The effect of iron therapy on oxidative stress and intestinal microbiota in inflammatory bowel diseases: A review on the conundrum.

One in five patients with Inflammatory Bowel Disease (IBD) suffers from anemia, most frequently caused by iron deficiency. Anemia and iron deficiency are associated with worse disease outcomes, reduced quality of life, decreased economic participation, and increased healthcare costs. International guidelines and consensus-based recommendations have emphasized the importance of treating anemia and iron deficiency. In this review, we draw attention to the rarely discussed effects of iron deficiency and iron therapy on the redox status, the intestinal microbiota, and the potential interplay between them, focusing on the clinical implications for patients with IBD. Current data are scarce, inconsistent, and do not provide definitive answers. Nevertheless, it is imperative to rule out infections and discern iron deficiency anemia from other types of anemia to prevent untargeted oral or intravenous iron supplementation and potential side effects, including oxidative stress. Further research is necessary to establish the clinical significance of changes in the redox status and the intestinal microbiota following iron supplementation.

[Gas embolism: another story related to a central venous catheter withdraw]. / Nouvelle observation d'une embolie gazeuse au retrait d'un cathéter veineux central.

Paradoxical gas embolism is rare but life threatening complication of central venous access. In this observation, we report a paradoxical gas embolism accompanied by an acute respiratory failure and a coma following a jugular central venous access withdrawal in a liver transplanted patient. Following this observation, we discuss the prevention of gas embolism accidents and the hyperbaric oxygen therapy for its management.

Distinct developmental changes in the distribution of calcium, phosphorus and sulphur during fetal growth-plate development.

Gradients in the concentrations of free phosphate (Pi) and calcium (Ca) exist in fully developed growth zones of long bones and ribs, with the highest concentrations closest to the site of mineralization. As high concentrations of Pi and Ca induce chondrocyte maturation and apoptosis, it has been hypothesized that Ca and Pi drive chondrocyte differentiation in growth plates. This study aimed to determine whether gradients in the important spectral elements phosphorus (P), Ca and sulphur (S) are already present in early stages of development, or whether they gradually develop with maturation of the growth zone. We quantified the concentration profiles of Ca, P, S, chloride and potassium at four different stages of early development of the distal growth plates of the porcine femurs, using particle-induced X-ray emission and forward- and backward-scattering spectrometry with a nuclear microprobe. A Ca concentration gradient towards the mineralized area and a stepwise increase in S was found to develop slowly with tissue maturation. The increase in S co-localizes with the onset of proliferation. A P gradient was not detected in the earliest developmental stages. High Ca levels, which may induce chondrocyte maturation, are present near the mineralization front. As total P concentrations do not correspond with former free Pi measurements, we hypothesize that the increase of free Pi towards the bone-forming site results from enzymatic cleavage of bound phosphate.

[Developmental delay in breastfed children due to inadequate diet of the mother]. / Ontwikkelingsachterstand bij borstgevoede kinderen door ontoereikend dieet van de moeder.

Two infant boys of 7 and 12 months respectively who presented with symptoms of failure to thrive and developmental delay were diagnosed with vitamin B12 deficiency. This deficiency is a rare condition in infants living in developed countries. It does occur, however, in infants who are breastfed by mothers with an inadequate diet. Both of the children studied were breastfed by vegetarian mothers. Following vitamin suppletion, both children showed signs of recovery. The importance of considering vitamin deficiencies in similar infants presenting with failure to thrive is emphasized. Moreover, maternal dietary habits in breastfed children should be checked. To prevent irreversible neurological damage, early recognition of any nutritional deficiencies is important.

A tomato homologue of the human protein PIRIN is induced during programmed cell death.

Programmed cell death (PCD), with similarities to animal apoptosis, was induced in tomato suspension cells by the topoisomerase I inhibitor camptothecin. Previously, a differential display screening was performed to isolate genes differentially expressed during camptothecin-induced cell death. As a result, the new tomato gene Le-pirin was isolated, whose mRNA levels dramatically increase during camptothecin-induced PCD. Le-pirin mRNA accumulation is also observed when cell death is triggered by the mycotoxin fumonisin-B1, but not when the suspension cells are treated with stress-related compounds such as ethylene, methyl jasmonate or salicylic acid. The caspase inhibitor Z-Asp-CH2-DCB and the calcium channel blocker LaCl3 effectively delayed whereas ethylene greatly stimulated camptothecin-induced PCD and the accumulation of Le-pirin mRNA. The Le-pirin encoded protein shows 56% identity with the human protein PIRIN, a nuclear factor reported to interact with the human oncogene Bcl-3. Human PIRIN stabilizes the formation of quaternary complexes between Bcl-3, the anti-apoptotic transcription factor NF-kappaB and its DNA target sequences in vitro. The isolation of Le-pirin and its implication in plant PCD provides new clues on the role of putative NF-kappaB-associated pathways in plant defence mechanisms.

[Determination of breakpoints for veterinary medically relevant antibiotics for resistance assessment of veterinary pathogens]. / Zur Festlegung von Grenzwertkonzentrationen (breakpoints) für veterinärmedizinisch relevante Antibiotika zur Resistenzbeurteilung bei tierpathogenen Erregern.

This article describes the meaning of the term clinical breakpoint. This is followed by a discussion of the parameters that need to be considered when setting valid breakpoints for active substances in veterinary medicine; in doing so we closely follow equivalent regulations and guidelines on the establishment of breakpoints in human medicine. Along with pharmacokinetic data and the results of clinical efficacy tests, susceptibility data of relevant organisms play a key role in the establishment of breakpoints. Published breakpoints are currently only available for a few modern drugs in veterinary medicine.

The ipiO gene of Phytophthora infestans is highly expressed in invading hyphae during infection.

The expression of the in planta-induced gene ipiO of the potato late blight pathogen Phytophthora infestans was analyzed during various developmental stages of its life cycle. ipiO mRNA was detected in zoospores, cysts, germinating cysts, and young mycelia, but not in sporangia or in old mycelia grown in vitro. ipiO is not only expressed in stages prior to infection but also during colonization of potato and tomato leaves. In disease lesions, ipiO mRNA was detected in the water-soaked area and the healthy-looking plant tissue surrounding it. In contrast, ipiO mRNA was not found in necrotized tissue or in sporulating areas of a lesion. To determine more precisely the location and time of ipiO gene expression in planta, cytological assays were performed using a P. infestans transformant expressing a transcriptional fusion between the ipiO1 promoter and the beta-glucuronidase (GUS) reporter gene. GUS staining was found specifically in the subapical and vacuolated area of tips of invading hyphae. The histochemical GUS assays demonstrate that ipiO is expressed during biotrophic stages of the disease cycle.

A gene encoding a protein elicitor of Phytophthora infestans is down-regulated during infection of potato.

Most species of the genus Phytophthora produce 10-kDa extracellular protein elicitors, collectively termed elicitins. Elicitins induce hypersensitive response in a restricted number of plants, particularly in the genus Nicotiana within the Solanaceae family. A cDNA encoding INF1, the major secreted elicitin of Phytophthora infestans, a pathogen of solanaceous plants, was isolated and characterized. The expression of the corresponding inf1 gene during the disease cycle of P. infestans was analyzed. inf1 was shown to be expressed in mycelium grown in various culture media, whereas it was not expressed in sporangiospores, zoospores, cysts, and germinating cysts. In planta, during infection of potato, particularly during the biotrophic stage, expression of inf1 was down-regulated compared to in vitro. The highest levels of expression of inf1 were observed in in vitro grown mycelium and in late stages of infection when profuse sporulation and leaf necrosis occur. The potential role of INF1 as an elicitor in interactions between P. infestans and Solanum species was investigated. Nineteen lines, representing nine solanaceous species with various levels of resistance to P. infestans, were tested for response to an Escherichia coli expressed INF1. Within the genus Solanum, resistance to P. infestans did not appear to be mediated by a defense response elicited by INF1. However, INF1 recognition could be a component of nonhost resistance of tobacco to P. infestans.

Characterization of chitinases able to rescue somatic embryos of the temperature-sensitive carrot variant ts 11.

To characterize the acidic endochitinase EP3, able to rescue somatic embryos of the carrot cell line ts11, the enzyme was purified from the medium of wild-type suspension cultures. Peptide sequences, deduced amino acid sequences of corresponding PCR-generated cDNA clones, serological relation and biochemical properties showed that there were at least five closely related chitinases, four of which could be identified as class IV EP3 chitinases with an apparent size of 30 kDa. Two other proteins were identified as a serologically related class I acidic chitinase (DcChitI) of 34 kDa, and a serologically unrelated 29 kDa class II acidic chitinase (DcChitII), respectively. Additional cDNA sequences, Western and Southern analysis showed the presence of a least two, but possibly more, highly homologous class IV EP3 genes in the carrot genome. Two class IV EP3 chitinases were tested and found to be able to increase the number of ts11 globular embryos formed under non-permissive conditions. One of the class IV EP3 chitinases as well as the class I chitinase DcChitI promoted the transition from globular to heart-stage ts11 embryos. The class II endochitinase and a heterologous class IV chitinase from sugar-beet were not active on ts11. This suggests that there are differences in the specificity of chitinases in terms of their effect on plant somatic embryos.

Home phototherapy: use and attitudes among community pediatricians.

Rather than using home phototherapy (HP), many pediatricians admit neonates to the hospital for the treatment of unconjugated hyperbilirubinemia. This study investigates the concerns and experiences of pediatricians related to HP use. A questionnaire was sent to 150 pediatricians in the Philadelphia, PA, area and 94 returned questionnaires. Of the responders, 30 of 94 had used HP. Twenty-nine users and 62 of 64 nonusers answered detailed questions regarding HP. Few practitioners follow American Academy of Pediatrics guidelines in selection of HP candidates. Among 29 pediatricians, prematurity (7), Rh incompatibility (13), positive direct Coombs (21), and ABO incompatibility (22) were not considered contraindications, although the American Academy of Pediatrics recommends all as contraindications. Almost all (29/30) HP users identified at least one problem with home treatment. The most commonly reported problems were parental anxiety, blood testing difficulties, and reimbursement issues. Nonusers (62) were asked their reasons for not using HP. The most common replies related to concerns about noncompliance (25), medical-legal issues (23), and administrative difficulties (22), none of which were cited as problems by HP users.

Effect of various triglycerides on plasma cholecystokinin levels in rats.

In the rat model, polyunsaturated vegetable oil has been shown to stimulate pancreatic secretion and promote pancreatic carcinogenesis, whereas dietary fish oil has been found to protect against carcinogenesis. Because cholecystokinin (CCK), a hormonal polypeptide secreted from the upper small intestine after food stimulation, is the most important known humoral stimulus of pancreatic secretion and also because this gut hormone has been shown to promote pancreatic carcinogenesis in the rat, we decided to study the effects of various triglycerides on CCK secretion in this species. Small amounts (2.5 mL) of corn oil, beef tallow, fish oil, medium-chain triglyceride (MCT) oil or saline (control) were administered to groups of five fasted rats. Plasma CCK levels were measured using a specific and sensitive radioimmunoassay. The maximal CCK increments for corn oil, beef tallow, fish oil and MCT oil were 3.0 +/- 0.5, 2.1 +/- 0.6 and 7.2 +/- 0.4 pmol/L, respectively. All the increments were significantly greater (p less than 0.05) than the change found after saline administration (-0.8 +/- 0.3 pmol/L). In another experiment, plasma CCK levels after intragastric administration of MCT oil reached a peak increment of 6.4 +/- 0.4 pmol/L after 240 min and continued to be significantly increased for the entire 480-min study period. It was concluded that all four triglycerides caused a significant CCK release in the rat and that the MCT oil was the most powerful stimulator of CCK secretion among the triglycerides studied.

Induction of non-bilayer lipid structures by functional signal peptides.

Using 31P NMR and freeze-fracture electron microscopy we investigated the effect of several synthetic signal peptides on lipid structure in model membranes mimicking the lipid composition of the Escherichia coli inner membrane. It is demonstrated that the signal peptide of the E. coli outer membrane protein PhoE, as well as that of the M13 phage coat protein, strongly promote the formation of non-bilayer lipid structures. This effect appears to be correlated to in vivo translocation efficiency, since a less functional analogue of the PhoE signal peptide was found to be less active in destabilizing the bilayer. It is proposed that signal sequences can induce local changes in lipid structure that are involved in protein translocation across the membrane.

Improvements of the infectivity of in vitro transcripts from cloned cowpea mosaic virus cDNA: impact of terminal nucleotide sequences.

Full-length DNA copies of both B- and M-RNA of cowpea mosaic virus (CPMV) were constructed downstream from a T7 promoter. By removal of nucleotides from the promoter sequence, B- and M-RNA-like transcripts with varying numbers of additional nonviral sequences at the 5' end were obtained upon transcription with T7 RNA polymerase. The infectivity of the transcripts in cowpea protoplasts was greatly affected by only a few extra nonviral nucleotides at the 5' end. The addition of about 400 nonviral nucleotides at the 3' end did not have any effect. Using the most infectious transcripts, in 40% of the cowpea protoplasts replication and expression of B-RNA like transcripts were observed and in 10% of the protoplasts both B- and M-RNA-like transcripts multiplied. Moreover, cowpea plants could also be infected with these transcripts. Sequence analysis showed that the 5' terminus of the M-RNA transcripts and the 3' terminus of the B-RNA transcripts were completely restored during replication in plants, including a poly(A) tail of variable length. Swapping experiments have been used to identify an influential point mutation in the coding region for the viral polymerase of a noninfectious B transcript. This experiment demonstrates the potential of the optimized infection system for future analysis of virus-encoded functions.

Elemental diet stimulates gallbladder contraction and secretion of cholecystokinin and pancreatic polypeptide in man.

This study was undertaken to investigate the effect of ingestion of 80 g Vivonex on gallbladder volume, plasma cholecystokinin (CCK), and pancreatic polypeptide (PP) in eight healthy volunteers and to compare the results with those obtained after ingestion of 60 ml corn oil. Gallbladder volumes were measured by ultrasonography. Plasma CCK was determined by radioimmunoassay using region-specific antibodies; antibody 1703 binds to COOH-terminal CCK-peptides containing at least 14 amino acid residues, while antibody T204 binds to COOH-terminal CCK-peptides containing the sulfated tyrosine region. Plasma PP was also measured by radioimmunoassay. Ingestion of Vivonex induced significant increases in plasma CCK (0.6 +/- 0.1 to 4.6 +/- 0.6 pM, antibody 1703; 1.8 +/- 0.3 to 5.9 +/- 0.5 pM, antibody (T204; P less than or equal to 0.0005) and decreases in gallbladder volume (21.4 +/- 2.8 to 11.2 +/- 2.3 cm3; P = 0.0001). Integrated plasma CCK secretion and gallbladder contraction after Vivonex were not significantly different from the results found after corn oil. Both Vivonex and corn oil-induced small increases in plasma PP. We conclude that Vivonex is a potent stimulus for the secretion of CCK and contraction of the gallbladder.

The colorimetric determination of cyanide in human food and animal feed.

The well-known Kröller method for the determination of cyanide requires the use of the harmful chemicals benzidine (carcinogenic) and bromine (toxic) in the colorimetric part; the analytical result depends strongly on the conduct of the liberation procedure. The substitution of barbituric acid and N-chlorosuccinimide for benzidine and bromine has been investigated. The reproducibility of both colorimetric reactions is similar, but the sensitivity of the barbituric acid colorimetry is approximately 50% higher. A reproducible liberation yield can be obtained by a proper control of the heating programme. The detection limit for cyanide in a solution is approximately equal to 10 micrograms/l.

Effect of dietary cod-liver oil on the lipid composition of human erythrocyte membranes.

The effect of dietary cod-liver oil on factors which characterize membrane lipid fluidity was studied. To six volunteers a daily supplement of 15 ml of cod-liver oil, providing 3 g of omega 3 fatty acids, was given for 2 weeks. Changes induced by the supplement in the fatty acid patterns of the individual erythrocyte phospholipid classes did not occur at the same rate or in the same degree. A rapid incorporation of omega 3 fatty acids in plasma lipids and in erythrocyte phosphatidyl choline, at the expense of linoleic acid, was seen, resulting in increased total unsaturation. A slower and quantitatively smaller incorporation of omega 3 fatty acids in erythrocyte phosphatidyl ethanolamine and phosphatidyl serine was seen. No change in the fatty acid pattern of sphingomyelin was seen. Withdrawal of the supplement for 2 weeks did partly reverse the cod-liver oil induced changes in erythrocyte phosphatidyl choline, while the changes in erythrocyte phosphatidyl ethanolamine and phosphatidyl serine lasted. Neither a change in distribution of erythrocyte phospholipid classes, nor in the erythrocyte cholesterol/phospholipid ratio was found. The observed changes in lipid composition are indicative of an increased lipid fluidity.

Hypothalamic influence on insulin and glucagon release in the rat.

Blood glucose, plasma insulin, and glucagon levels were measured in undisturbed and free-moving rats. The insulin and glucagon levels rise in the 1st min after the beginning of food ingestion, whereas the glucose level begins to increase only in the 3rd min if carbohydrate-rich food is eaten. This early rise in insulin and glucagon level is also observed under conditions in which carbohydrate-free food is eaten. A similar release of insulin and glucagon can be obtained by injection of 0.1 microgram of norepinephrine into the ventromedial hypothalamus, but the same injection made into the lateral hypothalamus causes release of insulin only, whereas injections in other hypothalamic areas are nearly without effect. Similar injections of isoproterenol did not cause changes in insulin, glucagon, and glucose levels. It is suggested that the early insulin and glucagon responses are of reflex origin and that the ventromedial and lateral hypothalamic areas are relay stations in the reflex pathways. The lack of effect of atropine to block the insulin and glucagon responses to noradrenergic stimulation of the ventromedial hypothalamus indicates that the efferent pathway is not cholinergic.

Hypnosis, stimulus preference and autonomic response.

We investigated whether stimuli consisting of beautiful and ugly colours as judged by human subjects elicit different autonomic response patterns. The autonomic functions recorded were heart rate (HR) respiration rate, skin conductance, number of GSFs (nGSR) and also eye movements, as an index of somatic activity. In order to obtain strong responses, i.e. to avoid inhibition of 'natural' responses by anxiety due to the laboratory setting, we made use of post-hypnotic suggestions regarding the nature of the stimuli the subjects were to expect. It appeared that for all but one autonomic function differences could be found between beautiful and ugly stimuli, in the sense that during the ugly stimuli more 'activation' occurred. The direction of HR change during the beauriful stimuli was opposite to those of the other functions. Effect of hypnosis on autonomic response could be substantiated for HR and nGSR. Apart from hypnosis it seems likely that the whole experimental set-up may have helped to reduce 'experimental anxiety'. One may conclude that response specificity for pleasant and unpleasant stimuli seems to exist.