scholarly journals STUDY OF CHRONIC TOXICITY PARAMETERS OF A DRUG WITH HEPATOPROTECTIVE ACTIVITY

Author(s):  
O.I. Vasiliadi ◽  
◽  
E.N. Rud ◽  
V.A. Grin ◽  
E.V. Kuzminova ◽  
...  

Currently, the most promising and developing area in the field of veterinary pharmacology is the method of obtaining and using an innovative dosage form such as phytosomes. The article presents the results of studies to determine the chronic toxicity of a phytosomal complex with hepatoprotective activity, including silymarin, dihydroquercetin and lecithin. It was determined that its application to laboratory nonlinear rats for sixty days at doses of 150, 75 and 30 mg per animal does not have a negative effect on the organism of rats and the biochemical parameters of their blood. The preservation index in all groups was 100%. The phytosomal complex stimulates body weight gains in animals, with a difference relative to control analogs – 24.2% (group 1), 22.3% (group 2) and 8.1% (group 3). Its long-term use improves the indicators of protein and lipid metabolism, as well as the functional state of the liver within the reference values. Autopsy of laboratory animals showed no signs of intoxication. Thus, long-term use of the phytosomal complex is harmless to warm-blooded animals.

Author(s):  
Tsuyoshi Yamabe ◽  
Yanling Zhao ◽  
Paul A Kurlansky ◽  
Suzuka Nitta ◽  
Saveliy Kelebeyev ◽  
...  

Abstract OBJECTIVES Chronic kidney disease (CKD) is prevalent in patients undergoing cardiovascular surgery, and it negatively impacts procedural outcomes; however, its influence on the outcomes of aortic surgery has not been well studied. This study aims to elucidate the importance of CKD on the outcomes of aortic root replacement (ARR). METHODS Patients who underwent ARR between 2005 and 2019 were retrospectively reviewed (n = 882). Patients were divided into 3 groups based on the Kidney Disease: Improving Global Outcomes criteria: Group 1 [estimated glomerular filtration rate (eGFR) ≥ 60 ml/min/1.73 m2, n = 421); Group 2 (eGFR = 30–59 ml/min/1.73 m2, n = 424); and Group 3 (eGFR < 30 ml/min/1.73 m2, n = 37). To reduce potential confounding, a propensity score matching was also performed between Group 1 and the combined group of Group 2 and Group 3. The primary end point was 10-year survival. Secondary end points were in-hospital mortality and perioperative morbidity. RESULTS Severe CKD patients presented with more advanced overall chronic and acute illnesses. Kaplan–Meier analysis showed a significant correlation between CKD stage and 10-year survival (log-rank P < 0.001). The number of events for Group 1 was 15, Group 2 was 49 and Group 3 was 11 in 10 years. Group 3 had significantly higher in-hospital mortality (13.5% vs 3.5% in Group 2 vs 0.7% in Group 1, P < 0.001) and stroke (8.1% vs 7.1% vs 1.2%, P < 0.001) as well as introduction to new dialysis (27.0% vs 5.4% vs 1.7%, P < 0.001). eGFR was shown to be an independent predictor of mortality (hazard ratio, 0.98; 95% confidence interval, 0.96–0.99). Comparison between propensity matched groups showed similar postoperative outcomes, and eGFR was still identified as a predictor of mortality (hazard ratio, 0.97; 95% confidence interval, 0.95–0.99). CONCLUSIONS Higher stage in CKD negatively impacts the long-term survival in patients who are undergoing ARR.


Circulation ◽  
2014 ◽  
Vol 130 (suppl_2) ◽  
Author(s):  
Teruhiko Imamura ◽  
Koichiro Kinugawa ◽  
Takeo Fujino ◽  
Toshiro Inaba ◽  
Hisataka Maki ◽  
...  

Introduction: Preserved function of collecting duct is essential for the response to tolvaptan (TLV), and urinary level of aquaporin 2 (U-AQP2) can be a marker for vasopressin-dependent activity of collecting duct. Hypothesis: Higher levels of U-AQP2 in proportion to plasma levels of vasopressin (P-AVP) may be associated with better initial responses to TLV and eventually result in the improved prognosis after long-term treatment of TLV. Methods: Consecutive 60 in-hospital patients with stage D heart failure (HF) who received TLV on a de novo basis were enrolled during 2011-2013. We also selected 60 HF patients by propensity score matching who were hospitalized during the same period but never treated with TLV. Events were defined as death and/or HF re-hospitalization. Results: TLV (3.75-15 mg/day) was continuously administered except death or ventricular assist device implantation occurred. There were 41 patients (group 1) who had increases in UV over the first 24 h after TLV initiation, and all of them had U-AQP2/P-AVP ≥0.5 х103 with higher U-AQP2 levels (5.42 ± 3.54 ng/mL) before TLV treatment. On the other hand, UV rather decreased even after TLV initiation in 19 patients over the first 24 h (group 2). Those in the group 2 universally had U-AQP2/P-AVP <0.5 х103, extremely low U-AQP2 levels (0.76 ± 0.59 ng/mL, p<0.001 vs. group 1), and similar P-AVP with the group 1 at baseline. The 41 and 19 patients without TLV treatment (group 3 and 4) were respectively matched to the group 1 and 2 by propensity scores. Interestingly, every patient in the group 3 had U-AQP2/P-AVP ≥0.5 х103, and vice versa in the group 4. Among the four groups, congestion-related symptoms were only improved in the group 1 after 1 month of enrollment. The patients in the group 1 had significantly better event-free survival over 2-year by TLV treatment compared with the group 3 (76% vs. 43%, p<0.014). In contrast, the patients in the group 2 and 4 had very poor prognoses regardless of TLV treatment (7% vs. 11%, p=0.823). Conclusions: U-AQP2/P-AVP is a novel predictor for the initial response to TLV in HF patients. Patients with higher U-AQP2/P-AVP may enjoy a better prognosis by long-term TLV treatment probably due to efficient resolution of congestion.


2016 ◽  
Vol 174 (4) ◽  
pp. 531-538 ◽  
Author(s):  
Julia Schulz ◽  
Kathrin R Frey ◽  
Mark S Cooper ◽  
Kathrin Zopf ◽  
Manfred Ventz ◽  
...  

ObjectiveIndividuals with primary adrenal insufficiency (PAI) or congenital adrenal hyperplasia (CAH) receive life-long glucocorticoid (GC) replacement therapy. Current daily GC doses are still higher than the reported adrenal cortisol production rate. This GC excess could result in long-term morbidities such as osteoporosis. No prospective trials have investigated the long-term effect of GC dose changes in PAI and CAH patients.MethodsThis is a prospective and longitudinal study including 57 subjects with PAI (42 women) and 33 with CAH (21 women). Bone mineral density (BMD) was measured by dual energy X-ray absorptiometry at baseline and after 2 years. Subjects were divided into three groups (similar baseline characteristics) depending on changes in daily hydrocortisone equivalent dose (group 1: unchanged 25.2±8.2 mg (mean±s.d., n=50); group 2: increased 18.7±10.3 to 25.9±12.0 mg (n=13); group 3: decreased 30.8±8.5 to 21.4±7.2 mg (n=27)).ResultsSubjects in group 1 showed normal lumbar and femoral Z-scores which were unchanged over time. Group 2 subjects showed a significant decrease in femoral neck Z-scores over time (−0.15±1.1 to −0.37±1.0 (P<0.05)), whereas group 3 subjects showed a significant increase in lumbar spine and hip Z-scores (L1–L4: −0.93±1.2 to –0.65±1.5 (P<0.05); total hip: −0.40±1.0 to −0.28±1.0 (P<0.05)). No changes in BMI over time were seen within any group. Reduction in GC dose did not increase the risk of adrenal crisis.ConclusionThis study demonstrates for the first time that cautious reduction in hydrocortisone equivalent doses leads to increases in BMD, whereas dose increments reduced BMD. These data emphasize the need for the lowest possible GC replacement dose in AI patients to maintain health and avoid long-term adverse effects.


2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
T.K.M Wang ◽  
K Akyuz ◽  
B Xu ◽  
M Gillinov ◽  
G Pettersson ◽  
...  

Abstract Background Isolated tricuspid surgery has markedly higher mortality rates (9–10%) in contemporary national registries compared to other single-valve operations. The optimal timing and indications remain controversial, and earlier surgery before developing ESC guidelines class 1 indications may improve the survival for isolated severe tricuspid regurgitation. Purpose We aimed to compare the characteristics and outcomes of isolated tricuspid regurgitation (TR) surgery by indication. Methods Consecutive patients undergoing isolated tricuspid valve surgery for TR without other concomitant valve surgery at Cleveland Clinic from 2004 to 2019 were studied. Indications were divided into group 1: ESC guidelines class 1 (severe symptomatic TR), group 2: infective endocarditis, and group 3: non-class 1 (asymptomatic severe TR with or without right ventricular dilation and/or dysfunction) and no endocarditis, for comparative analyses of characteristics and outcomes. Results The study included 207 patients (group 1: 115, group 2: 48 and group 3: 44) with mean age 54.1±17.8 years, 116 (56.0% females and 151. Tricuspid repair was performed in 72.9% (73.0%, 66.7% and 79.5% for Groups 1–3, P=0.381). Group 3 patients were younger, had higher prevalence of primary TR, lower prevalence of heart failure, atrial fibrillation, chronic lung disease, cirrhosis, renal impairment, right ventricular and left ventricular dysfunction than Group 1. Overall operative mortality rates were 4.9% ( group 1: 7.0%, group 2: 4.2% and group 3: 0.0%), while mortality during follow-up of 3.3±4.0 years was lower for group 3 than for groups 1 or 2 (Figure 1). Independent predictors of long-term mortality were Group 1 compared to Group 3 and reduced estimated glomerular filtration rate. Conclusion Patients without class I or endocarditis indications had superior unadjusted and adjusted survival compared to those with these indications. The high mortality rate of isolated TR surgery may be reduced by both earlier surgery and being performed at an experienced cardiac surgery center. Figure 1. Kaplan-Meier survival curves Funding Acknowledgement Type of funding source: Foundation. Main funding source(s): National Heart Foundation of New Zealand - Overseas Clinical and Research Fellowship


2020 ◽  
Vol 9 (12) ◽  
pp. 3904
Author(s):  
Ha-Rim So ◽  
Hae Young Lopilly Park ◽  
So-Hyang Chung ◽  
Hyun-Seung Kim ◽  
Yong-Soo Byun

Autologous serum eyedrops (ASE) are effective in treating various ocular surface diseases, including damages induced by long-term use of preserved glaucoma eyedrops. However, there has been no study on whether ASE is effective without stopping the causative eyedrops. This retrospective observational study included 55 patients with ocular-surface diseases caused by long-term use of preserved glaucoma eyedrops: 18 patients who used ASEs for 2 months without discontinuing the use of glaucoma eyedrops (Group 1), 22 patients who used ASEs for 2 months, discontinuing the use of glaucoma eyedrops for the first month (Group 2) and 15 patients who used non-preservative artificial tears for 2 months, discontinuing the use of glaucoma eyedrops for the first month (Group 3). There were no intergroup differences in the baseline values of the Schirmer I test results, tear breakup time (TBUT), ocular surface staining (OSS) score, loss of the meibomian gland, meibum quality and ocular-surface disease index (OSDI). Group 1 showed significant differences in TBUT, OSS score and OSDI at 2 months when compared to the baseline values before treatment, while Group 2 showed significant differences in those values at both 1 and 2 months. There were no differences in any of the parameters at baseline, 1 month or 2 months in Group 3. Our result suggested that ASE is effective for treating ocular surface diseases caused by glaucoma eyedrops containing preservatives and its effects can be expected without interruption of glaucoma eyedrop treatment.


2015 ◽  
Vol 86 (1) ◽  
pp. 3-9 ◽  
Author(s):  
Willian Juarez Granucci Guirro ◽  
Karina Maria Salvatore Freitas ◽  
Guilherme Janson ◽  
Marcos Roberto de Freitas ◽  
Camila Leite Quaglio

ABSTRACT Objective:  To compare the postretention stability of maxillary incisors alignment in subjects with Class I and II malocclusion treated with or without extractions. Materials and Methods:  The sample comprised 103 subjects with initial maxillary anterior irregularity greater than 3 mm and was divided into four groups: group 1 comprised 19 patients with Class I malocclusion treated with nonextraction (mean initial age = 13.06 years); group 2 comprised 19 patients with Class II malocclusion treated with nonextraction (mean initial age = 12.54 years); group 3 comprised 30 patients with Class I malocclusion treated with extractions (mean initial age = 13.16 years); group 4 comprised 35 patients with Class II malocclusion treated with extractions (mean initial age = 12.99 years). Dental casts were obtained at three different stages: pretreatment (T1), posttreatment (T2), and long-term posttreatment (T3). Maxillary incisor irregularity and arch dimensions were evaluated. Intergroup comparisons were performed by one-way analysis of variance followed by Tukey tests. Results:  In the long-term posttreatment period, relapse of maxillary crowding and arch dimensions was similar in all groups. Conclusion:  Changes in maxillary anterior alignment in Class I and Class II malocclusions treated with nonextractions and with extractions were similar in the long-term posttreatment period.


2020 ◽  
Vol 28 (3) ◽  
pp. 312-322
Author(s):  
Anton N. Kazantsev ◽  
Konstantin P. Chernykh ◽  
Nona E. Zarkua ◽  
Roman Yu. Lider ◽  
Ekaterina A. Burkova ◽  
...  

Aim. Analysis of hospital and long-term results of carotid endarterectomy (CEA) in different periods of acute cerebrovascular event (ACVE). Materials and Methods. The given study was retrospective and was conducted using the method of patients sampling. In the period from 2010 to 2019, 1113 patients with ACVE in history who were later conducted CEA, were selected. Depending on the time interval between the last ACVE and CAE, all the patients were divided into 4 groups: the 1st group in the acutest period of ACVE (1-3 days) (n=24; 2.2%); the 2nd group in the acute period of ACVE (up to 28 days) (n=493; 44.3%); the 3rd group in the early rehabilitation period of ACVE (up to 6 months) (n=481; 43.2%); the 4th group in the late rehabilitation period of ACVE (up to 2 years) (n=115; 10.3%). The long-term period was 34.812.5 months. Results. In the hospitalization period of observation the following complications were found: lethal outcome ((group 1 0%; group 2 0.4% (n=2); group 3 0.2% (n=1); group 4 0%; р=0.16)); myocardial infarction ((group 1 0%; group 2 0.4% (n=2); group 3 0%; group 4 0.9% (n=1); р=0.35)); ACVE/transient ischemic attack (TIA), ((group 1 4.2% (n=1); group 2 0.4% (n=2); group 3 0.2% (n=1); group 4 0%; р1-2=0.01; р1-3=0.009; р1-4=0.01)). By the end of hospitalization period the composite endpoint consisting of lethal outcome + myocardial infarction + ACVE/TIA made in group 1 4.2% (n=1), in group 2 1.2% (n=6), in group 3 0.4% (n=2), in group 4 2.6% (n=3), р=0.08. Complications of the long-term follow-up period were: lethal outcome from all causes ((group 1 25% (n=6); group 2 5.5% (n=27); group 3 7.3% (n=35); group 4 14% (n=16); р1-2=0.002; р1-3=0.008; р2-4=0.012)); lethal outcome from cardiovascular causes ((group 1 4.2% (n=1); group 2 3.6% (n=18); group 3 4.8% (n=23); group 4 5.2% (n=6); р=0.79)), myocardial infarction ((group 1 12.5% (n=3); group 2 3.6% (n=18); group 3 5.4% (n=26); group 4 6.1% (n=7); р=0.15)), ACVE/TIA ((group 1 16.6% (n=4); group 2 6.3% (n=31); group 3 6% (n=29); group 4 11.3% (n=13); р=0.05)); composite endpoint including lethal outcome + myocardial infarction + ACVE/TIA ((group 1 54.2% (n=13); group 2 15.4% (n=76); group 3 18.7% (n=90); group 4 31.3% (n=36); р1-2=0.0001; р1-3=0.0001; р1-4=0.005; р2-4=0.0006; р3-4=0.012)). Conclusion. Application of CEA demonstrated effectiveness and safety in the acute and early rehabilitation period of ACVE.


2021 ◽  
Vol 15 (4) ◽  
pp. 15-26
Author(s):  
Anton N. Kazantsev ◽  
Roman A. Vinogradov ◽  
Sergey V. Artyukhov ◽  
Lyudmila V. Roshkovskaya ◽  
Vyacheslav V. Matusevich ◽  
...  

The aim of this study was to analyse the inpatient and long-term results of hybrid surgery, incorporating percutaneous coronary intervention (PCI) and different types of carotid endarterectomy (CEA). Materials and methods. A prospective, open-label cohort comparison study was conducted in 20182020 and included 363 patients with atherosclerosis of both the internal carotid artery (ICA) and coronary artery, who underwent hybrid revascularization of the brain and myocardium. All patients were divided into four groups based on the revascularization strategy: group 1 (n = 107; 29.5%) PCI + eversion CEA; group 2 (n = 98; 27%) PCI + classic CEA with patch angioplasty; group 3 (n = 72; 19.8%) PCI + glomus-sparing CEA according to R.A. Vinogradov; and group 4 (n = 86; 23.7%) PCI + glomus-sparing CEA according to A.N. Kazantsev. The follow-up period was 20.8 8.0 months. The patient received a loading dose of clopidogrel (300 mg) before the PCI, and the procedure was then performed in an endovascular operating room. A radial artery catheter was inserted, and the patient received 10,000 IU of intravenous heparin before the procedure. After the PCI, the patient was taken to the vascular operating room, where they underwent the CEA. The patient received 5,000 IU of intravenous heparin before artery clamping. Glomus-sparing CEA according to A.N. Kazantsev was performed as follows: an arteriotomy was conducted along the internal edge of the external carotid artery (ECA), adjacent to the carotid sinus and 23 cm above the ostium, and extending to the common carotid artery (CCA) (also 23 cm below the ECA ostium), depending on the size of the atherosclerotic plaque. The ICA was transected in the area bound by the ECA and CCA walls. Eversion CEA of the ICA was performed, followed by open CEA of the ECA and CCA. The ICA was implanted in its previous position in the preserved area. Results. No mortality was recorded during the inpatient follow-up period. All cases of myocardial infarction occurred after eversion and classic CEA: 3 in group 1 (2.8%) and 1 in group 2 (1.02%); р = 0.2. No ischaemic stroke was recorded only in patients who underwent CAE according to A.N. Kazantsev (р = 0.66); however, ischaemic stroke occurred in two patients in group 1 (1.8%), in two patients in group 2 (2.04%) and in one patient in group 3 (1.38%). The highest number of cardiovascular events occurred in group 1, due to carotid glomus injury, which led to poorly controlled hypertension during the inpatient stay. This tendency influenced the composite endpoints (death + myocardial infarction + ischaemic stroke), which were highest in group 1 (5 or 4.6%) compared to 3 (3.06%), 1 (1.38%) and 0 in groups 24, respectively (р = 0.18). The groups were comparable in the frequency of long-term complications. However, the incidence of ICA restenosis was lowest and no ECA thrombosis/occlusion was observed after glomus-sparing CEA according to R.A. Vinogradov and A.N. Kazantsev. Conclusion. A hybrid PCI + CEA for brain revascularization should be glomus-sparing. CEA according to A.N. Kazantsev was characterized by lack of procedural arteriotomy complications. This procedure enables blood pressure monitoring in the postoperative period, thus minimizing the risk of cardiovascular complications.


2019 ◽  
Vol 100 (6) ◽  
pp. 892-897
Author(s):  
Stanislav Olegovich Artyukhin ◽  
Vladimir Georgievich Aristarhov ◽  
Denis Anatolyevich Puzin

Aim. To study the long-term results of surgical treatment of patients with thyroid adenomas. Methods. From 2004 to 2006, 667 patients with follicular adenomas of the thyroid gland, including 134 (20.1%) men and 533 (79.9%) women, were operated on in the surgical department №2 of city clinical hospital №11 of Ryazan. 3 groups of patients were defined: group 1 operated on for solitary adenomas of the thyroid gland, 103 patients, hemithyreoidectomy performed; group 2 operated on for multiple adenomas of the thyroid in both lobes, 101 patients, thyroidectomy performed; group 3 32 patients operated on for multiple adenomas of the thyroid in the same lobe, hemithyreoidectomy performed. Patients were examined 14 years after the surgery. Results. Hypothyroidism was diagnosed in: group 1 18 (17.5%) patients, group 2 101 (100%), group 3 0. All patients with hypothyroidism were compensated with hormone replacement therapy. Permanent hypoparathyroidism was diagnosed only in group 2 8 (4.8%) patients. Unilateral laryngeal paralysis was found in group 1 in 1 (0.9%) patient, group 2 in 2 (1.9%) patients, group 3 contained no such patients. Recurrence (node more than 1 cm according to ultrasound) was observed in group 1 in 12 (11.7%) patients; fine-needle aspiration found colloidal nodes in 8 (7.8%) patients (Bethesda II), in 4 (3.9%) follicular tumor (IV). Group 2 had no recurrences. In group 3 11 (34.3%) patients had recurrence; fine-needle aspiration found colloidal nodes in 1 (3.1%) patient (Bethesda II), in 10 (31.3%) follicular tumor (Bethesda IV). Conclusion. In solitary adenomas it is possible to perform organ-saving operations, which reduces the percentage of postoperative complications; in multiple adenomas, the optimal volume of surgery is thyroidectomy; when multiple adenomas are localized in one lobe, the chance of recurrence of the disease (31.3%) is high leading to re-surgery.


Kardiologiia ◽  
2019 ◽  
Vol 59 (11) ◽  
pp. 21-30 ◽  
Author(s):  
N. V. Pogosova ◽  
A. O. Salbieva ◽  
O. Y. Sokolova ◽  
A. K. Ausheva ◽  
A. V. Karpova ◽  
...  

Background Long-term secondary preventive programs in coronary heart disease (CHD) are of highest efficacy but numerous logistical problems often compromise their implementation. Contemporary remote technologies have a potential to overcome these barriers. Aim: To assess  the impact of 2 preventive counselling programs with subsequent remote support in CHD patients with concomitant obesity. Methods: A prospective randomized parallel-group study in 120 stable CHD patients hospitalized for elective coronary revascularization who were from 40 to 65 years old and had concomitant obesity. Patients were randomized (1:1:1) into 3 groups (n=40 each). Before discharge, Groups 1 and 2 received a single-session comprehensive counselling with focus on diet followed by remote counselling by phone (Group 1) or via text messages (Group 2). Remote counselling was delivered weekly (Months 1-3) and then monthly (Months 4-6). Group 3 received only standard advice from their attending physicians. The patients were followed for 12 months with assessment of adiposity measures, self-reported dietary patterns, physical activity (IPAQ questionnaire), smoking status, blood pressure (BP), fasting blood glucose, lipids and C-reactive protein (CRP) levels, as well as of clinical events. Results: At 1 year of follow-up, the patients from both intervention groups showed a marked improvement of several risk factors including obesity: the body mass index was reduced by 1.48±0.13 kg/m² in Group 1 and by 1.53±0.18 kg/m² in Group 2; the waist circumference went down by 7.62±0.49 and by 7.41±0.74 cm, respectively; the height-normalized fat mass decreased by 4.66±0.40 kg and 5.98±0.63 kg, respectively (all P values are <0.01 vs corresponding changes in the control group). These changes were coupled with more healthy dietary patterns and less sedentary lifestyles in both intervention groups: the proportion of patients with low activity level fell from 87.5% to 2.5% in Group 1 and from 80% to 10% in Group 2 (both p values <0.01 vs control). In Group 1, BP decreased by 18.08±2.20 mmHg (systolic) and 8.56±1.61 mmHg (diastolic); both р values <0.01 vs Group 3. In Group 2 systolic BP dropped by only 11.95±2.50 mmHg (non-significant) and diastolic BP by 6.33±1.52 mmHg (р<0.05 vs control). The proportion of smokers went down from 30% to 5% in Group 1 and from 22.5% to 0% in Group 2 (both p values <0.01 vs control). The fasting glucose levels decreased by 0.21±0.20 mmol/L in Group 1 and by 0.48±0.25 mmol/L in Group 2 (<0.01 vs control, both), but there were no meaningful improvements in blood lipids or CRP. Conclusion: Long-term (6 months) secondary prevention programs incorporating remote support technologies result into sustained improvement of key secondary prevention indicators in obese CHD patients, irrespective of the support modality (by phone or via electronic messaging).


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