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Oxytocin achieves its effects after binding the oxytocin receptor (OXTR). Oxytocin plays an important role in empathy. The aim of this study was to examine the influence of two single nucleotide polymorphisms (SNPs) of the OXTR gene (rs53576 and rs2254298) on empathy measures and plasma oxytocin levels. Seventy-four university students were screened for the OXTR rs53576 and rs2254298 SNPs using the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method. The level of oxytocin in the plasma was measured by the enzyme linked immunosorbent assay (ELISA). All subjects were assessed with the empathy quotient (EQ) questionnaire and Reading the Mind in the Eyes Test (RMET). Subjects carrying the rs53576 GG genotype had a higher EQ score, compared to GA/AA genotype carriers. By gender analysis, significance was reached only in females. Considering the influence of both examined polymorphisms on empathy, participants with the GGGG diplotype had a higher EQ in comparison with GAGG/AAGG carriers. These hormone effects were not correlated with plasma oxytocin levels. This is the first study implying that higher empathy in rs53576 GG genotype carriers may not depend on plasma oxytocin levels, but possibly on the number and function of OXTRs in the brain. [Project of the Serbian Ministry of Education, Science and Technological Development, Grant no. III41018]

The influence of ultraviolet (UV) radiation on the leaching of di(2- -ethylhexyl) phthalate (DEHP) from 8 different parts of plastic medical devices made of poly(vinyl chloride) (PVC) that are used in two important medical procedures (peritoneal dialysis and transfusion) was investigated. The investigation was performed for three different extraction times (6, 15 and 30 days). DEHP determination was realized by gas chromatography–mass spectrometry (GC-EI– –MS). All the investigated samples contained a significant amount of DEHP. The results showed that some of the set for peritoneal dialysis contained DEHP in higher amounts than samples from the transfusion set. All samples of tubing material showed higher concentration levels of DEHP than the coupled bags. Results obtained after UV treatment showed that UV radiation has a certain influence on DEHP leaching from samples of PVC medical devices. The smallest difference was in the case of the quadruple blood bag from the transfusion set (about 73 % remained), while the biggest difference was obtained for the SAG-M transfer bag, also from the transfusion set, where just 25 % of total content of DEHP remained. The results obtained for DEHP leaching from investigated samples by time showed that most of the samples showed significant differences in the amounts of DEHP leached after 6 and 30 days. [Project of the Serbian Ministry of Education, Science and Technological Development, Grant no. III 41018]

The presence of DEHP in dialysis and infusion sets for peritoneal dialysis and parenteral nutrition, which are made of PVC and other plastic polymeric materials, were investigated. Phthalate determination was carried out by gas chromatography - mass spectrometry method (GC-MS). The results showed that the peritoneal dialysis set (bag and tubing) made of PVC contains DEHP in significant amount, about 31 - 34%. Solution for peritoneal dialysis which was stored in the investigated PVC bag, contains low amount of DEHP, about 3.72 μg dm-3. Infusion bottles which are made of LDPE, also contain DEHP but in lower amount than PVC bags. LDPE bottle for packaging physiological saline solution (0.9% NaCl) showed higher amount of DEHP than LDPE bottle for packaging Ringer’s solution. In contrast, solution stored in bottle with lower DEHP level, i.e. Ringer’s solution contained about three times higher concentration of DEHP than physiological saline solution stored in bottle with higher DEHP level. Concentrations of DEHP in Ringer’s solution and physiological saline solution are 17.30 and 5.83 μg dm-3, respectively. The obtained values are under estimated upper-bound dose of DEHP received by adult patients undergoing procedures of peritoneal dialysis and parenteral nutrition. [Projekat Ministarstva nauke Republike Srbije, III 41018]

Background: The primary goal of this study was to evaluate the influence of cytochrome P450 (CYP) 3A5 (6986A>G) and ABCB1 (3435C>T) polymorphisms on tacrolimus (TAC) dosage regimen and exposure. Second, we evaluated the influence of TAC dosage regimen and the tested polymorphisms on renal oxidative injury, as well as the urinary activities of tubular ectoenzymes in a long-term period after transplantation. Also, we aimed to determine the association between renal oxidative stress and tubular damage markers in the renal transplant patients. Methods: The study included 72 patients who were on TAC based immunosuppression. Allele-specific PCR was used for polymorphism determination. We measured the urinary thiobarbituric acid reactive substances (TBARS) and reactive carbonyl derivates (RCD) in order to evaluate oxidative injury, as well as the urinary activities of ectoenzymes (N-acetyl-b-Dglucosaminidase, aminopeptidase N and dipeptidyl peptidase IV) to evaluate tubular damage. Results: The carriers of CYP 3A5*1 allele required statistically higher daily doses of TAC than CYP *3/*3 carriers, as well as the carriers of C allele of ABCB1 gene compared to those with T T genotype. Also, there were no differences in TBARS, RCD and the activities of ectoenzymes between the patients' genotypes. Our results showed significant correlations between urinary TBARS and RCD and the ectoenzymes' activities. Conclusions: Our findings suggest that CYP 3A5 and ABCB1 3435 polymorphism may affect TAC daily doses, but not the drug's tubular toxicity. Furthermore, tubular damage may be associated with increased renal oxidative stress.

Background: The aim of the study was to evaluate parameters of oxidative and nitrosative stress as well as antioxidative parameters in a group of renal transplant recipients with stable graft function and no clinical signs of cardiovascular disease. We also aimed to determine the correlations among these parameters and to evaluate potential differences in all the biomarkers with regard to the immunosuppression protocol. Methods: We enrolled 57 renal transplant recipients and 31 controls who were age and sex matched with the renal transplant recipients. All of the patients included in this study had post-renal transplant surgery at least 12 months earlier and were on standard immunosuppressive therapy. In this study, we determined thiobarbituric acid-reactive substances in plasma and red blood cells and advanced oxidation protein products, nitrosative stress parameters (asymmetric and symmetric dimethylarginine - ADMA and SDMA), and antioxidative parameters (total SH groups and catalase activity). Results: The results of our study demonstrated that the levels of oxidative and nitrosative stress were significantly increased compared to the healthy population (p < 0.01 except for plasma catalase activity p < 0.05). Correlation analysis showed significant positive correlations between: ADM A and SDMA (p < 0.01); ADM A and nitrates (p< 0.05); SDMA and nitrates (p < 0.05); between OS parameters in the experimental group; AOPP and SH groups (p < 0.05) and TBARS in plasma and SH groups (p < 0.01), SDMA and AOPP (p< 0.05); SDMA and TBARS in plasma (p < 0.05); SDMA and SH groups (p < 0.01); nitrates and SH groups (p < 0.05). Conclusion: There was no significant difference in oxidative and nitrosative stress parameters with respect to the immunosuppressive protocol.

Background: Episodic fever syndromes are commonly seen in pediatric practice. Episodic fever of unknown origin (FUO) lasts for a few days or weeks and is followed by a fever-free period with a sense of well-being. In this condition, activated neutrophils and monocytes intensively generate reactive oxidative species that may further damage various molecules. The aim of the study was to evaluate oxidative stress biomarkers, lipid peroxidation in erythrocytes and plasma, and advanced oxidation protein products (AOPP) in children with episodic FUO. Methods: The study enrolled 25 children with episodic FUO in afebrile phase and 25 healthy children as controls. Lipid peroxidation was evaluated by measuring malondialdehyde (MDA) production with the thiobarbituric-acid-reactive substances (TBARS) assay in erythrocytes and plasma. Oxidative modification of proteins was measured spectrophotometrically by the determination of AOPP in plasma. Results: Mean duration of episodic fevers was 3.96±2.8 years. Erythrocyte MDA levels were higher in children with FUO than in controls (86.26±10.75 vs. 78.0±3.21 nmol/g hemoglobin), although not significantly (p=0.202). The MDA plasma concentrations were similar (2.42±0.35 vs. 2.41±0.39 μmol/L) between the groups (p= 0.732). Unexpectedly, levels of AOPP were significantly lower in children with FUO than in healthy controls (18.8±5.04 vs. 25.1±3.35 μmol/L, p=0.047). Conclusions: Episodic fevers of unknown origin with an average duration of 3.96±2.8 years do not cause significant oxidative modifications of lipids and proteins in children.

The complexation of humic acid with certain heavy metal ions (Co(II), Ni(II), Cu(II), Zn(II) and Pb(II)) was investigated. The stability constants of humate complexes were determined by method which is based on distribution of metal ions between solution and resin in the presence and the absence of ligand, known as Schubert’s ion exchange method. Experiments were performed at 25 ºC, at pH 4.0 and ionic strength of 0.01 mol dm-3. It was found that the 1:1 complexes were formed between metal ions and humic acid. Obtained results of the stability constants, log βmn, of complexes formed between the metal ions and humic acid follow the order Co(II) < Ni(II) < Cu(II) > Zn(II) which is the same like in the Irving-Williams series for the binding strength of divalent metal ion complexes. Stability constant of complex between Pb(II) ions and humic acid is greater than stability constants of other investigated metal-humate complexes. The investigation of interaction between heavy metal ions and humics is important for the prediction of the distribution and control of the migration of heavy metals in natural environment. [Projekat Ministarstva nauke Republike Srbije, br. III 41018]

Nitric oxide (NO) is an important signaling molecule in a variety of physiological processes. NO, a gas, is produced from L-arginine by different isoforms of the nitric oxide synthase and serves as mediator in important physiological functions, such as promoting vasodilation of blood vessels and mediating communication between nervous system cells. Contradictory to its physiologic actions, free radical activity of NO can cause cellular damage by the induction of nitrosative stress with significant implications on nervous system diseases. Although the mechanism of NO-mediated neurodegeneration still remains unclear, numerous studies suggest its crucial role in modification of protein functions by nitrosylation and nitro-tyrosination. NO contributes to glutamate excitotoxicity, participates in organelle fragmentation, inhibits mitochondrial respiratory complexes and mobilizes zinc from the internal stores. Recently, NO has been emerged as a mediator of epigenetic gene expression and chromatin changes. Besides, NO is a key mediator in the regulation of inflammatory and immune response of the central nervous system. It is involved in down regulation of several aspects of CNS inflammation, but also has a dual role in that it is required for inflammation in some situations.

Introduction. Genetic markers are significant predictive factors in the assessment of therapeutic response of rheumatoid arthritis (RA) to biological medication. Objective. The aim of the study was to determinate the association of TNF-α -308 G/A polymorphism with a high RA activity and its predictive value in therapeutic response after 12 months of treatment with Etanercept. Methods. The study enrolled 132 patients with RA treated with Methotrexate (MTX) and 58 control subjects. The -308 TNF polymorphism was examined using the polymerase chain reaction - restriction fragment length polymorphism (PCR- RFLP). The patients were divided into two groups: group A with A/A and A/G genotype and group G with G/G genotype. After 12 months, beside MTX, Etanercept was introduced in 36 patients. We compared clinical activity among the groups at the beginning and after one year of therapy by using DAS28 SE (Disease activity score with sedimentation). Results. There was no significant difference found in the distribution of G and A allele in the RA group compared to the control group. A significantly higher disease activity was noticed in A compared to the G group (DAS28 SE: 6.31 to 5.81; p

Background/Aim. Reperfusion of previously ischemic tissue leads to injuries mediated by reactive oxygen species. The aim of the study was to investigate the effects of different anesthesia techniques on oxidative stress caused by tourniquetinduced ischemia-reperfusion (IR) injury during extremity operations at children's age. Methods. The study included 45 patients American Society of Anesthesiologists (ASA) classification I or II, 8 to 17 years of age, undergoing orthopedic procedures that required bloodless limb surgery. The children were randomized into three groups of 15 patients each: general inhalational anesthesia with sevoflurane (group S), total intravenous anesthesia with propofol (group T) and regional anesthesia (group R). Venous blood samples were obtained at four time points: before peripheral nerve block and induction of general anesthesia (baseline), 1 min before tourniquet release (BTR), 5 and 20 min after tourniquet release (ATR). Postischemic reperfusion injury was estimated by measurement of concentration of malondialdehyde (MDA) in plasma and erythrocytes as well as catalase (CAT) activity. Results. Plasma MDA concentration in the group S was significantly higher at 20 min ATR in comparison with the groups T and R (6.78 ± 0.33 μmolL-1-1 vs 4.07 ± 1.53 and 3.22 ± 0.9. μmolL-1-1, respectively). There was a significant difference in MDA concentration in erytrocythes between the groups S and T after 5 min of reperfusion (5.88 ± 0.88 vs 4.27 ± 1.04 nmol/mlEr, p < 0.05). Although not statistically significant, CAT activity was slightly increased as compared to baseline in both groups S and R. In the group T, CAT activity decreased at all time points when compared with baseline, but the observed decrease was only statistically significant at BTR (34.70 ± 9.27 vs 39.69 ± 12.91 UL-1, p < 0.05). Conclusion. Continuous propofol infusion and regional anesthesia techniques attenuate lipid peroxidation and IR injury connected with tourniquet application in pediatric extremity surgery.

Oxidative stress is considered to be a unifying link between diabetes mellitus (DM) and its complications, including nephropathy (DN). The aim of this study was to determine the parameters of oxidative injury of lipids and proteins as well as the activity of ectoenzymes in the urine of DN patients. The study included 40 individuals: 10 patients with type 2 diabetes mellitus and microalbuminuria (DMT2-MIA), 10 type 2 diabetic patients with macroalbuminuria (DMT2- MAA), 10 patients with type 1 diabetes and microalbuminuria (DMT1-MIA) and 10 age- and sex-matched healthy subjects (control). In the urine we determined TBA reactive substances (TBARS), reactive carbonyl groups (RCG), and the activity of ectoenzymes N-acetyl-b-d-glucosaminidase (NAG), plasma cell differentiation antigen (PC-1), aminopeptidase N (APN) and dipeptidyl peptidase IV (DPP IV). A higher concentration of TBARS in the urine was found in DMT2-MIA and DMT1-MIA, compared to the control group (p

Background/Aim. The aim of this study, which included patients with insulin-dependent diabetes mellitus, was to determine the influence of the application of various treatment modalities (intensive or conventional) on the total plasma antioxidative capacity and lipid peroxidation intensity expressed as malondialdehyde (MDA) level, catalase and xanthine oxidase activity, erythrocyte glutatione reduced concentration (GSH RBC), erythrocyte MDA level (MDA RBC), as well as susceptibility of erythrocyte to H2O2-induced oxidative stress. Methods. This study included 42 patients with insulin-dependent diabetes mellitus. In 24 of the patients intensive insulin treatment was applied using the model of short-acting insulin in each meal and medium- acting insulin before going to bed, while in 18 of the patients conventional insulin treatment was applied in two (morning and evening) doses. In the examined patients no presence of diabetes mellitus complications was recorded. The control group included 20 healthy adults out of a blood doner group. The plasma and erythrocytes taken from the blood samples were analyzed immediately. Results. This investigation proved that the application of intensive insulin treatment regime significantly improves total antioxidative plasma capacity as compared to the application of conventional therapy regime. The obtained results showed that the both plasma and lipoproteines apo B MDA increased significantly more in the patients on conventional therapy than in the patients on intensive insulin therapy, most probably due to intensified xanthine oxidase activity. The level of the MDA in fresh erythrocytes did not differ significantly between the groups on intensive and conventional therapy. The level of GSH and catalase activity, however, were significantly reduced in the patients on conventional therapy due to the increased susceptibility to H2O2-induced oxidative stress . Conclusion. The presented study confirmed positive effect of intensive insulin therapy on metabolic control expressed through glycemia level, glycolysed hemoglobine (HbAlc) and fructosamine, as well as through antioxidative/prooxidative homeostasis. This is the confirmation that an adequate treatment choice can prevent numerous diabetes mellitus complications induced by free radicals. .

In the CNS polyamines can exert opposite effects, depending on the concentration and conditions in the cell. Protective or neurotoxic polyamine effects were documented during seizures and repeated CNS excitation. Intensive research of exogenous polyamines effects during seizures induced by numerous agents did not clear up confusions about the duality of effects and the role of polyamines in seizures. In order to understand polyamine modulatory effects in seizures, the importance of NO and polyamine metabolism interdependence and the possible implication of changes of postulated NO and polyamine equillibrium in seizures, the effects of spermine alone and in combination with L-NAME (NOS inhibitor) on seizures induced by pentazol (PTZ) were investigated. To compare the obtained results, the effects of anticonvulsant midazolam on NO production during seizures were also investigated. Seizures were induced by i.p. application of pentazol (100 mg/kg b.w). Spermine and L-NAME were administered i.p. before PTZ. In the striatum and hippocampus, spermine induced increased NO production (p

Background/Aim. Oxidative stress plays a critical role in the pathogenesis of various diseases. Recent reports indicate that obesity may induce systemic oxidative stress. The aim of the study was to potentiate oxidative stress as a factor which may aggravate peripheral insulin sensitivity and insulinsecretory response in obesity in this way to potentiate development of diabetes. The aim of the study was also to establish whether insulin-secretory response after glucagonstimulated insulin secretion is susceptible to prooxidant/ antioxidant homeostasis status, as well as to determine the extent of these changes. Methods. A mathematical model of glucose/insulin interactions and C-peptide was used to indicate the degree of insulin resistance and to assess their possible relationship with altered antioxidant/prooxidant homeostasis. The study included 24 obese healthy and 16 obese newly diagnozed non-insulin dependent diabetic patients (NIDDM) as well as 20 control healthy subjects, matched in age. Results. Total plasma antioxidative capacity, erythrocyte and plasma reduced glutathione level were significantly decreased in obese diabetic patients, but also in obese healthy subjects, compared to the values in controls. The plasma lipid peroxidation products and protein carbonyl groups were significantly higher in obese diabetics, more than in obese healthy subjects, compared to the control healthy subjects. The increase of erythrocyte lipid peroxidation at basal state was shown to be more pronounced in obese daibetics, but the apparent difference was obtained in both the obese healthy subjects and obese diabetics, compared to the control values, after exposing of erythrocytes to oxidative stress induced by H2O2. Positive correlation was found between the malondialdehyde (MDA) level and index of insulin sensitivity (FIRI). Conclusion. Increased oxidative stress together with the decreased antioxidative defence seems to contribute to decreased insulin sensitivity and impaired insulin secretory response in obese diabetics, and may be hypothesized to favour the development of diabetes during obesity.

Vitamin D receptor (VDR) gene FokI (rs2228570) polymorphism was postulated to influence outcome of several inflammatory diseases. The aim of this study was to evaluate the influence of rs2228570 polymorphism on lipid profile and on outcome in patients with juvenile idiopathic arthritis (JIA) treated with etanercept. A total of 153 subjects (62 JIA patients and 91 controls) were screened for the rs2228570 using the PCR-RFLP method. Lipid profile (cholesterol, triacylglycerol, HDL-C, and LDL-C) was determined using standard biochemical analysis in controls, while in JIA patients, it was determined prior to and 12 months after anti-TNF (etanercept) therapy. Clinical outcome was assessed using the JIA—American College of Rheumatology (ACR) response criteria. There were significant differences in the distribution of genotypes (p = 0.024) and alleles (p = 0.006; OR = 2.222, 95% CI 1.136-4.348) of the rs2228570 between patients and controls. Etanercept treatment significantly increased HDL-C levels (p = 0.006) in JIA patients with FF genotype in comparison to baseline values. No significant differences were seen in JIA—ACR 30/50/70 responses at month 12 between FF and Ff/ff genotype carriers. This is the first study to demonstrate the protective effect of the VDR FokI FF genotype on lipid profile in JIA patients treated with etanercept. However, this has to be confirmed in a larger cohort of patients. [ABSTRACT FROM AUTHOR]

Copyright of Acta Medica Medianae is the property of Acta Medica Medianae and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Copyright of Acta Medica Medianae is the property of Acta Medica Medianae and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Copyright of Acta Medica Medianae is the property of Acta Medica Medianae and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Clinical practice and experimental studies have shown the necessity of sufficient quantities of folic acid intake for normal embryogenesis and fetal development in the prevention of neural tube defects (NTDs) and neurological malformations. So, women of childbearing age must be sure to have an adequate folate intake periconceptionally, prior to and during pregnancy. Folic acid fortification of all enriched cereal grain product flour has been implemented in many countries. Thus, hundreds of thousands of people have been exposed to an increased intake of folic acid. Folate plays an essential role in the biosynthesis of methionine. Methionine is the principal aminopropyl donor required for polyamine biosynthesis, which is up-regulated in actively growing cells, including cancer cells. Folates are important in RNA and DNA synthesis, DNA stability and integrity. Clinical and epidemiological evidence links folate deficiency to DNA damage and cancer. On the other hand, long-term folate oversupplementation leads to adverse toxic effects, resulting in the appearance of malignancy. Considering the relationship of polyamines and rapidly proliferating tissues (especially cancers), there is a need for better investigation of the relationship between the ingestion of high amounts of folic acid in food supplementation and polyamine metabolism, related to malignant processes in the human body.

The complexation of humic acid with certain heavy metal ions (Co(II), Ni(II), Cu(II), Zn(II) and Pb(II)) was investigated. The stability constants of humate complexes were determined by a method based on the distribution of metal ions between solution and resin in the presence and the absence of ligand, kn own as Schubert’s ion exchange method. Experiments were performed at 25 ° C, pH 4.0 and ionic strength of 0.01 mol dm –3. It was found that the 1:1 complexes were formed be tween metal ions and humic acid. Obtained results of the stability constants, log βmn, of complexes formed between the metal ions and humic acid follow the order Co(II) < Ni(II) < Cu(II) > Zn(II), which is the same as in the Irving–Williams series for the binding strength of divalent metal ion complexes. The stability constant of complex between Pb(II) ions and humic acid is greater than the stability constants of other investigated metal–humate complexes. The investigation o f interaction between heavy metal ions and humics is important for the prediction of the distribution and control of the migration of heavy metals in natural environment. [ABSTRACT FROM AUTHOR]

There is a higher mortality between patients with end-stage renal disease than patients in the general population. These circumstances have led to a search for risk factors as predictors of mortality in dialysis patients. Amongst those, inhibitors of the nitric-oxide (NO) synthesis deserve special attention, since patients with end-stage renal disease are also characterized by accelerated atherosclerosis. Asymmetric-dimethylarginine (ADMA) and symmetric-dimethylarginine (SDMA), as well as C-reactive protein (CRP), have also been recognized as predictors of mortality in patients on dialysis. The aim of our study was to compare the prediction power of ADMA, SDMA and CRP for all-cause mortality in patients with end stage renal disease during the fourteen month follow-up. In total 162 patients on hemodialysis were included. ADMA and SDMA were measured by the high-performance liquid chromatography (HPLC); CRP was measured using immunonephelometric assays. During the 14-month period 28 patients (34.1%) died from all-cause mortality. Using univariate analysis, hazard ratios (HR) of the potential independent predictors of mortality in hemodialysis patients were ADMA (HR 1.39 (1.01-1.91) p=0.043) and CRP (HR 1.024 (1.009-1.1.040) p=0.001). Further, multivariate analysis (MVA), however, showed that ADMA is the only predictor of all-cause mortality (HR 1.76 (1.002-3.11) P=0.049), while SDMA failed to predict death in this population. Therefore, our data shows that ADMA is an independent and better marker of all-cause mortality compared with CRP. [ABSTRACT FROM AUTHOR]

The patient presented is a 44-year-old female treated for cavitary changes in the lung apexes. Due to suspected tuberculosis, treatment began with anti-tuberculosis (AT) drugs, despite negative sputum smears for acid-fast bacilli. During hospitalization, the patient was febrile (up to 38°C), hypotensive, extremely cachectic (32 kg), had a dry cough, increased nitrogen products, hypokalemia and anemia. Because of poor response to the applied AT therapy, bronchoscopic tests were repeated and spores of aspergillus fungus were discovered in the pathohistological findings of transbronchial lung biopsy. The appropriate treatment with amphotericin B and voriconazole was initiated. A psychiatric opinion was requested because we suspected that the patient suffered from the anorexic syndrome (anorexia nervosa). This diagnosis was confirmed by a psychiatrist; her psychiatric treatment began simultaneously with the treatment in our facility. Anorexia was the cause of the cachexia, immunodeficiency and invasive pulmonary aspergillosis. The disorder was not recognized before the manifestation of the somatic disorder. There is little data in the available literature on the association between these two diseases. [ABSTRACT FROM AUTHOR]

Within the complex process of signal transduction through the cell under the influence of external factors, signal transmission is initiated through a specific communication, protein-protein interaction (phosphorylation, dephosphorylation, association, dissociation, oxidation, glycation, nitrosylation, proteolysis), determining the biologic response of the cell. Many of the cellular signal transduction pathways, such as JAK-STAT, MAP, PKC-kinase cascade, HF-κB signal transduction pathway, undergo down regulation mediated by N-acetyl-cystein and reduced, glutathione, while the decline of GSH concentration and redox stress initiate their activation. Activated redox signaling pathways are the mediators of mitogenic effects m cancerogenesis. Two types of genes, comprising only a small part of the human cell genome, have a key role in cancerogenesis. Proto-oncogene and tumor suppressor gene dysfunction induce disturbances in the regulation of signal transmission pathways which control the cell cycle, apoptosis, genome stability, differentiation and morphogenesis. Alterations in these important physiologic processes are responsible not only for the initiation and promotion of malignant transformation of the cell, but for further tumor progression as well Free radicals and their oxidatively modified products induce activation of critical sensory loci in the signal pathway proteoma, controling cellular proliferation, apoptosis and cellular phenotype alteration. Therefore, it is vital to define the therapeutic indications for antioxidants and other modulators of target places of redox cell signaling genomics and proteomics as they are all part of a complex network of multifactorial oncogene collaboration in the process of cancerogenesis. [ABSTRACT FROM AUTHOR]

The need for sufficient quantities of folic acid for normal embryogenesis and fetal development is well known. Women of childbearing age must be sure to have an adequate intake of folic acid periconceptionally prior to and during pregnancy. Folate plays an essential role in the biosynthesis of RNA and DNA, phospholipid and neurostransmitters synthesis, using S-adenosylmethionine (SAM) as the primary methyl group donor. In some countries, the knowledge that folic acid is preventable for the reduction of the risk for neural tube defects (NTD) and in lowering the high amount of homocysteine (Hcy) led to the recommendation that all women capable of becoming pregnant should consume 400 µg of folic acid daily. Later, in 1998, folic acid fortification of all enriched cereal grain product flour was implemented in some countries. In addition to careful monitoring of adverse effects, the studies are warranted in order to determine the potentially positive and deleterious effects of folic acid fortification and supplementation on the human health or human diseases. To further understand the metabolic action of folates we asked ourselves the question: Is the intake of a sufficient amount of this vitamin a benefit or risk for human health?

Polyamines, spennine, spermidine and putrescinc, small aliphatic nitrous bases, are normal constituents of microbial, plant and animal cells, where they fulfill an array of physiological roles. Metabolism of polyamines is associated with growth and differentiation of mammalian cells, spermine related to RNA and spermidine to DNA metabolism. Methyl-cobalamin, the coenzyme of methionine synthetase, catalyses the recycling of homocysteine to methionine using 5-methyltctrahydrofolate. By acceleration of methionine biosynthesis these vitamins may influence spermidine and spermine synthesis.