Effect of Molecular Weight and Degree of Acetylation on Adjuvantive Properties of Chitosan Derivatives

© 2018, Pleiades Publishing, Inc. The hemostatic and immunostimulating activity and cytotoxicity were determined for a number of chitosans differing in molecular weight (from 3 to 510 kDa) and degree of acetylation (from 1 to 25 mol%) that were used as adjuvants in inactivated poliomyelitic, influenza, and live influenza vaccines. It has been shown that the hemostatic activity of chitosan increased sharply with an increase in its molecular weight. In oligochitosan with a molecular weight of <16 kDa, it was smaller by a factor of 15–100 than in chitosan with a molecular weight of 20–510 kDa. The level of increase in the immunogenicity of vaccines containing oligochitosan as adjuvants was not lower than that for the vaccine including high-molecular chitosan. However, the immunostimulatory activity of oligochitosan depended on the degree of acetylation, reaching a maximum value at 6 mol%. It was shown that all oligochitosans and chitosans with a molecular mass below ~50 kDa showed almost no cytotoxicity at a concentration of ≤2.5 mg/mL, which enable their use as adjuvants for inactivated and live vaccines at the optimal ratio of molecular weight to the degree of acetylation

Challenges of Statin Therapy in Clinical Practice (According to Outpatient Register «PROFILE» Data)

Aim. To identify the main problems of statin therapy in patients with high and very high cardiovascular (CV) risk in real clinical practice.Material and methods. The general information of the study was based on data from 2,457 patients who were included in the register before November 30, 2020: 1,250 men (50.9%) and 1,207 (49.1%) women. A more detailed analysis was performed for groups of patients with high          and very high CV risk who had indications for statin treatment at the time of inclusion in the register: out of 2457 patients, 1166 people had very high CV risk, 395 was at high CV risk (a total of 1561 people, the average age of patients was 64.4±11.0 years).Results. Information on the parameters of the lipidogram – the level of total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-C) was available in 1918 (78.1%) and 1546 (62.9%) patients, respectively. Of 1561 patients with high and very high CV risk, TC and LDL-C levels were analyzed in 1221 (78.2%) and 956 (61.2%) cases, statistically significantly more often in patients with high CV risk (p&lt;0.05). Statins were recommended only to 823 (52.7%) patients with high and very high CV risk. Patients with very high CV risk received such appointments 4 times more often than patients with high CV risk: odds ratio (OR) 4.2; 95% confidence interval (CI) 3.2-5.3 (p&lt;0.001). Doctors preferred atorvastatin in prescriptions (n=456, 55.4%), rosuvastatin (n=244, 29.7%) and simvastatin (n=121, 14.7%) were in second and third places. The target level of LDLC was 2 times more often achieved in patients with high CVR, compared with patients with very high CV risk: OR = 2.0, 95% CI 1.4-3.0 (p&lt;0.001).Conclusion. The main problems of statin treatment in real clinical practice remain the non-assignment of these drugs to patients who have indications for such therapy and the failure to achieve the target levels of lipidogram indicators, which may probably be due to the clinical inertia of doctors regarding titration of statin doses, and in some cases caused by the choice of drugs that are not the most effective in reducing LDL cholesterol. Patients with very high CV risk are 4 times more likely to receive a recommendation to take statins compared to patients with high CV risk, but the target level of LDL cholesterol is reached in them 2 times less often

Detection and Treatment of Hyperuricemia in Clinical Practice (According to the PROFILE Outpatient Registry)

Aim. To study the frequency of detection of hyperuricemia (HU) in patients with high and very high cardiovascular risk and the frequency of prescribing drugs that lower serum uric acid (sUA) levels in real clinical practice.Material and methods: The general information of the study was based on the data of 2457 patients who were consistently included in the «PROFILE» registry until November 30, 2020: 1250 men (50.9%) and 1207 (49.1%) women. All patients with HU were selected (UA level ≥360 pmol/l in women, ≥420 pmol/l in men). At the stage of inclusion of the patient, data on MC indicators were available in 1777 (72.3%), upon re-examination - only 262 (33.2%) out of 790 patients who returned to the appointment.Results: The most common study of the level of sUA was performed in patients with gout (65.2%), with arterial hypertension (AH) and dyslipemia in 29.1% of cases, with diabetes mellitus (DM) - 30.1%, with impaired tolerance to glucose (IGT) - 40.2%, with other diseases, the proportion of patients with a known UA was even less. A positive relationship was found between the presence of AH and IGT with the frequency of UA control (p&lt;0.001). In patients with AH, an increase in the level of sUA was detected significantly more often than in patients without AH (p&lt;0.001), and less frequently in patients with DM and IGT (p&lt;0.001 and p&lt;0.01, respectively). The frequency of allopurinol prescribing was low: 49 (2%) patients received therapy, while of the 284 patients with HU, only 20 (7%) were prescribed allopurinol.Conclusion: in real clinical practice, only 29.1% of patients with AH and 20-25% of patients with other CVDs were monitored for sUA levels, every third patient had data on sUA levels at a repeat visit. In the presence of gout, the proportion of patients with current UA was higher (65%). For those with AH and IGT, positive correlations were found between the presence of the disease and control of sUA levels. A low frequency of prescribing drugs for the correction of HU was revealed

Long-term survival of patients with cerebrovascular accident in different age groups in the REGION-M registry

Aim. To study the two-year survival rate of patients with cerebrovascular accident (CVA) in different age groups.Material and methods. The outpatient part of the REGION-M registry included 684 patients assigned to the City Polyclinic № 64 in Moscow, discharged from the F. I. Inozemtsev City Clinical Hospital (Moscow) in the period from January 1, 2012 to April 30, 2017 with a confirmed diagnosis of stroke or transient ischemic attack. All patients were divided into 5 age groups: group 1 — from 18 to 50 years old (n=72 (10,5%)), group 2 — from 51 to 60 years old (n=122 (17,8%)), group 3 — from 61 to 70 years old (n=156 (22,8%)), group 4 — from 71 to 80 years old (n=185 (27,0%)) and group 5 — 81 years and above (n=149 (21,8%)). Patient survival was assessed after 2 years of follow-up.Results. The mortality rate of patients during the follow-up period significantly increased with age as follows: in patients of 18-50 years old — 4%, 51-60 years old — 9,8%, 61-70 years old — 23,7%, 71-80 years old — 34%, 81-100 years old — 55% (p&lt;0,0001). The relative death risk was 2,3 in group 2 (NA), 6,8 in group 3 (p&lt;0,001), 9,8 in group 4 (p&lt;0,0001) and 18,5 in group 5 (p&lt;0,0001) compared with group 1. With increasing age in the study cohort, the proportion of women increased as follows: from 47,2% in group 1 to 77,9% in group 5 (p&lt;0,0001). However, mortality among men and women in the groups did not differ. Patients in older age groups were more likely to have comorbidities and disability before the CVA. With increasing age, ischemic stroke was significantly more common and transient ischemic attack was less common (p&lt;0,001).Conclusion. Mortality of patients who underwent stroke was significantly higher in older age groups and did not differ among men and women

Group pursuit with state constraints in Pontryagin’s almost periodic example

Quam ... Praeside ... Dn. Samuele Strykio ... Pro Summis In Utroq[ue] Iure Honoribus Ac Privilegiis Doctoralibus Obtinendis Ipsis Idib. Martii. A.O.R. M.DC.LXX Horis Ante- Et Pomeridianis Placido Eruditorum Examini Submittit Fridericus Strykius, Lenzens. March

Effect of Molecular Weight and Degree of Acetylation on Adjuvantive Properties of Chitosan Derivatives

© 2018, Pleiades Publishing, Inc. The hemostatic and immunostimulating activity and cytotoxicity were determined for a number of chitosans differing in molecular weight (from 3 to 510 kDa) and degree of acetylation (from 1 to 25 mol%) that were used as adjuvants in inactivated poliomyelitic, influenza, and live influenza vaccines. It has been shown that the hemostatic activity of chitosan increased sharply with an increase in its molecular weight. In oligochitosan with a molecular weight of <16 kDa, it was smaller by a factor of 15–100 than in chitosan with a molecular weight of 20–510 kDa. The level of increase in the immunogenicity of vaccines containing oligochitosan as adjuvants was not lower than that for the vaccine including high-molecular chitosan. However, the immunostimulatory activity of oligochitosan depended on the degree of acetylation, reaching a maximum value at 6 mol%. It was shown that all oligochitosans and chitosans with a molecular mass below ~50 kDa showed almost no cytotoxicity at a concentration of ≤2.5 mg/mL, which enable their use as adjuvants for inactivated and live vaccines at the optimal ratio of molecular weight to the degree of acetylation