Endogenous Cardiotonics: Search And Problems

2021 ◽  
Vol 21 ◽  
Author(s):  
Arkady R. Kolpakov ◽  
Roman A. Knyazev
Keyword(s):  
Beta Blockers ◽  
Oxygen Demand ◽  
Current Data ◽  
The Body ◽  
Cardiotonic Activity ◽  
Chronic Cardiac Failure ◽  
Heart Performance ◽  
Term Administration ◽  
Dependent Mechanism

: Medicinal preparations currently used for the treatment of patients with chronic cardiac failure involve those that reduce the heart load (vasodilators, diuretics, beta-blockers, and angiotensin-converting enzyme (ACE) inhibitors). Cardiotonic drugs with the cAMP-dependent mechanism are unsuitable for long-term administration due to the intensification of metabolic processes and an increase in the oxygen demand of the myocardium and all tissues of the body. For many years, digoxin has remained the only preparation enhancing the efficiency of myocardial performance. The detection of digoxin and ouabain in intact animals has initiated a search for other compounds with cardiotonic activity. The review summarizes current data on the effect exerted on the heart performance by endogenous compounds, from simple, such as NO and CO, to steroids, fatty acids, polypeptides, and proteins. Controversial questions and problems with the introduction of scientific achievements into clinical practice are discussed. The results obtained by the authors and their colleagues after many years of studies on the cardiotropic properties of serum lipoproteins are also reported. The experimentally established cardiotonic activity of apoprotein A-1, which is accompanied by a decrease in the relative consumption of oxygen, maybe of great interest.

STUDIES IN THE SUPPOSED GOITROGENOUS EFFECT OF TAP WATER IN HELSINKI

1960 ◽  
Vol XXXIII (IV) ◽  
pp. 630-636
Author(s):  
F.-E. Krusius ◽  
P. Peltola
Keyword(s):  
Tap Water ◽  
Physiological Saline ◽  
Normal Weight ◽  
The Body ◽  
Iodine Uptake ◽  
Redistilled Water ◽  
Detectable Difference ◽  
Term Administration ◽  
Long Term Experiment

ABSTRACT The study reported here was performed in order to examine the tap water of Helsinki for its alleged goitrogenous effect. In a short-term, 24-hour experiment with rats, kept on an iodine-poor diet, we noticed no inhibition of the 4-hour 131I uptake, as compared with that of animals receiving physiological saline instead of tap water. Two similar groups of rats receiving 1 and 2 mg of mercazole in redistilled water showed a distinct blockage of the 4-hour uptake, which proved the effect of this substance. In a long-term experiment of 5 weeks' duration there was no detectable difference in the body weight, thyroid weight and the 4-hour 131I uptake when the rats receiving tap water or distilled water to which 0.45 per cent of sodium chloride was added were compared with each other. Replacement of tap water by a 10 mg per cent solution of mercazole in redistilled water enlarged the thyroid to double its normal weight and increased the 131I uptake to approximately five times that of the controls. Thus our experiments failed to demonstrate any goitrogenous effect in the tap water of Helsinki. Changes similar to those produced by a long-term administration of mercazole, i. e. an enlargement of the thyroid and an increased thyroidal iodine uptake, have been shown to be due to milk collected from goitrous areas. The observations here reported confirm the importance of milk in the genesis of the goitre endemia of Helsinki. Attention is further called to the fact that a thyroidal enlargement combined with an increased thyroidal iodine uptake cannot always be taken as a sign of iodine deficiency because similar changes may be produced by the administration of goitrogens.

scholarly journals GENERALIZED ARGINIA

2018 ◽  
Vol 21 (2) ◽  
pp. 101-105
Author(s):  
Alexander B. Krivosheev ◽  
L. A Khvan ◽  
D. N Bobokhidze ◽  
I. A Krivosheeva ◽  
D. V Morozov ◽  
...  
Keyword(s):  
Food Supplement ◽  
The Body ◽  
Review Of Literature ◽  
Internal Organs ◽  
Skin Hyperpigmentation ◽  
Comprehensive Examination ◽  
Term Administration ◽  
Inflammatory Drugs ◽  
The Moment

A brief review of literature on the problem of argyria is presented. Hyperpigmentation of the skin in 10-20% of cases has an iatrogenic cause. Hyperpigmentation of the skin can form on the background of taking non-steroidal anti-inflammatory drugs, amiodarone, cytostatics, antimalarials, etc. Systemic deposition of silver in various organs and tissues is known as generalized argyria. The disease is caused by the prolonged use of compounds containing silver (lapis pencil, silver nitrate, etc.). Clinically, generalized arginia is characterized by the gradual appearance of ashy-bluish coloration of the skin of open areas of the body (face, neck) and nail plates of the phalanges of the hands. The period from the moment of the beginning of reception of preparations of silver and before occurrence of the first dermatological changes varies on the average from 1 year to 5 years. Generalized argiria is a rare disease. This is due to the limited use of silver drugs in clinical practice, as well as the improvement of technological processes in pharmacological production. The patient’s own observation with generalized arginia formed against the background of the long-term administration of the drug Argovit-S, whose silver content is 0.75-0.85 mg/ml, is analyzed. The patient took the drug alone as a food supplement for 25 years. The diagnosis of generalized arginia is verified clinically, but is confirmed necessarily in the course of histological examination. It is shown that argyria is not only the iatrogenic cause of skin hyperpigmentation, but a serious risk factor for the manifestation and progression of liver cirrhosis. Patients with generalized arginia should undergo a comprehensive examination in order to verify the serious pathology of internal organs.

scholarly journals Comparative efficacy and safety of chimeric and recombinant anti-TNF-α mAbs

2021 ◽  
pp. 124-133
Author(s):  
V. N. Drozdov ◽  
E. V. Shikh ◽  
A. A. Astapovskiy ◽  
S. Yu. Serebrova ◽  
A. K. Starodubtsev
Keyword(s):  
Human Monoclonal Antibody ◽  
Current Data ◽  
The Body ◽  
Biological Processes ◽  
Chimeric Antibodies ◽  
Tnf Α ◽  
Monocytes And Macrophages ◽  
Homeostatic Function ◽  
Efficacy Profile

TNF-α has been known since 1985. It is a multifunctional proinflammatory cytokine, synthesized mainly by monocytes and macrophages. Since its discovery, many studies have been conducted that have proven that it provides homeostatic function and regulates many biological processes in the body. Violation of its regulation in humans is associated with the development of many autoimmune diseases. The intensive studies that led to the understanding of its polyfunctionality and its role in the immunopathogenesis of a number of diseases served as the basis for the development of anti-cytokine therapy with monoclonal antibodies. In 1975, a technique for producing such antibodies was developed. The first antibodies against TNF-α obtained were chimeric, consisting of 30% mouse protein. Because of this feature, drugs based on chimeric antibodies had immunogenicity, which was manifested in the formation of antibodies to the drug, which led to a decrease in their effectiveness. To reduce immunogenicity, scientists in 1990 created the first fully human monoclonal antibody based on a technology called phage display. This is how adalimumab was born, the  first fully human multi-clonal antibody to TNF-α. Humira®  (adalimumab) is currently considered a widely studied drug from the group of TNF-α inhibitors, with a good safety and efficacy profile. The article presents current data that demonstrate that the drug significantly improves the course of diseases such as rheumatoid and psoriatic arthritis, and will allow for long-term remission in Crohn’s disease. 

EFFECTS OF LONG TERM ADMINISTRATION OF GLUCAGON ON THE PANCREATIC ISLET TISSUE OF RATS AND GUINEA-PIGS

1963 ◽  
Vol 44 (1) ◽  
pp. 139-149 ◽  
Author(s):  
Birger Petersson ◽  
Bo Hellman
Keyword(s):  
Guinea Pigs ◽  
Cell Number ◽  
Dark Field ◽  
The Body ◽  
Initial Increase ◽  
Adult Age ◽  
Number Ratio ◽  
Islet Volume ◽  
Term Administration

ABSTRACT Rats and guinea-pigs were injected every eight hours with crystalline glucagon (0.3–0.6 mg/kg) and killed after different periods of treatment up to 30 days. Immature animals (glucagon treatment commenced on the second postnatal day) were also included among the rats investigated. While the immature glucagon treated rats grew almost as well as their litter mate controls, there was a marked reduction of the body and adrenal weights, when the injections were started at a more adult age. In the latter rats the total islet volume was significantly reduced and the A1/A2 cell number ratio increased from 0.24 ± 0.02 to 0.32 ± 0.02. In the guinea-pigs the glucagon treatment resulted in a considerable decrease in both the body and pancreatic weights. These changes were associated with a significant increase in the relative amount of the endocrine pancreas, the total islet volume being unchanged. While the A1 cells appeared unaffected by the glucagon treatment, the A2 cells were markedly atrophied. After an apparent initial increase there was a subsequent progressive diminution of the silvery-white dark field granulation of the A2 cells during the glucagon treatment. The postcoupled benzylidene reaction for tryptophane also decreased and became insignificant in guineapigs injected with glucagon for a long period. In the latter animals the percentage of A2 cells was only 3.4 ± 0.2 as compared with 24.4 ± 1.3 for the controls. As a consequence of this, the A1/A2 cell number ratio was about 6 times as high in the glucagon treated guinea-pigs. The data obtained for the longer term adaptation of the islets of Langerhans to the administration of glucagon support the concept that this hormone is secreted by the silver-negative A2 cells.

scholarly journals Evaluation of γ-oryzanol Accumulation and Lipid Metabolism in the Body of Mice Following Long-Term Administration of γ-oryzanol

Nutrients ◽  
2019 ◽  
Vol 11 (1) ◽  
pp. 104 ◽  
Author(s):  
Eri Kobayashi ◽  
Junya Ito ◽  
Naoki Shimizu ◽  
Takumi Kokumai ◽  
Shunji Kato ◽  
...  
Keyword(s):  
Lipid Metabolism ◽  
Plasma Lipids ◽  
Rice Bran Oil ◽  
The Body ◽  
Biologically Active ◽  
Lipid Lowering ◽  
Single Oral Administration ◽  
Term Administration

γ-Oryzanol (OZ), abundant in rice bran oil, has gained attention due to its physiological activities (e.g., lipid-lowering effects). However, the absorption and metabolism of orally ingested OZ have not yet been fully elucidated. In this study, diets containing normal or high contents of OZ were fed to obesity model mice for 8 weeks, and OZ concentrations in plasma and organs were analyzed by HPLC-MS/MS. To evaluate the relationship between OZ accumulation and lipid metabolism in vivo, lipid concentrations in the mice plasma and liver were also measured. As a result, the accumulation of intact OZ in plasma and organs was seen in mice fed diets containing OZ, where mice fed diets containing higher OZ contents demonstrated higher levels of OZ accumulation and lower amounts of plasma lipids. These results, in combination with our additional data from a single oral administration test, suggest the possibility that intact OZ, along with its metabolites (e.g., ferulic acid), is biologically-active.

scholarly journals EFFECTS OF LONG TERM ADMINISTRATION OF GENTAMICIN ON CLINICO-PATHOLOGICAL PARAMETERS IN SWISS ALBINO MICE

2012 ◽  
Vol 3 (1) ◽  
pp. 87-91 ◽  
Author(s):  
MAQ Miah ◽  
MA Awal ◽  
MM Rahman ◽  
MS Islam
Keyword(s):  
Clinical Signs ◽  
The Body ◽  
Recommended Dose ◽  
Coagulation Necrosis ◽  
Histopathological Study ◽  
Swiss Albino Mice ◽  
Term Administration ◽  
Albino Mice ◽  
Kg Medium

The effects of long-term intramuscular injection of gentamicin (Gentin® inj., Opsonin, Bangladesh Ltd.) were studied clinicopathologically on twenty 60 day-old Swiss Albino mice of either sex for 42 days during January to March 2002. All the mice were grouped into four, each consisting of one male and four female mice, of which one group (group A) served as control without giving any treatment while groups B, C and D received recommended (50 mg / kg), medium (75 mg / kg) and double the recommended (100 mg / kg) doses of gentamicin intramuscularly daily for 42 days. All the treated mice produced mild to severe clinical signs, i.e., roughness of the body coat, dullness, depression, anorexia and weakness. At recommended and medium doses the offspring were apparently normal but at double the recommended dose, 10% offspring were died and others were weak and emaciated. No significant gross change was found in lungs, spleen and heart of all the treated groups but the kidney was found soft, flabby and enlarged and the heart was found darker, congested with necrotic foci on the surface. Histopathological changes showed chronic interstitial nephritis in groups B and C following recommended (50 mg / kg) and medium (75 mg / kg) doses while severe glomerulonephritis was observed following double the recommended dose (100 mg / kg) of gentamicin. In liver, histopathological study showed coagulation necrosis following recommended dose, whereas, karyorrhoexis and tissue regeneration were found following medium and double the recommended doses. In lungs, haemorrhage and thickening of interstitial tissues were observed following double the recommended dose of gentamicin in mice. Thus long term administration of higher dose of gentamicin is detrimental to the vital organs.

5. Blood pressure and blood flow

2016 ◽  
pp. 83-102
Author(s):  
Chris Cooper
Keyword(s):  
Blood Pressure ◽  
Blood Flow ◽  
Driving Force ◽  
Beta Blockers ◽  
Venous Blood ◽  
The Body ◽  
Chronic Hypertension ◽  
Arterial Blood ◽  
Lifestyle Choices

The heart is the organ that pumps blood around the body. If the heart stops functioning, blood does not flow. The driving force for this flow is the pressure difference between the arterial blood leaving the heart and the returning venous blood. ‘Blood pressure and blood flow’ first considers how blood pressure is measured and how blood pressure can affect health. High blood pressure is called hypertension and low blood pressure hypotension. Chronic hypertension has serious long-term adverse health consequences, but can be treated with improved lifestyle choices and a range of medicines, including anti-hypertensive drugs, beta blockers, and ACE inhibitor drugs. The different molecules affecting blood flow are also considered.

scholarly journals EFFECT OF DICLOFENAС SODIUM ON MECHANISMS OF DIFFERENTIATION OF BONE MARROW CELLS AND PERIPHERAL BLOOD: A LITERATURE REVIEW

2018 ◽  
Vol 22 (5-6) ◽  
pp. 22-24
Author(s):  
Yu. Bahmut ◽  
O. S. Ivanov ◽  
G. V. Tsapko
Keyword(s):  
Bone Marrow ◽  
Toxic Effect ◽  
Bone Marrow Cells ◽  
Diclofenac Sodium ◽  
The Body ◽  
New Drugs ◽  
Term Administration ◽  
Long Time ◽  
Marrow Cells

The hematopoietic system is a population of many cells that perform certain functions in the body. The pharmaceutical industry creates new drugs from the group of nonsteroidal anti-inflammatory drugs, but the “gold” standard remains the drug Diclofenac Sodium. In some conditions, a person is forced to take the drug for a long time, and sometimes all life. The mechanism of the drug effect on the bone marrow cells under the condition of long-term administration remains unclear. In the process of analyzing the literature, it has been established that the use of the drug has a toxic effect on the blood cells and blood-forming organs. Gradually, the toxic effect is reduced, but the long-term effect of the drug on the rat organism contributes to the inhibition of the development of erythrocyte and myelocytic sprouts of the bone marrow. A period of up to 10 days is optimal for use, and then it is worthwhile to look for a drug that is safer for the body.

The efficacy and safety of long-term administration of alpha-interferon and lamivudine in patients with chronic hepatitits B

2001 ◽  
Vol 120 (5) ◽  
pp. A572-A572
Author(s):  
F JABOLI ◽  
E RODA ◽  
C FABBRI ◽  
S MARCHETTO ◽  
F FERRARA ◽  
...  
Keyword(s):  
Alpha Interferon ◽  
Efficacy And Safety ◽  
Term Administration
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