Stochastic resonance in a proton pumping Complex I of mitochondria membranes.

We make use of the physical mechanism of proton pumping in the so-called Complex I within mitochondria membranes. Our model is based on sequential charge transfer assisted by conformational changes which facilitate the indirect electron-proton coupling. The equations of motion for the proton operators are derived and solved numerically in combination with the phenomenological Langevin equation describing the periodic conformational changes. We show that with an appropriate set of parameters, protons can be transferred against an applied voltage. In addition, we demonstrate that only the joint action of the periodic energy modulation and thermal noise leads to efficient uphill proton transfer, being a manifestation of stochastic resonance.

[Platelet Metabolism in Clopidogrel Resistant and Sensitive Patients With Ischemic Heart Disease].

OBJECTIVE: to investigate relationship between activity of platelet nicotinamide adenine dinucleotide (NAD) and nicotinamide adenine dinucleotide phosphate (NADP) dependent dehydrogenases in patients with ischemic heart disease (IHD) after coronary artery bypass grafting (CABG) and their sensitivity to clopidogrel. MATERIAL AND METHODS: We studied 51 male patients with chronic IHD before and after CABG. Control group comprised 35 healthy men. In IHD patients spontaneous and induced platelet aggregation was measured by aggregometry before CABG (in 2 weeks after cessation of antiplatelet drugs), after CABG during therapy with clopidogrel (75 mg/day), and in 6 months after surgery. Patients were classified as clopidogrel sensitive or resistant using cutoff of 50% inhibition of initial ADP (5 M) induced platelet aggregation after 2 weeks of treatment with clopidogrel. Activity of platelet NAD and NADP dependent dehydrogenases was measured by bioluminescent method. RESULTS: There were 41 clopidogrel sensitive and 10 clopidogrel resistant patients. Irrespective of sensitivity to clopidogrel platelet metabolism in IHD patients was characterized by reduced activity of anaerobic energetics, glutathione-dependent antioxidant system, reactions that transport products of lipid catabolism on glycolysis, and NADPH-dependent transfer of substrates from citric acid cycle to amino acid metabolism. Metabolic features of platelets characteristic of clopidogrel resistance were low activity of the key reaction of pentose phosphate cycle reflecting state of plastic metabolism, and substrate flow in the tricarbonic acid cycle - determinant of intensity of aerobic energy. Clopidogrel-sensitive patients had increased platelets NADP-malate dehydrogenase activity (the key reaction of lipid anabolism).

[Damage of macular ganglion cell complex and peripapillary retinal nerve fiber layer in multiple sclerosis].

The aim of this study was to evaluate macular ganglion cell complex (GCC) characteristics and peripapillary retinal nerve fiber layer (RNFL) thickness in patients with multiple sclerosis (MS) and to investigate the associations between these parameters and clinical characteristics of patients for evaluation perspectives of using this method for monitoring of disability and neurodegenerative processes. We examined a total of 113 participants (analysis of 211 eyes), divided into three groups: 1. 48 MS patients (66 eyes) with a history of optic neuritis (ON); 2. 35 MS patients (70 eyes) without a history of ON; 3. 30 disease-free control subjects (45 eyes). The estudy included anamnesis collection, neurological examination with assessment of EDSS scores. Refracted visual acuity prior to optical coherence tomography (OCT) was tested. RTVue-100 ОСТ system was used to assess peripapillary RNFL thickness and macular inner parameter (protocol GCC). The strongly correlated decline of the most RNFL and GCC indices was characteristic of all groups of MS patients with and without ON compared to controls. The damage of GCC was greater in patients with ON. The inverse correlation was found between the indices studied and the level of patient's disability. The study of GCC and RNFL thickness can be used to describe and characterize the level of axonal damage in MS and for objectification of neurodegenerative process in studies on neuroprotection and neuroreparation.

IGHV gene rearrangements as outcome predictors for CLL patients: experience of Ukrainian group.

Important characteristics of chronic lymphocytic leukaemia (CLL) cells are biased immunoglobulin variable heavy chain (IGHV) gene repertoire and expression of stereotyped B-cell receptors (BCRs); however, their prognostic value (in contrast to the impact of IGHV gene mutational status) is less clear. To evaluate the impact of separate IGHV gene usage and expression of stereotyped BCRs in CLL prognosis. Clinical data and IGHV gene configuration were analysed in 319 consecutive patients with CLL. We found that the majority of clinical parameters of patients were defined by IGHV mutational status. Our data also provided new evidence supporting the prognostic relevance of separate IGHV genes or stereotyped BCR in CLL, namely: (a) a restricted non-mutated (UM) IGHV gene repertoire in CLL patients with autoimmune haemolytic anaemia (AIHA) (more frequent expression of UM IGHV1-69, IGHV3-11 and IGHV4-59 genes, P = 0.001), a shorter period of AIHA development for expressors of these genes (P = 0.001) and a tendency towards expression of a stereotypic HCDR3 (P = 0.029), (b) a high incidence of second solid tumour development in IGHV3-21-expressing patients (P = 0.005) and (c) differences in overall survival (OS) of UM CLL patients depending on the BCR structure. Further research of specific IGHV gene usage and subsets of stereotyped BCRs in CLL may be helpful in more precise prediction of CLL prognosis in individual patients.

[Characteristics of vitreous structure in rhegmatogenous hyaloid membrane detachment].

Special characteristics of volumetric acoustic digital images of different vitreous and hyaloid membrane changes were studied based on the analysis of results of ultrasound spatial examination of young healthy adults (30 patients) and patients with posterior hyaloid membrane detachment (329 patients). Morphological features of vitreous are presented considering topography and its acoustical structure. Spatial characteristics of planar and volumetric images are determined, special acoustic signs are revealed for normal vitreous and in different changes of posterior hyaloid membrane. These presentations are compared with earlier characterized changes of detached hyaloid membrane. Structural changes of vitreous resulted from posterior hyaloid membrane rapture after blunt trauma or total lens dislocation are estimated.

[Thromboprophylaxis in patients with multiply myeloma who receives chemotherapy with thalidomide].

Achievements of world practice about development and prophilaxis of tromboembolic events (VTE) in cancer patients. Particular attention is paid to prevention of VTE in patients with multiply myeloma who receive chemotherapy with Thalidomide.

IGHV3-21 gene expression in patients with B-cell chronic lymphocytic leukemia in Ukraine.

UNLABELLED: THE AIM of the study was to evaluate the frequency of IGHV3-21 gene usage and its clinical significance for patients with B-cell chronic lymphocytic leukemia (CLL) in Ukraine. PATIENTS AND METHODS: Immunoglobulin variable heavy chain (IGHV) gene repertoire was studied in 189 CLL patients using reverse transcribed polymerase chain reaction and direct sequence of amplified products. RESULTS: IGHV3-21 gene expression was found in 11 cases (5.8%), and its frequency was intermediate between Scandinavian (11.7%) and Mediterranean CLL (2.9%) cohorts. The most of cases (9 of 11) belonged to subset with heterogeneous HCDR3 (heteroHCDR3 subset), and only 2 cases--to subset with classical short ARDANGMDV motif (homHCDR3 subset). Six IGHV3-21 cases were mutated and 5 cases were unmutated. All unmutated cases (all were from heteroHCDR3 subset) had similarity of their HCDR3s with previously published sequences. The differences in overall (OS), progression-free (PFS) and treatment-free survival (TFS) for IGHV3-21 positive patients in comparison with CLL patients expressing the other IGHV genes were statistically insignificant. These survival parameters were comparable also for CLL patients with mutated IGHV3-21 gene usage and expression the others mutated IGHV genes. But remarkable feature of IGHV3-21 expressing patients was high incidence of solid tumors. They have developed in 4 IGHV3-21 positive cases (36.4%) and in 10 cases with expression of the others IGHV genes (5.6%, p=0.0002). Furthermore, in small group of 6 patients with mutated IGHV3-21 gene expression, 3 patients had solid tumors and one underwent Richter transformation. Unmutated IGHV3-21 gene expressed patients had worse OS and PFS in comparison with CLL patients that expressed the others unmutated IGHV genes. CONCLUSION: Presented data are in agreement with the opinion about negative prognostic significance of IGHV3-21 gene expression regardless its mutation status. IGHV3-21 expression was associated with development of secondary solid tumors. Revealed high level of homology in heteroHDR3s subset might suggest about possible antigenic influence also, in addition to homHCDR3 subset that was proposed earlier.

[Spatial ultrasound visualization of the eye and orbit].

The paper presents data on the diagnostic use of three-dimensional (3-D) ultrasound visualization, analyzes earlier existing and new ultrasound diagnostic technologies, and shows it expedient to apply them in ophthalmologic practice. A hundred and forty-six healthy individuals and 52 patients (60 eyes) with different diseases of the eye and orbital cavity (chorioidal melanoma, facial angiomatosis, retinal detachment, vitreoretinal changes, etc.) were examined. The results of the studies and the analysis of the data available in the literature on this problem allow the authors to state that 3-D ultrasound diagnostic technologies can detect occult masses undetectable during conventional visual and ultrasound studies and define the topography of the dislocation of structurally complicated changes in the tunics of the eyeball.

[Combined manifestations of natural foci in the territory of the Vologda province]. / Sochetannoe proiavlenie prirodnykh ochagov na territorii Vologodskoi oblasti.

Based on epizootological and epidemiological investigations in the Vologda province since 1958 till 2000, the combined territorial and temporal manifestations of natural foci of diseases was revealed. A natural focus occupies a complex of biotopes, and in different time the focus is activated in different areas, such as a river plain, marsh, meadow-field, and forest. Most commonly an activation of the natural focus appears in a border zone of three biotopes, namely, a forest, meadow-field, and river plain. A dependence of activation of various natural foci upon local climate conditions and fluctuations of micromammalian host number are considered.

Comparative studies of O,O-dialkyl-O-chloromethylchloroformimino phosphates: interaction with neuropathy target esterase and acetylcholinesterase.

Acetylcholinesterase (AChE) and neuropathy target esterase (neurotoxic esterase, NTE) are two major target enzymes for organophosphorus (OP) esters. The relative potency of an OP ester to react with AChE or with NTE in vitro correlates with its relative potency in vivo to cause acute toxicity (death) or organopohosphate-induced delayed neurotoxicity (OPIDN). On this basis extrapolation from in vitro to in vivo data now seems justifiable to predict risk of OPIDN. The kinetics of NTE and AChE inhibition by experimental pesticides of the general formula (RO)2P(O)ON=CClCH2Cl, where R = methyl, ethyl, isopropyl, propyl, isobutyl, butyl, pentyl, has been studied. Compounds with short R (methyl, ethyl) were shown to be far more potent inhibitors of AChE than NTE. Both anti-NTE activity, selectivity for NTE and, correspondingly, the propensity of compounds to cause OPIDN rise with increasing their hydrophobicity. A high value of ki(NTE)/ki(AChE) for R = pentyl suggests that this compound would have the potential to cause OPIDN at doses lower than the LD50. A quantitative structure-activity relationships (QSAR) analysis indicated that NTE and AChE have different structural and electronic requirements for their respective OP inhibitors.

[A comparative study of the interaction of phosphoric acid dichlorovinyl esters with a neurotoxic esterase from the brain of hens and rats]. / Sravnitel'noe issledovanie vzaimodeistviia dikhlorvinilovykh éfirov kislot fosfora s neirotoksichnoi ésterazoi mozga kur i krys.

In order to validate a rodent biochemical model of delayed neurotoxicity of organophosphates (OP) inhibition of rat and hen brain neurotoxic esterase (NTE) by some dichlorovinyl phosphates and phosphonates was studied in vitro and in vivo. It was shown that compounds investigated exhibited the similar inhibitory potency to NTE from both species in vitro, in addition rat and hen NTE showed the same sensitivity to variation of the structure of OP inhibitors. A good correlation was found between pI50 estimated with enzymes from rat and hen trains: r2 = 0.951, n = 18, p < or = 0.05. NTE activities were also measured in rat and hen brains after acute administration of various dosages of potent axonopathic compound dipropyldichlorovinyl phosphate. The results obtained indicate that difference in species susceptibility to neurotoxic action of OP, in particular the absence of ataxia in rats, is not caused by difference in target enzyme sensitivity to axonopathic organophosphates.

[Refraction epikeratoplasty in correction of high ametropia and treatment of keratoconus]. / Refraktsionnaia épikeratoplastika dlia korrektsii vysokikh ametropii i lecheniia keratokonusa.

The results of 48 surgeries (refraction epikeratoplasty) for aphakia, high ametropia, and keratoconus evidence the efficacy of such operation in the afore-said conditions. Further studies are necessary to elucidate the pathogenesis of complications, improve the technique of surgery and technology of the transplant preparation in order to make it more safe and improve its functional results.

[The 1st experience with complete stromaplasty--transplantation of the cornea]. / Pervyi opyt polnoi stromoplastiki--peresadki rogovoi obolochki.

The results of experimental and clinical trials of a new type of transplantation of the cornea, stromaplasty, have shown the possibility of a blunt detachment from Descemet's membrane and removal of the deep lamellae of recipient's stroma, followed by replacement of the defect with a through allotransplant. Further studies are necessary to validate this first successful surgery and to objectively assess the prospects of such surgery.

[Calculation of parameters and the technology for making biolenses in epikeratophakia]. / Raschet parametrov i tekhnologiia izgotovleniia biolinz dlia épikeratofakii.

The results of keratometry of 13 allotransplants have confirmed the rightfulness of the employed methods for calculation of the parameters of biolenses for epikeratophakia. For clinical application the initial intumescence should be taken into consideration, as well as the donor tissue thickening during its freezing for working on a lathe.