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PubMed1990

A pancreatic islet cell-specific enhancer-like element in the glucagon gene contains two domains binding distinct cellular proteins.

Interactions of nuclear proteins with cis-control elements are involved in the programmed developmental expression of the islet polypeptide hormone genes. Three transcriptional control elements within 300 base pairs of the 5'-flanking region of the rat glucagon gene interact with regulatory cellular proteins and direct transcription only in glucagon-producing islet cells. Two islet cell-specific enhancer-like elements (G2, G3) act together with the glucagon promoter (including the G1 element), which confers A cell specificity of glucagon gene expression. In the present study, the G3 element was analyzed in detail by protein binding and in vivo and in vitro transcription assays. Mutational analyses showed that the sequence of the G3 element comprises two distinct protein-binding domains: a more upstream domain A (5'-CGCCTGA-3'), and a more downstream domain B (5'GATTGAAGGGTGTA-3'). Binding of proteins to these two domains is mutually exclusive. Domain A, but not domain B, is responsible for both functional protein binding and the enhancement of transcription from the glucagon or thymidine kinase gene promoter chloramphenicol acetyltransferase reporter gene transfected in vivo into glucagon-producing islet cells (InR1-G9) and transcribed in vitro in a HeLa cell-free transcription system. In islet cell extracts, the Southwestern blot technique labeled a protein of 45 kDa binding to domain A within G3. We conclude that although the G3 sequence contains two protein-binding motifs, the organization of the G3 enhancer-like element is not bipartite. The islet cell specificity of the G3 element is conferred by a tissue-specific transcription factor or protein complex interacting with domain A of G3. This protein or protein complex recognizes different DNA sequences and provides promoter as well as enhancer activity because it binds also to the apparently unrelated sequence of the G1 promoter element.

Adenoma, Islet Cell↗

PubMed1997

Cooperative regulation of the human aromatase cytochrome P450 gene transcription by placenta-specific cis-acting elements.

Aromatase cytochrome P450 catalyses the reaction to convert androgens to estrogens by coupling with NADPH-cytochrome P450 reductase in the endoplasmic reticulum. The human aromatase cytochrome P450 gene (CYP19) is expressed in a variety of tissues under regulation of tissue-specific promoters. Previously, we localized a cell-type specific transcriptional enhancer element between -242 and -166 relative to the major cap site of the gene, by transient expression analysis in human BeWo choriocarcinoma cells. In the present study, we demonstrate that the enhancer element consists of two subelements, element I (located between -238 and -200), and element II (located between -196 and -176) as analysed by DNase I footprinting using the nuclear extracts of BeWo cells. The gel mobility shift assay shows that each of these subelements binds specific nuclear factor(s). The transient expression of the bacterial chloramphenicol acetyltransferase gene constructs involving the subelements in BeWo cells reveals that the elements activate reporter gene expression synergistically when present together, nevertheless each of the elements by itself also has an enhancer activity. The transient expression analysis further shows that element I is responsible for the transcriptional synergism with the binding site of a nuclear factor-interleukin-6 (NF-IL-6) (also known as CCAAT enhancer/binding protein beta), which is located between -2141 and -2115 relative to the major cap site of the gene. These results suggest that the enhancer element plays important roles in sustaining the high levels of CYP19 expression in placental cells in cooperation with other cis-acting transcritional regulatory elements.

Aromatase↗

PubMed1997

Effects of trace element and/or vitamin supplementation on vitamin and mineral status, free radical metabolism and immunological markers in elderly long term-hospitalized subjects. Geriatric Network MIN. VIT. AOX.

A randomized double-blind trial was performed in order to assess the efficacity of differing combinations of antioxidant nutrients on biochemical parameters of vitamin and trace element status, immunological parameters and free radical metabolism in elderly long term hospitalized subjects. A total of 756 institutionalized elderly subjects were recruited in 26 nursing homes in different areas of France. Four groups were constituted, receiving daily, for 1 year, either vitamins (beta-carotene, 6 mg; vitamin C, 120 mg; and vitamin E, 15 mg), trace elements (zinc, 20 mg and selenium, 100 micrograms), trace elements associated with vitamins, or a placebo. Biochemical indicators of trace elements and vitamin status and free radical parameters were measured before and after 6 months and 1 year of supplementation. Some immunological markers were investigated initially and after 6 months of supplementation on a subsample of 134 subjects. Mean plasma levels of alpha-tocopherol, gamma-tocopherol, vitamin C, alpha-carotene, beta-carotene and copper increased significantly after 6 months of supplementation in groups receiving vitamins alone or associated with trace elements. Serum selenium concentrations were significantly increased at 6 months of supplementation, and serum zinc only after one year in the trace element groups. Serum lycopene levels were significantly decreased by trace element supplementation. A significant increase in Se-glutathione peroxidase (GPx) levels was observed in groups receiving trace elements alone or associated with vitamins. No effect was noted on superoxide dismutase (SOD) activity or TBARs production. No effect of supplementation was found for in vitro lymphocyte proliferative responses or most lymphocyte subsets, except for a significantly lower percentage of CD2 subsets observed in groups receiving mineral supplementation either alone or associated with vitamins. A significant difference in CD19 subsets was found in groups receiving trace elements. Mean IL-1 production was significantly higher after 6 months of supplementation in the vitamin groups.

Aged↗

PubMed1980

Endodermal sinus (yolk sac) tumor elements in testicular germ-cell tumors in adults: comparison of prospective and retrospective studies.

The incidence of endodermal sinus tumor (EST) or yolk sac tumor (YST) elements has been studied in two series of testicular germ-cell neoplasms in adults. One series, consisting of 200 germ-cell neoplasms seen from 1053 through 1968, was studied retrospectively, and the other, consisting of 147 cases seen from May 1974 through February 1979, was studied prospectively. Excluding the cases of pure seminoma, EST(YST) elements were found in 21 (28.7%) of 73 cases in the retrospective series and in 27 (44.4%) of 61 cases in the prospective series. The EST(YST) elements were in all cases admixed with other neoplastic germ-cell elements and varied from microscopic foci to being the predominant element within a tumor. The EST(YST) elements were histologically similar to infantile EST(YST) and EST(YST) in other locations. Serum alphafetoprotein (AFP) was determined in the majority of patients in the prospective series, and there was good correlation between the presence of EST(YST) elements within the tumor and elevated levels of AFP. The results of the present study indicate that EST(YST) elements occur quite frequently in testicular germ-cell neoplasms in adults and provide an explanation for the raised levels of serum AFP found in many adults with testicular germ-cell tumors. The results emphasize the importance of a thorough and careful pathologic examination of testicular germ-cell tumors, and the value of AFP as a tumor marker in patients with EST(YST). The results also lend further support to the view that EST(YST) elements found in testicular germ-cell tumors in adults are homologous with infantile EST(YST) and that EST(YST) is a distinctive and specific type of germ-cell neoplasm and should be included as such in the classification of testicular tumors.

Adolescent↗

PubMed1986

Structure and genomic organization of proretrovirus-like elements partially eliminated from the somatic genome of Ascaris lumbricoides.

A clone containing a middle repetitive element next to satellite DNA has been isolated from a germ line genomic library of the chromatin eliminating nematode Ascaris lumbricoides var. suum. The structure of this element has been elucidated by comparison of several clones containing the element in different environments. It is flanked by 256-bp-long terminal repeats (LTRs) and has an internal region of approximately 7 kb. The nucleotide sequences of both the 5' and the 3' LTRs have been determined. The element has a strong structural similarity with retroviral proviruses and related mobile elements. It was therefore named 'Tas', for transposon-like element of Ascaris. Approximately 50 Tas copies are dispersed over approximately 20 different chromosomal sites. Their genomic distribution varies between individuals, indicating that Tas elements are mobile in the Ascaris genome. Two variant forms, Tas-1 and Tas-2, present in a ratio of approximately 2 to 1 in the germ line genome, have been characterized. They differ not only in their restriction pattern, but also in their elimination behaviour. While only about one-fourth of the Tas-1 elements are expelled from the somatic cell lineage, all Tas-2 copies are specifically eliminated and are thus confined to the germ line cells. We have demonstrated that a cloned representative of Tas-1 elements is expelled concomitantly with its flanking DNA sequences during the chromatin elimination process.

Animals↗

PubMed1989

A U-snRNA gene-specific upstream element and a -30 'TATA box' are required for transcription of the U2 snRNA gene of Arabidopsis thaliana.

The U2 and U5 snRNA genes of Arabidopsis thaliana contain in their promoter regions two elements with conserved sequence and position. To test the significance of this conservation we have made a construction in which the promoter of the U2 RNA gene is replaced by the synthetic 98 bp long sequence containing the two conserved elements: an upstream sequence element, GTCCCACATCG (USE, pos. -78 to -68), and a TATA-like sequence TATAAATA (-33 to -26), positioned approximately three helical turns apart, as in the wild-type promoter. This synthetic promoter efficiently drove transcription of the U2 gene in transfected protoplasts of Nicotiana plumbaginifolia. The importance of the individual elements and of their position within the promoter was investigated. Deletion of the USE, change of its orientation, and some single point mutations all decreased transcription 10- to 20-fold, and replacement of the TATA-like element by an unrelated sequence inactivated the promoter. Mutants in which the spacing between the USE and TATAAATA was changed were less active but no correlation was observed between promoter activity and insertion of either odd or even numbers of half helical turns. Insertion of a spacer between TATAAATA and the cap site resulted in accumulation of U2 RNA with an extended 5' end, indicating that the TATAAATA element is responsible for selection of the initiation site. The data indicate that the promoters of RNA polymerase II-specific U-snRNA genes in higher plants differ from their animal counter-parts and also from plant mRNA gene promoters. They contain two essential elements, an USE, an element found only in U-snRNA genes, and a TATA element which is indistinguishable from the TATA boxes of mRNA-coding genes.

Base Sequence↗

PubMed2004

HXT5 expression is under control of STRE and HAP elements in the HXT5 promoter.

Hexose transporter (Hxt) proteins transport glucose across the plasma membrane in the yeast Saccharomyces cerevisiae. Recently, we have shown that expression of HXT5 is regulated by the growth rate of the cells. Because gene expression is regulated by binding of specific transcription factors to regulatory elements in the promoters of genes, the presence of putative regulatory elements in the promoter of HXT5 was determined by computer-assisted analysis. This revealed the presence of two putative stress-responsive elements (STREs), one putative post-diauxic shift (PDS) element and two putative Hap2/3/4/5p (HAP) complex binding elements. The involvement of these elements was studied by using mutations in a HXT5 promoter-LacZ fusion construct. Growth during various conditions that result in low growth rates of yeast cells revealed that the STRE most proximal to the translation initiation site seemed to be involved in particular in regulation of HXT5 expression during growth at decreased growth rates. In addition, the HAP elements seemed to be required during growth on non-fermentable carbon sources. The PDS element and, to a lesser extent, the other STRE showed particular involvement in regulation of HXT5 expression during growth on ethanol. Finally, it was shown that the PKA pathway, which is known to be involved in expression of STRE-regulated genes, was also involved in regulation of HXT5 expression. A possible mechanism by which expression of HXT5 could be regulated by the transcriptional regulatory elements in the promoter is discussed.

Artificial Gene Fusion↗

PubMed1993

Promoter strength and structure dictate module composition in RNA polymerase III transcriptional activator elements.

RNA polymerase III transcription of genes with external promoters only (e.g. U6 snRNA) or containing in addition an internal B box (selenocysteine tRNA(Sec)) is stimulated by upstream elements; a distal sequence element (DSE) for U6 or an activator element in the tRNA(Sec) gene. In contrast to the composite structure of the DSE which requires an octamer motif, the Xenopus tRNA(Sec) activator element contains an SPH motif only. In vivo transcription is optimally stimulated by SPH in an absolute octamer-independent manner since adding octamer does not induce superstimulation. Experiments performed in the work presented here led to the following observations. Co-operation between SPH and octamer motifs can be detected in two distinct cases: first when these motifs are placed in front of B box-less tRNA(Sec) or U6 external promoters and second, if either element of the external promoter (proximal sequence element or TATA element), or the SPH motif itself, are altered. Altogether, our data provide evidence that an SPH motif can function alone in an optimized promoter only. In contrast, an octamer becomes indispensable when the basal promoter is weak or disabled. It follows that module composition of Pol III transcriptional activator elements is dependent on the structure and strength of the promoter. This reveals the existence of cross-talk between activator and promoter elements, mediated by the bound transcription factors, which are thus able to compensate for each other in order to allow successful assembly of the transcription complex.

Animals↗

PubMed1996

The effect of regulatory sequence elements upon the initiation of DNA replication of the minute virus of mice.

The minute virus of mice (MVM) genome is a linear single-stranded length of approximately 5000 nucleotides of DNA with unique terminal palindromic sequences at both ends. The left(3') hairpin is used to prime the initiation of DNA synthesis on parental single-strand DNA while the right (5') hairpin or stem-plus-arms structure can also prime the initiation of DNA synthesis during synthesis of dimer and higher oligomers as well as synthesis of progeny single strands. Previous studies have shown that if viral duplex DNA was input into an in vitro DNA replication system using extracts from uninfected HeLa cells, the 5' end of the molecule was able to form a hairpin and initiate DNA synthesis by DNA polymerase delta (Cossons et al. (1996), Virology 216, 258-264). In this study, the effect of the deletion of known cis-acting genetic elements upon the initiation of DNA replication was studied using a series of MVM mutants with deletions within the 5' terminal region. Mutants containing deletions of elements A (nucleotides 4489-4636), B (nucleotides 4636-4695), and either one or both of the 65-bp repeats (nucleotides 4720-4785 and 4785-4849) were used as template in the in vitro DNA replication system. When element A was deleted, the efficiency of initiation decreased significantly. Subsequent removal of element B, leaving just the two 65-bp repeats, restored levels of initiation back to those seen in the wild-type genome. In the absence of either A or B both 65-bp repeats were necessary for efficient initiation, and removal of one of these repeats caused a decrease in efficiency. Thus, element B appeared to have a negative regulatory effect (in the absence of element A), and element A appeared to have a positive regulatory effect, at least in the presence of element B. These data demonstrate, for the first time, a complex interaction between these cis-acting regulatory elements which can function as both positive or negative regulators in the initiation of MVM DNA replication.

Animals↗

PubMed1990

Interdependence and nodule specificity of cis-acting regulatory elements in the soybean leghemoglobin lbc3 and N23 gene promoters.

The qualitative and quantitative contributions of four separate cis-acting DNA elements controlling the root nodule-specific soybean leghemoglobin lbc3 gene were analyzed in transgenic Lotus corniculatus plants. Expression from internal deletions in the 5' region between positions -49 and -1956 was monitored from a CAT reporter gene. The strong positive element (SPE; -1090, -947) responsible for high-level expression was demonstrated to be an organ-specific element by deleting proximal nodule-specific control elements. Deletion of the downstream qualitative organ-specific element (OSE; -139, -102) containing the putative nodulin consensus sequences 5'AAAGAT and 5'CTCTT resulted in a low expression level. Efficient SPE enhancement is therefore dependent on the organ-specific element, which by itself does not enhance expression. This quantitative effect of the immediate upstream region carrying the consensus sequences was also found in hybrid promoter studies using the soybean nodulin N23 gene promoter, suggesting the involvement of these motifs in a regulatory mechanism for nodulin genes. Deletion of the lbc3 negative element (NE, -102, -49) linking the SPE and OSE onto the TATA box did not lead to unregulated expression. These results indicate that interaction between positive, negative and neutral qualitative elements controls lbc3 expression. Binding of the nuclear protein NAT2 at the lbc3 weak positive element (WPE; -230, -170) is probably not directly required for this mechanism.

Base Sequence↗

PubMed1998

Characterization and evolution of mariner elements from closely related species of fruit flies (Diptera: Tephritidae).

Mariner elements were amplified using the polymerase chain reaction from two species of tephritid flies, Ceratitis rosa and Trirhithrum coffeae. The sequences were approximately 1.3 kb in length. None of these elements appeared to be functional, as in every case the open reading frame (ORF) was disrupted by the presence of frameshifts or stop codons. These elements, Crmar1 and Tcmar1, are very similar to the Ccmar1 element previously amplified from the closely related tephritid species C. capitata and are members of the mellifera subfamily of mariner elements. The phylogeny and pattern of divergence of these elements were examined in relation to the phylogeny of the host species. It is highly probable that the elements were present in the ancestral lineage prior to the divergence of the three species. The copy numbers of the elements within each species are very different, ranging from about 10 in T. coffeae to 5,000 in C. rosa. The possible mechanisms which determine the copy number of an element in the host genome are discussed.

Amino Acid Sequence↗

PubMed2001

Microwave assisted digestion of atmospheric aerosol samples followed by inductively coupled plasma mass spectrometry determination of trace elements.

A microwave digestion method in a closed vessel was developed for the determination of trace metals in atmospheric aerosols using inductively coupled plasma mass spectrometry (ICP-MS). A recovery study for the elements V, Cr, Mn, Fe, Co, Ni, Cu, Zn, As, Se, Cd, Sb, and Pb was conducted using multi-elemental standard solutions, NIST 1633b Trace Elements in Coal Fly Ash, and NIST 1648 Urban Particulate Matter. A simple digestion method using only HNO3/H2O2 gave good recoveries (90%-108%) for all elements except Cr in SRM 1648, but yielded low recoveries for SRM 1633b. A more robust method using HNO3/H2O2/HF/H3BO3 yielded higher recoveries (82%-103%) for the lighter elements (V-Zn) in SRM 1633b, and improved the Cr recovery in SRM 1648, but decreased the Se recovery in both SRMs. A comparative analysis of aerosol samples obtained at a remote mountain location Nathiagali, Pakistan (2.5 km above mean sea level), and Mayville, New York, downwind from the highly industrialized Midwestern United States, was carried out using Instrumental Neutron Activation Analysis (INAA) for the elements Cr, Mn, Fe, Co, Zn, As, Se, and Sb. The simple digestion method yielded excellent agreement for Cr, Fe, Zn, As, Se, and Sb, with slopes of the ICP-MS vs. INAA regressions of 0.90-1.00 and R2 values of 0.96-1.00. The regressions for Mn and Co had slopes of 0.82 and 0.84 with R2 values of 0.83 and 0.82, respectively. Addition of HF/H3BO3 did not improve the correlation for any of the elements and degraded the precision somewhat. The technique provides sensitivity and accuracy for trace elements in relatively small aerosol samples used in atmospheric chemistry studies related to SO2 oxidation in cloud droplets. The ability to determine concentrations of a very large number of elements from a single analysis will permit source apportionment of various trace pollutants and hence strategies to control the sources of air pollution. This is particularly important as the health effects of particulate matter are increasingly recognized.

Aerosols↗

PubMed1996

Elemental fractionation in laser ablation inductively coupled plasma mass spectrometry.

The major challenge to the use of laser ablation sample introduction, combined with inductively coupled plasma mass spectrometry, is the problem of calibration. In the geological analysis of minerals, calibration is complicated by the extraordinarily wide variety of sample matrices which may be encountered. While there is a lack of mineral standards with well characterized concentrations near 1 microg/g, the NIST glass reference materials (SRM 610-617) have been demonstrated to be very useful for the analysis of a wide variety of lithophile elements in silicate samples. An internal reference element, for which the concentration is known in the sample, has been widely used to make corrections for the multiplicative effects of volume (or weight) of the sample ablated, instrument drift, and matrix effects. This procedure works extremely well where elements being determined and the internal reference element being used share similar ablation behaviours; i.e., they do not fractionate progressively during the ablation and transport process. In this study, it is demonstrated that, in terms of ablation behaviour, elements fall into several distinct clusters and that the elements within these clusters correlate well with each other during a period of ablation. Thus, elements within a cluster can be determined using an internal reference element from within the same cluster. While a combination of periodic varying properties typifies the clusters, the geochemical classification of elements into lithophile (silicate loving), and chalcophile (sulphide loving) appears to offer the best characterization of the major groups.

Journal Article↗

PubMed2005

The relative bioavailability in humans of elemental iron powders for use in food fortification.

BACKGROUND: Bioavailability data in humans of elemental iron powders is limited although elemental iron is a common form of iron when used as a fortificant. AIM OF THE STUDY: The relative bioavailability (RBV) of seven elemental iron powders, five commercially available and two developmental are evaluated. In addition, one commercial electrolytic iron powder given with ascorbic acid (AA) was examined. METHODS: Based on a validated method this double-blinded randomized crossover study included three groups of male blood donors (n = 3*16) who were served rolls fortified with different elemental iron powders or ferrous sulfate (FeSO(4)) nine weeks apart. Blood samples were drawn every hour for six hours. RBV was obtained by comparing the increase in serum iron concentration induced by the elemental iron with the increase induced by FeSO(4). RESULTS: All elemental iron powders studied were significantly less well absorbed compared to FeSO(4). The electrolytic iron given with 50-mg AA was as well absorbed as FeSO(4) (molar ratio = 1:6, AA:Fe). The mean RBVs of the iron powders were: electrolytic (A-131, RBV = 0.65); electrolytic (Electrolytic, RBV = 0.59); carbonyl (Ferronyl, RBV = 0.58); H-reduced (AC- 325, RBV = 0.56); H-reduced (Hi-Sol, RBV = 0.50); carbonyl (CF, RBV = 0.37); reduced (Atomet 95SP, RBV = 0.36). The reduced iron was distinguished by having significantly lower RBV (0.36) although no significant overall ranking was possible. CONCLUSION: Based on a validated method this doubleblinded cross-over study in humans showed that the evaluated elemental iron powders currently available for commercial use are significantly less well absorbed compared to FeSO(4). The results indicate that the reduced iron powder was absorbed to a lower extent compared to the other iron powders and only 36% compared to FeSO(4). Ascorbic acid seems to improve the bioavailability of elemental iron even though a rather low molar ratio is used. Thus, if confirmed, this enhancing effect of ascorbic acid on elemental iron when used as a fortificant could be used by co-fortifying them.

Adult↗

PubMed1995

Repeated amphetamine administration induces a prolonged augmentation of phosphorylated cyclase response element-binding protein and Fos-related antigen immunoreactivity in rat striatum.

Semi-quantitative immunocytochemistry was used to investigate the levels of cyclase response element-binding protein, phosphorylated cyclase response element-binding protein, Fos and Fos-related antigen immunoreactivity in the striatum of rats after acute or repeated amphetamine administration. Rats were perfused 20 min (phosphorylated cyclase response element-binding protein) or 2 h (cyclase response element-binding protein, phosphorylated cyclase response element-binding protein, Fos, Fos-related antigen) after a single injection (5 mg/kg, i.p.) or five daily injections of amphetamine. The latency to onset of stereotypical behaviors was significantly reduced in rats exposed to repeated amphetamine as compared to acute amphetamine, indicating development of behavioral sensitization. Cyclase response element-binding protein immunoreactivity was not altered in the dorsal or ventral striatum following acute or repeated amphetamine. Phosphorylated cyclase response element-binding protein immunoreactivity was significantly induced 20 min, but not 2 h, following acute amphetamine, whereas a significant induction of phosphorylated cyclase response element-binding protein immunoreactivity was found 20 min and 2 h after repeated amphetamine in the dorsal striatum only. Fos immunoreactivity was significantly induced in the dorsal striatum following acute and repeated amphetamine. Fos immunoreactivity in the core of the nucleus accumbens was significantly increased following repeated amphetamine only. Acute amphetamine induced, and repeated amphetamine further augmented, Fos-related antigen immunoreactivity in the dorsal striatum, while not affecting Fos-related antigen immunoreactivity in the nucleus accumbens. These data demonstrate that repeated amphetamine administration results in a prolonged induction of phosphorylated cyclase response element-binding protein and Fos-related antigen immunoreactivity in the dorsal striatum, indicating that alterations in striatal gene expression associated with the development of behavioral sensitization may be mediated, in part, by these transcription factors.

Amphetamine↗

PubMed1996

Elemental composition and water content of rat optic nerve myelinated axons during in vitro post-anoxia reoxygenation.

During transient hypoxic episodes, CNS nerve cells and their axons undergo structural and functional damage. However, additional injury occurs as a result of subsequent tissue reperfusion. To examine mechanisms of this secondary injury, we have characterized the temporal patterns of element (e.g. Na, K, Ca) and water deregulation in rat optic nerve myelinated axons and glia during in vitro exposure to post-anoxia reoxygenation. Isolated nerves were exposed to 1 h of anoxia followed by varying periods of reoxygenation (20, 40, 60 and 180 min). Changes in subcellular distribution of elements and water were determined using electron probe X-ray microanalysis. In response to reoxygenation, the majority of large and medium axons exhibited a progressive worsening of anoxia-induced elemental deregulation. Axoplasmic Na, Cl and Ca increased substantially while K concentrations remained at or slightly below anoxic levels. Respective mitochondria expressed similar elemental changes except that Ca levels increased dramatically. A limited number of large and medium axons and their mitochondria showed initial but transient improvements in elemental composition. In contrast, approximately 50% of small axons initiated early improvements in transmembrane elemental distribution that continued to advance throughout the reoxygenation period. Remaining axons of this group displayed severe elemental derangement similar to that of larger fibers. The elemental composition of reoxygenated glial cells and myelin remained comparable to that reported after 60 min of anoxia. These results indicate that while larger axons express eventual severe elemental deregulation in spite of reoxygenation, many small axons appear capable of re-establishing near-normal transmembrane ion gradients. Results of the present study suggest reoxygenation/reperfusion injury of CNS axons is mediated by exacerbation of Ca2+ entry and the generalized ion deregulation initiated during anoxic or ischemic episodes. These findings constitute basic information regarding damage induced by post-anoxia reoxygenation and could, therefore, contribute toward understanding the mechanism of reperfusion injury following hypoxic or ischemic episodes in CNS white matter. Furthermore, deciphering the route of Ca2+ influx during reoxygenation/reperfusion might provide a basis for rational design of effective pharmacotherapies.

Animals↗

PubMed2005

Is supplementation with elemental diet feasible in patients undergoing pelvic radiotherapy?

BACKGROUND: Acute gastrointestinal upset occurs in approximately 80% of patients undergoing radiotherapy for pelvic cancers. Underlying changes relate to denudation of the mucosal layer which renders the small intestine vulnerable to additional damage from proteolytic enzymes and bile acids. Severe acute bowel symptoms may predispose to progressive fibrotic and ischaemic changes. Elemental diet given during treatment may reduce acute and chronic bowel symptoms induced by pelvic radiotherapy. METHODS: This study aimed to assess compliance with elemental diet during pelvic radiotherapy. Patients with gynaecological, urological or rectal malignancy undergoing radical or adjuvant pelvic radiotherapy were randomised to one of five groups. Each group was assigned a target quantity of three different elemental sip feeds (Group 1, 20%, Group 2, 50%, Group 3, 75% of calorie requirements taken as E028 extra liquid; Group 4, 50% of calorie requirements taken as E028 extra powder; Group 5, 50% of calorie requirements taken as Emsogen powder). Compliance was assessed using a diary card and weekly assessment. Statistical analyses were conducted on an intention to treat basis. RESULTS: Fifty patients (44 female, six male) mean age 58 yr (95% CI 55-61), were recruited to the study (24 endometrial, 17 cervical, 7 rectal, 1 vulval and 1 bladder carcinoma). Mean weight at baseline was 74.5 kg (95% CI 69-80) and this did not change during treatment. Full compliance was achieved in three patients, all from Group 1. By week 5, only 46% of patients were consuming elemental diet. Post hoc analysis of variance with repeated measures indicated that there were no significant differences in volume of elemental diet consumed between groups (P = 0.937). There was a significant inverse linear relationship between intake of elemental diet and time (P < 0.001). CONCLUSIONS: Different formulations of elemental diet do not influence compliance. Patients are unlikely to be able to consume more than one-third of their calorie requirements in the form of an elemental sip feed. Further investigation is warranted to determine if intervention with this volume of elemental diet is beneficial.

Analysis of Variance↗

PubMed2006

Dissolved oxygen as a physico-chemical supporting element in the Water Framework Directive.

For transitional and coastal waters the Water Framework Directive identifies 5 "General chemical and physiochemical elements supporting the biological elements". The five elements are transparency, thermal conditions, oxygenation conditions, salinity and nutrient conditions. "Supporting" in the context of the directive means that the values of the physicochemical quality elements are such as to support a biological community of a certain ecological status, recognising the fact that biological communities are products of their physical and chemical environment. Physicochemical and hydromophological aspects fundamentally determine the type of water body and habitat, and hence the type specific biological community. The directive does not intended that these supporting elements should be used as surrogates for the biological elements in monitoring. The monitoring and assessment of the physical and physicochemical quality elements will support the interpretation, assessment and classification of the results arising from the monitoring of the biological quality elements. This paper considers the challenges involved in the development of oxygen standards for the directive, their relationship to the biological elements and normative conditions of the directive and to regulatory requirements.

Ecosystem↗