The mechanism of action of the alkaloid 1-(2´-bromine-4´,5´-dimethoxyphenyl) - 6,7-dimethoxy-1,2,3,4-tetrahydroisoquinoline (F-18) on the functional activity of smooth muscle cells of the rat aorta was studied. Isometric contraction activity was recorded using a Grass FT – 03 (Grass Instrument, USA) mechanotron. The relaxant effect of the F-18 alkaloid was found to be associated with blockade of Ca2 + (IP3R) channels in the SR, along with voltage- dependent and receptor-operated Ca2+channels in the aorta smooth muscle cell plasmalemma.
Relevance of the problem.Despite the great successes of angiosurgery, the problem of surgical treatment of abdominal aortic aneurysms does not lose its relevance. World health statistics records a steady increase in the incidence of abdominal aortic aneurysm (ABA). According to L.J. Melton et al. (1984) and L.K. Bickerstaff et al. (1984) in the USA the number of patients with abdominal aortic aneurysm has increased 7 times in 30 years since 1951. In England and Wales, according to F.G. Fowkers et al. (1989) for the same period revealed a 20-fold increase in abdominal aortic aneurysms in men and 11-fold in women. According to the results of multicentre screening studies ABA was detected in 8% of the examined (E.S. Vourvouri, 2001), and in the age group of 64-69 years ABA was detected in 5.7% of the examined, and in the age group of 75-81 years - in 8.9% (R.A.P. Skott et al., 2001). A similar trend is observed in other countries. Accordingly, mortality from ABA is also increasing - aneurysm rupture in a number of countries is one of the ten most frequent causes of death among elderly and senile people (F.A. Lederle et al., 1990)
Currently, planned aneurysm resection has become a recognised standard of radical treatment of ABA patients and the number of these operations is steadily increasing. For example, about 40,000 ABA resections are performed annually in the USA (J.J. Grange et al., 1997). In Sweden during the period from 1987-89 to 1993-95 the number of ABA operations increased 5 times and currently 10 operations per 100,000 population are performed (A.Hallin et al., 2001), although this is 1.5 - 2 times less than the required number. However, postoperative lethality is still quite high and makes 5-7% (A.V.Pokrovskiy et al., 1992; Y.V.Belov et al., 1992; V.V.Vakhidov et al., 1992; A.W. Bradbury et al. Bradbury et al., 1997; A.Hallin et al., 2001).
E.W. Steyeberg et al. (1995) summarised the data of literature on 17238 ABA resection operations and gave an average mortality of 6.8%.
Multicentre studies in five major hospitals in the Netherlands found that only 74% of patients underwent ABA resection without complications; 26% had some complications, 9% of which were severe and 4.1% of which were fatal (G.J. Akkersdijk et al., 1998). Similar results were obtained in the Canadian Cooperative Study (K.W. Johnston et al., 1990). It was established that the peculiarity of complications in the majority of patients was their systemic character (L.L. Lau et al, 2001) The course of the postoperative period is most often complicated by cardiac, respiratory, renal, cerebrovascular, as well as complications associated with thrombosis and bleeding (W.E. Lloyd et al., 1996; R.D. Sayers et al., 1997; J.D. Blankenstein et al., 1998; R. Ayari et al., 1998). Ayari et al., 2001)
The undisputed leadership, without doubt, belongs to cardiac complications, the incidence of which varies from 10% to 20%. Moreover, cardiac complications account for 50-70% of total mortality. Cerebrovascular complications, although not uncommon, account for no more than 1-1.5%, but their mortality reaches 40%. Complications associated with thromboses and haemorrhages in the perioperative period reach 2-5% (M.M.Reigel et al., 1987; K.W.Johnson et al., 1990; N.Franklin et al., 1993; A.A.Milne et al., 1994).
Certainly, a large number of complications after resection of abdominal aortic aneurysms is caused by the initial severity of patients' condition, however, many unresolved tactical and technical issues of patients' preparation for the operation, stage of performance in case of combined lesions of several vascular basins play a practically significant role. Adequate management of the operation itself and the immediate postoperative period is no less important, taking into account the possibility of such dreadful complications as thrombosis and embolism, cerebral and cardiac death. Until now there is no unified complex analysis of the results of treatment of uncomplicated abdominal aortic aneurysms and, accordingly, recommendations for the prevention of possible complications.
All this determined our aim and objectives of the study.
The aim of the study is to improve the results of surgical treatment of ABA by developing an effective system for determining the main risk factors of surgical treatment and optimal surgical tactics to prevent possible complications.
Scientific novelty.For the first time a complex analysis of indications and contraindications to surgical treatment of abdominal aortic aneurysms was carried out
The most significant concomitant pathology capable to lead to formidable complications and lethality during the intervention and in the nearest postoperative period was revealed. Adequate measures of their prevention and treatment were proposed.
The algorithm of surgical treatment tactics for patients with combined pathology of coronary arteries and aortic arch branch lesions was developed
The state of haemostasis system at all stages of reconstructive surgery on abdominal aorta, starting from skin incision to wound closure, was studied for the first time.
Conclusions:
1. The proposed original classification of ABA, based on mutual dependence on the etiology of the disease, localisation, concomitant diseases, clinic and its course, allows to determine the strategy of early diagnosis, to estimate the most significant risk factors, the stage of intervention in combined lesions of adjacent and distant vascular basins and, ultimately, to determine the ways to reduce complications and mortality in patients with ABA.
2. The most informative methods of ABA diagnostics are duplex scanning and computed tomography. Non-invasive diagnostics capabilities are enough to determine the aneurysm size, its relation to the renal arteries, as well as to find out the state of visceral branches and aortic bifurcation. Abdominal aortography is indicated in patients with concomitant arterial hypertension to identify the state of the renal arteries.
3. Significant risk factors in these patients are ischaemic heart disease (44.1%), arterial hypertension (49%), haemostasis disorders (almost 100%).
4. The leading concomitant disease in the development of postoperative complications is ischaemic heart disease. Its share in abdominal aortic aneurysms is 40%. Postoperative cardiac complications reach 14.9%. Diagnostics of ischaemic heart disease should be based on the stage-by-stage detection of coronary lesions and its functional-compensatory abilities.
5. The main complications of the postoperative period after ABA resections are acute heart failure (14,9%), cerebral circulatory disorders (1,5%), acute renal failure (3,33%).
6. When significant coronary vascular channel lesions are detected in patients with ABA, it is fundamental to solve the issue of intervention staging. At 3-4 functional classes of circulatory insufficiency, appearance of new zones of hypo- or akinesia, decrease of ejection fraction below 40%, the first stage should be myocardial revascularisation surgery
7. In patients with combined lesions of brachiocephalic vessels in patients with ABA it is reasonable to assess the cerebral blood flow. In the presence of 70% or more stenosis of VCA, presence of embologenic plaque, bilateral haemodynamically significant stenosis it is necessary to perform carotid artery intervention as the first stage.
8. One of the most difficult problems of reconstructive operations in ABA is the contiguous lesion of renal and visceral branches of the abdominal aorta. The principle is their one-stage reconstruction. The types of reconstruction of these branches should be variable depending on the volume and extent of the pathological process.
9. Patients with aneurysmal lesion of abdominal aorta initially always have significant disorders of haemostasis system. In 30% of patients with occlusive diseases of aorta and its branches in the preoperative period the activity of thrombocytic-vascular link of hemostasis is increased, antithrombotic ability of vascular wall endothelium is decreased and blood rheological properties are disturbed. Activation of fibrinolysis was noted in patients with aneurysmal lesion of abdominal aorta.
10. During the operation for abdominal aortic aneurysmal lesion, after starting the blood flow the level of plasminogen increases additionally by 30%, which is a risk factor for haemorrhagic complications in the perioperative period. On the 1-3 day after the operation there is a significant decrease of blood anticoagulant potential - antithrombin-Sh by 25-27%, protein C by 23-25%. This period is the most dangerous in terms of thrombohemorrhagic complications development.
11. When using standard heparin during the operation there is a consumption of antithrombin-Sh by 30-45% and increase of platelet aggregation by 10%, which is a threatening condition for the occurrence of thrombosis of deep veins of the lower extremities with subsequent TELA. When using fraxiparin during reconstructive vascular surgeries the consumption of antithrombin-Sh and increase in platelet aggregation do not occur, prothrombin time, activated partial thromboplastin time, thrombin time are lengthened insignificantly that testifies to expediency of its use for prevention of thrombohemorrhagic complications.
12. Application of the diagnostic methods proposed by us to detect the main risk factors during the operation and in the nearest postoperative period, use of the algorithm of stage and volume of intervention allowed to reduce significantly the number of threatening complications, thus the lethality decreased 4 times, and the number of non-fatal complications - 4 times non-fatal complications - 1.5 times.
Effect of dihydroatizin (5–250 μmol / L) on the contractile activity of rat smooth aorta muscle cells (SMC). Isometric tensile forces were recorded. Using a force transducer FT - 03 (Grass Instrument Co., USA). In it was found by experiments that the vasodilating effect of dihydroatizin mainly associated with the blockade of the Ca2 + L-channel.
Methods-Preparation of the aortic vessel muscle preparation, and recording the force of contraction.
Results- KCI-induced contraction of the aortic MMC is associated with the activation of potential–dependent Ca2+L channels of the plasma membranes of the MMC
Conclusions- The data obtained as a result of studying the mechanisms of action of the alkaloid dihydroathysine are of great practical importance and can be recommended for optimizing the process of purposeful creation of a new generation of vasorelaxant drugs.
Abstract: In this research, the results of the effects of vincamine hydrochloride and pyrozalin iodide alkaloids on the relaxation of aortic smooth muscle cells in the presence of Ca2+ L-channels have been reported. The isometric contraction activity of the aortic blood vessel smooth muscle derived from rabbits was studied using mechanography. The results, under in vitro conditions, demonstrated that the contraction activity of the rabbit aortic blood vessel smooth muscle preparation induced by 50 mM KCl was dependent on the potential of the plasma membrane, associated with the activity of the Ca2*L-channels. It was found that vincamine and pyrozalin iodide alkaloids affected the blockage of the Ca2+i-channels and a reduction in [Ca2*] concentration. The obtained results suggest that the relaxing effect of vincamine hydrochloride and pyrozalin iodide alkaloids is based on the blockage of the L-type Ca2+ channels, and they also affect the receptor-operated Ca2+ channels. In conclusion, the results indicate that in providing the relaxing effect of vincamine and pyrozalin iodide alkaloids, the blockage of potential-dependent L-type Ca2t channels, along with the blockage of receptor-operated Ca2+ channels plays an important role.
The manuscript shows a short data used using fluorescent probes to study the effect of polyphenol PС-7 on changes in the dynamics of intracellular Ca2+ content in rat brain synaptosomes, depending on the site of glutamate binding on calcium channels by a specific mediator with glutamate. To measure the amount of cytosolic Ca2+ synaptosomes, we calculated using the Grinkevich equation. It has been shown that polyphenol PС-7 binds to the β1-subunit of the voltage-gated calcium channel and allosterically changes its conformation so that the conductivity for Ca2+ ions increases through the channel, the blocking effect of polyphenol PС-7 can be explained by its binding to voltage-gated calcium channels and activating them.
The article studies a capillary electrophoretic (CE) method for the analysis of urinary extracts of the local anesthetic, bupivacaine, and its three main metabolites, desbutylbupi vacaine, 3’ hydroxybupivacaine, and 4’-hydroxybupivacaine, in rat urine. After collection of blank urine, the rats were given a 20 mg/kg intramuscular injection of bupivacaine, and urine was collected for 12 h after dosing. CE analyses were performed using the CAPEL®-205 capillary electrophoresis systems. The data was collected using the Elforan® specialized software. The use of methanol to reduce peak tailing was investigated at different concentrations, but 20% and 30% v/v were proved to be the most optimal at the preparatory stage of the experiment. The resolution of 3’ hydroxybupivacaine and 4’-hydroxybupivacaine was 1.09, 0.98, 0.89 and 0.89 at 15, 40, 70 and 110 s, respectively. The initial resolution (Rs) of desbutylbupi vacaine was achieved with all studied injection periods as Rs = 1.09, 0.97, 0.96 and 0.96 at 15, 40, 70 and 110 s, respectively. Separation efficiencies for 3’- and 4’ hydroxybupivacaine were312×10 3 , 257×10 3 , 196×10 3 и 169×10 3 μlat injection times of15, 40, 70 and 110 s, respectively. The results showed that the mass of bupivacaine, desbutylbupi vacaine, and 3’- and 4’ hydroxybupivacaine significantly recovered in the rat urine after the dose was administered. The recoveries as a percent of the dose were 0.04, 0.80, 0.15 and 0.05% for desbutylbupi vacaine, bupivacaine, 3’-hydroxybupivacaine, and 4’-hydroxybupivacaine, respectively. Separation of bupivacaine and its metabolites was achieved in 15 min. A particular advantage of this approach over published HPLC methods is that separation of the two hydroxy positional isomers of bupivacaine is possible. A number of unknown peaks were also observed in the electropherograms from the rats dosed with bupivacaine. These did not correspond to any peaks appearing in the blank urine samples. Characterization of these unknown peaks may prove useful for the further understanding of bupivacaine metabolism.
The present study aimed to assess the hepatic effects of the alcoholic extract of Citrullus colocynthis on rat livers and perform antibacterial screening of the plant. The alcoholic extract of Citrullus colocynthis was prepared using standard extraction techniques. Male rats were orally administered varying doses of the extract, and liver function parameters including serum liver enzymes (alanine transaminase, aspartate transaminase), total bilirubin, and histopathological changes were evaluated. Furthermore, the extract was subjected to antibacterial screening against selected bacterial strains using well diffusion and minimum inhibitory concentration (MIC) methods. The results indicated a dose-dependent increase in liver enzymes and total bilirubin levels, suggesting hepatotoxic effects of the extract. Histopathological examination revealed severe hepatocellular damage, including necrosis and inflammation, in the liver tissues of rats treated with high doses of the extract. In terms of antibacterial activity, the extract showed significant inhibitory effects against tested bacterial strains, including both Gram-positive and Gram-negative bacteria. These findings highlight the hepatotoxic potential of the alcoholic extract of Citrullus colocynthis and its promising antibacterial properties, warranting further investigation for the identification of active compounds and their potential therapeutic applications.
Aim of the work: assessment of laboratory characteristics in patients with type 2 diabetes, depending on the risk of developing CI-AKI.
Materials and methods: The study included 56 patients with type 2 diabetes, the average age of the patients was 58 years, the CG consisted of 20 healthy volunteers. In most patients, the reason for which the endovascular radiopaque procedure (EVRCP) was performed was associated with atherosclerotic lesions: coronary artery disease, chronic lower limb ischemia (CLLI), atherosclerosis of the brachiocephalic arteries (BCA). EVRCP was performed on the vessels of the coronary basin, BCA, abdominal aorta and its branches, lower extremities. A retrospective analysis included a comparative analysis of two groups of patients with type 2 diabetes who underwent EVRCP: 29 patients who developed CI-AKI (CI-AKI+ group) and 27 patients in whom the post-procedure period was uneventful.
Results: The CI-AKI+ and CI-AKI- groups did not differ in nosological distribution: in both groups, half of the patients with EVRCP were performed due to the presence of coronary pathology (51.72% and 48.15%, respectively), the rest in patients it was comparable for CCI and CVD (27.59% and 20.69% in the CI-AKI+ group and 25.93% each in the CI-AKI- group).
Conclusion: Thus, based on the results of this study, it was possible to identify risk factors for the development of CI-AKI in patients with DM in the post-procedure period and to develop a scale that allows identifying DM patients predisposed to the development of CI-AKI as a hospital complication of endovascular interventional procedures, which is especially often observed in patients with DM.
This article discusses the issues of early diagnosis of non-specific aortoarteritis are not generally accepted and therefore remain relevant. Takayasu syndrome (non-specific aortoarteritis) is an autoimmune inflammatory disease that affects the aorta and its branches, belongs to the group of systemic vasculitis, is characterized by the development of productive inflammation in the wall of large arteries leading to their obliteration, there is no pulsation due to frequent cases of loss of pulse in the upper extremities. The course of the disease is progressive with periodic exacerbations and deterioration of blood circulation in ischemic organs, as well as an unfavorable prognosis. Modern data on the etiology, pathogenesis, and clinical picture of Takayasu syndrome are presented. An important role in the diagnosis of non-specific aortoarteritis is played by computer and magnetic resonance imaging, as well as ultrasound examination of vessels that can detect typical signs of stenosis or aneurysm of the arteries. Treatment of the disease with the use of drugs aimed at suppressing the activity Of b cells of the immune system, as well as with the use of an IL-6 receptor inhibitor, is discussed. In order to attract the attention of General practitioners to a rare rheumatological problem – Takayasu aortoarteritis – the results of their own observations are presented. The clinical picture of the disease in a child is described.
Тиреоидным гормонам принадлежит ведущая роль в обмене веществ, вследствие выраженного регулирующего влияния их на основные его функции . По нашим и литературным данным установлено, что тиреоидные гормоны секретируются в грудное молоко женщин и могут оказывать определённое воздействие на развивающийся организм новорождённых. В то же время, до настоящего времени в этом вопросе, нет окончательного мнения
In this paper, the activity of lactobacilli in the small intestine and lactobacilli in the colon, which are involved in the digestion of milk sugar during lactotrophy using phenylhydrazine hydrochloride, studied the effects of toxic anemia on mother and child.
Erythrocyte counts, hemoglobin levels, lactase enzyme activity in the small intestine, and lactobacilli activity in the colon were determined in 12- and 24-day-old rats born to mother anemic rats with toxic anemia under the influence of phenylhydrazine hydrochloride, and in growing rats after mother and offspring toxic anemia.
Experiments in white rats have shown that in rats growing in experimental toxic anemia of mother and offspring, there is an increase in lactase activity in the small intestine and a decrease in lactobacilli activity depending on the degree of intoxication in the colon.
Protein substances form the basis of all vital cell structures; they are a part of the cytoplasm and are the basis of all living things. The protein synthesis is a complex and multistage process. It is performed in special organelles called ribosomes. Violation of synthesis is possible at all the three stages: replication, transcription and translation. In medical practice, medicinal substances are used that can stimulate protein synthesis in the body.