EPR Monitoring of Oxygenation Levels in Tumors After Chlorophyllide-Based Photodynamic Therapy May Allow for Early Prediction of Treatment Outcome.

PURPOSE: Molecular oxygen, besides a photosensitizer and light of appropriate wavelength, is one of the three factors necessary for photodynamic therapy (PDT). In tumor tissue, PDT leads to the killing of tumor cells, destruction of endothelial cells and vasculature collapse, and the induction of strong immune responses. All these effects may influence the oxygenation levels, but it is the vasculature changes that have the main impact on pO2. The purpose of our study was to monitor changes in tumor oxygenation after PDT and explore its significance for predicting long-term treatment response. PROCEDURES: Electron paramagnetic resonance (EPR) spectroscopy enables direct, quantitative, and sequential measurements of partial pressure of oxygen (pO2) in the same animal. The levels of chlorophyll derived photosensitizers in tumor tissue were determined by transdermal emission measurements. RESULTS: The noninvasive monitoring of pO2 in the tumor tissue after PDT showed that the higher ΔpO2 (pO2 after PDT minus pO2 before PDT), the greater the inhibition of tumor growth. ΔpO2 also correlated with higher levels of the photosensitizers in the tumor and with the occurrence of a severe edema/erythema after PDT. CONCLUSION: Monitoring of PDT-induced changes in tumor oxygenation is a valuable prognostic factor and could be also used to identify potentially resistant tumors, which is important in predicting long-term treatment response.

The Usefulness of Optical Coherence Tomography in Disease Progression Monitoring in Younger Patients with Relapsing-Remitting Multiple Sclerosis: A Single-Centre Study.

The purpose of the study was to assess the usefulness of optical coherence tomography (OCT) in the detection of the neurodegenerative process in younger patients with multiple sclerosis (MS). The study group consisted of 61 patients with a relapsing remitting course of MS (mean age 36.4 ± 6.7 years) divided into two groups: short (≤5 years) and long (>10 years) disease duration. OCT, P300 evoked potential, Montreal Cognitive Assessment, and performance subtests (Picture Completion and Digit Symbol) of the Wechsler Adult Intelligence Scale were performed in all patients. Mean values of most parameters assessed in OCT (pRNFL Total, pRNFL Inferior, pRNFL Superior, pRNFL Temporalis, mRNFL, GCIPL, mRNFL+GCIPL) were significantly lower in MS patients in comparison to controls. And in patients with longer disease duration in comparison to those with shorter. Most OCT parameters negatively correlated with the EDSS score (p < 0.05). No significant correlation was found between OCT results and both P300 latency and the results of psychometric tests. OCT, as a simple, non-invasive, quick, and inexpensive method, could be useful for monitoring the progression of disease in MS patients.

The impact of the aortic cusps fusion pattern and valve disease severity on the aortic wall mechanics in patients with bicuspid aortic valve.

The ascending aorta dilatation in the bicuspid aortic valve (BAV) patients is often attributed to congenital abnormalities of the aortic wall, but it may be related to hemodynamic disturbances in the course of BAV disease. At present, ascending aortic diameter is used as almost sole but weak predictor of aortic dissection and rupture in BAV. We examined the association between aortic wall mechanics and severity of aortic valve disease including different cusps fusion patterns using conventional echocardiography and tissue Doppler imaging (TDI). We prospectively studied 106 BAV patients: 72 with right-left (R-L) coronary cusp fusion were matched 1:1 to 34 patients with right-noncoronary (R-N) cusp fusion obtaining 34 pairs of patients. Peak systolic radial velocity and acceleration of the ascending aortic wall, measured by TDI, were used as an index of hemodynamic stress imposed on the aorta. Paired analysis showed higher aortic wall radial velocity (4.71 ± 1.61 cm/s vs. 3.33 ± 1.44 cm/s, p = 0.001) and acceleration (1.08 ± 0.46 m/s2 vs. 0.80 ± 0.34 m/s2, p = 0.015) in-R-L compared to R-N fusion. Pearson correlation showed association of ascending tubular aortic diameter with age (r = 0.258, p = 0.012), weight (r = 0.323, p = 0.001), peak aortic valve gradient (r = 0.386, p = 0.0001), aortic root diameter (r = 0.439, p < 0.0001), and R-N fusion pattern (r = 0.209, p = 0.043). Aortic root diameter was related to male gender (r = 0.296, p = 0.003), weight (r = 0.381, p = 0.0001), ascending aortic diameter (r = 0.439, p < 0.0001), and severity of aortic regurgitation (r = 0.337, p = 0.0009). Regional differences in aortic wall motion between different BAV cusp fusion patterns and association of aortic diameters with the severity of aortic valve disease, both suggest a deleterious hemodynamic impact of cusp fusion patterns and aortic valve dysfunction on ascending aortic wall. Assessment of aortic hemodynamic by TDI is feasible and could be potentially used to improve prediction of acute aortic complications, thus helping to establish optimal timing of aortic surgery in BAV patients.

Multiple sclerosis: oral health, behaviours and limitations of daily oral hygiene - a questionnaire study.

CLINICAL RATIONALE FOR THE STUDY: Neurological deficits and progressing disability in patients with multiple sclerosis (MS) may hamper daily oral hygiene, but their relations with oral problems have not yet been clearly determined. AIM OF THE STUDY: The aim of this study was to identify the most significant dental problems and limitations of daily oral hygiene in Polish patients with MS. MATERIAL AND METHODS: 199 patients with diagnosed MS (median age 37 years) treated in the neurological outpatient clinic were interviewed using a paper-based questionnaire. They provided answers on oral health, behaviours and the limitations of their daily oral hygiene. Clinical information regarding symptoms, MS phenotype, relapses, medication and degrees of disability was based on medical records. RESULTS: The most frequent symptoms were dry mouth (43.2%) and bleeding from gums (28.1%). Dry mouth was more frequent in patients with secondary-progressive MS (SPMS) than relapsing-remitting MS (65.4% vs 41.3%, p = 0.023). Patients with bleeding from gums had had MS for a longer duration (median 6 vs 4 years, p = 0.002). Difficulties in daily oral hygiene were more frequent in patients with SPMS (24.0% vs 8.1%; p = 0.016). Greater proportions of patients with muscle weakness of limbs, imbalance or pain brushed their teeth irregularly. Frequent (i.e. at least every six months) visits to the dentist's surgery were uncommon in patients with SPMS (12.0% vs 39.7%, p = 0.010). CONCLUSIONS AND CLINICAL IMPLICATIONS: Dry mouth and bleeding from gums are more frequent in patients with longer lasting and more advanced types of MS. Daily oral hygiene and oral health self-control is limited in patients with MS, mainly due to motor deficits, balance problems and pain, and this becomes worse with disease duration. To minimise the burden of the disease, patients with MS require better education and improvement in their awareness regarding proper oral health control, such as the use of electric toothbrushes. In addition, patients with chronic and progressive disability from multiple sclerosis may benefit from better organised access to dental care.

The aqueous environment as an active participant in the protein folding process.

Existing computational models applied in the protein structure prediction process do not sufficiently account for the presence of the aqueous solvent. The solvent is usually represented by a predetermined number of H2O molecules in the bounding box which contains the target chain. The fuzzy oil drop (FOD) model, presented in this paper, follows an alternative approach, with the solvent assuming the form of a continuous external hydrophobic force field, with a Gaussian distribution. The effect of this force field is to guide hydrophobic residues towards the center of the protein body, while promoting exposure of hydrophilic residues on its surface. This work focuses on the following sample proteins: Engrailed homeodomain (RCSB: 1enh), Chicken villin subdomain hp-35, n68h (RCSB: 1yrf), Chicken villin subdomain hp-35, k65(nle), n68h, k70(nle) (RCSB: 2f4k), Thermostable subdomain from chicken villin headpiece (RCSB: 1vii), de novo designed single chain three-helix bundle (a3d) (RCSB: 2a3d), albumin-binding domain (RCSB: 1prb) and lambda repressor-operator complex (RCSB: 1lmb).

[Eating habits of the youth from Ruda Slaska].

OBJECTIVE: Introduction: In recent years, interests on dietary and health food have grown considerably. Nutritional knowledge and eating habits determined in the youth have an impact on the health condition in adulthood. The aim: To evaluate the eating habits in the population of young people from Silesian province. PATIENTS AND METHODS: Materials and methods: The anonymous questionnaire survey was conducted in the group of high school students aged 17-21 years coming from Silesian province, randomly chosen from high schools in Ruda Slaska. The study group consisted of 262 students, 157 (59,9%) women and 105 (40,1%) men. The student`s participation in the study was voluntary. RESULTS: Results: The analysis showed that as many as 40% of high school students never eat regularly and eating of regular meals reported only 11,5%. Less than a half (46,9%) of participants eat breakfast every day. The most commonly consumed meals was lunch (n = 217; 82,8%) and dinner (n = 143; 54,6%). The vast majority of students (77,5%) didn't know the correct classification of the feeding pyramid floors. Moreover, in more than a half of young women (54,8%) and men (52,4%) the body mass deficiency was revealed (BMI<18kg/m2). CONCLUSION: Conclusions: The study showed abnormal nutritional behavior of high school youth. Therefore, there is a need to conduct activities under health prevention, which improve the eating habits of young people.

Is the hydrophobic core a universal structural element in proteins?

The hydrophobic core, when subjected to analysis based on the fuzzy oil drop model, appears to be a universal structural component of proteins irrespective of their secondary, supersecondary, and tertiary conformations. A study has been performed on a set of nonhomologous proteins representing a variety of CATH categories. The presence of a well-ordered hydrophobic core has been confirmed in each case, regardless of the protein's biological function, chain length or source organism. In light of fuzzy oil drop (FOD) analysis, various supersecondary forms seem to share a common structural factor in the form of a hydrophobic core, emerging either as part of the whole protein or a specific domain. The variable status of individual folds with respect to the FOD model reflects their propensity for conformational changes, frequently associated with biological function. Such flexibility is expressed as variable stability of the hydrophobic core, along with specific encoding of potential conformational changes which depend on the properties of helices and ß-folds.

Structural Interface Forms and Their Involvement in Stabilization of Multidomain Proteins or Protein Complexes.

The presented analysis concerns the inter-domain and inter-protein interface in protein complexes. We propose extending the traditional understanding of the protein domain as a function of local compactness with an additional criterion which refers to the presence of a well-defined hydrophobic core. Interface areas in selected homodimers vary with respect to their contribution to share as well as individual (domain-specific) hydrophobic cores. The basic definition of a protein domain, i.e., a structural unit characterized by tighter packing than its immediate environment, is extended in order to acknowledge the role of a structured hydrophobic core, which includes the interface area. The hydrophobic properties of interfaces vary depending on the status of interacting domains-In this context we can distinguish: (1) Shared hydrophobic cores (spanning the whole dimer); (2) Individual hydrophobic cores present in each monomer irrespective of whether the dimer contains a shared core. Analysis of interfaces in dystrophin and utrophin indicates the presence of an additional quasi-domain with a prominent hydrophobic core, consisting of fragments contributed by both monomers. In addition, we have also attempted to determine the relationship between the type of interface (as categorized above) and the biological function of each complex. This analysis is entirely based on the fuzzy oil drop model.

[Zygomatic localization of Langerhans cell histiocytosis - a case report].

Langerhans cell histocytosis is a rare disease. LCH is reported mainly in children aged less than 15 years, however it may appear at any age. In this work, the case of 17-month boy is reported. The boy was admitted to the pediatric ophthalmology department in order to diagnose the swelling and bruising in the lower part of left orbit, which had lasted for one month before. The clinical status, various imaging techniques' results (MRI, TK and PET) and immunohistochemistry led to the final diagnosis of multisystem LCH (spread to masticator muscle and zygomatic bone). After the pharmacological therapy the total remission was achieved. Since four years the child is regularly controlled by oncologists and hematologists with no relapse reported.

Contingency Table Browser - prediction of early stage protein structure.

The Early Stage (ES) intermediate represents the starting structure in protein folding simulations based on the Fuzzy Oil Drop (FOD) model. The accuracy of FOD predictions is greatly dependent on the accuracy of the chosen intermediate. A suitable intermediate can be constructed using the sequence-structure relationship information contained in the so-called contingency table - this table expresses the likelihood of encountering various structural motifs for each tetrapeptide fragment in the amino acid sequence. The limited accuracy with which such structures could previously be predicted provided the motivation for a more indepth study of the contingency table itself. The Contingency Table Browser is a tool which can visualize, search and analyze the table. Our work presents possible applications of Contingency Table Browser, among them - analysis of specific protein sequences from the point of view of their structural ambiguity.

The prevalence of Non-suicidal Self-Injury (NSSI) among high school students in relation to age and sex.

OBJECTIVES: The undertaken research aimed at determining the frequency of deliberate self-injurious behaviour (D-SIB) among the students of secondary schools and also the analysis of the frequency of repeated Non-Suicidal Self-Injury (NSSI) occurrences in accordance with DSM-5 criteria in reference to the age and sex in the studied population. METHODS: The data was collected via survey method according to the questionnaire prepared in compliance with the criteria DSM-5 and Self-Harm Inventory. The study included randomly selected students: 1193 boys and 1027 girls in Bialystok aged 12 and 19 (average age ± SD:16.8 ± 1.65). Statistical analysis of the data was carried out using the application Statistica 10.0 PL, StatSoft. RESULTS: These results indicate that D-SIB and NSSI affect both sexes. In the studied group 8.3 % of students engage in deliberate self-injurious behaviour. The percentage of NSSI was 4.8% (6.3% in the group of boys, 3.2 % among girls; p(Chi2)=0.01). Self-cutting was most common among 15-year-old pupils ((D-SIB:14.75%; NNSI:8.1%). The majority of respondents (82% of girls and 74% of boys) revealed that as a result of self-injury behaviour they experience relief. CONCLUSIONS: Conducting further research in the area of NSSI seems to be crucial due to chronicity and prevalence as well as the fact that numerous repeated self-injuries bringing relief or causing positive state of mind might indicate a mechanism similar to an addiction syndrome in adolescence.

Contribution to the prediction of the fold code: application to immunoglobulin and flavodoxin cases.

BACKGROUND: Folding nucleus of globular proteins formation starts by the mutual interaction of a group of hydrophobic amino acids whose close contacts allow subsequent formation and stability of the 3D structure. These early steps can be predicted by simulation of the folding process through a Monte Carlo (MC) coarse grain model in a discrete space. We previously defined MIRs (Most Interacting Residues), as the set of residues presenting a large number of non-covalent neighbour interactions during such simulation. MIRs are good candidates to define the minimal number of residues giving rise to a given fold instead of another one, although their proportion is rather high, typically [15-20]% of the sequences. Having in mind experiments with two sequences of very high levels of sequence identity (up to 90%) but different folds, we combined the MIR method, which takes sequence as single input, with the "fuzzy oil drop" (FOD) model that requires a 3D structure, in order to estimate the residues coding for the fold. FOD assumes that a globular protein follows an idealised 3D Gaussian distribution of hydrophobicity density, with the maximum in the centre and minima at the surface of the "drop". If the actual local density of hydrophobicity around a given amino acid is as high as the ideal one, then this amino acid is assigned to the core of the globular protein, and it is assumed to follow the FOD model. Therefore one obtains a distribution of the amino acids of a protein according to their agreement or rejection with the FOD model. RESULTS: We compared and combined MIR and FOD methods to define the minimal nucleus, or keystone, of two populated folds: immunoglobulin-like (Ig) and flavodoxins (Flav). The combination of these two approaches defines some positions both predicted as a MIR and assigned as accordant with the FOD model. It is shown here that for these two folds, the intersection of the predicted sets of residues significantly differs from random selection. It reduces the number of selected residues by each individual method and allows a reasonable agreement with experimentally determined key residues coding for the particular fold. In addition, the intersection of the two methods significantly increases the specificity of the prediction, providing a robust set of residues that constitute the folding nucleus.

Statistical dictionaries for hypothetical in silico model of the early-stage intermediate in protein folding.

The polypeptide chain folding process appears to be a multi-stage phenomenon. The scientific community has recently devoted much attention to early stages of this process, with numerous attempts at simulating them--either experimentally or in silico. This paper presents a comparative analysis of the predicted and observed results of folding simulations. The proposed technique, based on statistical dictionaries, yields a global accuracy of 57%--a marked improvement over older approaches (with an accuracy of approximately 46%).

Intrinsically disordered proteins--relation to general model expressing the active role of the water environment.

This work discusses the role of unstructured polypeptide chain fragments in shaping the protein's hydrophobic core. Based on the "fuzzy oil drop" model, which assumes an idealized distribution of hydrophobicity density described by the 3D Gaussian, we can determine which fragments make up the core and pinpoint residues whose location conflicts with theoretical predictions. We show that the structural influence of the water environment determines the positions of disordered fragments, leading to the formation of a hydrophobic core overlaid by a hydrophilic mantle. This phenomenon is further described by studying selected proteins which are known to be unstable and contain intrinsically disordered fragments. Their properties are established quantitatively, explaining the causative relation between the protein's structure and function and facilitating further comparative analyses of various structural models.

Hypothetical in silico model of the early-stage intermediate in protein folding.

This paper presents a method for determining the structure of the early stage (ES) intermediate in the multistage protein folding process. ES structure is modeled on the basis of a limited conformational subspace of the Ramachandran plot. The model distinguishes seven structural motifs corresponding to seven local probability maxima within the limited conformational subspace. Three of these are assigned to well-defined secondary structures, while the remaining four are found to represent various types of random coils. The presented heuristic approach also provides insight into the reasons behind incorrect predictions occurring when the folding process depends on external factors (e.g., ligands, ions or other proteins) rather than on the characteristics of the backbone itself. The accuracy of the presented method is estimated at around 48 %.

[Activity of antioxidative enzymes and concentration of malondialdehyde as oxidative status markers in women with non-autoimmunological subclinical hyperthyroidism]. / Aktywnosc enzymow antyoksydacyjnych i stezenie aldedydu dimalonowego jako wyklandniki stresu oksydacyjnego u kobiet z subkliniczna nieautoimmunogiczna nadczynnoscia tarzcycy.

INTRODUCTION: The recent investigations point out the significant role of oxidative stress in the development of thyroid gland disease. The present study was designed to investigate the variation of oxidative stae in women with non-autoimmunological subclinical hyperthyroidism. MATERIAL AND METHODS: The study was conducted on 20 females with non-autoimmunological subclinical hyperthyroidism and 15 healthy women. Manganase-containing superoxide dismutase (Mn-SOD) and extracellular superoxide dismutase (EC-SOD) plasma activity, and malondialdehyde (MDA) plasma concentration were measured. RESULTS: EC-SOD plasma activity was significantly higher in women with subclinical hyperthyroidism when compared with the control group (13.3 +/- 2.1 vs. 10.9 +/- 1.4 NU/ml; p < 0.05), unlike Mn-SOD (4.2 +/- 0.5 vs. 4.0 +/- 1.0 NU/ml). MDA plasma concentration increased significantly in women with subclinical hyperthyroidism (3.5 +/- 1.2 vs. 2.0 +/- 0.6 micromol/l; p < 0.05). CONCLUSIONS: The increased EC-SOD plasma activity may reflect disturbances of oxidative state in subclinical hyperthyroidism. Parallel increase of MDA plasma concentration may indicate enhancement of lipid peroxidationin in patients with subclinical hyperthyroidism.

sPECAM-1 and sVCAM-1: Role in Pathogenesis and Diagnosis of Chronic Hepatitis C and Association with Response to Antiviral Therapy.

AIM: To analyze the relationship between pretreatment clinical or histological features and the levels of soluble platelet-endothelial cell adhesion molecule-1 (sPECAM-1) and soluble vascular cell adhesion molecule-1 (sVCAM-1), to determine their serum concentration in responders and nonresponders, to evaluate the behavior under antiviral therapy, to explain their relationship in response to therapy and to assess the association between these two molecules in chronic hepatitis C (CHC). METHODS: The study analyzed 65 CHC patients, including 50 patients (Group 1) with marked fibrosis treated with peginterferon plus ribavirin, 15 patients without fibrosis (Group 2) and 13 healthy volunteers (the control group, Group 3). sPECAM-1 and sVCAM-1 levels were assessed by an immunoenzymatic method (ELISA) before and after therapy. RESULTS: sVCAM-1 and sPECAM-1 serum concentrations increased significantly in CHC patients (p<001). sPECAM-1 levels corresponded to inflammatory grade (p = 0.03) and fibrosis stage (p =0.01). sVCAM-1 increased only in advanced fibrosis. After therapy, sPECAM-1 levels decreased significantly (p<001) with no difference between responders and nonre-sponders. sPECAM-1 correlated positively with inflammatory activity (p = 0.02), fibrosis stage (p<001), sVCAM-1 (r=0.56, p<001) and alanine aminotransferase activity (r = 0.30, p = 0.05). Receiver operating characteristic curve analysis showed a good discriminant power of serum sPECAM-1 concentrations for detection of liver fibrosis - stage 0 versus stage 1-3, AUC 0.81; cut-off 221.0 ng/ml and a fair discriminant power for distinguishing bridging fibrosis, AUC 0.78; cut-off 237.1 ng/ml. CONCLUSIONS: Hepatitis C virus (HCV) infection results in upregulation of sPECAM-1 and sVCAM-1. sPECAM-1 levels are related to necroinflammatory activity and may also identify patients with advanced fibrosis. The sPECAM-1 value was decreased by therapy but its measurement cannot predict therapy outcome and confirm HCV persistence. sPECAM-1 may influence VCAM-1 expression.

Activity of antioxidative enzymes and concentration of malondialdehyde as oxidative status markers in women with newly diagnosed Graves-Basedow disease and after thiamazole therapy leading to euthyroidism.

UNLABELLED: INTRODUCTION. Hyperthyroidism in the course of Graves-Basedow disease leads to intensification of oxidative processes and increased production of free oxygen radicals. It results in abnormal oxidative status of the organism. OBJECTIVES: Aim of this work was to assess the dynamics of oxidative status changes in women with Graves-Basedow disease before and after treatment with thiamazole. PATIENTS AND METHODS: Studies were carried out in 20 women with newly diagnosed hyperthyroidism in the course of Graves-Basedow disease and in 15 healthy women. Measurements of activity of antioxidant enzymes--superoxide dismutase (cytosolic copper/zinc isoform--Cu/ZnSOD, mitochondrial manganese isoform--MnSOD and extracellular copper/zinc isoform--EC-SOD) and glutathione peroxidase (GPx), as well as of malondialdehyde (MDA) concentration were performed twice, i.e. before the treatment and after 3-7 months of thiamazole therapy (euthyroidism). RESULTS: Before the treatment, higher MnSOD plasma activity and lower EC-SOD activity were observed in women with hyperthyroidism in comparison with the control group, whereas the erythrocyte Cu/ZnSOD activity did not differ between the groups. Besides, women with hyperthyroidism had higher GPx activity in red blood cells. In this group studies have demonstrated higher plasma MDA levels, without any differences between the groups in MDA levels in red blood cells. After thiamazole therapy no differences could be demonstrated in MnSOD, EC-SOD, Cu/ZnSOD and GPx activities and MDA level between the groups. CONCLUSIONS: Women with hyperthyroidism in the course of Graves-Basedow disease experience abnormal oxidative status of the organism, and induction of euthyroidism after therapy with thiamazole results in resolution of these abnormalities.

[Assessment of blood superoxide dismutase, glutathione peroxidase activity and malondialdehyde concentration as oxidation status parameters in obese women]. / Ocena aktywnosci dysmutazy ponadtlenkowej i peroksydazy glutationowej oraz stezenia dwualdehydu malonowego w krwi jako parametrów stanu oksydacyjnego u otylych kobiet.

Obesity is accompanied by a high incidence of atherosclerosis, arterial hypertension and non-insulin dependent diabetes mellitus in the pathogenesis of which is associated with oxygen-derived free radicals. The aim of the study was to compare blood oxidation status in obese women without coexisting diseases and in healthy women with normal body mass index (BMI). Studies were performed in 29 premenopausal obese (BMI 35.79 +/- 4.62 kg/m2) and 31 lean (BMI 22.29 +/- 1.05 kg/m2) women. Plasma lipid profile, activities of antioxidant enzymes: copper/zinc (Cu/ZnSOD) and manganese-containing superoxide dismutase (MnSOD) and glutathione peroxidase (GSH-Px), as well as concentrations of malondialdehyde (MDA)--a product of lipid peroxidation, were examined. In obese women there were significantly higher concentrations of total cholesterol (5.02 +/- 0.83 vs. 4.15 +/- 0.43 mmol/l; p < 0.05), LDL-cholesterol (3.12 +/- 0.90 vs. 2.35 +/- 0.42 mmol/l; p < 0.05) and triglycerides (1.72 +/- 0.85 vs. 1.02 +/- 0.18 mmol/l; p < 0.01), while HDL-cholesterol level was lower (1.01 +/- 0.16 vs. 1.25 +/- 0.2 mmol/l; p < 0.05). Moreover, in comparison to the control group, obese women showed increased activities of plasma MnSOD (6.72 +/- 1.43 vs. 4.99 +/- 0.58 NU/ml; p < 0.05) and erythrocyte GSH-Px (35.38 +/- 10.31 vs. 19.15 +/- 7.12 mumol NADPH2/g Hb/min; p < 0.001), and concentrations of plasma MDA (2.93 +/- 0.53 vs. 2.16 +/- 0.31 mumol/l; p < 0.05) and erythrocyte MDA (2.24 +/- 0.30 vs. 1.59 +/- 0.36 mumol/g Hb; p < < 0.001). There were no differences between the two groups in activities of plasma and erythrocyte Cu/ZnSOD. In conclusion, the results demonstrate disturbances in oxidation status in premenopausal obese women with abnormal lipid profile, which may indicate the association between oxygen-derived free radicals and the increase in the incidence of obesity-related diseases.

Influence of SKF 91488, histamine N-methyltransferase inhibitor, on the central cardiovascular regulation during controlled, stepwise hemorrhagic hypotension in rats.

The histaminergic system influences various activities of the central nervous system, including cardiovascular regulation. Histamine administered intracerebroventricularly (i.c.v.) in anesthetized rats produces the increase in mean arterial pressure (MAP) and heart rate (HR), however, in contrast to normotensive animals, histamine-induced rises in MAP and HR in critically hypotensive animals are significantly higher. Similarly to exogenous histamine, inhibition of the central histamine N-methyltransferase (HNMT) activity (the enzyme catabolizing histamine in the central nervous system) resulting in the increase in endogenous histamine concentration, also leads to the pressor effect in normotensive rats. The present study was designed to determine the role of endogenous central histamine in cardiovascular regulation in a rat model of blood volume-blood pressure controlled hemorrhagic hypotension. In normotensive animals, HNMT inhibitor SKF 91488 produced dose-dependent (20-100 microg i.c.v.) pressor effect accompanied by tachycardia, similarly as exogenous histamine (0.5-5 microg i.c.v.) did. The subpressor dose of SKF 91488 (10 microg) evoked the increase in blood volumes necessary to induce hypotension of 40 and 20 mmHg and the action was accompanied by the rise in histamine concentrations in the hypothalamus (5.18 +/- 0.45 vs 4.23 +/- 0.41 nmol/g; p < 0.05) and medulla oblongata (0.41 +/- 0.05 vs 0.30 +/- 0.06 nmol/g; p < 0.05), with no changes in the cortical histamine concentrations (0.84 +/- 0.18 vs 0.75 +/- 0.17 nmol/g), compared to the control i.c.v. saline-treated group. The effect of SKF 91488 was inhibited by H1 histamine receptor antagonist chlorpheniramine, whereas neither H2 receptor blocker ranitidine, nor H3 receptor antagonist thioperamide affected the action. In conclusion, the study demonstrates that the histaminergic system influences the central cardiovascular regulation during pronounced hemorrhagic hypotension, probably as a result of the activation of compensatory mechanisms.