flavin-mononucleotide and Hypertension

This comparative study of the influence of cytoflavin and cardioxipin on the parameters of 24-hour arterial pressure monitoring in 56 patients with chronic cerebral circulation insufficiency, arterial hypertension and hypercholesterolemia included 32 women and 24 men aged 42-72 years divided into 3 groups matchedfor the stage of diseases, age, sex, severity of AH, total cholesterol level, and antihypertensive therapy. Patients of group 1 were treated without cytoflavin and cardioxipin. Those in group 2 received daily i/v droplet infusion of 10 mg/kg cardioxipin (20-30 droplets/min). Patients of group 3 were given daily i/v droplet infusion of 10 ml cytoflavin in 200 ml 0.9% sodium chloride solution for 10 days. 24-hour arterial pressure monitoring was used to estimate the influence of the two drugs on systolic and diastolic pressure, its daily rhythm, AP variability and frequency of elevation. The study showed that both therapeutic modalities improved daily AP rhythm as manifested in a significant increase of the number of patients with the dipper rhythm and a decrease in the number of systolic/diastolic non-dipper patients. Moreover cytoflavin significantly decreased the number of systolic over-dippers compared with control group.

Topics: Adult; Aged; Antihypertensive Agents; Arterial Pressure; Blood Pressure Monitoring, Ambulatory; Cerebrovascular Circulation; Cerebrovascular Disorders; Chronic Disease; Dose-Response Relationship, Drug; Drug Combinations; Drug Therapy, Combination; Female; Flavin Mononucleotide; Follow-Up Studies; Humans; Hypercholesterolemia; Hypertension; Infusions, Intravenous; Inosine Diphosphate; Male; Middle Aged; Niacinamide; Retrospective Studies; Succinates; Treatment Outcome

The molecular pharmacological effects of cytoflavin in patients with hypertensive encephalopathy (HE) and isolated systolic arterial hypertension (ISAH) have been investigated using the following methods: assessment of complaints, 24-hour arterial pressure monitoring, ultrasound diagnostics including echocardiography, measurement of lipid profiles and coagulograms, and molecular phenotyping by MALDI-TOF/TOF-MS. A combination of cytoflavin administration with standard therapy of HE and ISAH led to the most expressed return development of clinical symptoms, restoration of the hemodynamic, structural, and geometrical parameters of cardiovascular system, and normalization of the indices of lipid profiles and coagulograms in comparison to patients with HE and ISAH, which accepted only standard therapy. Molecular mechanisms of cytoflavin action have been revealed, which include control of the activity of cellular signaling pathways by means of intermolecular interactions. The optimized therapy of HE and ISAH is recommended for clinical application, which assumes a combined use of standard therapy and cytoflavin and provides a geroprotective action upon the cardiovascular system.

Topics: Aged; Aged, 80 and over; Amlodipine; Aspirin; Atorvastatin; Blood Pressure; Blood Proteins; Drug Combinations; Drug Therapy, Combination; Echocardiography; Female; Flavin Mononucleotide; Hemodynamics; Heptanoic Acids; Humans; Hypertension; Hypertensive Encephalopathy; Inosine Diphosphate; Male; Neuroprotective Agents; Niacinamide; Pyrroles; Signal Transduction; Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; Succinates; Systole; Tetrazoles; Valine; Valsartan

The aim of the research was the search of the mechanism of Cytoflavin action in patients with isolated systolic arterial hypertension (ISAH) as the aging model. The following research methods were applied: the assessment of complaints, 24-hour arterial pressure monitoring, ultrasound diagnostic, volume sphygmography, lipid profiles and coagulogram, molecular phenotyping by MALDI-TOF-TOF-MS. The combination of Cytoflavin with standard therapy of ISAH led to the most expressed return development of clinical symptoms, the restoration of the haemodynamics, structural and geometrical parameters of cardiovascular system, indicators lipid profiles and coagulogram in the comparison with patients with ISAH, who accepted standard therapy and those of the control groups. Molecular mechanisms of Cytoflavin action, including regulation of the activity of cell signaling pathways through intermolecular interactions were found. We recommend using Cytoflavin together with the standard therapy in treatment of ISAH, which provides the action of geroprotectors for cardiovascular system.

Topics: Aged; Aging; Blood Coagulation; Blood Flow Velocity; Blood Pressure; Blood Pressure Monitoring, Ambulatory; Brain; Cardiovascular System; Cerebrovascular Circulation; Cohort Studies; Drug Combinations; Female; Flavin Mononucleotide; Humans; Hypertension; Inosine Diphosphate; Lipids; Male; Niacinamide; Prospective Studies; Proteome; Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; Succinates; Ultrasonography, Doppler, Transcranial

We examined 60 patients with constitutional venous insufficiency, suffering from hypertensive encephalopathy of I and II stages, mean age 43,4± 6,3 years. Patients of the main group (n=30) received Cytoflavin (2 tablets twice a day) and standard therapy (acetylsalicylic acid and antihypertensive drugs). Thirty patients of the parallel group received only standard therapy. At the 25th day of the study, there were the decrease in the number of complaints, including specific "venous complaints", the reduction of cephalalgia syndrome, asthenic and autonomic disorders; the improvement of quality of life and better cerebral hemodynamics on all structural and functional levels.

Topics: Adult; Brain Damage, Chronic; Drug Administration Schedule; Drug Combinations; Female; Flavin Mononucleotide; Humans; Hypertension; Inosine Diphosphate; Male; Middle Aged; Niacinamide; Quality of Life; Succinates; Treatment Outcome; Venous Insufficiency

To evaluate the impact of incorporating cytoflavin in a treatment regimen for patients with different stages of hypertensive disease (HD).. The results of treatment were analyzed in 140 patients with HD (53 with Stage I, 50 with Stage II, and 37 with Stage III). According to the treatment regimen, the patients were divided into 2 groups. A study group (n=74) received combination treatment involving antihypertensive therapy and cytoflavin intravenously dropwisely in a single dose of 200 ml of 5% glucose solution for 10 days, then 2 tablets twice daily for 60 days, with a total cycle time being 70 days. A comparison group (n=66) had antihypertensive therapy only. Thirty apparently healthy individuals (a control group) were examined to have reference values. All the patients were examined using conventional clinical and laboratory studies. The patients' complaints and neurological status were assessed using respective questionnaires over time - before and after treatment.. The incorporation of cytoflavin in a treatment regimen was ascertained to reduce the degree of anxiety, depressive, dissomnic, and cognitive disorders, improves quality of life in patients with Stage I HD, and lowers the degree of asthenic and autonomic disorders in all disease stages.. The found efficacy and safety of the drug may recommend its incorporation in combination therapy regimens for Stages I-III HD.. Цель исследования. Изучение влияния включения препарата цитофлавин в схему лечения пациентов с различными стадиями гипертонической болезни. Материалы и методы. Проанализированы результаты лечения 140 пациентов с гипертонической болезнью - ГБ (53 с I стадией, 50 со II стадией и 37 с III стадией артериальной гипертонии). В зависимости от схемы терапии больных разделили на 2 группы: 74 пациента основной группы получали комплексную терапию, состоящую из антигипертензивной терапии и препарата цитофлавин внутривенно капельно однократно по 10 мл в 200 мл 5% раствора глюкозы 10 дней, затем 60 дней по 2 таблетки 2 раза в день, общий курс 70 дней; 66 больных группы сравнения получали только антигипертензивную терапию. Для получения референсных показателей обследовали 30 практически здоровых лиц (группа контроля). Все больные обследованы стандартными клинико-лабораторными методами, проведена оценка жалоб пациентов и их неврологического статуса с помощью соответствующих опросников в динамике - до и после лечения. Результаты. Установлено, что включение в схему терапии цитофлавина уменьшает выраженность тревожных, депрессивных, диссомнических и когнитивных расстройств, улучшает качество жизни у пациентов с I стадией ГБ и уменьшает выраженность астенических и вегетативных нарушений при всех стадиях заболевания. Заключение. Выявленная эффективность и безопасность препарата позволяют рекомендовать его включение в схемы комплексной терапии ГБ I-III стадий.

Topics: Adult; Aged; Antihypertensive Agents; Anxiety; Autonomic Nervous System Diseases; Cognition Disorders; Depression; Drug Combinations; Drug Therapy, Combination; Female; Flavin Mononucleotide; Humans; Hypertension; Inosine Diphosphate; Male; Middle Aged; Niacinamide; Severity of Illness Index; Succinates; Treatment Outcome

We studied the clinical efficacy of cytoflavin in 30 patients (group 1) with I and II stages of discirculatory encephalopathy (DE) and a depressive syndrome associated with arterial hypertension. Cytoflavin was added to standard treatment intravenously in drops in dose 10 ml per 200 ml of 0,9% NaCl during 10 days and then in dose 2 tablets twice a day during 25 days. The control group (n=29 patients) received placebo. The treatment duration was 35 days but patients were followed up for 90 days with control visits at 5, 10, 20-35 and 65-90 days of treatment. After the treatment, there was the reduction of neurological symptoms and subjective disorders in patients of group 1. The improvement of attention concentration, reasoning and speech activity as well as the gradual restoration of memory were noted at 20-35 days. The positive impact of cytoflavin on depression was dependent on its severity. The effect was higher in mild depression, also, the treatment decreased the severity of depression from "moderate" or "severe' to "mild". Cytoflavin may be recommended for patients with DE and a depressive syndrome associated with arterial hypertension as a preventive medication from the progression of cerebrovascular pathology and development of stroke.

Topics: Cerebrovascular Disorders; Depressive Disorder; Drug Combinations; Female; Flavin Mononucleotide; Humans; Hypertension; Inosine Diphosphate; Male; Middle Aged; Neuroprotective Agents; Niacinamide; Psychiatric Status Rating Scales; Stroke; Succinates; Treatment Outcome

Using 14C-labeled arginine to 14C-labeled citrulline conversion assays in brain homogenates from 14- to 18-day-old and adult spontaneously hypertensive rats, we tested the hypotheses that maturation increases neuronal nitric oxide synthase (nNOS) activity and that this increase involves changes in cofactor availability and/or nNOS kinetics. nNOS activity (in pmol x mg(-1) x min(-1)) was 46% higher in adults (19 +/- 2) than in pups (13 +/- 1). The addition of 264 microM calmodulin (CaM), 3 microM FAD, 3 microM flavin adenine mononucleotide (FMN), and 10 microM tetrahydrobiopterin (BH4) increased NOS activity by 3, 46, 45, and 88% in pups and by 19, 40, 36, and 102% in adults, respectively. All cofactor effects were significant except for CaM in the pup homogenates. Cofactor effects were not significantly different between pup and adult homogenates, except for BH4, which increased absolute NOS activity more in adults than in pups. Values of maximal enzyme velocity (Vmax) for nNOS in the absence of added cofactors were greater in adults than in pups (104 +/- 5 vs. 53 +/- 3, P < 0.05). Addition of 3 microM FAD or 3 microM FMN increased pup Vmax values to 68 +/- 2 and 99 +/- 5, respectively, but had no effect in adults. BH4 did not affect Vmax in either group. Control values of the Michaelis-Menten constant (Km) for L-arginine were greater (P < 0.05) in pups (5.7 +/- 0.4 microM) than in adults (4.3 +/- 0.2 microM) and were significantly reduced by 10 microM BH4 to 3.8 +/- 0.2 and 2.9 +/- 0.1 microM, respectively. Neither FAD nor FMN affected Km values in either group. The results indicate that endogenous nNOS cofactor levels are not saturating in either pups or adults, changes in cofactor levels differentially affect NOS kinetics in pups and adults, and age-related differences in NOS activity result from fundamental differences in NOS kinetics. These findings support the general hypothesis that the increased vulnerability to ischemic stroke associated with maturation is due in part to corresponding increases in the capacity for nitric oxide synthesis.

Topics: Aging; Animals; Animals, Newborn; Biopterins; Brain; Calmodulin; Flavin Mononucleotide; Flavin-Adenine Dinucleotide; Hypertension; Kinetics; Nitric Oxide Synthase; Rats; Rats, Inbred SHR