Publications by authors named "Victor Fomin"

30 Publications

  • Page 1 of 1

Efficacy of a Probiotic Consisting of Lacticaseibacillus rhamnosus PDV 1705, Bifidobacterium bifidum PDV 0903, Bifidobacterium longum subsp. infantis PDV 1911, and Bifidobacterium longum subsp. longum PDV 2301 in the Treatment of Hospitalized Patients with COVID-19: a Randomized Controlled Trial.

Probiotics Antimicrob Proteins 2021 Oct 13. Epub 2021 Oct 13.

Department of Internal Medicine, Gastroenterology and Hepatology, Sechenov University, Moscow, Russian Federation.

The treatment of coronavirus disease (COVID-19) and COVID-19-associated diarrhea remains challenging. This study aimed to evaluate the efficacy of a multi-strain probiotic in the treatment of COVID-19. This was a randomized, controlled, single-center, open-label trial (NCT04854941). Inpatients with confirmed COVID-19 and pneumonia were randomly assigned to a group that received a multi-strain probiotic (PRO group) or to the control group (CON group). There were 99 and 101 patients in the PRO and CON groups, respectively. No significant differences in mortality, total duration of disease and hospital stay, incidence of intensive care unit admission, need for mechanical ventilation or oxygen support, liver injury development, and changes in inflammatory biomarker levels were observed between the PRO and CON groups among all included patients as well as among subgroups delineated based on age younger or older than 65 years, and subgroups with chronic cardiovascular diseases and diabetes. Diarrhea on admission was observed in 11.5% of patients; it resolved earlier in the PRO group than in the CON group (2 [1-4] vs. 4 [3-6] days; p = 0.049). Hospital-acquired diarrhea developed less frequently in the PRO group than in the CON group among patients who received a single antibiotic (0% vs. 12.5%; p = 0.023) unlike among those who received > 1 antibiotic (10.5% vs. 13.3%; p = 0.696). The studied probiotic had no significant effect on mortality and changes in most biomarkers in COVID-19. However, it was effective in treating diarrhea associated with COVID-19 and in preventing hospital-acquired diarrhea in patients who received a single antibiotic.
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http://dx.doi.org/10.1007/s12602-021-09858-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8512595PMC
October 2021

Incidence and risk factors for persistent symptoms in adults previously hospitalized for COVID-19.

Clin Exp Allergy 2021 09 12;51(9):1107-1120. Epub 2021 Aug 12.

Inflammation, Repair and Development Section, Faculty of Medicine, National Heart and Lung Institute, Imperial College London, London, UK.

Background: The long-term sequalae of COVID-19 remain poorly characterized. We assessed persistent symptoms in previously hospitalized patients with COVID-19 and assessed potential risk factors.

Methods: Data were collected from patients discharged from 4 hospitals in Moscow, Russia between 8 April and 10 July 2020. Participants were interviewed via telephone using an ISARIC Long-term Follow-up Study questionnaire.

Results: 2,649 of 4755 (56%) discharged patients were successfully evaluated, at median 218 (IQR 200, 236) days post-discharge. COVID-19 diagnosis was clinical in 1291 and molecular in 1358. Most cases were mild, but 902 (34%) required supplemental oxygen and 68 (2.6%) needed ventilatory support. Median age was 56 years (IQR 46, 66) and 1,353 (51.1%) were women. Persistent symptoms were reported by 1247 (47.1%) participants, with fatigue (21.2%), shortness of breath (14.5%) and forgetfulness (9.1%) the most common symptoms and chronic fatigue (25%) and respiratory (17.2%) the most common symptom categories. Female sex was associated with any persistent symptom category OR 1.83 (95% CI 1.55 to 2.17) with association being strongest for dermatological (3.26, 2.36 to 4.57) symptoms. Asthma and chronic pulmonary disease were not associated with persistent symptoms overall, but asthma was associated with neurological (1.95, 1.25 to 2.98) and mood and behavioural changes (2.02, 1.24 to 3.18), and chronic pulmonary disease was associated with chronic fatigue (1.68, 1.21 to 2.32).

Conclusions: Almost half of adults admitted to hospital due to COVID-19 reported persistent symptoms 6 to 8 months after discharge. Fatigue and respiratory symptoms were most common, and female sex was associated with persistent symptoms.
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http://dx.doi.org/10.1111/cea.13997DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8444748PMC
September 2021

Serum Zinc, Copper, and Other Biometals Are Associated with COVID-19 Severity Markers.

Metabolites 2021 Apr 15;11(4). Epub 2021 Apr 15.

World-Class Research Center "Digital Biodesign and Personalized Healthcare", IM Sechenov First Moscow State Medical University (Sechenov University), 119435 Moscow, Russia.

The objective of the present study was to evaluate of serum metal levels in COVID-19 patients with different disease severity, and to investigate the independent association between serum metal profile and markers of lung damage. The cohort of COVID-19 patients consisted of groups of subjects with mild, moderate, and severe illness, 50 examinees each. Forty-four healthy subjects of the respective age were involved in the current study as the control group. Serum metal levels were evaluated using inductively-coupled plasma mass-spectrometry. Examination of COVID-19 patients demonstrated that heart rate, respiratory rate, body temperature, C-reactive protein levels, as well as lung damage increased significantly with COVID-19 severity, whereas SpO decreased gradually. Increasing COVID-19 severity was also associated with a significant gradual decrease in serum Ca, Fe, Se, Zn levels as compared to controls, whereas serum Cu and especially Cu/Zn ratio were elevated. No significant group differences in serum Mg and Mn levels were observed. Serum Ca, Fe, Se, Zn correlated positively with SpO, being inversely associated with fever, lung damage, and C-reactive protein concentrations. Opposite correlations were observed for Cu and Cu/Zn ratio. In regression models, serum Se levels were inversely associated with lung damage independently of other markers of disease severity, anthropometric, biochemical, and hemostatic parameters. Cu/Zn ratio was also considered as a significant predictor of lower SpO in adjusted regression models. Taken together, these findings demonstrated that metal metabolism significantly interferes with COVID-19 pathogenesis, although the causal relations as well as precise mechanisms are yet to be characterized.
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http://dx.doi.org/10.3390/metabo11040244DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8071197PMC
April 2021

Primary Undifferentiated Pericardial Sarcoma after Radiоtherapy for Hodgkin Lymphoma.

Case Rep Oncol 2020 Sep-Dec;13(3):1075-1081. Epub 2020 Sep 7.

I.M. Sechenov First Moscow State Medical University (Sechenov University), Moscow, Russian Federation.

Various types of sarcomas arise as a result of postradiation chronic fibrous pericarditis. A primary undifferentiated spindle cell pericardial sarcoma is a rare type of sarcoma after radiotherapy. The risk of sarcoma increases with time after treatment of cancer. A 55-year-old woman underwent successful radiation and chemotherapy for Hodgkin lymphoma 20 years ago. She was hospitalized with typical manifestations of severe heart failure. Echocardiography, сomputed tomography of the chest and magnetic resonance imaging scan of the heart detected neoplastic formations of the pericardium. A biopsy of the pericardium was performed. Histological, immunohistochemical, and genetic studies showed a primary undifferentiated spindle cell pericardial sarcoma (an extremely rare type of sarcoma).
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http://dx.doi.org/10.1159/000510068DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7548883PMC
September 2020

Stop COVID Cohort: An Observational Study of 3480 Patients Admitted to the Sechenov University Hospital Network in Moscow City for Suspected Coronavirus Disease 2019 (COVID-19) Infection.

Clin Infect Dis 2021 07;73(1):1-11

Sechenov First Moscow State Medical University (Sechenov University), Moscow, Russia.

Background: The epidemiology, clinical course, and outcomes of patients with coronavirus disease 2019 (COVID-19) in the Russian population are unknown. Information on the differences between laboratory-confirmed and clinically diagnosed COVID-19 in real-life settings is lacking.

Methods: We extracted data from the medical records of adult patients who were consecutively admitted for suspected COVID-19 infection in Moscow between 8 April and 28 May 2020.

Results: Of the 4261 patients hospitalized for suspected COVID-19, outcomes were available for 3480 patients (median age, 56 years; interquartile range, 45-66). The most common comorbidities were hypertension, obesity, chronic cardiovascular disease, and diabetes. Half of the patients (n = 1728) had a positive reverse transcriptase-polymerase chain reaction (RT-PCR), while 1748 had a negative RT-PCR but had clinical symptoms and characteristic computed tomography signs suggestive of COVID-19. No significant differences in frequency of symptoms, laboratory test results, and risk factors for in-hospital mortality were found between those exclusively clinically diagnosed or with positive severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) RT-PCR. In a multivariable logistic regression model the following were associated with in-hospital mortality: older age (per 1-year increase; odds ratio, 1.05; 95% confidence interval, 1.03-1.06), male sex (1.71; 1.24-2.37), chronic kidney disease (2.99; 1.89-4.64), diabetes (2.1; 1.46-2.99), chronic cardiovascular disease (1.78; 1.24-2.57), and dementia (2.73; 1.34-5.47).

Conclusions: Age, male sex, and chronic comorbidities were risk factors for in-hospital mortality. The combination of clinical features was sufficient to diagnose COVID-19 infection, indicating that laboratory testing is not critical in real-life clinical practice.
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http://dx.doi.org/10.1093/cid/ciaa1535DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7665333PMC
July 2021

Sex differences in mortality in the intensive care unit patients with severe COVID-19.

J Infect 2021 02 28;82(2):282-327. Epub 2020 Sep 28.

Tareev Clinic of Internal Diseases, Sechenov First Moscow State Medical University, 11/5 Rossolimo, Moscow 119435, Russia.

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http://dx.doi.org/10.1016/j.jinf.2020.09.031DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7521429PMC
February 2021

Immunosuppressive therapy of biopsy proved immune-mediated lymphocytic myocarditis in the virus-negative and virus-positive patients.

Cardiovasc Pathol 2020 Nov - Dec;49:107260. Epub 2020 Jul 5.

I.M. Sechenov First Moscow State Medical University (Sechenov University), Moscow, Russian Federation.

Purpose: to study the effect of immunosupressive therapy (IST) in the virus-negative and virus-positive patients with immune-mediated myocarditis.

Methods: in 60 patients (45 male, 46.7 ± 11.8 years, mean LV EDD, 6.7 ± 0.7 cm, EF 26.2 ± 9.1%) active/borderline myocarditis was verified by endomyocardial biopsy (n = 38), intraoperative biopsy (n = 10), examination of explanted heart (n = 3) and autopsy (n = 9). Indications for IST determined based on histological, immune activity. The follow-up was 19.0 [7.25; 40.25] months.

Results: The viral genome in the myocardium was detected in 32 patients (V+ group), incl. parvovirus B19 in 23. The anti-heart antibody level was equally high in the V+ and V- patients. Antiviral therapy was administered in 24 patients. IST (in 22 V+ and 24 V- patients) include steroids (n = 40), hydroxychloroquine (n = 20), azathioprine (n = 21). The significant decrease of LV EDD (6.7 ± 0.7 to 6.4 ± 0.8), PAP (48.9 ± 15.5 to 39.4 ± 11.5 mm Hg, р<0,01), increase of EF (26.5 ± 0.9 to 36.0 ± 10.8), and lower lethality (23.9% and 64.3%; RR 0.37, 95% CI 0.19-0.71), p<0.01, were found only in IST group. Significant improvement due to IST were achieved not only in V-, but also in V+ patients.

Conclusions: IST in patients with immune-mediated lymphocytic myocarditis is effective and is associated with lower lethality both in virus-negative and virus-positive patients.
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http://dx.doi.org/10.1016/j.carpath.2020.107260DOI Listing
October 2020

Virtual Care for Critically Ill Patients with COVID-19.

Telemed J E Health 2020 11 16;26(11):1326-1327. Epub 2020 Jun 16.

Clinic of Pulmonology, Sechenov First Moscow State, Medical University, Moscow, Russia.

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http://dx.doi.org/10.1089/tmj.2020.0214DOI Listing
November 2020

Cancer in intensive care unit patients with COVID-19.

J Infect 2020 08 28;81(2):e124-e125. Epub 2020 May 28.

Sechenov First Moscow State Medical University, 119882 Moscow, Russia.

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http://dx.doi.org/10.1016/j.jinf.2020.05.053DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7255725PMC
August 2020

Rheumatic diseases in intensive care unit patients with COVID-19.

Ann Rheum Dis 2021 02 20;80(2):e16. Epub 2020 May 20.

Vinogradov Clinic of Internal Diseases, Sechenov First Moscow State Medical University, Moscow, Russian Federation.

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http://dx.doi.org/10.1136/annrheumdis-2020-217676DOI Listing
February 2021

Is there a future for hydroxychloroquine/chloroquine in prevention of SARS-CoV-2 infection (COVID-19)?

Ann Rheum Dis 2021 02 21;80(2):e19. Epub 2020 Apr 21.

Vinogradov Clinic of Internal Diseases, Sechenov First Moscow State Medical University, Moscow, Russia.

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http://dx.doi.org/10.1136/annrheumdis-2020-217570DOI Listing
February 2021

Strategies of Screening for Fabry Disease in Patients with Unexplained Left Ventricular Hypertrophy.

Mayo Clin Proc 2019 08;94(8):1644-1646

Sechenov First Moscow State Medical University, Moscow, Russia.

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http://dx.doi.org/10.1016/j.mayocp.2019.05.003DOI Listing
August 2019

Diagnostic Value of Different Noninvasive Criteria of Latent Myocarditis in Comparison with Myocardial Biopsy.

Cardiology 2019;142(3):167-174. Epub 2019 Jun 12.

I.M. Sechenov First Moscow State Medical University (Sechenov University), Moscow, Russian Federation.

Purpose: The aim of this study was to quantify the value of various clinical, laboratory, and instrumental signs in the diagnosis of myocarditis in comparison with morphological studies of the myocardium.

Methods: In 100 patients (65 men, 44.7 ± 12.5 years old) with "idiopathic" arrhythmias (n = 20) and dilated cardiomyopathy (DCM; n = 80), we performed the following: 71 endomyocardial biopsies (EMB), 13 intraoperative biopsies, 5 studies of explanted hearts, and 11 autopsies with virus investigation (real-time PCR) of the blood and myocardium. Antiheart antibodies (AHA) were also measured as well as cardiac CT (n = 45), MRI (n = 25), and coronary angiography (n = 47). The comparison group included 50 patients (25 men, 53.7 ± 11.7 years old) with noninflammatory heart diseases who underwent open heart surgery.

Results: Active/borderline myocarditis was diagnosed in 76.0% of the study group and in 21.6% of patients in the comparison group (p < 0.001). The myocardial viral genome was observed more frequently in patients in the comparison group than in the study group (65.0 and 40.2%; p < 0.01). We evaluated the diagnostic value of noninvasive markers of myocarditis. The panel of AHA had the greatest importance in the identification of myocarditis: sensitivity was 81.5%, and the positive and negative predictive values were 75.0 and 60.5%. This defined the diagnostic value of noninvasive markers of myocarditis and established a diagnostic algorithm providing an individual assessment of the likelihood of myocarditis development.

Conclusion: AHA have the greatest significance in the diagnosis of latent myocarditis in patients with "idiopathic" arrhythmias and DCM. The use of a complex of noninvasive criteria allows the probability of myocarditis to be estimated and the indications for EMB to be determined.
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http://dx.doi.org/10.1159/000499865DOI Listing
December 2019

The effect of enzyme replacement therapy on clinical outcomes in male patients with Fabry disease: A systematic literature review by a European panel of experts.

Mol Genet Metab Rep 2019 Jun 6;19:100454. Epub 2019 Feb 6.

Department of Paediatrics, University of Torino, Torino, Italy.

Background: Enzyme replacement therapy (ERT) with recombinant human α-galactosidase has been available for the treatment of Fabry disease since 2001 in Europe and 2003 in the USA. Treatment outcomes with ERT are dependent on baseline patient characteristics, and published data are derived from heterogeneous study populations.

Methods: We conducted a comprehensive systematic literature review of all original articles on ERT in the treatment of Fabry disease published up until January 2017. This article presents the findings in adult male patients.

Results: Clinical evidence for the efficacy of ERT in adult male patients was available from 166 publications including 36 clinical trial publications. ERT significantly decreases globotriaosylceramide levels in plasma, urine, and in different kidney, heart, and skin cell types, slows the decline in estimated glomerular filtration rate, and reduces/stabilizes left ventricular mass and cardiac wall thickness. ERT also improves nervous system, gastrointestinal, pain, and quality of life outcomes.

Conclusions: ERT is a disease-specific treatment for patients with Fabry disease that may provide clinical benefits on several outcomes and organ systems. Better outcomes may be observed when treatment is started at an early age prior to the development of organ damage such as chronic kidney disease or cardiac fibrosis. Consolidated evidence suggests a dose effect. Data described in male patients, together with female and paediatric data, informs clinical practice and therapeutic goals for individualized treatment.
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http://dx.doi.org/10.1016/j.ymgmr.2019.100454DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6365982PMC
June 2019

The Prevalence and Clinical Features of Fabry Disease in Hemodialysis Patients: Russian Nationwide Fabry Dialysis Screening Program.

Nephron 2019 24;141(4):249-255. Epub 2019 Jan 24.

National Medical Research Center of Children's Health, Moscow, Russian Federation.

Aim: To evaluate the prevalence and clinical features of Fabry disease in patients with end-stage renal disease (ESRD) undergoing chronic hemodialysis.

Methods: α-Galactosidase A activity was measured in the dried blood spots by tandem mass spectrometry in 5,572 dialysis patients (63.7% males). Diagnosis of Fabry disease was confirmed by sequencing of the GLA gene and by evaluating the globotriaosylsphingosine level in the dried blood spots.

Results: Fabry disease was diagnosed in 20 (0.36%) patients at the median age of 43 years (28; 58). There were 19 males and 1 female. The prevalence of Fabry disease in dialysis patients was 0.53% in males and 0.05% in females. However, it was higher in males aged 30-49 years. Seventeen different GLA mutations were identified; 5 of them were novel. The median age at the initiation of hemodialysis was similar between patients with missense and nonsense mutations. Sixteen patients (80.0%) presented with typical symptoms of Fabry disease from childhood (neuropathic pain in 16, angiokeratoma in 7 and hypohidrosis/anhidrosis in 16). All patients had left ventricular hypertrophy, and 8 patients (40%) had a history of ischemic stroke. Two patients died (recurrent stroke in one and sudden cardiac death in another patient).

Conclusions: Screening in at-risk patients remains the feasible approach to diagnose Fabry disease in patients with ESRD and their family members, given a low awareness of Fabry disease among the Russian nephrologists.
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http://dx.doi.org/10.1159/000495886DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6492520PMC
December 2019

Low aquaporin-2 excretion in the nephrotic syndrome: an escape from the vasopressin regulating effect.

Int J Nephrol Renovasc Dis 2018 17;11:271-277. Epub 2018 Oct 17.

Sechenov First Moscow State Medical University, Moscow, Russia,

Purpose: Experimental studies suggest that the nephrotic syndrome is associated with "vasopressin escape", characterized by low aquaporin-2 (AQP2) expression in the collecting duct despite high vasopressin secretion. We investigated this phenomenon in patients with the nephrotic syndrome.

Patients And Methods: We recruited 47 patients with proteinuric kidney disease who were distributed into the following four groups: 1) nephrotic syndrome with kidney dysfunction (n=10); 2) nephrotic syndrome with normal kidney function (n=16); 3) partial remission of nephrotic syndrome (n=10); and 4) minimal proteinuria (n=11). Nine healthy volunteers comprised a control group. Serum copeptin level (as a marker of vasopressin secretion) and urinary AQP2 were measured using ELISA.

Results: Nephrotic syndrome was associated with a significant increase in serum copeptin levels compared with those in the other groups (all <0.05). In patients with nephrotic syndrome and a partial remission of nephrotic syndrome combined, there was more than a ten-fold decrease in the median urinary AQP2 excretion (0.03 ng/mL) compared with healthy volunteers (0.41 ng/mL; <0.001) and more than a five-fold decrease compared with patients with minimal proteinuria (0.21 ng/mL; <0.05). Unlike copeptin levels, the median urinary AQP2 excretion in patients with minimal proteinuria also decreased but less significantly than in those with nephrotic syndrome. There was a negative correlation between the urinary AQP2 excretion and daily proteinuria (R=-0.41; =0.005).

Conclusion: Our clinical study was the first to demonstrate low AQP2 excretion in nephrotic syndrome that may indicate an escape from the vasopressin regulating effect.
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http://dx.doi.org/10.2147/IJNRD.S177469DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6198888PMC
October 2018

European expert consensus statement on therapeutic goals in Fabry disease.

Mol Genet Metab 2018 07 12;124(3):189-203. Epub 2018 Jun 12.

Department of Neurology, University of Erlangen-Nuremberg, Erlangen, Germany.

Background: Fabry disease, an inherited lysosomal storage disorder, causes multi-organ pathology resulting in substantial morbidity and a reduced life expectancy. Although Fabry disease is an X-linked disorder, both genders may be affected, but generally to a lesser extent in females. The disease spectrum ranges from classic early-onset disease to non-classic later-onset phenotypes, with complications occurring in multiple organs or being confined to a single organ system depending on the stage of the disease. The impact of therapy depends upon patient- and disease-specific factors and timing of initiation.

Methods: A European panel of experts collaborated to develop a set of organ-specific therapeutic goals for Fabry disease, based on evidence identified in a recent systematic literature review and consensus opinion.

Results: A series of organ-specific treatment goals were developed. For each organ system, optimal treatment strategies accounted for inter-patient differences in disease severity, natural history, and treatment responses as well as the negative burden of therapy and the importance of multidisciplinary care. The consensus therapeutic goals and proposed patient management algorithm take into account the need for early disease-specific therapy to delay or slow the progression of disease as well as non-specific adjunctive therapies that prevent or treat the effects of organ damage on quality of life and long-term prognosis.

Conclusions: These consensus recommendations help advance Fabry disease management by considering the balance between anticipated clinical benefits and potential therapy-related challenges in order to facilitate individualized treatment, optimize patient care and improve quality of life.
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http://dx.doi.org/10.1016/j.ymgme.2018.06.004DOI Listing
July 2018

Effect of essential amino acid кetoanalogues and protein restriction diet on morphogenetic proteins (FGF-23 and Кlotho) in 3b-4 stages chronic кidney disease patients: a randomized pilot study.

Clin Exp Nephrol 2018 Dec 11;22(6):1351-1359. Epub 2018 Jun 11.

Sechenov First Moscow State Medical University (Sechenov University), Trubetskaya str. 8, bld.2, Moscow, 119991, Russian Federation.

Background: A low protein diet (LPD) with essential amino acid ketoanalogue supplementation (KA) may contribute in improving of chronic kidney disease (CKD), while the exact mechanisms of KA's effect are not established yet. We have conducted a prospective, randomized, controlled comparative study of LPD + KA and LPD alone in relation to serum Klotho, FGF-23 levels in CKD patients.

Methods: 79 non-diabetic CKD 3b-4 stage patients, compliant with LPD diet (0.6 g/kg of body weight/day), had been selected. The patients were randomized into two groups. The first group (42 patients) received LPD + КA. The second group (37 patients) continued the LРD alone. In addition to routine tests, serum Klotho, FGF-23 levels, as well as bioimpedance analysis, sphygmography (stiffness (augmentation) indices (AI), central (aortal) blood pressure) with a «SphygmaCor» device; echocardiography (valvular calcification score (VCS) and LVMMI), were performed.

Results: There were body mass indices' decrease (p = 0.046), including muscle body mass in men (p = 0.027) and woman (p = 0.044) in the LPD group to the end of study (14th month). In addition, lower FGF-23 (p = 0.029), and higher sKlotho (p = 0.037) were detected in the LPD + KA group compared to the LPD one. The increase in AI (p = 0.034), VCS (p = 0.048), and LVMMI (p = 0.023) was detected more often in the LPD group at the end of study.

Conclusion: LPD + KA provides support for nutrition status and contributes to more efficient correction of FGF-23 and Klotho abnormalities that may result in cardiovascular calcification and cardiac remodeling decreasing in CKD. At the same time, a prolonged LPD alone may lead to malnutrition.
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http://dx.doi.org/10.1007/s10157-018-1591-1DOI Listing
December 2018

Tocilizumab for polymyalgia rheumatica: a first or second line?

Ann Rheum Dis 2016 08 13;75(8):e47. Epub 2016 Apr 13.

Clinic of Nephrology, Internal and Occupational Diseases, Sechenov First Moscow State Medical University, Moscow, Russia.

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http://dx.doi.org/10.1136/annrheumdis-2016-209596DOI Listing
August 2016

CASK interacts with PMCA4b and JAM-A on the mouse sperm flagellum to regulate Ca2+ homeostasis and motility.

J Cell Physiol 2012 Aug;227(8):3138-50

Department of Biological Sciences, University of Delaware, Newark, DE 19716, USA.

Deletion of the highly conserved gene for the major Ca(2+) efflux pump, Plasma membrane calcium/calmodulin-dependent ATPase 4b (Pmca4b), in the mouse leads to loss of progressive and hyperactivated sperm motility and infertility. Here we first demonstrate that compared to wild-type (WT), Junctional adhesion molecule-A (Jam-A) null sperm, previously shown to have motility defects and an abnormal mitochondrial phenotype reminiscent of that seen in Pmca4b nulls, exhibit reduced (P < 0.001) ATP levels, significantly (P < 0.001) greater cytosolic Ca(2+) concentration ([Ca(2+) ](c)) and ∼10-fold higher mitochondrial sequestration, indicating Ca(2+) overload. Investigating the mechanism involved, we used co-immunoprecipitation studies to show that CASK (Ca(2+) /calmodulin-dependent serine kinase), identified for the first time on the sperm flagellum where it co-localizes with both PMCA4b and JAM-A on the proximal principal piece, acts as a common interacting partner of both. Importantly, CASK binds alternatively and non-synergistically with each of these molecules via its single PDZ (PDS-95/Dlg/ZO-1) domain to either inhibit or promote efflux. In the absence of CASK-JAM-A interaction in Jam-A null sperm, CASK-PMCA4b interaction is increased, resulting in inhibition of PMCA4b's enzymatic activity, consequent Ca(2+) accumulation, and a ∼6-fold over-expression of constitutively ATP-utilizing CASK, compared to WT. Thus, CASK negatively regulates PMCA4b by directly binding to it and JAM-A positively regulates it indirectly through CASK. The decreased motility is likely due to the collateral net deficit in ATP observed in nulls. Our data indicate that Ca(2+) homeostasis in sperm is maintained by the relative ratios of CASK-PMCA4b and CASK-JAM-A interactions.
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http://dx.doi.org/10.1002/jcp.24000DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3383836PMC
August 2012

Dynamic interactions between L-type voltage-sensitive calcium channel Cav1.2 subunits and ahnak in osteoblastic cells.

Am J Physiol Cell Physiol 2009 May 4;296(5):C1067-78. Epub 2009 Mar 4.

Dept. of Biological Sciences, University of Delaware, Newark, DE 19716, USA.

Voltage-sensitive Ca(2+) channels (VSCCs) mediate Ca(2+) permeability in osteoblasts. Association between VSCC alpha(1)- and beta-subunits targets channel complexes to the plasma membrane and modulates function. In mechanosensitive tissues, a 700-kDa ahnak protein anchors VSCCs to the actin cytoskeleton via the beta(2)-subunit of the L-type Ca(v)1.2 (alpha(1C)) VSCC complex. Ca(v)1.2 is the major alpha(1)-subunit in osteoblasts, but the cytoskeletal complex and subunit composition are unknown. Among the four beta-subtypes, the beta(2)-subunit and, to a lesser extent, the beta(3)-subunit coimmunoprecipitated with the Ca(v)1.2 subunit in MC3T3-E1 preosteoblasts. Fluorescence resonance energy transfer revealed a complex between Ca(v)1.2 and beta(2)-subunits and demonstrated their association in the plasma membrane and secretory pathway. Western blot and immunohistochemistry showed ahnak association with the channel complex in the plasma membrane via the beta(2)-subunit. Cytochalasin D exposure disrupted the actin cytoskeleton but did not disassemble or disrupt the function of the complex of L-type VSCC Ca(v)1.2 and beta(2)-subunits and ahnak. Similarly, small interfering RNA knockdown of ahnak did not disrupt the actin cytoskeleton but significantly impaired Ca(2+) influx. Collectively, we showed that Ca(v)1.2 and beta(2)-subunits and ahnak form a stable complex in osteoblastic cells that permits Ca(2+) signaling independently of association with the actin cytoskeleton.
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http://dx.doi.org/10.1152/ajpcell.00427.2008DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2681378PMC
May 2009

Role of protein kinase Calpha in regulation of [Ca2+](I) and force in human myometrium.

Reprod Sci 2009 Jan 15;16(1):71-9. Epub 2008 Dec 15.

Department of Biological Sciences, University of Delaware, Newark, Delaware 19716, USA.

Recent findings implicate protein kinase C in regulation of contraction of uterine muscle (myometrium). However, the role of protein kinase C isoforms in myometrial contraction remains uncertain. Therefore, this study examined protein kinase Calpha's role in regulation of contraction and intracellular calcium concentration ([Ca2+](I)) of myometrium from term pregnant women. The authors demonstrated that protein kinase Calpha inhibitor Go6976 decreased the amplitude of potassium chloride-induced myometrial contractions in a time-dependent manner. The treatment of the myometrial strips with protein kinase Calpha-specific antisense oligodeoxynucleotides decreased the potassium chloride-induced contraction and [Ca2+](I) response to 39.3% + 6.8% and 50.0% + 3.3%, respectively, compared to control. The sense oligonucleotides treatment did not significantly change the potassium chloride responses (89.8% + 6.8% and 93.9% + 4.5% of the control for the contraction and [Ca2+](I), respectively). These data, coupled with the observation that protein kinase Calpha levels are elevated in the pregnant myometrium, suggest the involvement of protein kinase Calpha in regulation of human uterine contraction.
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http://dx.doi.org/10.1177/1933719108324892DOI Listing
January 2009

Voltage-sensitive ion channels and cancer.

Cancer Metastasis Rev 2006 Sep;25(3):493-500

Laboratory for Cancer Ontogeny and Therapeutics, University of Delaware, Newark, DE 19716, USA.

Plasma membrane voltage-sensitive ion channels classically have been associated with a variety of inherited diseases or "channelopathies" that range in the severity of symptoms from mild to lethal. Ion channels are found throughout the body and are responsible for facilitated diffusion of ions down the electrochemical gradient across cells membranes in various tissues. Voltage-sensitive ion channels open in response to changes in the membrane potential and are primarily found in excitable cells and tissues. Potassium, calcium, and sodium channels play critical roles in the development of major diseases, such as hyperkalemia, epilepsy, congenital myotonia and several cardiac arrythmias. Recently, cancer studies have begun to define the role of voltage-sensitive ion channels in the progression of cancer to a more malignant phenotype. In cancer, the increased expression or increased kinetics of voltage-sensitive ion channels is associated with an increasing malignant potential as evinced by their role in cell proliferation, migration and survival; as such, these channels are becoming the targets of significant drug development efforts to block or reduce voltage-sensitive ion channel activity in order to prevent or combat malignant disease.
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http://dx.doi.org/10.1007/s10555-006-9017-zDOI Listing
September 2006

Effect of magnesium sulfate on contractile force and intracellular calcium concentration in pregnant human myometrium.

Am J Obstet Gynecol 2006 May;194(5):1384-90

Department of Obstetrics and Gynecology, Indiana University School of Medicine, Indianapolis, IN, USA.

Objective: This study was undertaken to evaluate the effects of magnesium sulfate (MgSO4) on contractile force and increases in free intracellular calcium concentration ([Ca2+]i) in human myometrial strips from pregnant women.

Study Design: Simultaneous measurements of isometric tension and [Ca2+]i were measured in myometrial strips obtained at the time of cesarean delivery from pregnant nonlaboring women at term with the use of a fluorescence spectrometer equipped with a displacement force transducer. Changes in [Ca2+]i were measured with fura-2, a Ca(2+)-sensitive fluorescent probe. Myometrial strips were exposed to MgSO4 (5 or 10 mmol/L) for 5, 10, 20, and 30 minutes and observed for spontaneous contractions or stimulated with either oxytocin (OT; 0.1 micromol/L) or potassium chloride (KCl; 90 mmol/L).

Results: MgSO4 reduced spontaneous, OT, and KCl-evoked contractions and increases in [Ca2+]i in a time and concentration-dependent manner. After 20 minutes exposure to 5 mmol/L MgSO4, the OT-elicited changes in contractile response and [Ca2+]i were significantly decreased. MgSO4 did not change [Ca2+]i/force relationship of the responses to OT or KCl, or during spontaneous activity.

Conclusion: At a pharmacologic concentration (5 mmol/L), MgSO4 inhibits contractile response and [Ca2+]i in pregnant human myometrial strips by a pattern that is consistent with both extra- and intracellular mechanisms. At a suprapharmacologic concentration (10 mmol/L), the more immediate effect of MgSO4 is consistent with an extracellular mechanism. MgSO4 does not appear to interfere at the level of the calcium-calmodulin interface, since the [Ca2+]i/force relationship was not changed.
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http://dx.doi.org/10.1016/j.ajog.2005.11.045DOI Listing
May 2006

Magnesium sulfate induces translocation of protein kinase C isoenzymes alpha and delta in myometrial cells from pregnant women.

Am J Obstet Gynecol 2004 Feb;190(2):522-7

Departments of Obstetrics and Gynecology, Indiana University School of Medicine, Indianapolis, IN, USA.

Objectives: The purpose of this study was to determine the effect of magnesium sulfate on protein kinase C (PKC) translocation in myometrial cells from pregnant women.

Study Design: Myometrium was obtained at the time of cesarean delivery from women at term before labor. Cultured myometrial cells were treated with magnesium sulfate (3, 5, and 10 mmol/L), oxytocin (0.1 micromol/L), or 12-O-tetradecanoylphorbol-13-acetate (TPA, 0.1 micromol/L). The translocation of PKC isozymes alpha (calcium dependent) and delta (calcium independent) from cytosol to membrane fractions was assessed with use of Western blot analysis.

Results: In unexposed control cells, the majority of PKC alpha and delta was located in the cytosol fraction. Exposure to magnesium sulfate for 60 minutes induced translocation of both PKC alpha and delta at concentrations as low as 5 and 3 mmol/L, respectively. The magnitude of magnesium sulfate induced translocation for PKC delta is similar to that seen after oxytocin or TPA exposure but less for PKC alpha. Exposure to oxytocin for 30 minutes and 60 minutes induced translocation of PKC alpha and delta, respectively. Exposure to TPA for 5 and 30 minutes induced translocation of PKC alpha and PKC delta, respectively. In calcium-free media, only TPA induced translocation of these two isoenzymes.

Conclusion: Magnesium sulfate stimulates PKC translocation in cultured myometrial cells from pregnant women. Magnesium sulfate and oxytocin require extracellular calcium to induce translocation of both PKC alpha and delta.
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http://dx.doi.org/10.1016/j.ajog.2003.09.009DOI Listing
February 2004

Role of Ca2+ in diperoxovanadate-induced cytoskeletal remodeling and endothelial cell barrier function.

Am J Physiol Lung Cell Mol Physiol 2003 Nov 25;285(5):L1006-17. Epub 2003 Jul 25.

Department of Medicine, Division of Pulmonary and Critical Care Medicine, Johns Hopkins University School of Medicine, Baltimore, MD 21224, USA.

Diperoxovanadate (DPV), a potent inhibitor of protein tyrosine phosphatases and activator of tyrosine kinases, alters endothelial barrier function via signaling pathways that are incompletely understood. One potential pathway is Src kinase-mediated tyrosine phosphorylation of proteins such as cortactin that regulate endothelial cell (EC) cytoskeleton assembly. As DPV modulates endothelial cell signaling via protein tyrosine phosphorylation, we determined the role of DPV-induced intracellular free calcium concentration ([Ca2+]i) in activation of Src kinase, cytoskeletal remodeling, and barrier function in bovine pulmonary artery endothelial cells (BPAECs). DPV in a dose- and time-dependent fashion increased [Ca2+]i, which was partially blocked by the calcium channel blockers nifedipine and Gd3+. Treatment of cells with thapsigargin released Ca2+ from the endoplasmic reticulum, and subsequent addition of DPV caused no further change in [Ca2+]i. These data suggest that DPV-induced [Ca2+]i includes Ca release from the endoplasmic reticulum and Ca influx through store-operated calcium entry. Furthermore, DPV induced an increase in protein tyrosine phosphorylation, phosphorylation of Src and cortactin, actin remodeling, and altered transendothelial electrical resistance in BPAECs. These DPV-mediated effects were significantly attenuated by BAPTA (25 microM), a chelator of [Ca2+]i. Immunofluorescence studies reveal that the DPV-mediated colocalization of cortactin with peripheral actin was also prevented by BAPTA. Chelation of extracellular Ca2+ by EGTA had marginal effects on DPV-induced phosphorylation of Src and cortactin; actin stress fibers formation, however, affected EC barrier function. These data suggest that DPV-induced changes in [Ca2+]i regulate endothelial barrier function using signaling pathways that involve Src and cytoskeleton remodeling.
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http://dx.doi.org/10.1152/ajplung.00408.2002DOI Listing
November 2003

Magnesium sulfate inhibits the oxytocin-induced production of inositol 1,4,5-trisphosphate in cultured human myometrial cells.

Am J Obstet Gynecol 2002 Aug;187(2):419-24

Department of Obstetrics and Gynecology, Wright State University School of Medicine, Dayton, Ohio, USA.

Objective: The purpose of this study was to determine the effects of magnesium sulfate on inositol trisphosphate production and the mechanism of these effects.

Study Design: Myometrium was obtained at the time of cesarean delivery from women before labor at term. Inositol trisphosphate was measured in the primary myometrial cell cultures after stimulation with oxytocin, sodium fluoride, or Bay K 8644 with or without preincubation with magnesium sulfate or nifedipine. Experiments were performed in either calcium-containing or calcium-free medium that contained egtazic acid and after preincubation with the intracellular calcium chelator BAPTA-acetoxymethylester. Inositol trisphosphate production was measured by radioreceptor assay. In separate experiments, changes in intracellular calcium concentrations ([Ca(2+)](i)) were measured with the use of Fura-2 and spectrophotofluorometry.

Results: Oxytocin, sodium fluoride, and Bay K 8644 increased inositol trisphosphate production 2- to 4-fold. Preincubation with magnesium sulfate (3 x 10(-3) mol/L) for > or = 5 minutes decreased oxytocin-, sodium fluoride-, and Bay K 8644-induced inositol trisphosphate production in either calcium-containing or calcium-free media. Preincubation with BAPTA-acetoxymethylester decreased oxytocin-stimulated inositol trisphosphate production by 78% in calcium-containing media and completely prevented the oxytocin response in calcium-free media. Magnesium sulfate decreased inositol trisphosphate production in calcium-containing media but had no additional effect in calcium-free media. Oxytocin and Bay K 8644 increased [Ca(2+)](i) in either calcium-containing or calcium-free media, and magnesium sulfate reduced this in both cases.

Conclusion: Magnesium sulfate appears to inhibit phosphatidylinositol-4, 5-bisphosphate-specific phospholipase C activity and subsequent calcium release in cultured myometrial cells by a direct effect on phospholipase C.
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http://dx.doi.org/10.1067/mob.2002.123897DOI Listing
August 2002
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