Protein-mediated surface structuring in biomembranes

The lipids and proteins of biomembranes exhibit highly dissimilar conformations, geometrical shapes, amphipathicity, and thermodynamic properties which constrain their two-dimensional molecular packing, electrostatics, and interaction preferences. This causes inevitable development of large local tensions that frequently relax into phase or compositional immiscibility along lateral and transverse planes of the membrane. On the other hand, these effects constitute the very codes that mediate molecular and structural changes determining and controlling the possibilities for enzymatic activity, apposition and recombination in biomembranes. The presence of proteins constitutes a major perturbing factor for the membrane sculpturing both in terms of its surface topography and dynamics. We will focus on some results from our group within this context and summarize some recent evidence for the active involvement of extrinsic (myelin basic protein), integral (Folch-Lees proteolipid protein) and amphitropic (c-Fos and c-Jun) proteins, as well as a membrane-active amphitropic phosphohydrolytic enzyme (neutral sphingomyelinase), in the process of lateral segregation and dynamics of phase domains, sculpturing of the surface topography, and the bi-directional modulation of the membrane biochemical reactivity.

Protein-mediated surface structuring in biomembranes.

The lipids and proteins of biomembranes exhibit highly dissimilar conformations, geometrical shapes, amphipathicity, and thermodynamic properties which constrain their two-dimensional molecular packing, electrostatics, and interaction preferences. This causes inevitable development of large local tensions that frequently relax into phase or compositional immiscibility along lateral and transverse planes of the membrane. On the other hand, these effects constitute the very codes that mediate molecular and structural changes determining and controlling the possibilities for enzymatic activity, apposition and recombination in biomembranes. The presence of proteins constitutes a major perturbing factor for the membrane sculpturing both in terms of its surface topography and dynamics. We will focus on some results from our group within this context and summarize some recent evidence for the active involvement of extrinsic (myelin basic protein), integral (Folch-Lees proteolipid protein) and amphitropic (c-Fos and c-Jun) proteins, as well as a membrane-active amphitropic phosphohydrolytic enzyme (neutral sphingomyelinase), in the process of lateral segregation and dynamics of phase domains, sculpturing of the surface topography, and the bi-directional modulation of the membrane biochemical reactivity.

[Complex therapy of chronic hepatic encephalopathy supplemented with probiotic: comparison of two studies]. / Komplexná liecba chronickej hepatálnej encefalopatie doplnená probiotikom. Porovnanie dvoch stúdií.

BACKGROUND: Several reports about usefulness of probiotics, including Enterococcus faecium in the treatment of chronic hepatic encephalopathy in patients with liver cirrhosis have been recently published. The results obtained by the administration of Enterococcus faecium M-74 + selenium will be evaluated and compared with those published by Loguercio et al. for Enterococcus faecium SF 68. METHODS AND RESULTS: Fifteen patients with liver cirrhosis, portal hypertension and chronic hepatic encephalopathy were treated, beside the standard therapy, also with one capsule of probiotic "Enterococcus faecium M-74 + Selenium" per day in three four-week periods, separated by two fortnight pauses. During the treatment, every patient was examined 9-times. The severity of chronic hepatic encephalopathy was evaluated with the aid of the portal systemic encephalopathy index, calculated from 5 parameters (mental stage, asterixis, number connecting test, blood ammonia, EEG). The indexes of initial and final values were compared. The time course of blood ammonia levels and that of results from number connecting test in either study were mutually compared on the basis of interval estimates of quadratic regression function. Significant improvement of the portal systemic encephalopathy index after the treatment was found: it decreased in average by 70% (55 to 85%, interval 95% confidence interval). The mental stage improved and the asterixis disappeared. The blood ammonia levels as well as the results from the number-connecting test after 8-9 weeks significantly approached the normal pattern. EEG findings improved and they were often normalised. Our starting blood ammonia levels (increased by 31% above norm) and results from the connecting test (increased by 60%) were significantly lower accordingly the Loguercio et al. (increased by 243 and 238%, respectively). During the treatment, the values in our study decreased by 25% and 30%, in the compared study by 50% and 70%. CONCLUSIONS: Our results proved the hypothetical favourable effect of probioticum Enterococcus faecium M-74 + Selenium on chronic hepatic encephalopathy. Interestingly, a markedly higher relative therapeutic effect has been achieved in more serious disorder in comparison with the less severe disorders in the present study.

[Primary hemochromatosis]. / Primárna hemochromatóza.

Authors describe in the case report a development of the primary hemochromatosis. At the time of the diagnosis in 1979 from organ complication the liver fibrosis and secondary diabetes mellitus were presented. Patient was treated with the venepunctions and with desferoxamine. In the 1998 the primary hepatocellular tumor was found and resected. Instead of the chemotherapy occurred the progression of the disease with multiple metastases and liver insufficiency and 66-years old patient died 19 months after surgery in the 20th year of the disease.

Strong cooperativeness in the mononuclear iron(II) derivative exhibiting an abrupt spin transition above 400 K.

The spin crossover system, [Fe(bzimpy)(2)](ClO(4))(2).0.25H(2)O, was reinvestigated above room temperature (bzimpy = 2,6-bis(benzimidazol-2-yl)pyridine). The system exhibits an abrupt low-spin to high-spin transition at T(c) = 403 K. Liberation of a fractional amount of water does not affect the spin crossover: the system is perfectly reversible with a hysteresis width of DeltaT = 12 K. The existence of the hysteresis at such high temperature determines that the lowest limit of the solid-state cooperativity parameter is J/k > 403 K despite long iron(II) separations (10 A). The high cooperativeness has been assigned to a perfect pi-stacking of the benzimidazole rings in the crystal lattice at a distance as short as 3.6 A. Variable-temperature IR data and the heat capacity measurements match well the magnetic data. The thermodynamic properties are DeltaH = 17 kJ mol(-)(1), DeltaS = 43 J K(-)(1) mol(-)(1), so that the entropy of the spin transition shows a considerable contribution from the molecular vibrations. A theoretical model has been applied in fitting the magnetic data along the whole hysteresis path. A statistical distribution of the cooperativity parameter led to the feature that angled walls of the hysteresis loop are well reproduced.

Selective imidazolidine ring opening during complex formation of iron(III), copper(II), and zinc(II) with a multidentate ligand obtained from 2-pyridinecarboxaldehyde N-oxide and triethylenetetramine.

The condensation of 2-pyridinecarboxaldehyde N-oxide and triethylenetetramine yields a product with two imidazolidine rings, as proven by a solid-state X-ray structure analysis as well as by NMR solution spectra. This ligand, L1, undergoes a ring-opening reaction on complex formation with Cu(II), yielding [CuL2]2+ where L2 functions as a pentadentate ligand, containing only one imidazolidine ring. On complexation with Zn(II) and Fe(III), both rings are opened and the complexes [ZnL3]2+ and [FeL3]3+ with a hexadentate L3 ligand are formed. The recrystallization of [ZnL3]2+ from DMSO solution results in the complex [ZnL1(DMSO)2]2+ in which L1 behaves as a tetradentate ligand. Thus L1, L2, and L3 are structural isomers with two, one, or no imidazolidine rings, as confirmed by X-ray structure analyses. The intramolecular ring formation is the result of the nucleophilic addition of the N(amino) group to the electrophilic sp2-hybridized -HC delta+=N site. Owing to the absence of the chelate effect on the sp3-hybridized carbon atom belonging to the imidazolidine ring, the ring opening is facilitated and readily observed upon complex formation with Cu(II), Zn(II), and Fe(III).

[Lactilol (Importal, 10g in powder made by ZYMA) in the treatment of portal systemic encephalopathy]. / Lactitol, Importal prások 10 g ZYMA, v liecbe portálnej systémovej encefalopatie.

In a group of 15 patients with portal systemic encephalopathy (PSE) associated with cirrhosis of the liver with portal hypertension and spontaneous systemic shunt of the portal circulation the authors administered Lactitol (Importal, powder à 10 g Zyma), in amounts up to 40 g/day for a period of 56 days. In the course of treatment every patient was repeatedly examined before the onset of treatment and three times during treatment. The grade of PSE was assessed on the basis of the score of the neuropsychiatric examination from which the PSE index was worked out. In the investigated group of patients with PSE the authors found a significant improvement of the PSE index during treatment with Importal Zyma. The mental condition of the patients improved, the NCT period was reduced, asterixis receded, on the EEG the delta and theta activity receded and normal alpha activity developed. The serum ammonia levels declined but did not reach statistical significance. During treatment the authors did not record changes of normal values of glucose, sodium and potassium in serum and did not detect any adverse side effects. Based on the assembled results the authors conclude that lactitol treatment extends possibilities of PSE treatment.

Biochemical pattern of the ascitic fluid in liver cirrhosis and in neoplastic diseases.

In 22 subjects with liver cirrhosis and in 18 with malignancy, both with ascites, 10 biochemical parameters have been investigated in ascitic fluid. The evaluation of data by cluster analysis, optimized with the aid of multivariate normality testing, was able to recognize correctly a majority of cases. For diagnosis of malignancy, an 89% sensitivity and 82% specificity was obtained. The described way of data collecting and processing is recommended for the clinical practice.

[Essential phospholipids in the treatment of chronic hepatitis B virus infection]. / Esenciálne fosfolipidy v liecbe chronickej infekcie vírusom hepatitidy B.

The authors investigated 24 patients with chronic infection with the hepatitis B virus. HBeAg-positive patients had significantly (alpha = 0.05) more frequently pathological initial values of biochemical and immunological indicators, as compared with anti-HBe-positive patients. Delta antigen in the liver and anti-delta antibodies in serum if examined, were always negative. All patients were subjected to 16-week treatment with Essentiale forte (Natterman). After treatment and after the subsequent 16 weeks in none of the patients loss of HBsAg or seroconversion of HBeAg-positive to anti-HBe-positive was recorded. In the sub-group of HBeAg-positive subjects after treatment a significant drop of gamma-globulins and circulating immunocomplexes occurred, in the sub-group of anti-HBe-positive subjects a significant rise of active and total T-lymphocytes was found. The authors recommend to test Essentiale forte in the prevention and treatment of immunocomplex disease in chronic infection with the hepatitis B virus.

[Larval toxocariasis--a severe course of the manifest infection]. / Larválna toxokaróza--t'azký priebeh manifestnej nákazy.

The case of a 17 year old patient with severe course of toxocariasis is reported. Over a period of 6 months the patient developed signs of serious systemic condition with fever, respiratory infections, diarrhea, urticaria, weight loss, and muscular atrophies. The most remarkable organ derangements involved bilateral exudative neuroretinitis, severe degree of peripheral motoneuron derangement, and grave kidney damage with developing polyuria, hypokalemia, metabolic alkalosis and therapeutically hardly tractable hypertension. The most important laboratory findings were high erythrocyte sedimentation, absolute and relative eosinophilia, and hypergammaglobulinemia. Serological examination exhibited weak larval toxocariasis positivity. Treatment with Mintezol and subsequent administration of prednisone resulted in complete restoration of the clinical state, including organ and laboratory manifestations. The reported case documents the occurrence of larval toxocariasis in our population as well as the possibility of a very severe course of this parasitic infection in man. The therapeutic effect is remarkable since literary data have so far reported mostly unsatisfactory results of toxocariasis treatment.

[Hemorrhagic accidents in palatal tonsil surgery]. / Accidente hemoragice in chirurgia amigdalei palatine.

Here is shown that, even though tonsillectomy is the most frequently performed operation in ORL, it may sometimes cause severe hemorrhaging that could imperil the patient's life if not rapidly and competently dealt with. Tonsil hemorrhaging is favoured by the anatomical situating, tonsils being greatly vascularized, as well as by the specific of the pharyngeal wounds. There are discussed here the cases in the Bistrita ORL Clinic between 1981-1987.