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1.
Arkh Patol ; 84(5): 43-49, 2022.
Article in Russian | MEDLINE | ID: mdl-36178222

ABSTRACT

The problem of fungal infections in the era of COVID-19 has acquired special significance. This infection, directly or indirectly, through the use of glucocorticoids and antibiotics in its treatment, as well as poorer self-management of chronic diseases, has led to a wide spread of risk factors for fungal diseases among people who have had a novel coronavirus infection. The article presents two cases of COVID-19-associated mycosis, more related to mucormycosis, which were diagnosed by ophthalmologists in the Volgograd region. In the first case, the severe course of rhino-orbito-cerebral form of mucormycosis required a number of surgical interventions and prolonged treatment in the intensive care unit. In the second case, the patient asked for help without signs of aggravation of the general condition, but with irreversible local manifestations. In both cases, the eyeball was removed. Morphological examination revealed aseptal ribbon hyphae of different diameters, branching mainly at right angles, more typical for fungi of the Mucorales family. Due to the severe consequences of the disease, clinicians, including ophthalmologists, need to be especially alertness in patients with the described symptoms and risk factors in the post-COVID period.


Subject(s)
COVID-19 , Mucorales , Mucormycosis , Anti-Bacterial Agents , Humans , Mucormycosis/diagnosis , Mucormycosis/microbiology , Mucormycosis/therapy , Risk Factors
2.
Angiol Sosud Khir ; 27(3): 153-158, 2021.
Article in Russian | MEDLINE | ID: mdl-34528600

ABSTRACT

Presented herein is a clinical case report demonstrating uncontrolled development of fatal complications in a young parturient woman with vascular Ehlers-Danlos syndrome. The disease had not been known previously. In the third period of natural term delivery we revealed a complete linear vertical uterine rupture with a clinical picture of haemorrhagic shock. After hysterectomy we encountered sequential ruptures of the iliac veins, arteries, abdominal portion of the aorta and inferior vena cava. Attempts at restoring the integrity of vessels followed by ligation thereof, terminating in cutting of vascular walls, with the appearance of new sources of bleeding. The diagnosis was later on verified by the findings of autopsy and genetic typing.


Subject(s)
Ehlers-Danlos Syndrome , Ehlers-Danlos Syndrome/complications , Ehlers-Danlos Syndrome/diagnosis , Female , Hemorrhage , Humans , Iliac Artery , Pregnancy , Rupture, Spontaneous , Uterus
3.
Article in Russian | MEDLINE | ID: mdl-34156209

ABSTRACT

The authors report resection of anaplastic convexital meningioma in a middle-aged woman complicated by expected massive blood loss. The most intense bleeding occurred at the final stage of resection and it was impossible to stop it with traditional approaches. The surgeon pressed a standard tachocomb plate moistened with a diluted solution of recombinant activated factor VII (coagil, Russia) to the most bleeding area for 5 minutes. Subsequently, surgeon replaced finger pressure with a permanent napkin. Hemostatic effect of recombinant activated factor VII following its systemic administration is well known and convincingly proven in many surgical areas including neurosurgery. However, we do not know any descriptions of its local application in neurosurgical patients.


Subject(s)
Factor VIIa/therapeutic use , Hemostatics , Meningeal Neoplasms , Blood Loss, Surgical , Female , Humans , Meningeal Neoplasms/surgery , Middle Aged , Recombinant Proteins/therapeutic use , Russia
4.
Article in Russian | MEDLINE | ID: mdl-33864673

ABSTRACT

Congenital coagulation disorders account about 1-2% and can pose a serious risk for neurosurgical patients. Indeed, coagulation management in these patients is essential to ensure normal hemostasis. Analysis of available literature devoted to this issue and case series of neurosurgical patients with congenital coagulation disorders. Literature data were obtained from the PubMed, Cochrane Library, Medline and Google Scholar databases for the period from 2019 to 2020. Over 200 reports devoted to our scientific issue were selected. We determined the key features of perioperative management of neurosurgical patients with congenital coagulation disorders. We have also analyzed 10 similar patients for the period from 2008 to 2020. Comprehensive analysis of anamnesis, adequate diagnosis, perioperative planning and multidisciplinary approach are essential for successful elective surgery in patients with congenital coagulation disorders.


Subject(s)
von Willebrand Diseases , Blood Coagulation , Humans
5.
Vestn Oftalmol ; 136(4): 124-129, 2020.
Article in Russian | MEDLINE | ID: mdl-32779466

ABSTRACT

The review summarizes experimental and clinical data attesting to the important role the choroid plays in the development of refraction through optically oriented thickness changes and the release of growth factors. Because of its unique anatomical position, the choroid can influence the transmission of a cascade of chemical signals from the retina to the sclera and thereby affect the growth of the eye. Understanding the relationship between the optical defocus and the response of the choroid to it will help uncover the fundamental mechanisms for controlling eye growth and develop new strategies for preventing the progression of myopia.


Subject(s)
Choroid , Myopia , Disease Progression , Humans , Retina , Sclera
6.
Vestn Oftalmol ; 135(5): 46-53, 2019.
Article in Russian | MEDLINE | ID: mdl-31714512

ABSTRACT

Peripheral defocus plays a significant role in the formation of refraction. Perifocal spectacles allow differentiating correction of central and peripheral refraction of the eye along the horizontal meridian and can correct or reduce peripheral hyperopia. PURPOSE: To study the long-term results of wearing perifocal spectacles on the refraction in children with progressive myopia. MATERIAL AND METHODS: Perifocal spectacles were assigned to children of 7-14 years old with progressive myopia from -1.0 to -6.0 D in terms of refractive spherical equivalent. The children were examined before the prescription of perifocal spectacles and after 6 months, 12-18 months, 2 years, 3 years and 4-5 years. We measured visual acuity, the character of vision, refractive error before and after cycloplegia, performed biomicroscopy, ophthalmoscopy and biometry. Peripheral refraction was studied at 15° and 30° points in the nasal (N15 and N30) and temporal (T15 and T30) meridians without correction and while wearing perifocal spectacles. RESULTS: In perifocal spectacles, in the 15° zone, 100% of the eyes formed myopic defocus, which averaged -0.05±0.1 D in T15°, -0.25±0.16 D in N15° and -0.44±0.03 D in T30°. In the N30° zone, the hypermetropic defocus decreased by 4 times and amounted to 0.38±0.03 D. The rate of progression of myopia decreased from 0.8 D of baseline values to 0.17 D at 4-5 years of follow-up. After 6 months of wearing perifocal spectacles, the refraction gain was -0.2±0.02 D (in the control group it was -0.38±0.04 D), after 12-18 months - (-)0.38±0.04 D (-0.63±0.09 D in the control group), after 2 years - (-)0,78±0,06 D (-1.18±0,15 D in the control group), after 3 years - (-)0.99±0.12 D (-1.65±0.20D in the control group). During the 4-5 years of the follow-up, the refractive error in the main group was -1.16±0.2 D, which is 60% less than in the control group (-1.95±0.2 D). CONCLUSION: Constant wearing of perifocal spectacles reduces the rate of myopia progression in children by 4.5 times compared with the initial rate, and by 1.6 times (by 60%) in comparison with the control group. Perifocal spectacles are recommended as optical means to slow the progression of myopia.


Subject(s)
Hyperopia , Myopia, Degenerative , Adolescent , Child , Eye , Eyeglasses , Humans , Refraction, Ocular
7.
Khirurgiia (Mosk) ; (10): 36-42, 2019.
Article in Russian | MEDLINE | ID: mdl-31626237

ABSTRACT

OBJECTIVE: To study the causes of recurrent postoperative ventral hernias and methods for their prevention. MATERIAL AND METHODS: There were 58 patients with recurrent postoperative ventral hernias after various methods of abdominal wall repair for the period 2005-2017. RESULTS: The main causes of recurrent postoperative ventral hernias were identified. Local tissue rearrangement resulted recurrent hernia in 21 (36.2%) patients, that was observed even in patients with small hernia. Size discrepancy between endoprosthesis and hernial orifice caused a recurrence in 20 (34.5%) patients. In 11 (19%) patients, implant detachment followed by recurrent hernia occurred. Postoperative wound complications followed by recurrent hernia were diagnosed in 6 (10.3%) patients. Non-compliance with recommendations for wearing a bandage and restricting physical exertion also contributed to the development of recurrent hernia. Moreover, recurrent hernia occurred mainly in obese patients. Mean body mass index was 34.27±2.2 kg/m2. Recurrent hernia was again detected in 12 out of 35 patients in long-term period after surgical treatment. CONCLUSION: It is necessary to abandon local tissue rearrangement and to select a correct size of synthetic material for prevention of recurrent postoperative hernia. Preoperative body weight control is essential in patients with obesity. Wearing a bandage and restricting physical exertion are obligatory in postoperative period. Annual examination during 3-5 years after surgery is essential for timely diagnosis of recurrent hernia.


Subject(s)
Hernia, Ventral/surgery , Incisional Hernia/surgery , Hernia, Ventral/etiology , Humans , Incisional Hernia/etiology , Recurrence , Surgical Mesh , Treatment Outcome
8.
Vestn Oftalmol ; 135(4): 60-69, 2019.
Article in Russian | MEDLINE | ID: mdl-31573558

ABSTRACT

INTRODUCTION: Peripheral defocus was experimentally found to control the development of refraction. PURPOSE: To evaluate peripheral refraction (PR) of myopic eyes in terms of different means of correction and the direction of gaze. MATERIAL AND METHODS: The study examined 128 patients (256 eyes) aged 8-14 years (average 11.07±0.39 years) with myopia from -1.0 to -7.0 (average -3.57±0.27 D). PR was measured without correction, in perifocal (PF), monofocal (MF), progressive glasses (PAL), monofocal soft contact lenses (ΜCL) and after orthokeratological (OCL) correction with the gaze directed straightforward or head angled outward, inward, upward and downward; all measurements were performed using binocular open-field auto ref/keratometer. RESULTS: PR profile without correction and with contact (OCL, ΜCL) correction does not depend on the direction of the gaze. In glasses, peripheral defocus is different with straightforward and skewed gaze directions. OCL forms a significant myopic defocus throughout the periphery of the retina. When using MCL, hyperopic defocus increases in all zones except the extreme temporal. In MF glasses, hyperopic defocus is formed and enhanced in all areas, significantly greater with skewed gaze than with straightforward. In PALs, myopic defocus is formed with gaze directed upward and downward, as well as at the extreme temporal periphery of the retina with straightforward gaze. In all other zones, hypermetropic defocus increases. In PF, in most zones myopic defocus is formed with all gaze directions. The greatest inhibitory effect on myopia progression is provided by OCL (YPR=0.28 D/year) and PF glasses (YPR=0.26 D/year). CONCLUSION: In contrast to correction with contact lenses, PR in glasses does depend on the direction of gaze. The inhibitory effect of the optics correlates with correction of hypermetropic defocus in myopic eyes.


Subject(s)
Contact Lenses, Hydrophilic , Hyperopia , Myopia , Adolescent , Child , Eyeglasses , Humans , Refraction, Ocular
9.
Vestn Oftalmol ; 135(6): 11-16, 2019.
Article in Russian | MEDLINE | ID: mdl-32015303

ABSTRACT

PURPOSE: To develop an objective method of determining binocular accommodative response (AR) and concomitant accommodation in patients with strabismus. MATERIAL AND METHODS: The study included 34 patients (68 eyes) with concomitant horizontal strabismus aged 6 to 32 years. The parameters of accommodation were measured using open field Binocular Auto Ref/Keratometer Grand Seiko WR-5100K (Grand Seiko Co. Ltd., Japan). The prism was placed in front of the deviated eye or the prisms were distributed evenly in front of both eyes until the deviation was eliminated. RESULTS: The addition of prisms had no effect on the refractometry results. In convergent strabismus monocular, binocular, direct and consensual accommodation responses were significantly higher than in divergent: -2.15±0.1 D and -1.66±0.12 D; -2.13±0.09 D and -1.33±0.14 D; -2,04±0,15 D and -1,16±0,1 D; -1.97±0.15 D and -1.06±0.09 D, respectively. In divergent strabismus and myopia, the binocular response was 2.8 times higher than in hyperopia (-1.8±0.09 D and -0.63±0.04 D, respectively). Resting tonus of accommodation (RTA) value was higher in patients with hyperopia, both with convergent (mean -2.27±0.41 D) and divergent strabismus (-2.36±0.47 D). Minimal RTA was observed in patients with convergent strabismus and myopia (mean -0.75±0.1 D). CONCLUSION: The study resulted in the development of a method of objective accommodometry of strabismic patients with deviation eliminated by prisms. Monocular and binocular AR were significantly higher in convergent strabismus compared to divergent, where consensual accommodation of the squinting eye is significantly reduced compared to the paired one. In patients with consensual strabismus, RTA is significantly higher in hyperopia than in myopia regardless of the form of strabismus.


Subject(s)
Hyperopia , Myopia , Strabismus , Accommodation, Ocular , Adolescent , Adult , Child , Eye , Humans , Young Adult
10.
Eur Biophys J ; 47(8): 881-889, 2018 Dec.
Article in English | MEDLINE | ID: mdl-29858914

ABSTRACT

The protein hormone insulin exists in several forms in nature, and a large number of modified sequences are used in pharmacy. They differ by physicochemical properties and efficiency of biological action. Pancreatic bovine insulin was studied in an acidic solution by nuclear magnetic resonance spectroscopy. [Formula: see text]H and [Formula: see text]C NMR signal assignment of backbone and side chains was made by analysis of a set of 2D spectra obtained on a sample with natural isotope abundance. The presence of certain secondary structure elements was revealed on a qualitative level based on nuclear Overhauser effect spectroscopy, which are similar to those observed in the crystal structure. The C-terminus of the B-chain possessed a remarkable flexibility. The molecule was shown to exist in exchange with oligomers based on its self-diffusion coefficient and correlation time measurements performed at different concentrations. Certain signals in the NOESY and HSQC spectra are consistent with the presence of minor conformers; this is an obstacle in simulating the molecular structure under the conditions used in the experiment.


Subject(s)
Insulin/chemistry , Nuclear Magnetic Resonance, Biomolecular , Protein Multimerization , Amino Acid Sequence , Animals , Cattle , Protein Structure, Quaternary , Solutions
12.
Acta Physiol (Oxf) ; 223(3): e13044, 2018 07.
Article in English | MEDLINE | ID: mdl-29383848

ABSTRACT

AIM: During early post-natal development, arterial contraction depends less on Ca2+ -signalling pathways but more on changes in Ca2+ -sensitivity compared to adult animals. Whether this difference is related to Rho-kinase, one of the major players affecting Ca2+ -sensitivity, is unknown for intact vessels. Thus, we tested the hypothesis that Rho-kinase critically contributes to the higher Ca2+ -sensitivity of contraction in intact arteries of 1-week-old rats. METHODS: We studied 1-week-old, 4- to 5-week-old and 10- to 12-week-old rats performing isometric myography, Ca2+ -fluorimetry and Western blotting using intact saphenous arteries and arterial pressure measurements under urethane anaesthesia. RESULTS: In 10- to 12-week-old rats, methoxamine (MX) produced vasoconstriction associated with an increase in [Ca2+ ]i and Ca2+ -sensitivity. In contrast, in 1-week-old rats these contractions were accompanied only by an increase in Ca2+ -sensitivity. All MX-induced effects were reduced by the Rho-kinase inhibitor Y-27632; this reduction was complete only in 1-week-old rats. The Rho-kinase specific site Thr855 on MYPT1 was increasingly phosphorylated by MX in vessels of 1-week-old, but not 10- to 12-week-old rats; this effect was also inhibited completely by Y-27632. The Rho-kinase inhibitor fasudil in a dose not affecting the pressor response to MX in 4- to 5-week-old rats reduced it considerably in 1-week-old rats. CONCLUSION: Our results suggest that the higher Ca2+ -sensitivity of arterial contraction in 1-week-old compared to 10- to 12-week-old rats is due to a greater Rho-kinase activity. Constitutively active Rho-kinase contributes to MX-induced contraction in 10- to 12-week-old rats. In 1-week-old rats, additional Rho-kinase activation is involved. This remodelling of the Rho-kinase pathway is associated with its increased contribution to adrenergic arterial pressure responses.


Subject(s)
Aging/metabolism , Arteries/physiology , Calcium Signaling , Vasoconstriction , rho-Associated Kinases/metabolism , Animals , Male , Methoxamine , Muscle, Smooth, Vascular/metabolism , Protein Kinase C/metabolism , Rats, Wistar
13.
Vestn Otorinolaringol ; 82(6): 39-43, 2017.
Article in Russian | MEDLINE | ID: mdl-29260780

ABSTRACT

The objective of the present study was the prospective analysis of the results of bilateral cochlear implantation (CI) in the children presenting with bilateral ossification of the cochlea after they had survived meningitis. A total of 15 patients underwent the surgical intervention. In those exhibiting bilateral ossification of the basal cochlear helix over the 5 mm segment (up to first bend of the cochlear turn) and partial ossification of the second helix (in 6 children), the affected portions were removed with the placement of two choleostomies, the lower one (from the ossified membrane of the cochlear window) and the upper one (toward the second helix). Activation of the speech processors of the CI systems was carried out within 4-6 weeks after surgery. The hearing abilities of the children were evaluated in accordance with the 'Estimation of the auditory perception categories', 'Estimation of the child's apprehension capacity', and 'Analysis of speech intelligibility rating' guidelines. In all the children with ossification over less than 5 mm of the basal cochlear helix, it proved possible to introduce the whole intracochlear electrode grid whereas only half of the electrode array was implanted in the cases of overall ossification of the basal helix. The first results obtained by telemetry and surdopedagogical testing gave evidence of the possibility of identifying various sources of non-verbal and speech stimuli in all the treated children at a small (up to 3 meters) distance.


Subject(s)
Cochlear Diseases , Cochlear Implantation , Hearing Loss, Sensorineural , Meningitis, Bacterial/complications , Ossification, Heterotopic , Child, Preschool , Cochlear Diseases/diagnosis , Cochlear Diseases/etiology , Cochlear Diseases/physiopathology , Cochlear Diseases/surgery , Cochlear Implantation/adverse effects , Cochlear Implantation/methods , Cochlear Implants , Female , Hearing Loss, Sensorineural/diagnosis , Hearing Loss, Sensorineural/etiology , Hearing Loss, Sensorineural/physiopathology , Hearing Loss, Sensorineural/prevention & control , Hearing Tests/methods , Humans , Male , Ossification, Heterotopic/diagnosis , Ossification, Heterotopic/etiology , Ossification, Heterotopic/physiopathology , Ossification, Heterotopic/surgery , Speech Intelligibility , Treatment Outcome
14.
Vestn Oftalmol ; 133(4): 37-41, 2017.
Article in Russian | MEDLINE | ID: mdl-28980564

ABSTRACT

AIM: To study the magnitude of objective accommodative response (OAR) with account to the method of image defocusing. The latter can be realized by bringing the object nearer to the eye or by adding a minus lens in front of the viewer. MATERIAL AND METHODS: We examined 63 patients (126 eyes) with different refraction aged from 7 to 31 years. All patients underwent a series of OAR measurements on WR-5100K Grand Seiko Binocular Open-Field Autorefkeratometer under different conditions, including negative spherical lenses of -3.0 D and -5.0 D, test optotypes corresponding to visual acuity of 0.2 and 0.7 and presented at a distance of 5 m, and a set of variably sized optotypes presented at a distance of 33 cm and 20 cm. RESULTS: A disparity was found between the magnitude of accommodative responses evoked through different means: placing a negative lens in front of the viewer while he/she looks into the distance or bringing the object closer to the eye. In almost all cases lens-induced responses were less pronounced than distance-induced. In all myopic children, accommodative lag was longer at near than at distance. Generally, in all groups, OAR to distant objects as well as responses to a 3.0 D accommodative task at near did not depend on the size of the object. There was an insignificant and statistically unreliable difference for objects placed 20 cm away (5.0 D accommodative task): OAR to a smaller font was stronger than that to a larger one. CONCLUSION: In children and adults with emmetropia, hyperopic children, and myopic adults, longer accommodative lags were characteristic of lens-induced responses. In children with myopia, longer lags were observed at near. Moreover, at near, OAR to a smaller font was stronger than that to a larger one.


Subject(s)
Accommodation, Ocular/physiology , Refraction, Ocular , Refractive Errors/diagnosis , Visual Acuity , Adolescent , Adult , Child , Female , Humans , Lens, Crystalline/pathology , Lens, Crystalline/physiopathology , Lenses/classification , Male , Refractive Errors/physiopathology , Reproducibility of Results
15.
Philos Trans A Math Phys Eng Sci ; 373(2048)2015 Aug 13.
Article in English | MEDLINE | ID: mdl-26170426

ABSTRACT

Results are presented from experimental studies of the initiation of combustion in a stoichiometric methane-oxygen mixture by a freely localized laser spark and by a high-current multispark discharge in a closed chamber. It is shown that, preceding the stage of 'explosive' inflammation of a gas mixture, there appear two luminous objects moving away from the initiator along an axis: a relatively fast and uniform wave of 'incomplete combustion' under laser spark ignition and a wave with a brightly glowing plasmoid behind under ignition from high-current slipping surface discharge. The gas mixtures in both the 'preflame' and developed-flame states are characterized by a high degree of ionization as the result of chemical ionization (plasma density n(e)≈10(12) cm(-3)) and a high frequency of electron-neutral collisions (ν(en)≈10(12) s(-1)). The role of chemical ionization in constructing an adequate theory for the ignition of a gas mixture is discussed. The feasibility of the microwave heating of both the preflame and developed-flame plasma, supplementary to a chemical energy source, is also discussed.

16.
Vestn Oftalmol ; 131(1): 24-29, 2015.
Article in Russian | MEDLINE | ID: mdl-25872383

ABSTRACT

OBJECTIVE: To evaluate the effectiveness of non-surgical treatment of accommodation disorders and progressive myopia in children. MATERIAL AND METHODS: A total of 190 patients (380 eyes) with myopia aged from 6 to 18 years (10.79±0.18 years on average) were enrolled and divided into 9 groups depending on the treatment prescribed. RESULTS: Comparative evaluation of different hardware-based treatment modalities for progressive myopia allowed to work out their optimal combination: "Visotronic", "MACDEL 09", and magnetophoresis of Taufon 4%. Such courses, provided twice a year, were associated with optimization of accommodative response and 1.9-2.8 times reduction of the rate of myopia progression. On the contrary, pleoptic therapy showed a negative effect on accommodative tonus and the rate of progression of acquired myopia. CONCLUSIONS: Comparative evaluation of different hardware-based treatment modalities for progressive myopia and accommodation disorders allowed to work out their optimal combination: "Visotronic", "MACDEL 09" and magnetophoresis of Taufon 4%. This treatment, provided twice a year, allows to increase accommodative reserves and volume, improve objective accommodative response, and reduce accommodative hypertonus as well as the rate of myopia progression (1.9-2.8 times over a 1.5-year period). Under pleoptic therapy (specialized software, near field speckles, color pulse therapy, Ambliokor device), both accommodative tonus and the rate of myopia progression increased (1.3-1.5 and 1.6 times correspondingly).


Subject(s)
Accommodation, Ocular/physiology , Myopia/therapy , Ocular Motility Disorders/therapy , Orthoptics/methods , Refraction, Ocular/physiology , Adolescent , Child , Disease Progression , Follow-Up Studies , Humans , Myopia/physiopathology , Ocular Motility Disorders/physiopathology , Time Factors , Treatment Outcome , Visual Acuity
17.
Bull Exp Biol Med ; 158(4): 566-72, 2015 Feb.
Article in English | MEDLINE | ID: mdl-25705043

ABSTRACT

Intrasplenic allogeneic transplantation of multipotent stromal cells from the umbilical cord stimulates hepatocyte proliferation and promotes recovery of liver weight in rats after subtotal resection (80% organ weight). It can be hypothesized that this effect of multipotent stromal cells is due to more rapid recovery of the number of mitochondria and normalization of mitochondrial function of liver hepatocytes.


Subject(s)
Liver Regeneration/physiology , Mesenchymal Stem Cells/physiology , Mitochondria/physiology , Umbilical Cord/cytology , Analysis of Variance , Animals , Hepatocytes/physiology , Mesenchymal Stem Cell Transplantation/methods , Rats , Rats, Sprague-Dawley , Spectrophotometry, Ultraviolet , Transplantation, Homologous
18.
Cell Death Dis ; 5: e1240, 2014 May 22.
Article in English | MEDLINE | ID: mdl-24853418

ABSTRACT

HKH40A, the 8-methoxy analog of WMC79, is a synthetic agent with promising in vitro and in vivo antitumor activity, especially against solid tumors. However, molecular mechanisms underlying its antitumor effects are poorly understood. Here, we report that HKH40A markedly reduces the level of GRP78/BiP protein in cancer cell lines of various origin. In this study, we show that HKH40A not only downregulates transcription of GRP78 but also directly binds to the isolated protein and induces its proteosomal degradation. Knockdown of BiP increased the efficacy of the drug and overexpression of BiP diminished its activity. BiP is generally highly elevated in solid tumors having a pivotal role in cancer cell survival and chemoresistance, and has been suggested as a novel target for therapeutic intervention. We show that reduction of BiP level by HKH40A impairs its function and induces unfolded protein response as evidenced by the activation of IRE1α, ATF6 and PERK. This leads to a series of downstream events, including sustained eIF2α phosphorylation, increased abundance of spliced XBP1 mRNA and protein levels of ATF4 and CHOP. We also demonstrate that HKH40A inhibited tumor formation in an in vivo xenograft tumor model. Collectively, our data show that HKH40A reduces BiP levels and this could have an important role in the activity of HKH40A against cancer cells.


Subject(s)
Acridones/pharmacology , Antineoplastic Agents/pharmacology , Heat-Shock Proteins/metabolism , Naphthalimides/pharmacology , Neoplasms/drug therapy , Activating Transcription Factor 6/metabolism , Animals , Down-Regulation , Endoplasmic Reticulum Chaperone BiP , Endoribonucleases/metabolism , Female , Gene Expression Regulation, Neoplastic/drug effects , HCT116 Cells , HT29 Cells , Heat-Shock Proteins/genetics , Hep G2 Cells , Humans , Mice , Mice, Nude , Neoplasms/genetics , Neoplasms/metabolism , Neoplasms/pathology , Proteasome Endopeptidase Complex/drug effects , Proteasome Endopeptidase Complex/metabolism , Protein Serine-Threonine Kinases/metabolism , Proteolysis , RNA Interference , Time Factors , Transcription, Genetic/drug effects , Transfection , Tumor Burden/drug effects , Unfolded Protein Response/drug effects , Xenograft Model Antitumor Assays , eIF-2 Kinase/metabolism
19.
Vestn Oftalmol ; 130(6): 44-9, 2014.
Article in Russian | MEDLINE | ID: mdl-25715552

ABSTRACT

OBJECTIVE: To determine the posterior pole contour of the eye based on the relative peripheral refractive error and relative eye length. MATERIAL AND METHODS: A parallel study was performed, which enrolled 38 children (76 eyes) with myopia from -1.25 to -10.82 diopters. The patients underwent peripheral refraction assessment with WR-5100K Binocular Auto Refractometer ("Grand Seiko", Japan) and partial coherence tomography with IOLMaster ("Carl Zeiss", Germany) for the relative eye length in areas located 15 and 30 degrees nasal and temporal from the central fovea along the horizontal meridian. RESULTS: In general, refractometry and interferometry showed high coincidence of defocus signs and values for the areas located 15 and 30 degrees nasal as well as 15 degrees temporal from the fovea. However, in 41% of patients defocus signs determined by the two methods mismatched in one or more areas. Most of the mismatch cases were mild myopia. CONCLUSION: We suppose that such a mismatch is caused by optical peculiarities of the anterior eye segment that have an impact on refractometry results.


Subject(s)
Eye , Myopia , Refraction, Ocular , Child , Eye/pathology , Eye/physiopathology , Female , Humans , Interferometry/methods , Male , Myopia/diagnosis , Myopia/physiopathology , Refractometry/methods , Severity of Illness Index , Statistics as Topic , Tomography, Optical Coherence/methods
20.
Vestn Oftalmol ; 129(6): 28-32, 2013.
Article in Russian | MEDLINE | ID: mdl-24624799

ABSTRACT

A total of 150 patients (300 eyes) aged from 6 to 23 with myopia of different degrees were assessed to define differential diagnostic criteria of accommodative disorders such as accommodative insufficiency, habitual excess, and spasm. The patients were divided into 4 groups. Group 1 included 88 patients (175 eyes) with myopia from -0.75 to -8.5 diopters (general group), group 2-23 patients (46 eyes) with accommodative insufficiency, group 3-20 patients (39 eyes) with habitual accommodative excess, and group 4-20 patients (40 eyes) with accommodative spasm. In all cases subjective and objective parameters of accommodation were fully assessed and differential diagnostic criteria identified.


Subject(s)
Accommodation, Ocular/physiology , Myopia/diagnosis , Vision Tests/methods , Adolescent , Child , Female , Humans , Male , Myopia/physiopathology , Refraction, Ocular/physiology , Severity of Illness Index , Young Adult
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