Serum and hair zinc in severely malnourished Bangladeshi children associated with or without acute lower respiratory infection

Objective  To assess the zinc status in Bangladeshi children suffering from severe protein energy malnutrition (severe PEM), acute lower respiratory infection (ALRI), PEM presented with ALRI and to evaluate the relationship of zinc status with aforementioned clinical conditions. Methods  We assessed zinc status by simultaneous estimation of serum and hair zinc of Bangladeshi children less than 5 yr of age suffering from severe PEM, ALRI, severe PEM presented with ALRI and compared them with zinc status of well-nourished healthy children (control) in a hospital based cross sectional four cell study. Zinc concentration was estimated by Flame atomic absorption spectrophotometry. Results  Total one hundred and fifty two children were enrolled and number of children enrolled in severe PEM, ALRI, ALRI with PEM and control were 47, 35, 32 and 38 respectively. Both serum and hair zinc in univariate analysis were found significantly (p<0.05) low in severe PEM, ALRI and severe PEM associated with ALRI. However, in multivariate analysis, when serum and hair zinc were included in the same model, both serum and hair zinc were found to have significant negative association with PEM (p=0.002 & 0.013 respectively) and with ALRI only when ALRI was associated with PEM (p=0.043 and 0.034 respectively). Conclusion  Severe PEM and PEM with ALRI were significantly associated with low zinc status.     

Natural frequency of polymorphisms linked to the chondroitin 4-sulfotransferase genes and its association with placental malaria

Our understanding about the role of the maternal genetic factors on placental malaria is scarce. The general aim of this work was to examine whether common polymorphisms of genes involved in chondroitin sulphate A (CSA) synthesis influence susceptibility to and manifestation of malaria during pregnancy. To achieve this, 96 women with placental malaria and 180 healthy controls without malaria from the province of Luanda, Angola, were genotyped using six microsatellite loci. No associations were found between polymorphisms of genes involved in CSA synthesis and placental malaria. All these findings suggest that there is no genetic susceptibility or increased risk attributed to polymorphisms of the enzymes involved on the synthesis of CSA.     

Metal complexing agents as therapies for Alzheimer's disease

Modern research approaches into drug development for Alzheimer’s disease (AD) target β-amyloid (Aβ) accumulation in the brain. The main approaches attempt to prevent Aβ production (secretase inhibitors) or to clear Aβ (vaccine). However, there is now compelling evidence that Aβ does not spontaneously aggregate, but that there is an age-dependent reaction with excess brain metal (copper, iron and zinc), which induces the protein to precipitate into metal-enriched masses (plaques). The abnormal combination of Aβ with Cu or Fe induces the production of hydrogen peroxide, which may mediate the conspicuous oxidative damage to the brain in AD. We have developed metal-binding compounds that inhibit the in vitro generation of hydrogen peroxide by Aβ, as well as reverse the aggregation of the peptide in vitro and from human brain post-mortem specimens. Most recently, one of the compounds, clioquinol (CQ; a USP antibiotic) was given orally for 9 weeks to amyloid-bearing transgenic mice, and succeeded in markedly inhibiting Aβ accumulation. On the basis of these results, CQ is being tested in clinical trials.     

Increased lymphocyte trafficking to colonic microvessels is dependent on MAdCAM-1 and C-C chemokine mLARC/CCL20 in DSS-induced mice colitis

Although enhanced lymphocyte trafficking is associated with colitis formation, little information about its regulation is available. The aim of this study was to examine how the murine liver and activation-regulated chemokine (mLARC/CCL20) contributes to lymphocyte recruitment in concert with vascular adhesion molecules in murine chronic experimental colitis. T and B lymphocytes isolated from the spleen were fluorescence-labelled and administered to recipient mice. Lymphocyte adhesion to microvessels of the colonic mucosa and submucosa was observed with an intravital microscope. To induce colitis, the mice received two cycles of treatment with 2% dextran sodium sulphate (DSS). In some of the experiments antibodies against the adhesion molecules or anti-mLARC/CCL20 were administered, or CC chemokine receptor 6 (CCR6) of the lymphocytes was desensitized with excess amounts of mLARC/CCL20. Significant increases in T and B cell adhesion to the microvessels of the DSS-treated mucosa and submucosa were observed. In chronic colitis, the accumulation of lymphocytes was significantly inhibited by anti-mucosal addressin cell adhesion molecule (MAdCAM)-1 mAb, but not by anti-vascular cell adhesion molecule-1. In DSS-treated colonic tissue, the expression of mLARC/CCL20 was significantly increased, the blocking of mLARC/CCL20 by monoclonal antibody or the desensitization of CCR6 with mLARC/CCL20 significantly attenuated the DSS-induced T and B cell accumulation. However, the combination of blocking CCR6 with MAdCAM-1 did not further inhibit these accumulations. These results suggest that in chronic DSS-induced colitis, both MAdCAM-1 and mLARC/CCL20 may play important roles in T and B lymphocyte adhesion in the inflamed colon under flow conditions.     

Enhanced zinc consumption causes memory deficits and increased brain levels of zinc

Zinc deficiency has been shown to impair cognitive functioning, but little work has been done on the effects of elevated zinc. This research examined the effect on memory of raising Sprague-Dawley rats on enhanced levels of zinc (10 ppm ZnCO3; 0.153 mM) in the drinking water for periods of 3 or 9 months, both pre- and postnatally. Controls were raised on lab water. Memory was tested in a series of Morris Water Maze (MWM) experiments, and zinc-treated rats were found to have impairments in both reference and working memory. They were significantly slower to find a stationary platform and showed greater thigmotaxicity, a measure of anxiety. On a working memory task, where the platform was moved each day, zinc-treated animals had longer latencies over both trials and days, swam further from the platform, and showed greater thigmotaxicity. On trials using an Atlantis platform, which remained in one place but was lowered on probe trials, the zinc-treated animals had significantly fewer platform crossings, spent less time in the target quadrant, and did not swim as close to the platform position. They had significantly greater latency on nonprobe trials. Microprobe synchrotron X-ray fluorescence (microSXRF) confirmed that brain zinc levels were increased by adding ZnCO3 to the drinking water. These data show that long-term dietary administration of zinc can lead to impairments in cognitive function.     

The COX-2 inhibitor, rofecoxib, ameliorates dextran sulphate sodium induced colitis in mice

Objective: We have evaluated the efficacy of the selective cyclo-oxygenase (COX)-2 inhibitor, rofecoxib, for the prevention of experimental colitis.Material and methods: To induce colitis BALB/c mice received 5% dextran sulphate sodium (DSS) in their drinking water continuously for 7 days. Rofecoxib (2.5–10 mg/kg body weight, p.o.) was administered throughout the treatment period with DSS. Colitis was quantified by a clinical damage score, colon length, weight loss, stool consistency and rectal bleeding. Inflammatory response was assessed by neutrophil infiltration, determined by histology and myeloperoxidase (MPO) activity. Interleukin (IL)-1, prostaglandin (PG)E₂ and PGD₂ levels in colon mucosa and the immunohistochemical expression of COX-1 and –2 were also studied.Results: The COX-2 inhibitor ameliorated severe colitis, reduced the degree of inflammation through reduction of neutrophil infiltration and IL-1 levels. PGE₂, and PGD₂ synthesis were significantly reduced in DSS-treated groups. Indeed, treatment with rofecoxib diminished the lost of COX-1 caused by DSS in the crypt epithelium whereas expression of COX-2 remained unaffected.Conclusions: Rofecoxib is protective in acute DSS – induced colitis, probably by reducing neutrophil infiltration, inhibiting up-regulation of IL-1 and returning to normal COX-1 expression in the inflamed colonic mucosa.Received 19 April 2004; returned for revision 17 June 2004; accepted by I. Ahnfelt-Rønne 23 November 2004     

A novel protocol for postpartum magnesium sulphate in severe pre-eclampsia: a randomized controlled pilot trial

Objective: Magnesium sulphate is the preferred anticonvulsant used to prevent the development of fits in severe pre-eclampsia; we aim to compare between three different protocols of postpartum magnesium sulphate in the effectiveness of preventing the development of fits in severe pre-eclampsia.

Methods: Double-blind randomized controlled pilot trial, done in Cairo university hospital, Cairo, Egypt during 2013–2014, on 240 women with severe pre-eclampsia. Magnesium sulphate intravenous infusion was given in the postpartum period to all the patients, women were randomly allocated to group I (Single loading dose only), group II (12?h abbreviated protocol) or group III (24?h standard protocol) (n?=?80 in each group).

Results: There were no significant difference between the three groups as regards the incidence of eclampsia, elevated liver enzymes and low platelets syndrome, maternal ICU admission and; however The incidence of flushing was significantly higher in group III than group II and I (24 [30%] versus 12 [15%] versus 4 [5%]; p?<?0.001) respectively.

Conclusion: The pilot study demonstrates that the single-loading dose of postpartum magnesium sulphate is a promising alternative to the standard and the abbreviated protocol in preventing eclampsia; however, a large clinical trial is necessary to prove this.     

Placental IGF-I, IGFBP-1, zinc, and iron, and maternal and infant anthropometry at birth

Aim: To correlate placental protein levels of insulin‐like growth factor (IGF)‐I and insulin‐like growth factor binding protein (IGFBP)‐1, with previously determined levels of IGF‐I and IGF‐II mRNA expression, and the micronutrients zinc and iron, and maternal and newborn anthropometry. Methods: Placental samples were collected from rural field sites in Pakistan. Samples were divided into small and large for gestational age groups (SGA and LGA, respectively). IGFBP‐1 levels were assessed using Western immunoblotting. IGF‐I protein levels were assessed using ELISA techniques. IGF mRNA expression, zinc, and iron, were quantified as previously described and were used for comparative purposes only. Results: Thirty‐three subjects were included (SGA, n = 12; LGA n = 21). Higher levels of IGFBP‐1 were seen in the SGA group (p < 0.01). IGFBP‐1 correlated positively with maternal and infant triceps skin‐fold thickness in the LGA and SGA groups, respectively (p < 0.05). Significantly lower IGF‐I protein levels were seen in the SGA group. IGF‐I levels correlated significantly with maternal and newborn anthropometry. IGFBP‐1 correlated significantly with IGF‐II mRNA expression (p < 0.05). Conclusion: Placental protein levels of IGF‐I and IGFBP‐1 appear to be associated with maternal anthropometry. Maternal anthropometry may thus influence IGFBP‐1 and IGF‐I levels and may possibly be used for screening of pregnancies, with the potential for timely identification of these high‐risk pregnancies.     

锌原卟啉测定对孕妇缺铁性贫血的临床诊断意义

为探讨锌原卟啉（ZPP）作为缺铁性贫血诊断指标的意义及孕妇早、中、晚期缺铁发病率，本文对139例孕早期，280例孕中期以及208例孕晚期共627例孕妇ZPP含量进行了测定分析，另对17例孕早期，182例孕中期以及152例孕晚期共351例孕妇的（血红蛋白）Hb、（红细胞）RBC、（红细胞压积）HCT、（红细胞平均容积）MCV、（红细胞平均血红蛋白）MCH及（红细胞平均血红蛋白浓度）MCHC共6项指标进行了测定，结果表明：孕晚期ZPP含量显著高于孕早、中期组（P＜0．01），而孕早、中期间无显著性差异。孕晚期组的Hb、RBC、MCH及MCHC与早孕期组相比显著降低（P＜0．01），HCT各组间无显著性差异（P＞0．05），ZPP含量与Hb呈显著负相关，与RBC呈正相关，综上结果看出孕晚期ZPP含量增高明显，提示ZPP的检测可作为监测孕妇缺铁性贫血一项指标。