained through ES of 786 asymptomatic and 147 hospitalized individuals are publicly available at http://espocovid.ceinge.unina.it/     

The haematology ofTrypanosoma congolense infection in cattle II. Macrophage structure and function in the bone marrow of Boran cattle

Macrophages (Mø) in smears and sections of sternal bone marrow (BM) derived by weekly sequential biopsies from five adult Boran cattle re-challenged withTrypanosoma congolense were studied by light and transmission electron microscopy (TEM). Cells of the mononuclear phagocyte system including monoblasts, promonocytes, monocytes and Mø increased several-fold in the sinusoids and haemopoietic compartment (HC) of the BM during infection. Mø activation occurred with significant increases (p<0.001) in Mø size and numbers of organelles including mitochondria, lysosomes and rough endoplasmic reticulum.Light microscopic examination of the BM smears showed that 25.8% of 1200 Mø examined phagocytosed many non-mitotic haemopoietic cells of the erythroid and granulocytic series as well as mature erythrocytes and thrombocytes but seldom lymphocytes from day 29 postinfection (dpi), when the first peak of parasitaemia occurred, until and termination of the experiment on 98 dpi. Some of the Mø with phagocytosed cells (10.4%) had cells from more than one lineage. TEM confirmed cytophagia and showed that the process begins with cell to Mø attraction characterised by development of microvilli at the surface of contact by the target cell and of envoloping pseudopodia by the Mø. This was followed by target cell to Mø adhesion and finally phagocytosis. The cells being phagocytosed and those freshly engulfed appeared morphologically normal.TEM showed that the activated Mø in the BM Many Mø were heavily laden with haemosiderin in the chronic phase of the infection (78 and 98 dpi).TEM showed that the activated Mø in the BM developed extensive contacts through reciprocal blunt microvilli with the haemopoietic cells. Macrophages were absent from the sinusoids of the BM prior to infection but became numerous during infection, and were adhered to sinusoidal endothelial cells by reciprocal blunt microvilli. These Mø phagocytosed blood cells (erythrocytes, neutrophils, thrombocytes), and free trypanosomes which, though present in the arterioles of the BM, were never seen in the sinusoids and HC of the BM. This study indicates that the Mø plays very vital roles in regulating and executing the events in the BM duringT. congolense infection of cattle.     

IgG and IgA antibody levels to cow's milk are low at age 10 years in children born preterm

BACKGROUND: Both innate and specific defenses of the preterm infant are even less developed than those of term infants, and the immune systems of preterm infants might be skewed differently at birth. Their immune responses to food antigens started early in life might therefore differ from those of term infants. OBJECTIVE: We sought to compare antibody levels to cow's milk, ovalbumin, and gliadin at age 10 years in children who had been born either preterm or at term. METHODS: IgG and IgA isotype antibodies to whole cow's milk, beta-lactoglobulin, alpha-casein, and ovalbumin, as well as IgG antibody levels to gliadin and to tetanus and diphtheria toxoids, were measured for a group of 62 children born preterm and 61 control subjects born at term. These children were studied at the same time for atopy. RESULTS: Children born preterm had markedly lower levels of antibodies to cow's milk and to its protein fractions (P <.0001 for IgA and IgG antibodies to cow's milk and alpha-casein and IgG beta-lactoglobulin antibodies). IgG gliadin antibodies were also significantly lower in the preterm group (P =.03), although the difference was not significant for IgG ovalbumin antibodies. In the preterm group both those born before gestational week 30 and those given cow's milk-based formula early (before day 50) had the lowest levels of cow's milk antibodies. In the preterm group atopy was associated with low levels of IgG cow's milk antibodies but with high levels of IgG ovalbumin antibodies. CONCLUSIONS: Early introduction of food antigens into the immature gastrointestinal tract of preterm infants might result in tolerance. The presence of less atopy in these children might also be a result of tolerance development.     

Changes in BiP (GRP78) levels upon HSV-1 infection are strain dependent.

BiP (grp78) is a chaperone protein which can also regulate the unfolded protein response of the cell. Levels of BiP increased in cells infected by the small plaque producing, cell associated, neuroinvasive strains of HSV-1 (SP7, 490) but decreased in cells infected with KOS, a large plaque, attenuated strain. BiP protein synthesis continued early in infection and BiP was sequestered and its degradation was limited during SP7 infection. BiP protein synthesis stopped and the protein was degraded in KOS infected cells. These viral strain dependent differences in BiP concentration may influence other aspects of the viral interaction with the target cell and its host.