SELENIUM STATUS IN AUTOIMMUNE THYROIDITIS.

UNLABELLED: Selenium (Se) is an important element that exerts its effects through selenoproteins. The thyroid gland has the highest Se concentration and specific selenoprotein enzymes families are crucial in the thyroid hormone metabolism. There is little evidence on the link between Se and thyroid autoimmune disease, therefore future studies are required to elucidate the nature of this associ ation. AIM: To evaluate the Se status in euthyroid subjects with autoimmune thyroiditis. MATERIAL AND METHODS: From January 2014 to January 2015 we recruited 100 consecutive euthyroid subjects with autoimmune thyroiditis, living in the same region and with normal iodine intake. Serum concentrations of Se, thyroid antibodies (antithyroperoxidase--TPOAb--and antithyroglobulin--TgAb), thyroid-stimulating hormone (TSH), and thyroid ultrasound were performed in all patients. RESULTS: Mean age of the study group was 48.87 ± 12.83 years, range: 18-82 years. Since thyroid pathology is more frequent in the 5th - 6th decades of life we selected the age of 50 for the comparative analysis of the results (51% of patients were under 50). No statistical age-group differences in antibody levels were found: mean TPOAb = 420.95 IU/ml, p = 0.840; mean TgAb = 327.98 IU/ml, p = 0.977. TSH mean was 2.14 [µIU/ml, with no significant age-group differences (p = 0.176). Se levels ranged between 8.05 - 998.50 µg/ with a mean value of 294.96 µg/L and no significant differences between age groups (p = 0.158). Thyroid ultrasound showed inhomogeneity in 89%, nodules in 35% of patients, and a mean thyroid volume of 11.72ml, with no significant age-group differences (p = 0.366). The low TSH levels were associated with low Se levels in 11.6% of cases, but the direct correlation was statistically insignificant (r = 0.116; R2 = 0.0161; p = 0.371). Depend ing on TSH percentiles, mean Selevels showed no significant differences, however pointing out the highest mean value at the 25th percentile (F = 0.441, df = 61, p = 0.646). A negative correlation trend was found between Se and TPOAb (r = -0.2276) or TgAb (r = -0.2190) but lacking statistical significance (p=0.099). CONCLUSION: Our results showed a weak negative correlation between Se and antithyroid antibodies, suggesting that selenium supplementation may improve the course of thyroid autoimmunity.

[Considerations on in vitro and in vivo magnetic nanoparticles hemocompatibility testing]. / O evaluare asupra metodelor de apreciere a hemocompatibilitatii nanoparticulelor magnetice.

The aim of this paper is to summarize few aspects and underline some difficulties that hemocompatibility testing come up. The purpose of hemocompatibility testing is to look for possible undesirable changes in the blood caused directly by a medical device, by chemicals leaching from a device or biomaterials. Undesirable effects of device materials on the blood may include alterations in coagulation parameters, thrombus formation, hemolysis, and immunological changes. For each different event the literature is rich in showing tests, not different in principle, but in testing conditions. ISO 10993-4 describes hemocompatibility tests in five different categories (thrombosis, coagulation, platelets, hematology, and immunology). Here we put together the tests that ISO 10993 and/or American Society for Testing and Materials (ASTM) suggest to evaluate hemocompatibility and we emphases on their utility for magnetic nanoparticules testing. The individual tests are not discussed in detail; they may be performed either in vivo or, preferably, in vitro. For each test we made few considerations with criticism. There is still some uncertainty with respect to what is actually required by the regulatory authorities for the hemocompatibility test, and there is still no harmony between ASTM and ISO 10993 regulations regarding some aspects to be standardised.

[Production of chemoattractant-induced reactive oxygen species in human neutrophils--role of protein kinase C isoforms]. / Productia de specii reactive ale oxigenului indusa de chemoatractanti in neutrofile umane. Rolul isoformelor protein-kinazei C.

UNLABELLED: The aim of our study was to characterize the priming effect of extracellular nucleotides on reactive oxygen species (ROS) production induced by formyl-methionyl-leucyl-phenylalanine (fMLP), interleukin-8 (IL-8), leukotriene B4 (LTB4), and platelet activating factor (PAF). Also, we investigated the roles played by different protein kinase C (PKC) isoforms in nucleotide-induced priming. ROS production was determined by an isoluminol-based assay. MATERIAL AND METHOD: Nucleotide-induced priming was concentration- and time-dependent. The concentration of UTP able to cause maximal priming was 10 microM. When UTP (10 microM) was administered prior the agonist, the increase of the amplitude of the response reached the maximum at 1 minute of preincubation with the nucleotide. RESULTS: Calcium depletion of neutrophil caused significant inhibition of ROS production induced by all agonists tested, but did not affect the priming effect of the nucleotides. We tested the effect of several PKC inhibitors on the nucleotide-induced priming. GF 109203X (5 microM), an inhibitor of all neutrophil's PKC isoforms, or RO 31-8220 (5uM), an inhibitor of classical and novel PKC isoforms, abolished the responses induced by fMLP (10 nM) IL-8 (10 nM), LTB4 (100 nM) or PAF (100 nM). Go 6976 (100 nM), a selective inhibitor of classical PKC isoforms, had no effect on nucleotide-induced priming, suggesting that activation of these PKC isoforms does not play a role in the priming effect. Rottlerin (5 microM), a PKC delta inhibitor, almost abolished the effect of fMLP in the absence or in the presence of UTP, indicating that PKC delta is essential for the fMLP-induced effect; rottlerin also caused inhibition of ROS production induced by IL-8, LTB4 or PAF, however the priming effect of UTP was not affected for these chemoattractants. Our data suggest that classical PKC isoforms do not play a role in chemoattractant-induced ROS production. CONCLUSION: Although fMLP induced effect appears to be highly dependent on PKC delta activation, other chemoattractants are able to cause ROS production through PKC delta-independent mechanisms.

[The neutrophil in human pathology]. / Neutrofilul in patologia umana.

The aim of this paper is to present few aspects of neutrophil role in some human diseases. New clinical and experimental findings and challenging hypothesis are briefly reviewed. The major role of neutrophils in host defense is a rapid response to invading microorganisms. To select their targets, neutrophils do not differentiate well between strange and host antigens without the support of soluble components of the immune system. The powerful weapons of neutrophils and the nonspecific response are the two major mechanisms by which they may damage normal tissue. The host-harming potential of the neutrophils is restricted by elimination of the primary event that initiates inflammatory response and by means that inactivate neutrophils. Inactivation of mediators and temporal adjustment in the pattern of chemokines production lowers the neutrophil influx; apoptosis provide safe clearance of dying neutrophils from the inflammatory site. Neutrophils become the major factor for tissue injury if these regulatory mechanisms are disturbed or if the acute episode cannot be resolved.

[Preliminary pharmacological study on a "magnetic" drug complex]. / Studiu farmacologic preliminar al unui complex medicamentos "magnetic".

Standard therapy requires high amounts of drugs, with subsequent risks of harmful effects on normal tissues. A treatment method that possible can avoid these risks is based on magnetic carriers (the method is designated also as magnetic carrier technique). The method consists in the selective attachment on a micro particle (permanent or reversible bonds), with strong magnetic moment, of an entity with no intrinsic magnetic properties (cells, microorganisms, antibody, antigens or chemicals), followed by external magnetic field targeting of the complexes ("active targeting"). The aims of this study were (1) to evaluate the acute toxicity of two original ferro-fluid (ammonium oleate and sodium oleate-based ferro-fluid) and (2) to assess the diclofenac (non-steroidal antiinflammatory drug, NSAIDS)--sodium oleate-based ferro-fluid efficiency in an acute inflammation model. We founded ammonium oleate-based ferro-fluid to have a strong dose-dependent toxicity, possible trough in vivo ammonium ions release; sodium oleate based-ferro-fluid seems to have a less toxicity. Diclofenac, diclofenac-ferro-fluid complex and ferro-fluid alone, each blocks the 6 hours inflammatory peak and the first two block also the 72 hours inflammatory peak. We conclude that the diclofenac-ferro-fluid complex is probably concentrated in the area of external magnetic field application, leading to a stronger effect of the antiinflammatory drug. Taking in consider our results we cannot exclude a possible summation of the individual effects of diclofenac, ferro-fluid, and external magnetic field on the inflammatory phenomenon.

[Functional characteristics of nucleotide-receptors in human neutrophils]. / Caracteristici functionale ale receptorilor pentru nucleotide în neutrofilele umane.

Nucleotides are important extracellular signaling molecules. It has been established that nucleotides are released from damaged cells, activated platelets and endothelial cells. Thus, at the site of vascular injury, the concentrations of extracellular nucleotides can become elevated. Nucleotides have been shown to cause mobilization of intracellular calcium, upregulation of Mac-1 (CD11b/CD18), degranulation, and chemotaxis in human neutrophils. The goal of this work is to investigate the functional characteristics of nucleotide-receptors in human neutrophils. Nucleotides (ATP and UTP), caused intracellular calcium mobilization in a dose dependent manner. Pharmacological characterization using selective agonists (ATP, UTP), pertussis toxin in human neutrophils and human astrocytoma cells 1321N1 stably expressing P2Y2 or P2Y4 receptors, revealed that human neutrophils express only functional P2Y2 receptors. Treatment of neutrophils with pertussis toxin causes a partial inhibition of nucleotide-induced calcium mobilization. Similarly, by using 1321N astrocytoma cells expressing the P2Y2 receptor we confirmed that calcium mobilization is only partially inhibited by pertussis toxin. The partial resistance of P2Y2-mediated intracellular calcium mobilization suggests that this receptor subtype is coupled not only to a Gi protein, but also to a protein belonging to the Gq-family (most likely G16). In conclusion, we have shown that human neutrophils express functional P2Y2 receptors and all the nucleotide responses are mediated by P2Y2 receptor subtype and that P2Y2 receptors are the functional able to trigger intracellular signaling event in human neutrophils through dual activation of different G proteins.

[Experimental modeling of the blood vessels magnetic embolization]. / Modelare experimentala a embolizarii vaselor sangvine pe cale magnetica.

The embolization of blood vessels is used on a large scale: the method is applied in different diseases, in the ablation of organs, but especially in tumor necrosis. The embolization can be also magnetic, if the embolus is obtained through the deposit in the vessel of magnetic nano or microparticles in the presence of an external magnetic field. The objective of our study was the modeling of the magnetic embolization using amorphous magnetic microspheres that have strong magnetic properties and are biocompatible. Experimental tests were made in order to observe the building of the magnetic embolus inside a thin spiral tube and to determine the influence of some parameters on the efficiency of occlusions: the dimensions of magnetic microspheres (1-300 mm), the debit of the liquid (4.66 - 16.5 ml/min), the viscosity of the carrier liquid (1.007 - 7.34 cSt), the direction and the intensity of the external magnetic field (340 - 600 Gs), the shape of the tube and the linear length of the deposit (5 - 50 mm). Under pre-established experimental conditions the efficiencies of occlusions were between 67% and 100%.

[Preclinical assay on a magnetic carrier type ferrofluid]. / Studiu preclinic asupra unui purtator magnetic tip ferofluid.

UNLABELLED: The aim of the study was to determine the acute toxicity and the antimicrobial actions of an original magnetic carrier, type ferrofluid. The hydrophilic ferrofluid was prepared by covering the Fe3O4 nannoparticles with ammoniumoleate. The absolute amount of iron was of 40 mg/ml ferrofluid. METHODS: Acute toxicity was evaluated on five groups of Swiss male mice, after a single intraperitoneal administration of 1, 0.75, 0.5, 0.25 and 0.125 ml dose of pure ferrofluid/100 g body weight (b.w.), using step-level toxicity method. The study groups of mice were follow-up for 10 days. We did not use the same volume of solution for all the study groups because we were concerned about not to modify the behavior of the ferrofluid (but for each group we used the same volume of solution). The tasks of this part of the study were: 1) the record of the mice death in the first 10 days after intraperitoneal administration of ferrofluid; 2) the behavior of the animal subjects; 3) the morphopathologic examination of kidney, lung, heart, liver and peritoneum samples from the death mice and from the after ten days survivors which were sacrificed. We also investigated the possible antibacterial actions of the ferrofluid on E. coli spp., Klebsiella spp., Staphylococcus aureus Streptococcus group D., in the second part of the study, using standard lab kit. The validation of the results was performed using controls for E. colli and Staphylococcus aureus. RESULTS: The death of the mice was registered between 24 and finished after 96 hours. The maximum tolerated dose (MTD), was of 0.25 ml (10 mg iron/100 g b.w.) and the lethal dose hundred percent (LD100) was of 0.75 ml/(30 mg iron/100 b.w.). In our study we did not determined any kind of antibacterial action of the ferrofluid. CONCLUSIONS: 1) LD100, in our study, was of 30 mg iron/100 g b.w., and DMT of 10 mg iron/100 g b.w. 2) The death of the mice may be due to toxic aggression of ammonium ions released, in vivo, from the ammoniumoleate coverage of magnetite nannoparticles. 3) There were no in vitro antibacterial actions for this ferrofluid.

[Actual modalities of separation by magnetic methods of active biological compounds, cells and pathogenic agents]. / Modalitati actuale de separare prin tehnici magnetice a compusilor biologic activi, celulelor si agentilor patogeni.

The paper presents an overview on magnetic techniques of bio-processing and some of their possible applications. These techniques are in fact direct, or more frequently, indirect magnetic means for separation of particulate substances. A brief presentation of direct and of the most important indirect methods (magnetic carrier and magnetic fluids technologies) is made. There are shown some of the possible applications of magnetic bio-processing in bio-technology and medicine: active biological compounds fixation, isolation and modification, cells and cells organelles separation, removal of xenobiotics, immuno-magnetic testing, pathogen microbes identification.

[Magnetic carrier method- an expectation for antitumoral therapy]. / Metoda purtatorului magnetic--o perspectiva în tratamentul antitumoral.

In order to enhance antineoplastic agents efficiency new therapy methods were developed one of which being magnetic targeted chemotherapy (MTC). MTC method consists in a permanent or reversible selective binding of highly magnetic particles (carriers) with drugs, antibodies et. al., followed by targeting or adhesion of these complexes to the tumor using an external magnetic field. At this early stage of targeting tumors with magnetic particles, there are reasons to be optimistic.

[An analysis of the articles published in Revista Medico-Chirurgicala over the last 7 years]. / O analiza a articolelor publicate în Revista Medico-Chirurgicala din ultimii 7 ani.

INTRODUCTION: As the number of medical journals is continuously increasing, their quality becomes a very reliable tool used by the editors in order to increase readership. As a consequence, the structure and the content of submitted papers are carefully revised before publication. OBJECTIVES: The purpose of our study is to describe structural aspects and the use of descriptive and inferential statistics methods in papers published by the Medical-Surgical Journal between 1990 and 1997. METHODS: Fifteen items were collected for each paper. Ten of them were related to the general structure: type of paper, number of authors, town of authors, professional environment, medical topic covered by the paper, pluridisciplinarity, the existence of a bibliography, the number of titles in the bibliography, language of publication, presence of abstract. The other five were related to data analysis and reporting: description of statistical methods, the existence of significant results without method description, presence of tables and graphics, use of descriptive and inferential statistics. RESULTS: A number of 477 papers were analysed. Original papers represented 57.4%, 71.5% of the authors were involved in medical/non-medical teaching, 58.3% of papers were related to clinical sciences, 29.8% were related to basic medical sciences; pluridisciplinarity was present in 26.8% of papers (significantly increasing trend, p < 0.01), the bibliography was not present in 27.3% of papers (significantly decreasing trend, p < 0.001), romanian was the language of publication in 83% of papers, followed by english (10.9%), french (4.6%) and german (1.5%). Papers without abstract represented 29.9%, the median number of authors is 3(range 1-15) and the mean number of titles in reference list 14.7(SD = 12). Eighteen papers (3.8%) reported significant results without description of methods, 51.4% used tables and graphics, 13.4% used descriptive statistics methods and only 6.9% of the papers have used inferential statistics methods. CONCLUSION: The structural problems of papers published in Medical Surgical Journal should be avoided using a more restrictive editorial policy. The use of such a policy shows positive results for the last 2 years (1995 and 1996). Statistical methods are poorly used in this Romanian medical journal and much progress is to be made before speaking about statistical assessment of submitted papers.