Asymmetric charge balanced waveforms direct retinal ganglion cell axon growth.

Failure to direct axon regeneration to appropriate targets is a major barrier to restoring function after nerve injury. Development of strategies that can direct targeted regeneration of neurons such as retinal ganglion cells (RGCs) are needed to delay or reverse blindness in diseases like glaucoma. Here, we demonstrate that a new class of asymmetric, charge balanced (ACB) waveforms are effective at directing RGC axon growth, in vitro, without compromising cell viability. Unlike previously proposed direct current (DC) stimulation approaches, charge neutrality of ACB waveforms ensures the safety of stimulation while asymmetry ensures its efficacy. Furthermore, we demonstrate the relative influence of pulse amplitude and pulse width on the overall effectiveness of stimulation. This work can serve as a practical guideline for the potential deployment of electrical stimulation as a treatment strategy for nerve injury.

[Combined surgical treatment of a patient with kidney cancer stage 4 and coronary artery disease]. / Sochetannoe radikal'noe khirurgicheskoe lechenie bol'nykh s rakom pochki IV stadii i ishemicheskoi bolezn'yu serdtsa.

We report 3 patients with coronary artery disease and kidney cancer followed by thrombosis of inferior vena cava and right cardiac chambers undergoing simultaneous surgery.

Morpho­functional study of the hypothalamic proline­rich polypeptide apoptotic activity against mouse Ehrlich ascites carcinoma.

A new type of bioactive polypeptides of the neurosecretory hypothalamus called proline­rich peptides (PRPs), which are isolated from bovine neurosecretory granules of the neurohypophysis, are synthesized in the form of a common precursor protein (neurophysin vasopressin­associated glycoprotein). Proline­rich polypetide 1 (PRP­1; also known as galarmin) is comprised of 15 amino acids residues, and has been suggested to possess anti­neurodegenerative, immunoregulatory, hematopoietic, antimicrobial and antitumor properties. The cytostatic, antiproliferative effect of PRP­1 was demonstrated in the human chondrosarcoma JJ012 and triple negative breast carcinoma MDA MB 231 cell lines. PRP­1 action is disease and tissue specific. To further explore the antitumorigenic and possible cytotoxic effects of PRP­1, a morpho­functional study on the effect of PRP­1 on a mouse Ehrlich ascites carcinoma (EAC) model was conducted. The PRP­1­induced morphological features of EAC cells confirmed the apoptotic nature of PRP­1, as manifested by cell shrinkage, membrane blebbing, chromosome condensation (pyknosis) and nuclear fragmentation (karyorrhexis). The effect of PRP­1 on the number of tumor cells incubated for 24 h and their viability in trypan blue­stained samples lead to a 44% reduction in the number of viable cells on day 11 post­inoculation vs. 22% inhibition of viable cells after PRP­1 treatment (0.1 µg/ml) on day 7 post­inoculation. Apoptosis experiments using an Annexin V­cyanine 3 apoptosis detection kit indicated that 24 h incubation with 0.1 µg/ml PRP­1 caused a significant increase in the number of apoptotic cells, reaching 50.33%, compared to 8.33% in the sample control on day 7 post­inoculation.

[Surgical treatment of pulmonary trunk malignancy]. / Khirurgicheskoe lechenie zlokachestvennoi opukholi legochnogo stvola.

Surgical treatment of a patient with primary sarcoma of pulmonary trunk is presented in the article. This rare disease is characterized by poor prognosis if early diagnosis and adequate surgical treatment are absent.

[Short-segment percutaneous transpedicular stabilization of thoraco-lumbar spine fracture at an elderly patients with osteopenia.]

The analysis of surgical treatment of 75 patients of the senior age group with fractures of thoraco-lumbar spine against the background of an osteopenia is provided in article. To all patients short-segment percutaneous transpedicular fixation was carried out. According to indications augmentation of a body of the broken vertebra and screws of the fixing system was carried out. Assessment the reposition of opportunities of a technique, assessment of solvency of fixing is carried out. In 100% of cases good correction of kyphosis deformation of the spine is received. At dynamic observation of secondary deformations it hasn't been revealed.

Clastogenecity evaluation of water of Lake Sevan (Armenia) using Tradescantia micronucleus assay.

The clastogenic effects of water samples in seven locations of Lake Sevan (Armenia) with the application of Trad-MCN (micronuclei) bioassay using Tradescantia (clone 02) were investigated. A significant increase in the frequency of micronuclei in tetrads of pollen microspores and tetrads with micronuclei exposed to the test samples compared to the control has been revealed. A multivariate analysis indicated linkage between the frequencies of occurrence of micronuclei in the cells and Ni and Co ions. The results were compared with the endpoints of another Tradescantia-based test system (stamen hair mutation test) performed on the same water samples and generation of the plant: occurrences of micronuclei in sporogenic cells coincided with that of non-surviving stamen hair.

Assessment of mutagenicity of water from Lake Sevan, Armenia with application of Tradescantia (clone 02).

For many decades water resources in Armenia have been affected by anthropogenic activity, therefore, a regular bioindication of genotoxic effects of the water bodies is desirable. The genotoxicity of water samples collected from different parts of Lake Sevan were assessed by means of Trad-SHM (stamen hair mutation) assay using Tradescantia (clone 02). Here we report a significant increase in the frequency of somatic mutations and morphological changes in the Tradescantia inflorescences exposed to the water samples compared to the control. The somatic mutations (recessive mutation and white mutation events) were mostly linked to the concentration of Al, Ni, As, Co and Pb in Artanish, Tsapatakh and Karchaghbyur, Noradus, Martuni and Litchk, while morphological changes (non-surviving hairs) were related to Co level in Tsapatakh and Karchaghbyur. The results obtained show that Lake Sevan contains substances which may cause genotoxicity and teratogenicity in Tradescantia and probably also in aquatic animals. The results also show that Trad-SHM assay can be used for monitoring natural resources.

Protective abilities of pyridoxine in experimental oxidative stress settings in vivo and in vitro.

BACKGROUND: Pyridoxine (Pr, B6) or its active form pyridoxal phosphate (PLP, B6) deficiency promotes oxidative lipid peroxidation and exacerbates the oxidative stress. From the other hand, by our previous experiments we proved that B6 is able strongly inhibit Xanthine Oxidase (XO) activity, which is an enzyme responsible for the formation of uric acid and hydrogen peroxide. METHODS: Cells were cultured by Mattson M. method and treated with 3%% hydrogen peroxide. Before and after treatment we added allopurinol as well as B6 into the cell culture media. Hydrogen peroxide after limited craniotomy was injected into the brain parenchyma in accordance to the following coordinates from bregma: 2mm lateral to midline, 3mm anterior to the coronal suture, and 2mm below the surface of the skull. Blood Brain Barrier (BBB) disruption was evaluated spectrophotometrically (λ=550nm). RESULTS: were evidencing - B6 as well as allourinol are protective against oxidative stress and support cells maintenance in the culture, protect them from death. In in vivo studies animals treated with pyridoxine and allopurnol from days 1-6 and 1-12 (p<0.035) had less damaged BBB in comparison with the control group. CONCLUSION: Antioxidative abilities via XO inhibition of B6 are proposed.

A New Approach to Feedback for Robust Signaling Gradients.

The patterning of many developing tissues is orchestrated by gradients of morphogens through a variety of elaborate regulatory interactions. Such interactions are thought to make gradients robust, that is, resistant to changes induced by genetic or environmental perturbations; but just how this might be done is a major unanswered question. Recently extensive numerical simulations suggest that robustness of signaling gradients cannot be attained by negative feedback (of the Hill's function type) on signaling receptors but can be achieved through binding with nonsignaling receptors (or nonreceptors for short) such as heparan sulfate proteoglycans with the resulting complexes degrading after endocytosis. These were followed by a number of analytical and numerical studies in support of the aforementioned observations. However, evidence of feedback regulating signaling gradients has been reported in literature. The present paper undertakes a different approach to the role of feedback in robust signaling gradients. The overall goal of the project is to investigate the effectiveness of feedback mechanisms on ligand synthesis, receptor synthesis, nonreceptor synthesis, and other regulatory processes in the morphogen gradient system. As a first step, we embark herein a proof-of-concept examination of a new spatially uniform feedback process that is distinctly different from the conventional spatially nonuniform Hill function approach.

40-kDa protein from thin filaments of the mussel Crenomytilus grayanus changes the conformation of F-actin during the ATPase cycle.

Polarized fluorimetry was used to study in ghost muscle fibers the influence of a 40-kDa protein from the thin filaments of the mussel Crenomytilus grayanus on conformational changes of F-actin modified by the fluorescent probes 1,5-IAEDANS and FITC-phalloidin during myosin subfragment (S1) binding in the absence of nucleotides and in the presence of MgADP or MgATP. The fluorescence probes were rigidly bound with actin, which made the absorption and emission dipoles of the probes sensitive to changes in the orientation and mobility of both actin monomer and its subdomain-1 in thin filaments of the muscle fiber. On modeling different intermediate states of actomyosin, the orientation and mobility of oscillators of the dyes were changed discretely, which suggests multistep changes in the actin conformation during the cycle of ATP hydrolysis. The 40-kDa protein influenced the orientation and mobility of the fluorescent probes markedly, suppressing changes in their orientation and mobility in the absence of nucleotides and in the presence of MgADP, but enhancing these changes in the presence of MgATP. The calponin-like 40-kDa protein is supposed to prevent formation of the strong binding state of actomyosin in the absence of nucleotides and in the presence of MgADP but to activate formation of this state in the presence of MgATP.

40-kDa actin-binding protein of thin filaments of the mussel Crenomytilus grayanus inhibits the strong bond formation between actin and myosin head during the ATPase cycle.

Mobility and spatial orientation of a novel 40-kDa actin-binding protein from the smooth muscle of the mussel Crenomytilus grayanus was studied by polarized fluorometry. The influence of this protein on orientation and mobility of the myosin heads was investigated during modeling the different stages of the ATPase cycle. The 40-kDa actin-binding protein affected the strong actin-myosin binding. We suggest that the 40-kDa actin-binding protein is involved in regulation of the actin-myosin interaction in the smooth muscle of the mussel.