Kinetic Study of Ethylene Polymerization Over Supported Bis(imino)pyridine Iron (II) Catalysts

Summary: The number of active centers (C_P) and propagation rate constants (k_P) for polymerization of ethylene with supported catalysts LFeCl₂/SiO₂, LFeCl₂/Al₂O₃ and LFeCl₂/MgCl₂ (L = 2,6‐(2,6‐(Me)₂C₆H₃NCMe)₂C₅H₃N), activated by an Al(i‐Bu)₃ co‐catalyst, were determined by a method of polymerization inhibition with radioactive ¹⁴CO. In contrast to homogeneous systems based on LFeCl₂, the supported catalysts are highly active and stable in ethylene polymerization at 70–80 °C. In the presence of hydrogen, the activity of the supported catalysts substantially increases (2–4 fold). The data obtained on the effect of hydrogen on the calculated C_P and k_P values suggests that for ethylene polymerization without hydrogen, the “dormant” active centers are formed in the catalytic systems. A scheme for the formation of these “dormant” centers and their reactivation in presence of hydrogen is suggested. For the investigated supported catalysts the C_P values were found to be only 2 to 4% of the total iron complex content in the catalysts. The k_P value for the catalysts prepared using different supports (SiO₂, Al₂O₃ and MgCl₂) were close (3.2 × 10⁴ to 4.5 × 10⁴ L · (mol · s)⁻¹ at 70 °C). The support composition affects neither the molecular mass (MM) nor the molecular mass distribution (MMD) of the polymers produced. The obtained C_P and k_P values and data on the polymer MM and MMD lead to conclusion that the nature of the support has almost no effect on the structure of the active centers and the distribution of their reactivity.

Effect of support on the MMD of PE produced over supported LFeCl₂ catalysts.     

The immunity during the pre-clinical period of type I diabetes mellitus

The purpose of the study was to investigate the condition of immunity (blood lymphocyte immune phenotype and ultrastructure) in healthy children with a family background of type 1 diabetes mellitus (DM 1) having or not having diabetes-associated autoantibodies (DAAB). The subjects of the study were divided into three groups. Group 1 consisted of 90 children with a family background of DM 1 (first line relatives had DM 1), DAAB- (GADA, IA-2A, and IAA) positive or negative; group 2 consisted of 51 children with newly revealed DM 1; group 3 included 45 healthy controls, normoglycemic DAAB-negative children with no family background of DM 1. GADA, IA-2A, and IAA titers were measured using radioimmunoassay. The immune phenotype of lymphocytes (CD3+, CD4+, CDr8, CD20+, and CD56+ cells) were studied using flow cytometry (FACS-analysis); their ultrastructure was studied by means of electron microscopy. The study found a significantly lower total number of T-lymphocytes (CD3+ cells), T-helpers/inductors (CD4+ cells), and natural killer cells (CD56+ cells and large granule-containing lymphocytes) in the DAAB-positive children vs. the DAAB-negative ones and especially the controls. In the DAAB-positive children, electron microscopy found distinct changes in the ultrastructure of CD4+ lymphocytes and large granule-containing lymphocytes (CD56+ cells), which evidences changes in the secretory and cytostatic function. Such changes in the number and ultrastructure of these lymphocyte subpopulations are found in patients with newly revealed DM 1. Thus, immune changes happen in the organism of a healthy person a long time before clinical manifestations of DM 1 develop; these changes reflect a concealed autoimmune process in Langerhans islets. Detection of DAAB plays a significant role not only in studying poorly understood pre-diabetes nature, but also in the development of new, scientifically based methods of its prevention and treatment.     

Hepatitis G virus

A number of new hepatitis viruses （G, TT, SEN） were discovered late in the past century. We review the data available in the literature and our own findings suggesting that the new hepatitis G virus （HGV）, disclosed in the late 1990s, has been rather well studied. Analysis of many studies dealing with HGV mainly suggests the lymphotropicity of this virus. HGV or GBV-C has been ascertained to influence course and prognosis in the HIV-infected patient. Until now, the frequent presence of GBV-C in coinfections, hematological diseases, and biliary pathology gives no grounds to determine it as an ＂accidental tourist＂ that is of no significance. The similarity in properties of GBV-C and hepatitis C virus （HCV） offers the possibility of using HGV, and its induced experimental infection, as a model to study hepatitis C and to develop a hepatitis C vaccine.     

Screening commercial drivers for obstructive sleep apnea: translation and validation of Serbian version of Berlin Questionnaire

Purpose

Obstructive sleep apnea (OSA) can lead to severe health consequences. Drivers of motor vehicles with untreated or undiagnosed OSA have a greater risk of traffic accidents. Use of self-reported questionnaires is the first step in OSA diagnosis. The main aim of this study was to perform the translation and validation of Berlin Questionnaire in a sample of commercial drivers.

Methods

After formal translation, validation was performed on a sample of commercial drivers and included evaluation of internal consistency, test–retest reliability, construct and criterion validity. Full-night attended polysomnography or cardiorespiratory polygraphy was used for OSA diagnosis.

Results

One hundred male participants, 24–62 years old, were included. Berlin Questionnaire classified 35 % subjects as potential OSA patients. Polysomnography confirmed OSA in 58 % of the subjects. Berlin Questionnaire showed good internal consistency (Cronbach’s alpha 0.82—first category, 0.73–0.95—second category). Test–retest reliability (Cohen’s kappa 0.78) was adequate. Berlin score was significantly correlated with OSA category and apnea–hypopnea index (AHI). Sensitivity of Berlin Questionnaire was from 50.9 (AHI ≥ 5) to 75 % (AHI ≥ 30), while specificity ranged from 86 to 70.5 %.

Conclusions

Berlin Questionnaire (Serbian version) showed good measurement properties, creating basis for further research of its usefulness as OSA screening tool in populations of interest.

     

Systemic vascular diseases in the antiphospholipid syndrome. What is the best diagnostic choice?

Antiphospholipid syndrome (APS) is an autoimmune disease which is characterized by arterial and venous thromboses, fetal loss, and the presence of antiphospholipid antibodies in the serum (aPL). It is characterized by accelerated atherosclerosis and that together with an increased tendency towards thrombosis leading to the occurrence of various vascular events. Timely diagnosis of vascular changes, preferably in subclinical phase, is required due both to their severity and to the high mortality rate. Detection of arterial and venous changes nowadays is performed through diversity of invasive and non invasive diagnostic methods. 64-multi slice computed tomographic angiography (64-MSCT) seems to be the most precise method with low exposure time, giving the opportunity for clinicians to early diagnose and timely treat APS patients.     

Asymmetric dimethylarginine--mechanisms and targets for therapeutic management

Evidence has been accrued recently that chronic high levels of asymmetric dimethylarginine (ADMA) can be directly beneficial to the treatment of atherosclerotic vascular disorders thus making the substance a promising new therapeutic target. A therapeutic target can be theoretically each stage in the process of generation and elimination of asymmetric dimethylarginine. The methylation of L-arginine residues is a universal biological process involving hundreds of proteins but still with unknown effects. Interference with these mechanisms can generate ambiguous and speculative discussions. Supplementation with L-arginine seems to be the most natural way to reverse the detrimental effect of ADMA on the endothelium. The enzymatic activity of endogenous nitric oxide synthase is regulated by the ratio between the concentrations of L-arginine (the natural substrate) and that of ADMA (the endogenous inhibitor): in the presence of normal L-arginine levels, any elevation ofADMA levels may cause relative L-arginine deficiency thus attenuating the activity of the endogenous nitric oxide synthase. Target replacement therapy with L-arginine to increase the L-arginine plasma levels results in the normalisation of the L-arginine/ADMA ratio in the presence of higher levels of the latter. There is still some controversy about the effects of the most frequently used drugs on asymmetric dimethylarginine. Most of the relevant studies show that statins do not affect the ADMA levels. On the other hand, patients with high levels of ADMA are resistant to statin therapy--to improve the endothelium-dependent vasodilation they need a combined therapy with L-arginine. The angiotensin-converting enzyme inhibitors and the angiotensin receptor blockers are the most extensively studied substances, the studies predominantly centring on confirming their ADMA reducing effect. Until the specific ADMA-reducing therapy becomes readily available, it is the therapies of modification of the risk factors causing the increase of ADMA or the depletion of L-arginine, and the L-arginine replacement therapy that are the most realistic therapeutic solutions for patients with high plasma levels of ADMA because the synthesis of nitric oxide correlates with the L-arginine/ADMA ratio. A study was conducted in the Surgery of Preventive Cardiology with the Clinic of Cardiology in Plovdiv which included 40 patients with pronounced hypercholesterolemia (HC)--it was found that a one-month therapy with 40 mg simvastatin did not change statistically significantly ADMA plasma levels in spite of the optimal lipid regulation.     

Comparison of mesencephalic free-floating tissue culture grafts and cell suspension grafts in the 6-hydroxydopamine-lesioned rat

Ventral mesencephalon (VM) of fetal rat and human origin grown as free-floating roller-tube (FFRT) cultures can survive subsequent grafting to the adult rat striatum. To further explore the functional efficacy of such grafts, embryonic day 13 ventral mesencephalic tissue was grafted either after 7 days in culture or directly as dissociated cell suspensions, and compared with regard to neuronal survival and ability to normalize rotational behavior in adult rats with unilateral 6-hydroxydopamine (6-OHDA) lesions. Other lesioned rats received injections of cell-free medium and served as controls. The amphetamine-induced rotational behavior of all 6-OHDA-lesioned animals was monitored at various time points from 18 days before transplantation and up to 80 days after transplantation. Tyrosine hydroxylase (TH) immunostaining of the histologically processed brains served to assess the long-term survival of grafted dopaminergic neurons and to correlate that with the behavioral effects. Additional cultures and acutely prepared explants were also fixed and stored for histological investigation in order to estimate the loss of dopaminergic neurons in culture and after transplantation. Similar behavioral improvements in terms of significant reductions in amphetamine-induced rotations were observed in rats grafted with FFRT cultures (127%) and rats grafted with cell suspensions (122%), while control animals showed no normalization of rotational behavior. At 84 days after transplantation, there were similar numbers of TH-immunoreactive (TH-ir) neurons in grafts of cultured tissue (775 ± 98, mean ± SEM) and grafts of fresh, dissociated cell suspension (806 ± 105, mean ± SEM). Cell counts in fresh explants, 7-day-old cultures, and grafted cultures revealed a 68.2% loss of TH-ir cells 7 days after explantation, with an additional 23.1% loss after grafting, leaving 8.7% of the original number of TH-ir cells in the intracerebral grafts. This is to be compared with a survival rate of 9.1% for the TH-ir cells in the cell-suspension grafts. Immunostaining for the calcium-binding proteins calretinin, calbindin, and parvalbumin showed no differences in the neuronal expression of these proteins between the two graft types. In conclusion, we found comparable dopaminergic cell survival and functional effects of tissue-culture grafts and cell-suspension grafts, which currently is the type of graft most commonly used for experimental and clinical grafting. In this sense the result is promising for the development of an effective in vitro storage of fetal nigral tissue, which at the same time would allow neuroprotective and neurotrophic treatment prior to intracerebral transplantation. Received: 11 March 1997 / Accepted: 19 August 1997