Treatment of Iron Deficiency with or without Anaemia with Intravenous Ferric Carboxymaltose in Gynaecological Practices - A Non-Interventional Study.

In this multi-centre, prospective, non-interventional study, the effectiveness and tolerance of ferric carboxymaltose (ferinject®; FCM) was tested through use in standard gynaecological practice. In total, data from 273 patients was evaluated. 193 of these patients displayed iron deficiency anaemia (IDA), and 68 had iron deficiency without anaemia (ID). The reasons for the ID/IDA were hypermenorrhoea (HyM) (n = 170), post-partum condition (PP) (n = 53) or another indication (n = 53). The average age of the patients was 40 years old, with 8 % of them being vegetarians. Half of the patients had already been treated for anaemia, primarily with oral iron products (94 %). The primary, serious accompanying symptoms of anaemia were fatigue (72 %), lack of concentration (42 %), pale mucous membranes (42 %), headache (26 %) and sleep disorders (21 %). Only one patient did not show serious symptoms at the start of the study. The most frequent indications for parenteral therapy were the need for rapid iron substitution to reduce symptoms (> 70 %), followed by the lower effectiveness or intolerance of oral products (42 % each) as well as patients not completing the course of treatment with oral products (12 %). Patient information was collected at both the beginning and the end of the observation period, which lasted 15 weeks on average. FCM was most frequently administered via infusion (92 %; average infusion duration 21 minutes). Seven percent of patients received bolus injections. The average total iron dosage per patient was 788.7 mg (median 550 mg; range: 50-3000 mg); the median individual dosage was 500 mg (range: 50-1000 mg). The total dosage was, in most cases, administered through a single application (range: 1-10). Symptoms, blood values (Hb), iron stores (serum-ferritin [S-ferritin]) and transport iron (transferrin saturation [TSAT]) normalised to a large extent. In all subgroups, 92 % of women displayed a marked improvement in all of their symptoms. The average increase in Hb-value in the group as a whole was statistically significant, increasing from 10.5 to 13.0 g/dl. In the group with anaemia, the value increased from 9.9 to 13.3 g/dl, with 80 % of women reaching normal Hb-values. The average S-ferritin value increased by a statistically significant > 70 µg/L from 17.2 to 88.8 µg/l and the value for the TSAT increased from 16.3 % to 22.8 %. Seven patients reported experiencing side effects. None of the results were severe. Overall, as part of this non-interventional study for everyday routine in a gynaecological practice, a rapid improvement in symptoms accompanied by the rectification of iron deficiency and anaemia was shown with low occurrences of mild undesirable events, and therefore the data obtained from controlled clinical studies on the effectiveness and tolerance of intravenous ferric carboxymaltose could be confirmed.

Effect of dietary fatty acid pattern on growth, body fat composition and antioxidant parameters in broilers.

The effects of dietary fat supplementation on performance, fatty acid (FA) composition of tissues and antioxidant defence system of broilers were studied. Male broilers were placed in 20 floor pens (60 broilers per pen). The broilers were fed by diets with added different energy sources: lard (L); sunflower oil (SFO); soybean oil (SBO); and linseed oil (LSO). The treatments did not modify significantly growth performance and feed intake of the broilers. There was no effect of dietary FA pattern on reduced glutathione level and glutathione peroxidase activity of plasma, erythrocyte and liver samples. However, higher PUFA content of the diet resulted in a significant increase in malondialdehyde level of erythrocytes and liver. The broilers fed LSO diet more effectively maintained their antioxidant status with enhanced plasma radical scavenger capacity. FA composition in tissues reflected the FA pattern of the diets, although proportion of FAs with four or more double bonds was metabolic specific. LSO diet increased the level of C18:3, C20:5 and C22:6 in tissue lipids in relation to L, SFO and SBO diets. Significantly increased plasma radical scavenging capacity in concert with the enhanced C20:5 and C22:6 proportion in liver and muscle during LSO feeding indicate metabolic changes to counteract the oxidative injury. This may be related to the compounds produced after different biochemical pathways of n-6 and n-3 FAs.

The effect of citrus flavonoids on the redox state of alimentary-induced fatty liver in rats.

Both chronic venous insufficiency (CVI) and fatty liver may develop at the same time. Hesperidin and diosmin are used for the treatment CVI. There is no information, however, on the effect of these flavonoids in the redox state of fatty liver. In this study, male Wistar albino rats were fed a lipid-rich diet with or without 450 mg diosmin-50 mg hesperidin-containing drug (60 mg kg(-1) body weight/day, per os) for 9 days to determine the impact of treatment on antioxidant defence system of the fatty liver. We detected free SH-group concentration (SHC), hydrogen-donating ability (HDA), and natural scavenger capacity were decreased and hepatic malonaldehyde content and dien conjugate (DC) content in rats with fatty liver were increased compared to the control. After treatment in fatty liver, these parameters (except DC) significantly improved and approached the control value. Our results indicate that diosmin-hesperidin-containing drug may be a useful agent in improving the antioxidant defensive system in alimentary-induced fatty liver disease.

Three mechanisms in the pathogenesis of pre-eclampsia suggested by over-represented transcription factor-binding sites detected with comparative promoter analysis.

Microarray studies generating lists of genes with altered expression in placentas from pregnancies complicated with pre-eclampsia (PE) have so far been published in several different studies. Working under the assumption that altered gene expression in PE may be the result of altered expression of regulatory transcription factors (TFs), we looked for over-represented TF-binding sites (TFBSs)-which indicate the involvement of TFs in gene regulatory networks-in lists of genes (n = 143) compiled in these studies. We compared the prevalence of TFBSs in the promoter regions of 68 genes with the background prevalence of TFBSs in promoters of the human genome. The prevalence of the E47, sterol regulatory element binding protein (SREBP) and NFKB-p50 TFBSs was higher (P < 0.005) in the promoter sequences of the PE gene lists than in the background model. Each of these TFBSs could be implicated in the development of PE. The E47 protein is an E-protein or basic helix-loop-helix (bHLH) TF. Data support the role of bHLHs in the differentiation of placental tissue. SREBP-1, a lipid-sensing sterol regulatory element-binding protein, is a critical regulator of fatty acid homeostasis in the placenta. The target genes of NFKB-p50 determine inflammatory response, and aberrant cytokine homeostasis is a further sign of PE. These TFs may provide an insight into the pathogenesis of the disease.

Bilateral striatal lesion associated with varicella.

Bilateral striatal lesion is characterised by a specific clinical syndrome (encephalopathy with rigidity, irritability, variable pyramidal, and extrapyramidal symptoms, speech abnormalities) and symmetrical lesion of the basal ganglia including the caudate nucleus, the putamen, and occasionally other nuclei. We report three cases in whom bilateral striatal lesion developed in association with varicella. Each patient recovered completely and showed no signs of cognitive deficiency, chorea or hyperkinetic syndrome, all of which have been reported as sequelae of BSL associated with other conditions. These cases suggest that bilateral striatal lesion may be an immune-mediated complication of varicella.

HbA1c levels and erythrocyte transport functions in complication-free type 1 diabetic children and adolescents.

Higher erythrocyte sodium-lithium countertransport activity (SLC) is implicated in the development of diabetic nephropathy. Altered glucose homeostasis and genetic susceptibility are claimed to play a role in the elevation of SLC. We aimed to test whether metabolic control or the genetic variants of G protein beta 3 (Gb3) subunits determine SLC and other erythrocyte transport activities in complication-free stage of type 1 diabetes. A total of 96 complication-free type 1 diabetic children and adolescents were enrolled. SLC, Na(+)/K(+)-ATPase (NAK) and Ca(2+)-ATPase (CA) were measured by functional assays in erythrocytes. Gb3-C825T polymorphism was determined by PCR-RFLP. Results were related to HbA(1c) and were compared to those of 97 healthy controls. SLC activity was higher in diabetics (387+/-146 vs. 280+/-65 mmol/RBC. hour) and correlated with HbA(1c) levels (y=0.004x+6.42, r=0.33, n=96, p<0.01). NAK and CA activities were unaltered. The prevalence of (825)T allele was similar in the patient and control groups (0.34 vs 0.37) and no differences in enzyme activities were observed between the (825)T allele-positive and negative subjects. Although metabolic control correlated with SLC, other membrane functions were not affected. Therefore we hypothesize that the relationship between advanced glycation and SLC elevation is not causative. Rather, a genetic susceptibility for the coexistence of poor metabolic control and higher SLC is more likely. However, the presence of Gb3-C825T variant is not likely to be a risk factor for SLC-elevation and altered metabolic control diabetes.

Short-term omeprazole treatment does not influence biochemical parameters of bone turnover in children.

Gastric proton pump inhibitors are widely used in the treatment of dyspeptic problems and for the eradication of H. pylori infection. Data are not available on whether omeprazole, a representative of proton pump inhibitors, influences the function of osteoclastic H+-pump in children. We studied the impact of short-term omeprazole administration on the biochemical parameters of bone turnover in pediatric patients. Urinary calcium excretion, serum total alkaline phosphatase activity, collagen type 1 crosslinked C-telopeptide, and osteocalcin levels were determined in 34 children [20 girls (9 prepubertal) and 14 boys (6 prepubertal)] before and after 2 weeks of omeprazole treatment at a dose of 20 mg/day. The measured parameters were within the healthy reference range in each patient. None of them altered during the study in any age or in any gender. We conclude that omeprazole, at a dose of 20 mg/day, does not significantly influence the investigated biochemical parameters of osteoclast and osteoblast function in pediatric patients.

Plasma concentration of myeloperoxidase enzyme in pre- and post-climacterial people: related superoxide anion generation.

Neutrophil granulocytes are involved in the pathogenesis of atherosclerosis also through their free radical generation. The aim of the study was to test how extracellular levels of myeloperoxidase (MPO; a granulocyte enzyme playing role in free radical production) change by age and what effect this change has on the production of the free radical superoxide anion by neutrophils. We also wanted to examine whether the antioxidant effect of different steroid hormones is realized through the MPO. Plasma myeloperoxidase concentrations of healthy blood donors were quantified by ELISA. Superoxide anion production was measured by photometry. Myeloperoxidase concentration was significantly lower in plasmas obtained from older women and men than in those from younger subjects. Adding the MPO inhibitors 4-aminobenzoic acid hydrazide (ABAH) and indomethacin to the granulocytes, the generation of superoxide anion increased and the decreasing effect of the steroids on superoxide production was inhibited. Incubating the neutrophils with the product of the reaction catalyzed by MPO itself (hypochlorite anion), we found significant decrease in superoxide generation. According to our results MPO seems to diminish the production of superoxide anion and so probably has an antioxidant ability. Therefore, its lower plasma levels may contribute to the increasing incidence of atherosclerosis and other free radical mediated disorders in old people. Thus, after further studies MPO might become one of the indicators of cardiovascular risk and the scavenger capacity in general.

Genetic variants of the tumour necrosis factor-alpha promoter gene do not influence the development of necrotizing enterocolitis.

UNLABELLED: Previous studies indicated that elevated tumour necrosis factor-alpha (TNF-alpha) levels may play a role in the development of necrotizing enterocolitis (NEC). The A(-308) and A(-238) variants of the promoter region of the TNF-alpha gene are reportedly associated with altered TNF-alpha production. The aim of our study was to determine the impact of these gene polymorphisms on the development and course of NEC in very-low-birthweight (VLBW) infants. Dried blood samples from 46 VLBW neonates with NEC were analysed using the method of restriction fragment length polymorphism. Samples from 90 VLBW neonates without NEC were used as controls. The prevalence of alleles with guanine-adenine transition in the -308 and -238 positions was the same in NEC and control subjects (12% vs 10% and 3% vs 4%, respectively). CONCLUSION: The investigated genetic variants of the TNF-alpha gene promoter region have no influence on the risk and course of NEC in VLBW infants.

Expression and activity of the Ca(2+)-atpase enzyme in human neonatal erythrocytes.

The plasma membrane Ca(2+)-ATPase (PMCA) is one of the main regulators of Ca(2+) homeostasis. We studied the perinatal alteration of the abundance and the activity of PMCA molecules in human erythrocytes in pre-term and full-term neonates and children at the age of 1-4 years. The lower abundance of the 4b isoform was associated with lower enzyme activity in full-term neonates compared to children. Although the number of PMCA molecules was higher in pre-term neonates, their total PMCA activities were identical to those of full-term neonates. Our findings suggest that the abundance of PMCA molecules changes during the perinatal development. The same activity at higher enzyme molecule numbers might indicate a potential immaturity of the enzyme in the pre-term infant.

Abundance and activity of Ca2+-ATPase in hypercalciuric children.

The plasma membrane Ca2+-ATPase (PMCA) is one of the main regulators of cell Ca2+ homeostasis. The aim of our study was to determine whether the abundance and activity of PMCA are altered in erythrocytes of children with idiopathic hypercalciuria. Twenty-four children with idiopathic hypercalciuria (13 girls and 11 boys, mean age 10.6+/-4.8 years; mean urinary calcium concentration 0.85+/-0.20 mmol/mmol creatinine) and 30 healthy age-matched children were enrolled. PMCA protein abundance was determined by Western blot analysis. Enzyme activity was determined spectrophotometrically. The abundance of PMCA did not differ in hypercalciuric patients from that of control subjects (98+/-22% vs 100+/-18%). Moreover, the activity was not different between the studied groups (3141+/-1494 vs 2953+/-780 nmol ATP/mg protein/h). The extent of hypercalciuria did not correlate with enzyme abundance or activity. Assuming that erythrocytes may reflect the renal tubular transporting processes, our data suggest that other Ca2+-transport mechanisms than PMCA might be involved in the development of idiopathic hypercalciuria in children.

Percutaneous ureterolithotomy: direct method for removal of impacted ureteral stones.

PURPOSE: We report 52 percutaneous urterolithotomies in 51 patients having large, impacted middle ureteral stones. Direct percutaneous stone removal can be performed as successfully as in cases of renal stones treated with percutaneous nephrolithotomy. METHODS: The operation is performed under local anesthesia; therefore, the procedure is quicker and simpler than the laparoscopic or retroperitoneoscopic intervention. All patients became stone free. In two patients (4%), ultrasound disintegration was necessary; in the remaining cases, there was no need for any fragmentation: the stone was removed intact. A retroperitoneal drain was always left at the end of the procedure. With the exception of two cases, the ureter was always stented without closure of the ureteral incision. RESULTS: Fever (> or = 38 degrees C) was observed in 15 patients (29%) for 2 days. Retroperitoneal hematoma 5 cm in diameter was seen in one patient. One patient had urine leakage through the retroperitoneal drain in the postoperative period for 18 days. Also, one patient came back 3 days after discharge with urine leakage through the percutaneous retroperitoneal tract. CONCLUSION: Direct percutaneous ureterolithotomy is an effective way to remove impacted middle ureteral stones but is advisable only for endourologists with considerable experience.

Oxidative damage in alcoholic liver disease.

OBJECTIVE: The metabolic effects of alcohol are due both to its direct action and to that of its first metabolite, and can also be connected with the changes in redox state. Differences in ethanol distribution, bioavailability and hepatic metabolism can provide insight into the protective and predisposing factors in alcoholism, as well as gender differences of alcohol toxicity. Oxidative stress occurs following various conditions of ethanol consumption. DESIGN: Twenty-six Caucasian patients with alcoholism and 32 healthy, abstinent controls of both sexes were investigated with special regard to reduction-oxidation status and ad hoc free-radical-antioxidant balance. METHOD: Plasma free SH-group concentration, H-donating ability, and reducing power property were measured by simple spectrophotometric methods. Total scavenger capacity was determined by a newly developed chemiluminometric method in plasma and erythrocytes. RESULTS: Alcoholics showed a decrease of free SH-group concentration, hydrogen-donating ability and an increase of reducing power property in plasma. A decreased total scavenger capacity of erythrocytes and plasma of alcoholic patients, combined with gender differences, could be detected. CONCLUSIONS: Alcoholic dependence causes gradual exhaustion of the antioxidant capacity of erythrocytes, therefore this non-invasive measurement may be useful as a follow-up of the evolution of alcoholic liver disease. The results also suggest a gender susceptibility of alcohol toxicity.

Variance of ACE and AT1 receptor gene does not influence the risk of neonatal acute renal failure.

High neonatal activity of the renin-angiotensin system (RAS) is crucial for the maintenance of glomerular filtration of the newborn. The aim of the present study was to investigate whether genetic polymorphisms leading to lower angiotensin converting enzyme activity (ACE) or impaired functionality of angiotensin II (AII) type 1 receptor (AT1R) might predispose very low birth weight newborns (VLBWs) to the development of acute renal failure (ARF). The medical records of 110 VLBW infants were analyzed. ARF developed in 42 of them during the first postnatal week, while 68 neonates exhibited normal renal function. The ACE I/D polymorphism and the A1166C variants of AT1R were determined from dried blood samples. The frequency of the ACE I allele did not differ in ARF and non-ARF groups (0.307 and 0.284); the frequency of the AT1R C1166 variant was also the same in ARF and non-ARF groups (0.250 and 0.227). Although low activity of RAS has been implicated in the development of neonatal ARF and data indicated that the functionality of RAS is influenced by the I/D variants of the ACE gene and the A1166C variant of the AT1R gene, we could not demonstrate any effect of these polymorphisms on the development of ARF in VLBW infants.

Determination of H+/K+-ATPase activity in human gastric biopsy specimens.

The aim of our work was to develop a method to determine the the H+/K+-ATPase activity of human gastric biopsy samples. Our method is based on the phosphatase activity and the K+-inducible property of the enzyme. K+-inducible pNPPase activity was determined from homogenated corpus and antrum biopsy samples. H+/K+-ase activity was calculated as the difference between the corpus and antrum K+-inducible pNPPase activities. Quality control measurements were done during 20 successive days from pooled homogenates. The total, between-day and between-run, within-day and within-run coefficients of variations were between 10 and 16%. The healthy mean and reference range of K+-inducible pNPPase activity in the corpus was 95.8 (95% CI: 83.4-108.2 mU/mg protein); in the antrum it was 28.3 (21.6-35.0) mU/mg protein. The calculated H+/K+-ATPase activity was 67.2 (56.9-77.5) mU/mg protein. The measured activities were independent of the age and gender. Summarizing our results we have concluded, that our novel method might be a potential tool to gather data about the functional acid producing capability of human gastric mucosa.

Developmental changes in erythrocyte Na(+),K(+)-ATPase subunit abundance and enzyme activity in neonates.

AIM: To study the relation between erythrocyte Na(+),K(+)-ATPase subunit isoform composition, Na(+),K(+)-ATPase activity, and cation pump function in preterm and term neonates. DESIGN: Erythrocyte Na(+),K(+)-ATPase subunit isoform abundance, Na(+),K(+)-ATPase activity, and cation pump function were studied in blood samples obtained from 56 preterm neonates of 28-32 weeks gestation (group 1), 58 preterm neonates of 33-36 weeks gestation (group 2), and 122 term neonates (group 3) during the first two postnatal days. RESULTS: alpha(1) isoform abundance was higher and beta(2) isoform abundance was lower in group 1 than in group 3 (p = 0.0002). alpha(2) and beta(1) isoform abundance did not change with maturation and there was no evidence for the presence of the alpha(3) isoform. Gestational age was inversely related to Na(+), K(+)-ATPase activity (p = 0.0001) and directly related to intracellular Na(+) concentration (p = 0.0025). CONCLUSIONS: Expression of the alpha(1) and beta(2) Na(+),K(+)-ATPase subunit isoforms is developmentally regulated. The increased abundance of alpha(1) isoforms of immature neonates translates to increased ATPase activity. The lower intracellular Na(+) concentration of immature neonates suggests that their erythrocyte Na(+),K(+)-ATPase cation pump function may also be increased.

[Changes in the myeloperoxidase activity of human neutrophilic granulocytes and the amount of enzyme deriving from them under the effect of estrogen]. / Emberi neutrophil granulocyták mieloperoxidáz-aktivitásának és a belölük felszabaduló enzim mennyiségének változása ösztrogén hatására.

Free radicals which are produced constantly in the human body have a significant role in the development of atherosclerosis. The responsibility of leukocytes for vascular disease has been proved in several ways. Hormonally active women are protected much more against myocardial infarction than men, which fact can be explained partly by endocrinological reasons, too. The authors have set the aim to investigate whether estrogen therapy effects on the one hand the intracellular activity of the granulocyte-enzyme, myeloperoxidase (MPO), which takes place in free radical reactions and on the other hand the amount of MPO released from neutrophils. In the case of women having menopause and being treated with hormone replacement (n = 11) the intracellular activity and the amount of MPO-release increased significantly as compared to the level at the time of starting taking the medicine (p < 0.001). Based on the results it can be supposed that the vasoprotective effect of estrogens is fulfilled through their influence on the MPO enzyme, too. Besides the fact that intensified MPO activity through enhanced consumption might induce the decreased accumulation of H2O2 (a reactive oxygen species, substrate of MPO), MPO also has a role in the termination of the whole process of free radical production in granulocytes by the inactivation of the NADPH-oxidase system. This means that the growing intracellular MPO activity and the increased amount of enzyme released induce the decrease of the amount of free radicals produced during the "respiratory burst" and this is advantageous from the point of view of vasoprotection. The increased MPO activity and the NADPH-oxidase inactivation supposed to be elicited by it, might have further positive consequences since MPO has an effect on HDL-metabolism and the outflow of cholesterol from "foam cells", NADPH-oxidase has a suspected role in LDL-oxidation and NADPH is one of the cofactors of NO-synthase (NOS). The decreased superoxide anion level on the other hand may mitigate the chance of the neutralizing of nitric oxide (NO) by it. The superoxide anion is a potent vasoconstrictor and therefore, its diminished production may be beneficial, i.e. decreases the risk of coronary spasm. The new conceptual synthesis worked out by the authors may provide a possible explanation of the increased susceptibility to infections during steroid treatment, too.