The effect of candesartan on pentraxin-3 plasma levels as marker of endothelial dysfunction in patients with essential arterial hypertension.

BACKGROUND: In the last decades, the studies performed on the field of endothelial dysfunction confirmed the fact that the starting point of this pathology is the inflammation. Several inflammatory biomarkers had been discovered and studied, ones showing systemic inflammation, and others being more specific biomarkers and showing the local inflammation. Pentraxin-3 (PTX3) is a new inflammatory biomarker, from the same family as high-selectivity C-reactive protein (hs-CRP), but it is a more specific biomarker, due to its local production: the endothelial cells and not the liver like in the case of hs-CRP. AIMS: Several antihypertensive classes of drugs seem to have a positive impact on reducing the local endothelial inflammation, beyond their effect of lowering the blood pressure, so this study aims to analyze the effect of candesartan on the two inflammatory biomarkers: PTX3 and CRP, compared with other antihypertensive drugs, in hypertensive patients with endothelial dysfunction. METHODS: A total of 365 patients were included in the study: 127 hypertensive patients were under treatment with candesartan, 134 patients were under treatment with other hypotensive medication (beta blockers, calcium channel blockers, and diuretics), both groups with controlled values of blood pressure, and 104 were normotensive persons. Classical methods of assessing the endothelial function were correlated with these biochemical markers. RESULTS: The patients treated with candesartan had a significant lower value of PTX3 and hs-CRP, compared with those under treatment with other antihypertensive medication as follows: PTX3: 0.61 ± 0.49 vs 0.95 ± 1.04 ng/ml, P = 0.006 and hs-CRP: 0.19 ± 0.20 vs 0.20 ± 0.22 mg/dl, P = 0.54. CONCLUSIONS: Candesartan decreases PTX3 and hs-CRP plasma levels more powerful than other classes of antihypertensive drugs (beta blockers, calcium channel blockers, and diuretics), so we may assume that candesartan has a more potent action in reversing endothelial dysfunction and that it offers a higher vascular protection than other classes of antihypertensive drugs. We are suggesting that this new biochemical marker, PTX3, might be better and more specific marker for endothelial dysfunction, than hs-CRP.

Evaluation of patients diagnosed with essential arterial hypertension through network analysis.

BACKGROUND: Essential hypertension is a chronic pathology that causes long-term complications due to late diagnosis of patients, the inability to control the disease through medication, or due to the complexity of associated risk factors. AIMS: Our study sets out to identify specific patterns of response to arterial hypertension treatment, by taking into consideration the multiple connections between risk factors in a relevant population of hypertensive patients. METHODS: Network science is an emerging paradigm, branching over multiple aspects of physical, biological and social phenomena. One such branch, which has brought significant contributions to medical science, is the field of network medicine. To apply this methodology, we create a complex network of hypertensive patients based on their common medical conditions. Consequently, we obtain a community-based representation which pinpoints specific-and previously uncharted-patterns of hypertension development. This approach creates incentives for evaluating patient's treatment efficacy, by considering its network topological position. RESULTS: Distinct clusters of patients with common properties have emerged for each study group (group A-treated with nebivolol, group B-treated with perindopril and group C-treated with candesartan cilexetil). Therefore, our network-based clustering allows for a better treatment assessment.

Nonlinear analysis of saccade speed fluctuations during combined action and perception tasks.

BACKGROUND: Saccades are rapid eye movements used to gather information about a scene which requires both action and perception. These are usually studied separately, so that how perception influences action is not well understood. In a dual task, where the subject looks at a target and reports a decision, subtle changes in the saccades might be caused by action-perception interactions. Studying saccades might provide insight into how brain pathways for action and for perception interact. NEW METHOD: We applied two complementary methods, multifractal detrended fluctuation analysis and Lempel-Ziv complexity index to eye peak speed recorded in two experiments, a pure action task and a combined action-perception task. RESULTS: Multifractality strength is significantly different in the two experiments, showing smaller values for dual decision task saccades compared to simple-task saccades. The normalized Lempel-Ziv complexity index behaves similarly i.e. is significantly smaller in the decision saccade task than in the simple task. COMPARISON WITH EXISTING METHODS: Compared to the usual statistical and linear approaches, these analyses emphasize the character of the dynamics involved in the fluctuations and offer a sensitive tool for quantitative evaluation of the multifractal features and of the complexity measure in the saccades peak speeds when different brain circuits are involved. CONCLUSION: Our results prove that the peak speed fluctuations have multifractal characteristics with lower magnitude for the multifractality strength and for the complexity index when two neural pathways are simultaneously activated, demonstrating the nonlinear interaction in the brain pathways for action and perception.

Endometriosis - clinical approach based on histological findings.

Endometriosis is a benign disease defined by the presence of endometrial glands and stroma outside of the uterus and is associated with both pelvic pain and infertility. The most common sites of endometriosis, in decreasing order of frequency, are the ovaries, anterior and posterior cul-de-sac, posterior broad ligaments, uterosacral ligaments, uterus, fallopian tubes, sigmoid colon, appendix, and round ligaments. The main treatment is surgical, but often-microscopic islands of endometrial tissue remain, which proliferate and are responsible for relapses. We tested the efficacy of two drugs (Medroxyprogesterone and Triptorelinum), administered for six months to prevent recurrence after surgery. Treatment with Medroxyprogesterone was 100% effective in terms of relapse, while Triptorelinum could not prevent recurrence of endometriosis.

Investigation on series of length of coding and non-coding DNA sequences of bacteria using multifractal detrended cross-correlation analysis.

In the framework of multifractal detrended cross-correlation analysis, we investigate characteristics of series of length of coding and non-coding DNA sequences of some bacteria and archaea. We propose the use of a multifractal cross-correlation series that can be defined for any pair of equal lengths data sequences (or time series) and that can be characterized by the full set of parameters that are attributed to any time series. Comparison between characteristics of series of length of coding and non-coding DNA sequences and of their associated multifractal cross-correlation series for selected groups is used for the identification of class affiliation of certain bacteria and archaea. The analysis is carried out using the dependence of the generalized Hurst exponent on the size of fluctuations, the shape of the singularity spectra, the shape and relative disposition of the curves of the singular measures scaling exponent and the values of the associated parameters. Empirically, we demonstrate that the series of lengths of coding and non-coding sequences as well as the associated multifractal cross-correlation series can be approximated as universal multifractals.

Anti-Mullerian hormone--a prognostic marker for metformin therapy efficiency in the treatment of women with infertility and polycystic ovary syndrome.

BACKGROUND: The anti-Mullerian hormone (AMH) is secreted in women exclusively by the granulosa cells of the ovarian follicles. The serum level of AMH is a precise marker of follicle pool size. In recent clinical studies of polycystic ovary syndrome (PCOS), the serum levels of AMH were elevated about two to threefold. The use of metformin in women with infertility and PCOS has proved to be efficient: restoring ovulation and reducing metabolic dysfunctions. The aim of our study is to assess AMH as a prognostic marker for metformin therapy efficiency in the treatment of women with infertility and polycystic ovary syndrome (PCOS). METHODS: Eleven patients with infertility and PCOS were enrolled; PCOS was diagnosed according to the criteria of Androgen Excess and Polycystic Ovarian Syndrome Society 2006 (AE/PCOS). All patients have received metformin therapy. Serum AMH was recorded before and after 2 months of treatment; the normal laboratory values were 2.0-6.8 ng/ml. RESULTS: The primary serum AMH level of all women in study was very high: 8.99±0.99 ng/ml. After 2 months of treatment with metformin ovulation was restored in all the patients and the serum AMH levels were significantly decreased. CONCLUSIONS: In clinical practice, serum AMH levels of women with infertility and PCOS receiving metformin are a useful predictive marker for the treatment efficiency.

Matrix metalloproteinases: useful and deleterious.

MMPs (matrix metalloproteinases) are zinc-dependent endopeptidases that degrade both matrix and non-matrix proteins. They play an important role in morphogenesis, and in a wide range of processes including tissue repair and remodelling. Their abnormal expression contributes to pathological processes including arthritis, cancer, and cardiac and central nervous system diseases, which explains the large interest in finding specific MMP inhibitors for therapeutic use. In this review we describe the structural features of MMPs, with special emphasis on their interaction with specific inhibitors. The effect of new, hydroxamatebased inhibitors on MMP isolated from bovine brain is evaluated.

Chaos supported stochastic resonance in a metal-ferroelectric-semiconductor heterostructure.

An experimental study is presented on a complex nonlinear system showing a particular type of dynamics that can be interpreted as stochastic resonance. The system consists of a metal-ferroelectric-semiconductor structure, which plays the role of a nonlinear element in an electric circuit with linear resistance, inductance, and capacitance connected in series (RLC series circuit) driven externally by a high-amplitude harmonic voltage source. The system presents various kinds of nonlinear behavior, of which the simplest, consisting of a period-doubling evolution to chaos, is of interest to this study. The broadband intrinsic chaos emerging after a period-doubling sequence exists for a large range of frequencies of the driving voltage. The appearance of the chaotic dynamics is associated with the promotion of a low-frequency harmonic spectral component. This is interpreted as stochastic resonance with intrinsic chaos replacing noise, the usual variable in regular SR.

Dynamic control by sinusoidal perturbation and by Gaussian noise of a system of two nonlinear oscillators: computation and experimental results.

In this paper we report numerical and experimental studies of the dynamic control of the inter-anode plasma of a double electrical discharge and of a system of two coupled nonlinear oscillators modeling this plasma. We compare the transition between chaotic dynamics and periodic dynamics induced by a sinusoidal perturbation and by small-dispersion Gaussian noise. Besides considerable differences between the effect of the two types of perturbation we also find important similarities. For small amplitude, both the sinusoidal and the white noise perturbations can induce the system to change from chaotic to regular dynamics. In the case of sinusoidal perturbation, the transition time from the chaotic to regular state has a definite duration that depends on the values of the perturbation parameters. The suppression of the perturbation has no influence on the state - the system remains in the same regular state. Subsequent reinstatement of the same type of perturbation with the same amplitude does not change the periodic state of the system but, for considerably higher amplitude, the system is switched back to its chaotic state. For moderate-amplitude sinusoidal perturbation, intermittent transitions between the chaotic and regular states is observed. Most of these predictions of the model have been observed experimentally in a system of two coupled electrical discharges. Our results suggest practical methods that can be used for controlling the discharge plasma dynamics.

Control of chaos by random noise in a system of two coupled perturbed van der Pol oscillators modeling an electrical discharge plasma.

The control of chaos in nonlinear systems by different methods is still a high interest topic particularly when this is achieved by random noise as in this work. The change of chaotic dynamics into periodic dynamics induced by random noise in a system of two coupled perturbed van der Pol oscillators and comparison with the experimentally observed behavior of a double discharge plasma that it models is presented. Methods specific to nonlinear analysis such as phase portraits, Lyapunov exponents, and Fourier spectra are used to demonstrate the changeover from chaotic to regular dynamics induced by random noise. A phase diagram determines the range of noise parameters corresponding to the lowest orders of an observed bifurcation sequence of 3 x 2(n) type and particulars of the transitions are presented.

As-triazine derivatives with potential therapeutic action. XXVI. Syntheses of 5-substituted-6-azauracil acyclonucleosides.

5-Substituted 6-azauracils were alkylated with (2-acetoxyethoxy)methly bromide to give protected acyclic nucleosides which were protected to afford acyclonucleosides of 5-substituted 6-azauracils. Their structures have been established by the UV and 1H-NMR spectra and by elemental analysis.

Study of the antiviral activity of some new classes of AS-triazine derivatives (preliminary note).

The inhibitory activity exerted by some derivatives with an asymmetrical triazine structure on the multiplication of certain viruses [parainfluenza type 1 Sendai virus, vesicular stomatitis virus, (VSV) herpes simplex type 1 virus (HSV)] was determined: the role of coupling with ribose and that of substitution by halogens on the lateral chain was pointed out.

Identification of anti-idiotypic antibodies to anti-phosphotyrosine antibodies in human sera.

We have recently identified in SLE sera antibodies against phosphotyrosine. They were also detected in normal sera and gammaglobulin preparations, suggesting that they belong to natural autoantibodies. In this paper, the occurrence of anti-idiotypic antibodies against anti-phosphotyrosine antibodies, in the above mentioned samples, is investigated. In order to identify these anti-idiotypic antibodies ELISA, immunoprecipitation and immunoblotting are performed. Our data demonstrate the presence of anti-idiotypic antibodies specific to anti-phosphotyrosine antibodies in SLE sera as well as in normal sera, suggesting that these anti-idiotypic antibodies are also auto-anti-idiotypic antibodies. The densitometry of immunoblots reveals significantly higher levels of anti-idiotypic antibodies in SLE sera. Based on the competition inhibition studies we conclude that some of these anti-idiotypic antibodies belong to beta/gamma type.

Anti-phosphotyrosine and anti-phosphoserine antibodies in SLE sera.

By using an ELISA method, we identified antiPTyr and antiPSer antibodies in the sera of some SLE patients. Afterwards, antiPTyr and antiPSer antibodies were purified by affinity chromatography on phosphotyramine-CNBr-Sepharose column and on phosphoethanolamine-CNBr-Sepharose, respectively, and the specificity of the purified antibodies was demonstrated by inhibition assays. The study pointed out a higher incidence of antiPTyr than anti PSer antibodies in the sera of these patients, which suggests that some "autoantigens" from membrane might be involved.

Anti-phosphotyrosine antibodies--obtaining and purification.

Anti-phosphotyrosine antibodies were obtained by rabbits immunization using bovine serum albumin-phosphotyrosine complex. Hyperimmune rabbit serum was purified on affinity chromatography column obtained by phosphotyramine binding on Sepharose 4 B, CNBr-activated. The antibodies obtained after purification were tested by ELISA and immunoblotting.

Viral infection correlated with superoxide anion radicals production and natural and synthetic copper complexes.

Studies conducted on asymmetric triazine derivatives synthetized at the Chemical and Pharmaceutical Research Institute showed that products S1, S16, S17, S19, S20 and S22 have a remarkable O2- radical scavenger activity. Among these derivatives, the product S1 is the most efficient as an antiviral agent.

Effects of asymmetrical triazine copper complexes on superoxide radical formation and on the Sendai virus multiplication.

The O2- scavenging activity of some ligands of asymmetrical triazine seems to be enhanced when complexed with copper. S1 Cu complex in concentration of 10(-8) M inhibits the multiplication of type 1 (Sendai) parainfluenza virus cultivated on MCA fragments. The possible mechanism of inhibition is discussed.

The effect of some asymmetric triazine derivatives on the in vitro formation of free superoxide radicals.

According to their chemical structure, asymmetric triazine derivatives have an activator or scavenger action in a superoxide radical generating system. Complexation with Cu2+ of one of the derivatives enhanced its scavenger activity.