[Autologous fibrin glue for endoscopic skull base repair in patients with cerebrospinal fluid leakage]. / Primenenie autologichnogo fibrinovogo kleya v endoskopicheskoi plastike defektov osnovaniya cherepa pri nazal'nykh likvoreyakh.

The main stages of endoscopic skull base repair in patients with cerebrospinal fluid (CSF) leakage are identification of bone boundaries of the fistula and its closure by auto- and allografts. Fibrin glue can be used to fix plastic materials and additionally seal skull base defect. OBJECTIVE: To analyze efficacy and safety of Vivostat autologous fibrin glue for endoscopic skull base repair in patients with nasal CSF leakage and to compare postoperative outcomes after defect closure by Vivostat fibrin glue and allogeneic fibrin glue. MATERIAL AND METHODS: A retro- and prospective analysis included 56 patients with nasal CSF leakage who were treated at the Burdenko Neurosurgery Center between January 2021 and June 2022. Patients were divided into 2 groups: Vivostat fibrin glue (n=27, 48.2%) and allogeneic fibrin glue (n=29, 51.8%). Demographic and clinical perioperative data were analyzed. RESULTS: No early postoperative recurrence of CSF leakage was registered in both groups, whereas meningitis occurred in 2 cases in each group. Recurrent CSF leakage in delayed postoperative period occurred in 1 patient (3.4%) of the control group (p>0.05). Incidence of perioperative complications, subfebrile temperature in early postoperative period, surgery time and hospital-stay were similar. CONCLUSION: Vivostat autologous fibrin glue is a safe and effective method for fixing the grafts in endoscopic skull base repair. The advantages of this approach are easy application, elimination of the risk of allergic, immunological and infectious complications, as well as acceleration of tissue regeneration.

[Principles of diagnosis and treatment of tinnitus]. / Printsipy diagnostiki i lecheniya shuma v ushakh.

Tinnitus is one of the most common otological symptoms and can be defined as the conscious perception of sound lasting more than 5 minutes in the absence of an external auditory stimulus. Based on the review of articles, a comparative analysis of modern methods of diagnosis and treatment of tinnitus was carried out in order to substantiate the most effective and promising algorithms for providing care to patients. Diagnosis of tinnitus includes taking anamnesis, assessing the severity of tinnitus using questionnaires, otoscopy, hearing examination, and performing additional tests. In case of secondary murmur, etiotropic therapy should be started as soon as possible to prevent hearing loss and other complications. For primary noise, the most effective treatments are cognitive-behavioral therapy, tinnitus maskers and sound therapy, transcutaneous electrical stimulation, and biofeedback. Magnetic stimulation, invasive neuromodulation, drug therapy have a lower level of effectiveness and evidence base.

The proteolytic control of restriction activity in Escherichia coli K-12.

The endonuclease activity of EcoKI is regulated by the ClpXP-dependent degradation of the subunit that is essential for restriction, but not modification. We monitored proteolysis in mutants blocked at different steps in the restriction pathway. Mutations that prevent DNA translocation render EcoKI refractory to proteolysis, whereas those that permit DNA translocation, but block endonuclease activity, do not. Although proteolysis alleviates restriction in a mutant that lacks modification activity, some restriction activity remains; our evidence indicates residual EcoKI associated with the membrane fraction. ClpXP protects the bacterial chromosome, but little effect was detected on unmodified foreign DNA within the cytoplasm of a restriction-proficient cell. The molecular basis for the distinction between unmodified resident and foreign DNA remains to be determined.

Regulation of endonuclease activity by proteolysis prevents breakage of unmodified bacterial chromosomes by type I restriction enzymes.

ClpXP-dependent proteolysis has been implicated in the delayed detection of restriction activity after the acquisition of the genes (hsdR, hsdM, and hsdS) that specify EcoKI and EcoAI, representatives of two families of type I restriction and modification (R-M) systems. Modification, once established, has been assumed to provide adequate protection against a resident restriction system. However, unmodified targets may be generated in the DNA of an hsd(+) bacterium as the result of replication errors or recombination-dependent repair. We show that ClpXP-dependent regulation of the endonuclease activity enables bacteria that acquire unmodified chromosomal target sequences to survive. In such bacteria, HsdR, the polypeptide of the R-M complex essential for restriction but not modification, is degraded in the presence of ClpXP. A mutation that blocks only the modification activity of EcoKI, leaving the cell with approximately 600 unmodified targets, is not lethal provided that ClpXP is present. Our data support a model in which the HsdR component of a type I restriction endonuclease becomes a substrate for proteolysis after the endonuclease has bound to unmodified target sequences, but before completion of the pathway that would result in DNA breakage.