ß-glucan in the lymph nodes in sarcoidosis and in Kveim-Siltzbach test reagent.

Background: Previous studies have demonstrated a relationship between biomass of fungi exposure in the home and the risk of sarcoidosis. ß-glucan was present in the bronchial alveolar lavage fluid (BALF) of patients with sarcoidosis. The Kveim-Siltzbach test reagent (KSTR) induces a sarcoidosis specific, granulomatous, cutaneous response and was used to establish the diagnosis. To date, the granuloma-inducing component of KSTR is still unknown. The present study was undertaken to investigate the presence of ß-glucan in the lymph nodes of patients with sarcoidosis and to determine the relationship between the amounts of this agent with disease severity and to investigate the presence of ß-glucan in KSTR. Materials and methods: Lymph node aspirations were collected by transbronchial needle aspiration (TBNA) in region R4 or 7 from patients with newly diagnosed sarcoidosis. The samples were treated to isolate ß-glucan and analyzed using a Limulus-based assay. Cultures of Propionibacterium ac. and Mycobacterium gordonae as well as samples of Kveim-Siltzbach test reagent were analyzed to determine ß-glucan content. Results: A significant relationship was observed between the amount of the ß-glucan in the lymph nodes and the extent of granuloma formation in the lung parenchyma, and the size of the lymph nodes in the mediastinum (r=0.787, p=0.0001 and r=0.664, p<0.001 respectively, Spearman's test). The samples of Kveim-Siltzbach test reagent contained high levels of ß-glucan. Cultures of Propionibacterium ac. and Mycobacterium gordonae contained ß-glucan, the levels of which were lower in the Mycobacterium cultures. Comments: The results support the hypothesis that ß-glucan, and thus fungal exposure, are involved in the pathogenesis of sarcoidosis. (Sarcoidosis Vasc Diffuse Lung Dis 2017; 34: 130-135).

Magnesium Status in Alzheimer's Disease: A Systematic Review.

The interest in poor magnesium (Mg) status as risk factor for Alzheimer's disease (AD) is increasing due to its antioxidant and neuroprotective properties. A systematic PubMed literature search of studies investigating Mg status was undertaken comparing AD to healthy controls (HCs) or patients with medical illness (medical controls [MCs]). Standardized mean differences (SMDs) ± 95% confidence intervals (CIs) were calculated for all outcomes. Of 192 potentially eligible studies, 13 were included (559 patients with AD, 381 HCs, and 126 MCs). Compared to HCs, patients with AD had significantly lower Mg in cerebrospinal fluid (2 studies; SMD = -0.35;P= .02) and in hair (2 studies; SMD = -0.75;P= .0001). No differences between AD and controls were evident for serum Mg. In conclusion, AD seems to be associated with a lower Mg status when compared to HCs, while the scarcity of studies limited the findings about MCs.

Pre-eclampsia during pregnancy and cardiovascular disease later in life: the case for a risk group.

INTRODUCTION: Women with pre-eclampsia (PE) have an increased risk of cardiovascular disease (CVD) later in life. This association might reflect an effect of pre-eclampsia on mechanisms inducing a higher risk of CVD or the presence of a group at risk. MATERIALS AND METHODS: The possibility that women with a magnesium deficiency might constitute a risk group was examined using published evidence form investigations on PE and CVD. RESULTS: Available data strongly suggest that a magnesium deficiency is a major risk factor for both PE and for CVD disease later in life. CONCLUSIONS: Magnesium homeostasis studies in women with PE should be undertaken for validation purposes. The results suggest that women with PE should be given dietary counselling to decrease future risks of CVD.

Diastolic blood pressure increase is a risk indicator for pre-eclampsia.

OBJECTIVES: A previous study demonstrated that the increase in diastolic blood pressure during pregnancy was reduced by supplementation with magnesium. The present study was undertaken to explore if increases in diastolic blood pressure could be useful for early identification of pre-eclampsia. STUDY DESIGN: Hospital records of nulliparous, singleton normal pregnancies (n = 100) and those diagnosed with pre-eclampsia (n = 109) were obtained from a register at an antenatal health care unit. Data on blood pressure at the regular visits to the unit were collected and analysed. RESULTS: The systolic and diastolic blood pressures were significantly higher at pregnancy week 12 among those who developed pre-eclampsia (p = 0.046 and 0.001, resp). An increase in diastolic blood pressure ≥15 mmHg occurred more frequently among women with pre-eclampsia. In 93 % of the cases, this increase was present before and at the same time as the clinical diagnosis of pre-eclampsia was established. CONCLUSION: The results suggest that a base-line diastolic blood pressure of ≥80 mmHg and an increase in diastolic blood pressure of ≥15 mmHg could be used to identify women at risk of pre-eclampsia (sensitivity 92 %, specificity 44 %) and as a selection criterion in treatment or prevention assays.

Sarcoidosis treatment with antifungal medication: a follow-up.

INTRODUCTION: The aim of the study was to compare treatment of sarcoidosis with antifungal or corticosteroid medication. METHODS: In patients with sarcoidosis antifungal medication (n = 29), corticosteroids (n = 21) or a combination (n = 27) was given. Nine patients allotted to antifungal medication were later given corticosteroids because of the lack of regression of the disease. X-ray scores for the severity of granuloma infiltration were determined. Chitotriosidase and angiotensin converting enzyme were determined. The time in months till remission was observed as well as the number of recurrences.

Fungal exposure and low levels of IL-10 in patients with sarcoidosis.

BACKGROUND AND OBJECTIVES: Sarcoidosis is an inflammatory disease with increased levels of inflammatory cytokines. Previous studies have shown a relation between the degree of granuloma infiltration and serum cytokine levels, except for interleukin- (IL-) 10. The aim of the study was to further investigate the serum levels of IL-10 in patients with sarcoidosis and relate them to fungal exposure in terms of the amount of fungi in the air of their homes and ß-glucan in bronchoalveolar lavage (BAL) fluid. METHODS: Patients with sarcoidosis (n = 71) and healthy controls (n = 27) were enrolled. IL-10 was determined in serum. BAL was performed and the amount of ß-glucan was measured. Domestic exposure to fungi was determined by measuring airborne ß-N-acetylhexosaminidase (NAHA) in the bedrooms. RESULTS: At high levels of fungal exposure (domestic fungal exposure and ß-glucan in BAL), serum IL-10 values were lower than at low and intermediate exposure levels. CONCLUSION: The low serum IL-10 values at high fungal exposure suggest that fungal cell wall agents play a role in granuloma formation in sarcoidosis by inhibiting the secretion of the anti-inflammatory cytokine IL-10.

Magnesium in drinking water - a case for prevention?

Studies in many countries have demonstrated a relationship between drinking water mineral content and the risk of death in cardiovascular disease (CVD). Particularly strong relationships have been found for magnesium and it has been suggested that magnesium be added to drinking water. The aim of this article is to evaluate the validity of this suggestion by reviewing information on possible causative agents. Major epidemiological studies on the drinking water content of calcium, magnesium, and hardness were analysed regarding exposure specificity, confounding factors, dose-response relationships and biological plausibility. Intervention experiments were analysed. The risk of death in CVD was related to the content of Ca, Mg and HCO(3-). The data demonstrate that Ca and Mg need to be considered together, and that HCO(3-) could play a role by intervening with the body acid load. There is no evidence to justify the addition of magnesium only to drinking water for preventive purposes. The data suggest that Ca and Mg could be administered together but no data are available regarding the relative proportions for an optimal effect.

Blood pressure in pregnancy and magnesium sensitive genes.

OBJECTIVES: High blood pressure during the last part of pregnancy is a risk indicator of pre-eclampsia and eclampsia which augment infant and maternal morbidity and mortality. Magnesium deficiency has been related to the risk of hypertension. A study was performed to assess the relation between pregnancy induced hypertension, excretion of urinary magnesium and expression of magnesium sensitive genes (MgSG). METHODS: A cohort of healthy, nulliparous women with singleton pregnancies was recruited. Blood pressure was recorded throughout pregnancy. Urinary magnesium excretion and expression of MgSGs in leukocytes were determined. RESULTS: The expression of the gene TRPM6 was higher among pregnant women compared to non-pregnant controls at week 12. All other genes had lower expressions in pregnant women. At week 37 the expressions of all genes were lower than at week 12. The expressions of SLC41A1, SLC41A3, and TRPM7 were related to the systolic and diastolic blood pressures. Furthermore, the expression of TRPM6 was related to the urinary excretion of magnesium and the change in diastolic blood pressure weeks 12-37 was inversely related to the change in magnesium excretion. CONCLUSIONS: Systolic and diastolic blood pressure and the excretion of magnesium during pregnancy were related to the expression of different MgSGs. The results suggest that magnesium is involved in the regulation of blood pressure during pregnancy.

Magnesium in pregnancy blood pressure and pre-eclampsia - A review.

Magnesium is an important cation present in more than 300 enzymes in the body. This review evaluates the information on magnesium and pregnancy. In normal pregnancies Mg responsive genes are upregulated, suggesting Mg deficiency. Blood pressure increase is related to the urinary excretion of Mg. In pregnancies complicated by preeclampsia the Mg homeostasis is different from normal pregnancies. Supplementation with Mg has shown beneficial effects on high blood pressure and infant conditions in some studies. Although several studies show important relationships between Mg homeostasis and pregnancy, particularly those with pre-eclampsia, further studies are needed to assess the relationship and formulate requirements for intervention programmes.

Inflammatory markers and pulmonary granuloma infiltration in sarcoidosis.

BACKGROUND AND OBJECTIVE: Previous studies have demonstrated increases of inflammatory mediators in sarcoidosis while epidemiological studies have also demonstrated an association with increased fungi exposure. This study measured the level of ß-glucan in the lungs and of inflammatory mediators in serum, and correlated both with the extent of pulmonary granuloma infiltration. METHODS: This is a cross-sectional study of 98 patients with sarcoidosis and 26 controls. ß-glucan, a cell wall constituent of fungi, was measured in bronchoalveolar lavage. Inflammatory mediator levels were determined in serum. The extent of granuloma infiltration was estimated on the chest X-ray. Exposure to fungi at home was determined by taking air samples in bedrooms and analysing for the presence of ß-N-acetylhexosaminidase. RESULTS: Significantly, higher levels of ß-glucan were found in broncho-alveolar lavage in subjects with sarcoidosis as compared with controls. There were significant positive relationships between the extent of granuloma infiltration and the levels of the different inflammatory mediators, except for interleukin-10. Domestic fungal exposure was higher among subjects with sarcoidosis. CONCLUSIONS: This is the first time that a specific agent, previously suspected to be related to the risk of sarcoidosis, has been detected in the lung of subjects with sarcoidosis and related to the levels of inflammatory mediators and the degree of home exposure to fungi. The results suggest that exposure to fungi should be explored when investigating patients with sarcoidosis.

Magnesium supplementation to prevent high blood pressure in pregnancy: a randomised placebo control trial.

PURPOSE: To assess if hypertension during the last part of pregnancy could be prevented by magnesium supplementation. METHODS: Pregnant primagravida women from a local antenatal care unit were given an oral supply of 300 mg magnesium as citrate or placebo from pregnancy week 25 in a randomised double-blind setup. Blood pressure was recorded during pregnancy as well as pregnancy outcome. RESULTS: In the magnesium-supplemented group, the average diastolic blood pressure at week 37 was significantly lower than in the placebo group (72/1.4 mean/SEM vs 77/1.4, p = 0.031). The number of women with an increase in diastolic blood pressure of ≥15 mmHg was significantly lower in the magnesium group compared with the women who received placebo (p = 0.011). There was an inverse relation between the urinary excretion of magnesium during pregnancy and the diastolic blood pressure (p = 0.005). CONCLUSIONS: Magnesium supplementation prevented an increase in diastolic blood pressure during the last weeks of pregnancy. The relation between diastolic blood pressure and urinary excretion of magnesium suggests that magnesium is involved in the regulation of blood pressure and that the increase in diastolic blood pressure in pregnancy could be due to a lack of magnesium.

Antifungal medication is efficient in the treatment of sarcoidosis.

OBJECTIVES: Fungi have been suspected of contributing to the pathogenesis of sarcoidosis. A previous intervention study demonstrated an improvement in the clinical condition in 15 out of 18 patients with a long-term history of sarcoidosis when antifungal medication was added to corticosteroids. The present study was performed to compare the effects of antifungal treatment with corticosteroid treatment in sarcoidosis. METHODS: Patients with newly diagnosed sarcoidosis were recruited. Corticosteroids were given to 39 subjects, corticosteroid + antifungal to 31, and antifungal only to 22 subjects. The effects of the treatments were evaluated at 6 months. X-ray scores were measured before and after treatment together with pulmonary diffusion capacity and two markers of sarcoidosis activity, that is, angiotensin-converting enzyme in serum (sACE) and chitotriosidase (CTO). RESULTS: X-ray scores as well as sACE and CTO decreased significantly in all groups. The X-ray score decreased slightly more among subjects in the groups that received antifungal medication compared with corticosteroids only (p < 0.001). CONCLUSION: The results suggest that antifungal treatment is as efficient as corticosteroid treatment against the granulomatous and inflammatory manifestations of sarcoidosis. This is probably because this treatment is directed towards the causative agent. Additional studies are required to define the phenotype, where the antifungal treatment was not efficient (4/22) and to perform long-term follow up to determine the risk of recurrence.

Fungal cell wall agents suppress the innate inflammatory cytokine responses of human peripheral blood mononuclear cells challenged with lipopolysaccharide in vitro.

Exposure to high levels of fungi might lead to diseases, such as airway inflammation, hypersensitivity pneumonitis and allergy. To comprehend the mechanisms behind the exposure to fungi and a disease, we examined the in vitro innate inflammatory cytokine response of human peripheral blood mononuclear cells (PBMC) challenged by fungal cell wall agents (FCWAs), i.e., soluble and particulate (1→3)-ß-D-glucan-curdlan (BGS and BGP), zymosan (ZYM) and chitosan (CHT) in the absence or presence of lipopolysaccharide (LPS). We also studied FCWA effects on the mRNA expression of dectin-1, TLR2, TLR4 and mannose receptor (MR) by real-time RT-PCR. Our results demonstrated that BGP strongly induced the secretion of TNF-α, IL-6, IL-10 and IL-12; BGS, ZYM and CHT were weaker, but still significant cytokine inducers. We showed that BGS significantly augmented the LPS-induced in vitro secretion of TNF-α. On the other hand, BGP, ZYM and CHT suppressed the LPS-induced production of all cytokines. At the mRNA level, the dectin-1, TLR2 and TLR4 expressions were significantly reduced by all FCWAs in the absence of LPS and even more in the presence of LPS. While we demonstrated that the innate inflammatory cytokine response of PBMC induced by CHT was mediated by MR, the MR mRNA expression was significantly reduced by CHT. On the contrary, BGS significantly enhanced the MR mRNA expression. In conclusion, a long-term and massive exposure to LPS and FCWA (e.g., organic dust) may cause an important disruption of normal immune response and allow development and/or persistence of various immunopathological events.

Fungal exposure in homes of patients with sarcoidosis - an environmental exposure study.

BACKGROUND: There is increasing evidence that exposure to moulds (fungi) may influence the development of sarcoidosis. To assess the influence of the environmental exposure, a study was undertaken to determine the exposure to fungi in homes of subjects with sarcoidosis. METHODS: Subjects were patients with clinically established sarcoidosis recruited during the period September 2007 till June 2010. Of these 55 were newly diagnosed and currently under treatment for less than one year, 25 had been treated and had no recurrence and 27 had been treated but had recurrence of the disease. Controls were healthy subjects without any respiratory symptoms (n = 30). Samples of air (about 2.5 m3) were taken in the bedroom of the subjects using a portable pump and cellulose ester filters. The filters were analysed for the content of the enzyme N-acetylhexosaminidase (NAHA) as a marker of fungal cell biomass, using a specific substrate and a fluorescent technique and expressed as NAHA units (U)/m3. RESULTS: Compared to controls, subjects undergoing treatment of the disease (newly diagnosed or with recurrence) had significantly higher activities of NAHA in their homes than controls (33.6 and 39.9 vs 10.0 U/m3, p < 0.001 and <0.001). Among controls only 5 out of 30 subjects had levels of NAHA above the second quartile value (14 U/m3). In homes of subjects with newly diagnosed disease with treatment less than one year, values above 14 NAHA U/m3 were found among 35 out of 55 and among those with recurrent disease among 18 out of 27. CONCLUSIONS: The higher activities of NAHA enzyme found in homes of subjects with active and recurrent sarcoidosis suggest that exposure to fungi is related to the risk of sarcoidosis. Further environmental studies to assess the importance of this exposure for subjects with sarcoidosis are warranted. The results suggest that remedial actions in homes with high levels of fungi may be justified.

Urinary calcium and magnesium excretion relates to increase in blood pressure during pregnancy.

OBJECTIVE: Pregnancy-induced hypertension and preeclampsia are serious clinical manifestations during late pregnancy and the cause for increased maternal and foetal morbidity and mortality. The pathogenesis is unknown but experience from treatment schemes suggests that minerals may be of importance. Mineral homeostasis is influenced by acid-base conditions. The aim of the study was to elucidate the relation between acid-base balance, urinary mineral excretion and blood pressure during pregnancy. DESIGN: A prospective observational study of a general population. MATERIALS AND METHODS: The study was performed at the Midwife Health Center in Borås, Sweden, where practically all pregnant subjects in the catchment area are registered. First time pregnant subjects (n = 123) were voluntarily recruited without exclusion criteria. A 24 h urine sample was collected at pregnancy week 12 and analyzed for creatinine, calcium, magnesium, and urea as a proxy for acid conditions. Blood pressure was recorded every 2-3 weeks until delivery. RESULTS: There was a relation between the excretion of urea and calcium and magnesium at week 12. A blood pressure increase was found after pregnancy week 30 but only among subjects who had a high excretion of calcium and magnesium at week 12. CONCLUSIONS: If an increase in blood pressure during the later part of pregnancy a risk indicator for preeclampsia, the results suggest that an excessive secretion of calcium leading to a functional deficit might be a risk indicator for gestational hypertension and preeclampsia. Intervention experiments are required to assess this hypothesis.

Maternal exposures and risk of spontaneous abortion before and after a community oriented health education campaign.

BACKGROUND: In a district of Veneto (North-east Italy) where numerous females of childbearing age were occupationally exposed to organic solvents in nearly 400 shoe factories, a case-control study found significant associations between maternal exposures (from occupation and risky behavior) and spontaneous abortion (SAB). Thereafter, a health education campaign was undertaken to increase awareness of risk factors for pregnancy in the population. To evaluate the effects of this campaign maternal exposures and SAB risks were compared before and after the campaign. METHODS: Hospital records were collected from a local hospital for SAB cases and age- residence-matched controls with normal deliveries. Information on solvent exposure, coffee and alcohol consumption, smoking and the use of medication was collected using a questionnaire. Before and after differences were tested through a modified Chi-square test and linear and logistic regressions for survey data. Odds ratios (ORs) with 95% confidence interval (CI) were estimated using logistic regression models. RESULTS: The consumption of coffee (P = 0.003) and alcohol (P < 0.001) was lower after than before the campaign, controlling for age at pregnancy and level of education. There were no differences in reported solvent exposure or smoking (smokers were few). The previously detected increased risks of SAB in relation to solvent exposure and coffee consumption were no longer present. CONCLUSION: The results suggest that health education campaigns might reduce harmful maternal exposures and the risk of SAB.