Relationship of Circulating Soluble Urokinase Plasminogen Activator Receptor (suPAR) Levels to Disease Control in Asthma and Asthmatic Pregnancy

Asthma has a high burden of morbidity if not controlled and may frequently complicate pregnancy, posing a risk for pregnancy outcomes. Elevated plasma level of the inflammatory biomarker soluble urokinase plasminogen activator receptor (suPAR) is related to a worse prognosis in many conditions such as infectious, autoimmune, or pregnancy-related diseases; however the value of suPAR in asthma and asthmatic pregnancy is unknown. The present study aimed to investigate the suPAR, CRP and IL-6 levels in asthma (asthmatic non-pregnant, ANP; N = 38; female N = 27) and asthmatic pregnancy (AP; N = 15), compared to healthy non-pregnant controls (HNP; N = 29; female N = 19) and to healthy pregnant women (HP; N = 58). The relationship between suPAR levels and asthma control was also evaluated. The diagnostic efficacy of suPAR in asthma control was analyzed using ROC analysis. IL-6 and CRP levels were comparable in all study groups. Circulating suPAR levels were lower in HP and AP than in HNP and ANP subjects, respectively (2.01 [1.81–2.38] and 2.39 [2.07–2.69] vs. 2.60 [1.82–3.49] and 2.84 [2.33–3.72] ng/mL, respectively, p = 0.0001). suPAR and airway resistance correlated in ANP (r = 0.47, p = 0.004). ROC analysis of suPAR values in ANP patients with PEF above and below 80% yielded an AUC of 0.75 (95% CI: 0.57–0.92, p = 0.023) and with ACT total score above and below 20 an AUC of 0.80 (95% CI: 0.64–0.95, p = 0.006). The cut-off value of suPAR to discriminate between controlled and not controlled AP and ANP was 4.04 ng/mL. In conclusion, suPAR may help the objective assessment of asthma control, since it correlates with airway resistance and has good sensitivity in the detection of impaired asthma control. Decrease in circulating suPAR levels detected both in healthy and asthmatic pregnant women presumably represents pregnancy induced immune tolerance.     

CD44 Binding to Hyaluronic Acid Is Redox Regulated by a Labile Disulfide Bond in the Hyaluronic Acid Binding Site

CD44 is the primary leukocyte cell surface receptor for hyaluronic acid (HA), a component of the extracellular matrix. Enzymatic post translational cleavage of labile disulfide bonds is a mechanism by which proteins are structurally regulated by imparting an allosteric change and altering activity. We have identified one such disulfide bond in CD44 formed by Cys77 and Cys97 that stabilises the HA binding groove. This bond is labile on the surface of leukocytes treated with chemical and enzymatic reducing agents. Analysis of CD44 crystal structures reveal the disulfide bond to be solvent accessible and in the–LH hook configuration characteristic of labile disulfide bonds. Kinetic trapping and binding experiments on CD44-Fc chimeric proteins show the bond is preferentially reduced over the other disulfide bonds in CD44 and reduction inhibits the CD44-HA interaction. Furthermore cells transfected with CD44 no longer adhere to HA coated surfaces after pre-treatment with reducing agents. The implications of CD44 redox regulation are discussed in the context of immune function, disease and therapeutic strategies.     

透明质酸的制备及应用研究进展

透明质酸(hyaluronic acid,HA)是一种高分子量的直链酸性粘多糖。由于其具有特殊的生理作用、独特的流变学性质和极强的持水保湿能力,在化妆品工业、医学研究、临床治疗等领域有着广泛的应用。概述了透明质酸的制备及其在化妆品、保健食品和医药方面的应用研究进展。     

Airway Microbiota in Severe Asthma and Relationship to Asthma Severity and Phenotypes

BackgroundThe lower airways harbor a community of bacterial species which is altered in asthma.ObjectivesWe examined whether the lower airway microbiota were related to measures of asthma severity.MethodsWe prospectively recruited 26 severe asthma, 18 non-severe asthma and 12 healthy subjects. DNA was extracted from induced sputum and PCR amplification of the V3-V5 region of bacterial 16S rRNA gene was performed.ResultsWe obtained 138,218 high quality sequences which were rarefied at 133 sequences/sample. Twenty OTUs had sequences ≥1% of total. There were marked differences in the distribution of Phyla between groups (P = 2.8x10^-118). Bacteroidetes and Fusobacteria were reduced in non-severe and severe asthmatic groups. Proteobacteria were more common in non-severe asthmatics compared to controls (OR = 2.26; 95% CI = 1.94–2.64) and Firmicutes were increased in severe asthmatics compared to controls (OR = 2.15; 95%CI = 1.89–2.45). Streptococcal OTUs amongst the Firmicutes were associated with recent onset asthma, rhinosinusitis and sputum eosinophilia.ConclusionsSputum microbiota in severe asthma differs from healthy controls and non-severe asthmatics, and is characterized by the presence of Streptococcus spp with eosinophilia. Whether these organisms are causative for the pathophysiology of asthma remains to be determined.     

The Role of Hyaluronic Acid Precursor Concentrations in Molecular Weight Control in Streptococcus zooepidemicus

The biosynthetic pathway responsible for the production of hyaluronic acid (HA) has been thoroughly studied; however, many aspects remain elusive regarding the mechanisms that control molecular weight (MW). Previously, we demonstrated a positive correlation between MW and the concentration of the HA precursor sugar UDP-N acetylglucosamine (UDP-GlcNAc). To further investigate the role of UDP-GlcNAc in MW control, we increased the intracellular concentration of this monomer using both feeding strategies and genetic engineering approaches. Feeding cells glucosamine dramatically increased intracellular levels of UDP-GlcNAc, but unexpectedly, produced HA of a lower MW. This was subsequently attributed to an equally dramatic decrease in the level of the other HA precursor sugar UDP-glucuronic acid (UDP-GlcUA). Feeding cells a mixture of glucose and GlcNAc addressed this imbalance of precursor sugars, leading to an increase in both UDP-GlcNAc and UDP-GlcUA; however, no significant increase in MW was observed. Despite the increase in UDP-sugars, RNA sequencing identified no increase in the expression of the genes involved in production of HA. Returning to genetic engineering approaches to examine UDP-GlcNAc and MW, genes known to contribute to the production of UDP-GlcNAc were over-expressed, both individually and together. Using this approach, UDP-GlcNAc and MW increased. At lower levels of UDP-GlcNAc, the positive correlation between UDP-GlcNAc levels and MW was maintained, however this relationship stalled at higher concentrations of UDP-GlcNAc. Taken together, these results suggest that while optimising HA precursor levels using feeding or genetic engineering approaches can improve HA MW, there is a point at which excess availability of precursors is no longer advantageous. Once precursor concentrations are addressed, it would seem that other uncharacterised factor(s) (e.g. rate of HA synthesis) also contribute to HA MW control.     

Synthesis of Oligosaccharides Structurally Related to Hyaluronic Acid Fragments

Russian Journal of Bioorganic Chemistry - Hyaluronic acid (HA) is a natural polysaccharide constructed from the alternating residues of β-D-glucuronic acid and N-acetyl-β-D-glucosamine....     

Relationship between Inflammatory Cytokines and Uric Acid Levels with Adverse Cardiovascular Outcomes in Patients with Stable Coronary Heart Disease

Background

So far it is unclear whether the association between serum uric acid (SUA), inflammatory cytokines and risk of atherosclerosis is causal or an epiphenomenon. The aim of the project is to investigate the independent prognostic relationship of inflammatory markers and SUA levels with adverse cardiovascular outcomes in a patient population with stable coronary heart disease (CHD).

Methods

SUA, C-reactive protein (CRP) and interleukin (IL)-6 were measured at baseline in a cohort of 1,056 patients aged 30–70 years with CHD. Cox proportional hazards model was used to determine the prognostic value of these markers on a combined CVD endpoint during eight year follow-up after adjustment for covariates.

Results

For 1,056 patients with stable coronary heart disease aged 30–70 years (mean age 58.9 years, SD 8.0) follow-up information and serum measurements were complete and n = 151 patients (incidence 21.1 per 1000 patients years) experienced a fatal or non-fatal CVD event during follow-up (p-value = 0.05 for quartiles of SUA, p = 0.002 for quartiles of CRP, p = 0.13 for quartiles of IL-6 in Kaplan-Meier analysis). After adjustment for age, gender and hospital site the hazard ratio (HR) for SUA increased from 1.37 to 1.65 and 2.27 in the second, third, and top quartile, when compared to the bottom one (p for trend <0.0005). The HR for CRP increased from 0.85 to 0.98 and 1.64 in the respective quartiles (p for trend 0.02). After further adjustment for covariates SUA still showed a clear statistically significant relationship with the outcome (p for trend 0.045), whereas CRP did not (p for trend 0.10).

Conclusion

The data suggest that compared to inflammatory markers such as CRP and IL-6 serum uric acid levels may predict future CVD risk in patients with stable CHD with a risk increase even at levels considered normal.     

Hyaluronic Acid Degradation by Ascorbic Acid and Influence of Iron

The effects of ascorbic acid, iron and ADP on hyaluronic acid, a compound present in inflamed joints, were investigated in an in vitro system. Ascorbic acid induces degradation of hyaluronic acid which increased in the presence of FeCl, and which is additionally stimulated by ADP chelated ferric ions. The hyaluronic acid degrading reactions induced by the Fe-III/ADP/ascorbic acid system were inhibited by catalase and formate to various extents whereas the presence of superoxide dismutase did not exert any inhibitory effect. Desferrioxamine, a specific iron chelator, completely inhibited hyaluronic acid depolymerisation by ascorbic acid as well as in combination with FeCl₃ or FeCl₃/ADP, respectively. We suggest that the ultimate hyaluronic acid degrading species is OH', generated via the Fe-III/ADP catalysed Haber Weiss reaction. There is also an indication for the involvement of perferryl or/and ferryl species in the degradation process.     

Hyaluronic Acid Degradation by Ascorbic Acid and Influence of Iron

The effects of ascorbic acid, iron and ADP on hyaluronic acid, a compound present in inflamed joints, were investigated in an in vitro system. Ascorbic acid induces degradation of hyaluronic acid which increased in the presence of FeCl, and which is additionally stimulated by ADP chelated ferric ions. The hyaluronic acid degrading reactions induced by the Fe-III/ADP/ascorbic acid system were inhibited by catalase and formate to various extents whereas the presence of superoxide dismutase did not exert any inhibitory effect. Desferrioxamine, a specific iron chelator, completely inhibited hyaluronic acid depolymerisation by ascorbic acid as well as in combination with FeCl₃ or FeCl₃/ADP, respectively. We suggest that the ultimate hyaluronic acid degrading species is OH', generated via the Fe-III/ADP catalysed Haber Weiss reaction. There is also an indication for the involvement of perferryl or/and ferryl species in the degradation process.     

Increased Circulating Levels of Alpha-Ketoglutarate in Morbidly Obese Women with Non-Alcoholic Fatty Liver Disease

BackgroundNon-alcoholic fatty liver disease (NAFLD) causes a wide spectrum of liver damage, ranging from simple steatosis to cirrhosis. However, simple steatosis (SS) and steatohepatitis (NASH) cannot yet be distinguished by clinical or laboratory features. The aim of this study was to assess the relationship between alpha-ketoglutarate and the degrees of NAFLD in morbidly obese patients.ResultsWe found that serum levels of alpha-ketoglutarate were significantly higher in morbidly obese women than in normal-weight women. We showed that circulating levels of alpha-ketoglutarate were lower in lean controls and morbidly obese patients without NAFLD. We also found that alpha-ketoglutarate serum levels were higher in both SS and NASH than in normal liver of morbidly obese patients. However, there was no difference between SS and NASH. Moreover, we observed that circulating levels of alpha-ketoglutarate were associated with glucose metabolism parameters, lipid profile, hepatic enzymes and steatosis degree. In addition, diagnostic performance of alpha-ketoglutarate has been analyzed in NAFLD patients. The AUROC curves from patients with liver steatosis exhibited an acceptable clinical utility. Finally, we showed that the combination of biomarkers (AST, ALT and alpha-ketoglutarate) had the highest accuracy in diagnosing liver steatosis.ConclusionThese findings suggest that alpha-ketoglutarate can determine the presence of non-alcoholic fatty liver in morbidly obese patients but it is not valid a biomarker for NASH.     

Association between Low Levels of Mannan-Binding Lectin and Markers of Autoimmune Thyroid Disease in Pregnancy

Functional deficiency of mannan-binding lectin (MBL) has been associated with adverse pregnancy outcome. Adverse events during pregnancy have also been described in women with autoimmune thyroid diseases (AITD), and thyroid hormones have been shown to influence serum levels of MBL. Therefore, the aim of this study was to analyse the impact of MBL-deficiency on the outcome of pregnancy in relation to the presence of AITD. Almost one year after delivery, we assessed serum MBL levels and MBL2-genotypes in 212 women positively screened for AITD in pregnancy. In 103 of these women, we could also measure MBL levels in frozen serum samples from the 9-12^th gestational week, obtaining 96 pairs of MBL values (pregnancy vs. follow-up). As controls, 80 sera of pregnant women screened negatively for AITD were used. MBL2-genotyping was performed using multiplex PCR. Women with thyroid dysfunction and/or thyroid peroxidase antibodies (TPOAb) had lower MBL levels during pregnancy than controls, (3275 vs. 5000 ng/ml, p<0.05). The lowest levels were found in women with elevated thyroid-stimulating hormone (TSH) levels in the absence of TPOAb (2207 ng/ml; p<0.01 as compared to controls). MBL2 genotype distribution did not differ between subgroups. At a median follow-up period of 17 months (range: 3–78 months) after delivery, median MBL level had decreased further to 1923 ng/ml (p<0.0001) without significant changes in TSH. In an explorative survey, functional MBL-deficiency was neither linked to a history of spontaneous abortion, nor other obstetric complications, severe infections throughout life/pregnancy or antibiotics use in pregnancy. In conclusion, hypothyroidism during pregnancy is associated with decreased MBL levels, and the levels decreased further after delivery.     

Association of Small Dense LDL Serum Levels and Circulating Monocyte Subsets in Stable Coronary Artery Disease

Objective

Atherosclerosis is considered to be an inflammatory disease in which monocytes and monocyte-derived macrophages play a key role. Circulating monocytes can be divided into three distinct subtypes, namely in classical monocytes (CM; CD14++CD16-), intermediate monocytes (IM; CD14++CD16+) and non-classical monocytes (NCM; CD14+CD16++). Low density lipoprotein particles are heterogeneous in size and density, with small, dense LDL (sdLDL) crucially implicated in atherogenesis. The aim of this study was to examine whether monocyte subsets are associated with sdLDL serum levels.

Methods

We included 90 patients with angiographically documented stable coronary artery disease and determined monocyte subtypes by flow cytometry. sdLDL was measured by an electrophoresis method on polyacrylamide gel.

Results

Patients with sdLDL levels in the highest tertile (sdLDL≥4mg/dL;T3) showed the highest levels of pro-inflammatory NCM (15.2±7% vs. 11.4±6% and 10.9±4%, respectively; p<0.01) when compared with patients in the middle (sdLDL=2-3mg/dL;T2) and lowest tertile (sdLDL=0-1mg/dL;T1). Furthermore, patients in the highest sdLDL tertile showed lower CM levels than patients in the middle and lowest tertile (79.2±8% vs. 83.9±7% and 82.7±5%; p<0.01 for T3 vs. T2+T1). Levels of IM were not related to sdLDL levels (5.6±4% vs. 4.6±3% vs. 6.4±3% for T3, T2 and T1, respectively). In contrast to monocyte subset distribution, levels of circulating pro- and anti-inflammatory markers were not associated with sdLDL levels.

Conclusion

The atherogenic lipoprotein fraction sdLDL is associated with an increase of NCM and a decrease of CM. This could be a new link between lipid metabolism dysregulation, innate immunity and atherosclerosis.     

Circulating Levels of Dimethylarginines,Chronic Kidney Disease and Long-Term Clinical Outcome in Non-ST-Elevation Myocardial Infarction

Background

Mechanisms linking chronic kidney disease (CKD) and adverse outcomes in acute coronary syndromes (ACS) are not fully understood. Among potential key players, reduced nitric oxide (NO) synthesis due to its endogenous inhibitors, asymmetric (ADMA) and symmetric (SDMA) dimethylarginine could be involved. We measured plasma concentration of arginine, ADMA and SDMA and investigated their relationship with CKD and long-term outcome in non-ST-elevation myocardial infarction (NSTEMI).

Methodology/Principal Findings

We prospectively measured arginine, ADMA, and SDMA at hospital admission in 104 NSTEMI patients. CKD was defined as an estimated glomerular filtration rate (eGFR) <60 ml/min/1.73 m². We considered a primary end point of combined cardiac death and re-infarction at a median follow-up of 21 months. In CKD (n = 33) and no-CKD (n = 71) patients, arginine and ADMA were similar, whereas SDMA was significantly higher in CKD patients (0.65±0.23 vs. 0.42±0.12 µmol/L; P<0.0001). Twenty-four (23%) patients had an adverse cardiac event during follow-up: 12 (36%) were CKD and 12 (17%) no-CKD patients (P = 0.02). When study population was stratified according to arginine, ADMA and SDMA median values, only SDMA (median 0.46 µmol/L) was associated with the primary end-point (P = 0.0016). In models adjusted for age, hemoglobin and left ventricular ejection fraction, the hazard ratio (HR) for CKD and SDMA were high (HR 2.93, interquartile range [IQR] 1.15–7.53; P = 0.02 and HR 6.80, IQR 2.09–22.2; P = 0.001, respectively) but, after mutual adjustment, only SDMA remained significantly associated with the primary end point (HR 5.73, IQR 1.55–21.2; P = 0.009).

Conclusions/Significance

In NSTEMI patients, elevated SDMA plasma levels are associated with CKD and worse long-term prognosis.     

Associations of Circulating Gut Hormone and Adipocytokine Levels with the Spectrum of Gastroesophageal Reflux Disease

Objective

The pathogenesis of gastroesophageal reflux disease (GERD) is complex and poorly understood. We aim to investigate the association of various circulating peptide hormones with heterogenous manifestations of GERD.

Methods

One hundred and four patients that had experienced typical GERD symptoms (heartburn and/or acid regurgitation) for at least 3 episodes per week in the past 3 months were enrolled. All patients received a baseline assessment of symptom severity and frequency with the Reflux Disease Questionnaire and an upper endoscopy to classify GERD into erosive esophagitis (EE, n = 67), non-erosive esophagitis (NE, n = 37), and Barrett’s esophagus (BE, n = 8). Fifty asymptomatic subjects with an endoscopically normal esophagus were recruited as the control group. Complete anthropometric measures and blood biochemistry were obtained and fasting serum levels of adipocytokines (adiponectin and leptin) and gut hormones (ghrelin and peptide YY (PYY)) were determined by enzyme-linked immunosorbent assay in all subjects.

Results

All circulating peptide hormone levels were not statistically different between the GERD and control groups. However, GERD patients appeared to have lower PYY levels [median (25^th-75^th percentile), 80.1 (49.8–108.3) vs. 99.4 (65.8–131.9) pg/ml, p = 0.057] compared with control subjects. Among the GERD patients, ghrelin levels were inversely associated with the frequency and severity of acid regurgitation. In male GERD patients, EE was associated with significantly higher PYY levels [107.0 (55.0–120.8) vs. 32.8 (28.7–84.5) pg/ml, p = 0.026] but lower adiponectin levels [6.7 (5.6–9.3) vs. 9.9 (9.6–10.6) μg/ml, p = 0.034] than NE. Patients with BE had significantly lower adiponectin levels [6.0 (5.1–9.2) vs. 9.2 (7.1–11.2) μg/ml, p = 0.026] than those without BE.

Conclusions

Humoral derangement of circulating peptide hormones might participate in inflammation and symptom perception in patients suffering from GERD. Further studies to clarify the exact role of these hormones in the pathogenesis of GERD are warranted.     

Persistence of Asthmatic Response after Ammonium Persulfate-Induced Occupational Asthma in Mice

Introduction

Since persulfate salts are an important cause of occupational asthma (OA), we aimed to study the persistence of respiratory symptoms after a single exposure to ammonium persulfate (AP) in AP-sensitized mice.

Material and Methods

BALB/c mice received dermal applications of AP or dimethylsulfoxide (DMSO) on days 1 and 8. On day 15, they received a single nasal instillation of AP or saline. Airway hyperresponsiveness (AHR) was assessed using methacholine provocation, while pulmonary inflammation was evaluated in bronchoalveolar lavage (BAL), and total serum immunoglobulin E (IgE), IgG1 and IgG2a were measured in blood at 1, 4, 8, 24 hours and 4, 8, 15 days after the single exposure to the causal agent. Histological studies of lungs were assessed.

Results

AP-treated mice showed a sustained increase in AHR, lasting up to 4 days after the challenge. There was a significant increase in the percentage of neutrophils 8 hours after the challenge, which persisted for 24 hours in AP-treated mice. The extent of airway inflammation was also seen in the histological analysis of the lungs from challenged mice. Slight increases in total serum IgE 4 days after the challenge were found, while IgG gradually increased further 4 to 15 days after the AP challenge in AP-sensitized mice.

Conclusions

In AP-sensitized mice, an Ig-independent response is induced after AP challenge. AHR appears immediately, but airway neutrophil inflammation appears later. This response decreases in time; at early stages only respiratory and inflammatory responses decrease, but later on immunological response decreases as well.     

透明质酸在组织工程领域的应用研究进展

透明质酸是由β(1-3)-N - 乙酰-D- 葡萄糖胺和 β(1-4)-D- 葡萄糖醛酸的双糖反复交替连接而构成的酸性黏多糖,广泛分布于脊 椎动物体内各种组织细胞间质中,具有重要生理功能。而外源性透明质酸具有理想的生物相容性和可降解性,其作为支架材料在组织工 程领域的应用具有独特优势。综述近年来透明质酸在组织工程不同领域的应用研究进展。     

Counter-Regulatory Response to a Fall in Circulating Fatty Acid Levels in Rainbow Trout. Possible Involvement of the Hypothalamus-Pituitary-Interrenal Axis

We hypothesize that a decrease in circulating levels of fatty acid (FA) in rainbow trout Oncorhynchus mykiss would result in the inhibition of putative hypothalamic FA sensing systems with concomitant changes in the expression of orexigenic and anorexigenic factors ultimately leading to a stimulation of food intake. To assess this hypothesis, we lowered circulating FA levels treating fish with SDZ WAG 994 (SDZ), a selective A1 adenosine receptor agonist that inhibits lipolysis. In additional groups, we also evaluated if the presence of intralipid was able to counteract changes induced by SDZ treatment, and the possible involvement of the hypothalamus-pituitary-interrenal (HPI) axis by treating fish with SDZ in the presence of metyrapone, which decreases cortisol synthesis in fish. The decrease in circulating levels of FA in rainbow trout induced a clear increase in food intake that was associated with the decrease of the anorexigenic potential in hypothalamus (decreased POMC-A1 and CART mRNA abundance), and with changes in several parameters related to putative FA-sensing mechanisms in hypothalamus. Intralipid treatment counteracted these changes. SDZ treatment also induced increased cortisol levels and the activation of different components of the HPI axis whereas these changes disappeared in the presence of intralipid or metyrapone. These results suggest that the HPI axis is involved in a counter-regulatory response in rainbow trout to restore FA levels in plasma.     

Maternal Cadmium Levels During Pregnancy and the Relationship with Preeclampsia and Fetal Biometric Parameters

Preeclampsia, which is caused by multiple factors, still remains one of the most serious complications of pregnancy. This study was designed to determine cadmium levels in women with preeclampsia compared to those of normotensive women. In this case-control study, maternal blood, umbilical cord blood, and placental cadmium levels were measured by an inductively coupled plasma mass spectrometry system in 51 women presenting consecutively with preeclampsia and 51 normotensive pregnant women. Groups were matched for maternal age, parity, and gestational age. Birth outcomes were recorded, such as gestational age at delivery, birth weight, and Apgar score. Median (interquartile range [IQR]) blood cadmium concentration was 1.21 μg/L (0.76–1.84 μg/L) and 1.09 μg/L (0.72–1.31 μg/L) in women with preeclampsia and normotensive, respectively; values for placental cadmium levels of women with preeclampsia and normotensive were 3.61 μg/kg (2.19–4.37 μg/kg) and 4.28 μg/kg (3.06–5.71 μg/kg), respectively. We observed a statistically significant increase in blood and placental cadmium levels in women with preeclampsia compared to healthy pregnant women. After adjusting for pre-pregnancy body mass index, maternal age, parity, gestational age at sample collection, and maternal calcium and magnesium levels, the odds ratio of having preeclampsia in the high tertile was markedly increased (odds ratio, 7.83 [95% CI, 1.64–37.26]) compared with the low tertile. Interestingly, there was no difference in the cadmium level in umbilical cord blood between the groups. Within the preeclamptic group, higher cadmium status was significantly associated with decreased birth weight. Our study suggested that elevated cadmium level in the maternal circulation could potentially increase the risk of preeclampsia. The results also demonstrate that higher cadmium status may contribute to fetal growth restriction in preeclamptic patients.     

Liquor Bilirubin Levels in Normal Pregnancy: A Reassessment of Early Prediction of Haemolytic Disease

A comparison was made between chemically and spectrophotometrically determined concentrations of total bile pigment in the liquor amnii. For the period 16 to 26 weeks'' gestation the upper limit of normal bile pigment to protein ratio was found to be 0·4. Levels above this would be required as an indication for intrauterine transfusion. In 110 cases of isoimmunization of pregnancy these criteria were applied in the diagnosis of severity of the condition. The ratio of the bile pigment to protein was used rather than a simple bile pigment measurement, and found to be valuable.Nevertheless, it is important to emphasize that fallacious high bilirubin readings may arise by using whatever method, particularly owing to bilirubin and other breakdown products of blood contaminating the liquor.