Publications by authors named "Kheĭfets V"

Age is the primary risk factor for the vast majority of disorders, including neurodegenerative diseases impacting brain function. Whether the consequences of aging at the biological level can be reversed, or age-related changes prevented, to change the trajectory of such disorders is thus of extreme interest and value. Studies using young plasma, the acellular component of blood, have demonstrated that aging is malleable, with the ability to restore functions in old animals.

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The effectiveness of overactive bladder treatment with M-cholinoblocker solifenacin (Vesicare) as monotherapy and in combination with α1-andrenoblocker terazosin (Setegis) or bladdrer training in elderly patients was evaluated. The results of 12 weeks treatment in all treatment modality groups were comparable. Use of solifenacin in combination with α1-andrenoblocker in comparison to solifenacin monotherapy resulted in longer symptoms remission.

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Results of treatment of 204 elderly and senile patients who underwent cystprostatectomy or anterior pelvic exenteration are analyzed. A comparative analysis of two groups of patients whose operation ended with the traditional drainage through the anterior abdominal wall (n = 100), and bilateral perineal drainage (n = 104) is presented. Bilateral perineal drainage after operations on the pelvic organs, accompanied by cystectomy and extended lymphadenectomy in conjunction with the restoration of the peritoneum lateral pelvic walls, improves postoperative recovery of intestinal peristalsis, promotes an earlier reduction in the intensity of pain and morbidity in the early postoperative period.

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The article presents the issues of the characteristics of the course, diagnostics and treatment of hyperactive urinary bubble in older men. Conservative treatment of urinary incontinence includes changes in lifestyle, behavioural and medical therapy with m-anticholinergic drugs. The combination solifenacini in a dose of 5 mg/day and α1-adrenoceptor blocking agent terasolini in a dose of 2 mg/day significantly improves the results of treatment and well tolerated.

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While decreased ATP production and redox imbalance are central to mitochondrial disease pathogenesis, efforts to develop effective treatments have been hampered by the lack of imaging markers of oxidative stress. In this study we wished to determine if Tc99m-HMPAO, a SPECT imaging marker of cerebral blood flow and glutathione/protein thiol content, could be used to monitor the effect(s) of EPI-743, an oral redox modulating, para-benzoquinone based therapeutic for mitochondrial disease. We hypothesized that treatment changes in HMPAO uptake would be inversely proportional to changes in oxidative stress within the brain and directly correlate to clinical response to EPI-743 therapy.

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Background: Genetically defined Leigh syndrome is a rare, fatal inherited neurodegenerative disorder that predominantly affects children. No treatment is available. EPI-743 is a novel small molecule developed for the treatment of Leigh syndrome and other inherited mitochondrial diseases.

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We report on the synthesis, biological and pharmacological activity of the tocoquinone natural product, α-tocopherol quinone (ATQ); an oxidative metabolite of α-tocopherol. ATQ is a potent cellular protectant against oxidative stress, whose biological activity is dependent upon its ability to undergo reversible two-electron redox cycling. ATQ is orally bioavailable, with a favorable pharmacokinetic profile and has demonstrated a beneficial clinical response in patients with Friedreich's ataxia.

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Inherited mitochondrial respiratory chain disorders are progressive, life-threatening conditions for which there are limited supportive treatment options and no approved drugs. Because of this unmet medical need, as well as the implication of mitochondrial dysfunction as a contributor to more common age-related and neurodegenerative disorders, mitochondrial diseases represent an important therapeutic target. Thirteen children and one adult with genetically-confirmed mitochondrial disease (polymerase γ deficiency, n=4; Leigh syndrome, n=4; MELAS, n=3; mtDNA deletion syndrome, n=2; Friedreich ataxia, n=1) at risk for progressing to end-of-life care within 90 days were treated with EPI-743, a novel para-benzoquinone therapeutic, in a subject controlled, open-label study.

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We report that α-tocotrienol quinone (ATQ3) is a metabolite of α-tocotrienol, and that ATQ3 is a potent cellular protectant against oxidative stress and aging. ATQ3 is orally bioavailable, crosses the blood-brain barrier, and has demonstrated clinical response in inherited mitochondrial disease in open label studies. ATQ3 activity is dependent upon reversible 2e-redox-cycling.

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The present study is devoted to improving quality of life of patients in elderly and senile age after operation of Bricker by finding the optimal method of forming ureterointestinal anastomosis. From 2007 to 2009 103 patients of elderly and senile age with diseases requiring removal of the bladder were treated in the Lenigrad Regional Oncology Centre. All the patients were made cystectomy.

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A comparative study of radical transurethral resection (TUR) of bladder carcinomas (BC) was performed in standard conditions and the application of fluorescence cystoscopy (FCS) for diagnosis of early recurrence of BC and the extent of tumor aggressiveness and prognosis of the disease. We examined 174 elderly and senile age patients with BC through 4-6 weeks after surgery to re-endoscopic study, which includes the standard cystoscopy (CS), fluorescent cystoscopy (FCS) and the TUR--the area of post-biopsy scar and the fluorescent sites. The first group consisted of 95 patients who performed a traditional TUR, the second one of 79 patients whom TUR on the fluorescent control (TUR-FCS) was performed.

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Protein kinase C (PKC) is a family of kinases that are critical in many cellular events. These enzymes are activated by lipid-derived second messengers, are dependent on binding to negatively charged phospholipids and some members also require calcium to attain full activation. The interaction with lipids and calcium activators is mediated by binding to the regulatory domains C1 and C2.

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Protein kinase C (PKC) plays a critical role in diseases such as cancer, stroke, and cardiac ischemia, and participates in a variety of signal transduction pathways such as apoptosis, cell proliferation, and tumor suppression. Though much is known about PKC downstream signaling events, the mechanisms of regulation of PKC activation and subsequent translocation have not been elucidated. Protein-protein interactions regulate and determine the specificity of many cellular signaling events.

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In the sickness rate's structure of the malignant neoplasms the urological localization take 6.8 per cent (%). Among them 70% is cancer of the urinary organs.

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Disruption of intramolecular interactions, translocation from one intracellular compartment to another, and binding to isozyme-specific anchoring proteins termed RACKs, accompany protein kinase C (PKC) activation. We hypothesized that in inactive epsilonPKC, the RACK-binding site is engaged in an intramolecular interaction with a sequence resembling its RACK, termed psiepsilonRACK. An amino acid difference between the psiepsilonRACK sequence in epsilonPKC and its homologous sequence in epsilonRACK constitutes a change from a polar non-charged amino acid (asparagine) in epsilonRACK to a polar charged amino acid (aspartate) in epsilonPKC.

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Activating oncogenic mutations of receptor tyrosine kinases (RTKs) have been reported in several types of cancers. In many cases, genomic rearrangements lead to the fusion of unrelated genes to the DNA coding for the kinase domain of RTKs. All RTK-derived fusion proteins reported so far display oligomerization sequences within the 5' fusion partners that are responsible for oncogenic activation.

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Protein kinase C (PKC) isozymes comprise a family of related enzymes that play a central role in many intracellular eukaryotic signaling events. Isozyme specificity is mediated by association of each PKC isozyme with specific anchoring proteins, termed RACKs. The C2 domain of betaPKC contains at least part of the RACK-binding sites.

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The efficacy of spinal anesthesia with lidocaine (1 mg/kg) combined with moradol (0.005 mg/kg) during urologic surgery has been compared with that of spinal anesthesia with lidocaine (1 mg/kg) combined with morphine (0.01 mg/kg).

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