Method of treating experimental myocardial infraction in rats
SUBSTANCE: modelling a myocardial infraction is followed in a rat is followed by intravenous introduction of the immune corrector tamerite 3 mg/kg. The preparation is injected daily for seven days. The histological results of the myocardial tissue presented after the first, third and seventh days show the sufficiency and efficacy of the therapy.
EFFECT: effective therapy of the acute myocardial infraction with high possibility of cure ensured by reduced manifestations of systemic inflammation response syndrome, faster granulation tissue formation and necrotic zone replacement by cicatricial tissue.
The invention relates to experimental medicine for the treatment of experimental myocardial infarction in rats by medical intervention to monitor the effectiveness of the latter.
Myocardial infarction is one of the most frequent forms of diseases and is 3.9% among males and 2.2% among women, which puts it on one of the first places in the world. In Russia from myocardial infarction die 330 men and 154 women per 100 thousand population, which is 3.2 times more than in the US. These circumstances indicate a high relevance of the problem to THEM, in particular his treatment.
The Recommendations of the working group of the European society of Cardiology (2000) and based on them the Russian Recommendations (2001), the treatment of the developed myocardial infarction is based on the use of beta-blockers, nitrates, calcium antagonists and antiplatelet agents (aspirin, thienopyridine, antagonists of glycoprotein IIb/IIIa receptors on platelets). Despite the large number of different surgical and conservative methods of treatment mortality in acute myocardial infarction continues to be high: early complications lead to 10-15% of hospital mortality.
The main causes of death is heart failure and arrhythmias and conduction, subject to the first value of developing myocardial infarction and progressive involvement in the process of intact cells of the myocardium. High mortality dictates the need to develop new treatments for this debilitating disease that would prevent the development or reduced the severity of these complications of myocardial infarction.
Modeling of acute myocardial infarction in rats, in our opinion, is the most reasonable, because these laboratory animals are similar to humans during physiological and pathological processes, which allows to use the results of animal studies to develop new methods of treatment of this disease in humans.
Known for the treatment of myocardial infarction drug atenolol, which has a complex mechanism of action: blocks beta-1-adrenergic receptors, which decreases the stimulating effect on the heart sympathetic innervation and circulating in the blood catecholamines, has antianginal, hypotensive and antiarrhythmic effect.
Introduction: a basic introduction is given intravenously in a dose of 5 mg, after 5 minutes, another 5 mg, then after an hour it starts taking the drug inside of 50-100 mg per day.
Disadvantage: the drug is contraindicated in bronchial obstructive syndrome, syndrome, sick sinus, AV-blockade and congestive heart failure; reliable performance in ischemia of repeated heart attacks and reducing mortality prospect who is only in long-term care (about 2 years).
1. "Selected topics in internal medicine", Ekaterinburg, 2007. Volume 4, p.101-172.
2. Drugs in Russia: a Handbook. M: Attraversare, 2003, p.3-1104. Str-188.
Known drug acetylsalicylic acid, which is included in international and national recommendations for the treatment of myocardial infarction PROTOTYPE.
Acetylsalicylic acid inhibits the activity of COX - the main enzyme of arachidonic acid metabolism, which is a precursor of prostaglandins, which provides anti-inflammatory, analgesic and antipyretic effects, and inhibits formation of THE, thereby inhibiting platelet aggregation.
Its positive side: with long-term use (at least 2 years) reduces the frequency of repeated heart attacks.
Negative sides: the drug is contraindicated in peptic ulcers, local bleeding, hemorrhagic diathesis; 40% of patients do not manifest antiaggregatory effect, considered to be the basic element protivoinfektsionnogo of action of the drug.
3. "Selected topics in internal medicine", Ekaterinburg, 2007. Volume 4, p.101-172.
4. Drugs in Russia: a Handbook. M: Attraversare, 2003, p.3-1104.
An object of the invention is to increase the effectiveness of treatment of myocardial infarction more what ereatest cure.
To solve this problem is proposed a method of treatment of experimental myocardial infarction in rats after simulation-based medical intervention, characterized in that after creating a model of myocardial infarction perform intravenous immunocorrector Tamarit in the dosage of 3 mg/kg every day for seven days with histological studies of myocardial tissue after the first, third and seventh days, and the results of these studies are judged on the adequacy and effectiveness of the treatment.
The treatment is as follows.
Is intravenous connection tamerica after creating a model of myocardial infarction with subsequent study of indicators of cytolytic syndrome - transaminase and histological examination of tissue infarction within 7 days.
Drug Tamarit belongs to the class of immunomodulators. The action of these substances differs from that currently used in medical practice drugs.
Influencing the nature of the acute inflammatory reaction (reducing intake of neutrophilic leukocytes that produce factors that stimulate inflammation Tamarit in the dosage of 3 mg/kg corrects for the acute phase of the syndrome of systemic inflammatory response, which leads to a decrease in the expression of the leukocyte is nuclear biological chemical (NBC reactions stimulates migration immunocompetent cells - lymphocytes, plasma cells, mast cells, macrophages in the necrotic foci, accelerates the formation of granulation tissue with proliferation of fibroblastic cells number and calls the substitution necrosis scar tissue, represented by the active fibroblasts and fibrous structures, without the effects of purulent inflammation of scar tissue.
Traced the action of tamerica during acute phase of experimental myocardial infarction in 50 cases.
The experimental results.
On the first day of myocardial infarction without the introduction of the drug was observed pronounced dystrophic reaction with stromal edema, loss of transverse and longitudinal iscertainly myofibrils, and in the future - grained and glycated decay.
Areas adjacent to the area of infarction, were subject to significant changes and expressed partial atrophy of myocardiocytes and structural changes similar to those in the zone of necrosis, until dystrophic and necrobiotic changes in individual muscle fibers and their groups, lokalizovalsya in the wall of the left ventricle Area of the heart (in most cases transmural) was represented by cardiomyocytes events karyolysis, plasmolysis and plasmolysis. Showed moderate diffuse infiltration, Prime is asih structures observed phenomena edema, the plethora of vessels, Indonesia with the formation of the sludge systems.
On the first day of myocardial infarction with drug Area of infarction localized subepicardial on the lateral wall of the left and right ventricles. Presents necrotic modified cardiomyocytes with the phenomena of plasmolysis and plasmolysis. In the border zone vessels diperkirakan. Migration of polymorphonuclear leukocytes was not found. Demarcation shaft is not formed. Saved infarction remains moderate swelling.
On the fifth day of myocardial infarction without injection area of infarction was defined as mainly transmural. The necrotic cardiomyocytes were surrounded demarcation shaft, showed signs of formation of granulation tissue, fibroblasts appear, emocapella. In adjacent structures were detected distribution of infiltration on Indonesia
On the fifth day of myocardial infarction with drug Area of infarction presents a deathly modified cardiomyocytes with the phenomena of plasmolysis, plasmolysis and karyolysis. Infarction zone defined sanguineous capillaries sinusoidal type. On the periphery of the perifocal region detected accumulations of lymphocytes and macrophages. There is a proliferation of fibroblasts, i.e. elements of granulation the Noah fabric. In areas adjacent to the infarction area in the myocardium remains moderate edema and plethora of vessels Indonesia. Polymorphonuclear leukocytes in the demarcation lines are not defined. On the lateral wall of the right ventricle cardiomyocytes is not damaged, but the vessels Indonesia full-blooded, gleams them expanded.
On the seventh day of myocardial infarction without injection area of necrosis in the wall of the left ventricle in 100% of cases were characterized as transmural. Histological signs of stage (formation of granulation tissue at the edges of the zone of necrosis with a large number of fibroblasts and macrophages, sinusoidal emocapella, substitute the affected area) when the continuing disintegration of muscle cells and the continuing infiltration of the myocardium by lymphocyte and segmented by leukocytes. In some cases the vessels was determined by the boundary distance of cells with signs of leukodepleted.
On the seventh day of myocardial infarction with drug area of infarction localized subepicardial on the lateral wall of the left ventricle. Presented by granulation tissue of proliferating fibroblasts and macrophages. Determined capillaries and vessels sine wave type with a well-formed vascular wall, which is composed of endothelium and basement membrane in the wall of the vessel entrance is t smooth muscle cells. In the area of the scar is determined moderate lymphocytic infiltration and macrophages in moderation. On the lateral wall of the right ventricle cardiomyocytes is not damaged, but the vessels Indonesia full-blooded, gleams them expanded.
Treatment of experimental myocardial infarction in rats after simulation-based medical intervention, characterized in that after creating a model of myocardial infarction perform intravenous immunocorrector Tamarit in the dosage of 3 mg/kg every day for seven days with histological studies of myocardial tissue after the first, third and seventh days, and the results of these studies are judged on the adequacy and effectiveness of the treatment.
SUBSTANCE: hypoestrogen-induced endothelial dysfunction correction in white female Wistar rats, hypoestrogen-induced endothelial dysfunction is simulated by bilateral ovariectomy. The dysfunction correction is ensured by daily intragastric introduction of lozartan 6 mg/kg and daily introduction of mixed solutions of homoeopathic dilutions of polyclonal rabbit C12, C30, C200 antibodies to human endothelial nitrogen oxide synthase once a day added to drinking bowls.
EFFECT: method provides effective correction with reducing an endothelial dysfunction coefficient in females to the level observed in intact animals ensured by the effect on various developmental mechanisms of this dysfunction in hypoestrogenic conditions.
1 ex, 2 tbl
SUBSTANCE: reservatrol efficacy is studied in female Wistar rats with simulated osteoporosis by bilateral ovariectomy. For osteoporosis correction, reservatrol is administered in animal intraperitoneally for eight weeks after ovariectomy daily once a day in single dose 2 mg/kg. Osteoprotective action of reservatrol is estimated by a bone tissue microcirculation level and width of trabeculas of bone.
EFFECT: improved blood circulation and microarchitectonics of bone tissue in hypoestrogenic condition.
1 tbl, 1 ex
SUBSTANCE: efficacy is studied in female Wistar rats. Osteoporosis is simulated by bilateral ovariectomy. Osteoporosis is corrected by intraperitoneal introduction of reservatrol 2 mg/kg and intragastric introduction of enalapril 0.5 mg/kg daily once a day for eight weeks after ovariectomy. Osteoprotective action of reservatrol combined with enalapril is estimated by a bone tissue microcirculation level and width of trabeculas of bone.
EFFECT: improved blood circulation and microarchitectonics of bone tissue in hypoestrogen condition.
1 tbl, 2 ex
SUBSTANCE: delimitation of a high-grade glioma invasion is ensured by imaging of an astroglial bank surrounding the high-grade glioma. An immunogenic recombinant human GFAP is prepared and used to immunise a Balb/C mouse; spleen B-lymphocyte of this mouse are recovered and fused with myeloma cells of Sp 2/0-Ag14 mice; hybridomas are produced. Supernatants of the prepared hybridomas are tested by immunochemical techniques for the presence of anti-GFAP antibodies used to select a hybrid cell clone producing the anti-GFAP antibodies able to distinguish GFAP in vivo. The anti-GFAP antibodies are cleaned from the supernatant of the selected clone and covalently bound with liposomal nanocontainers containing a diagnostic mark. The antibodies of the selected hybrid cell clone is modified by g-amino groups of lysine residues and incubated with the stelths-liposome solution. The prepared nanosystem is introduced in a patient's vascular bed, and the astroglial bank is imaged by the arrangement of the diagnostic mark in cerebral tissues.
EFFECT: method allows preventing relapses of high-grade gliomas after their surgical management by choosing an optimal extent of a pending surgery ensured by delimitation of a tumour invasion by means of imaging of the astroglial bank.
6 cl, 4 dwg, 1 ex
SUBSTANCE: originally, epiphysial hip dysplasia is formed in 10-day-old golden hamsters with projection of the joint exposed to local infra-red pulse laser light daily for 20 days. Then, on the following day, simple hip dislocation of an experimental extremity of a hamster is performed by gradual extension of a capsular-ligamentous apparatus of the hip joint. Ventral and dorsal zones of a joint space are subject to mechanical vibrations by a border of a thin metal plate fixed in a stably fixed vibrator. The following parameters are used: joint capsule pressure 1 kg, vibration frequency 100 Hz, amplitude 0.3 mm for 15 minutes to the moment of femoral head exit from an acetabular cavity. Then, the femoral head is displaced manually behind an external surface of the cavity. In 2 days, the hamster is laid on its back, and the experimental hip is gradually taken aside from a vertical plane to a position of an apex of the head of the hip joint in a horizontal plane. The procedure is performed daily for at least 3 times for 7 days.
EFFECT: use of the given invention allows performing sparing simulation of the simple hip dislocation similar to a mechanism of hip dislocation pathogenesis in children that testifies to possibility of the use of this model for studying macro- and microscopic changes in the ends of the bones formed during growth.
5 dwg, 4 ex
SUBSTANCE: in order to develop methods of treating obstructive purulent cholangitis narrowing of general bile duct at 2/3 of lumen is carried out by application of cup. After that, emptying of gallbladder is realised with simultaneous introduction as microbial suspension - suspension of E.Coli strain 303 in dilution 0.95*10^5 CFU/ml on sterile solution of 0.9% sodium chloride, in volume 0.5 ml. Microbial suspension is introduced into lumen of general gall duct above the place of cup application. Said narrowing of general bile duct lumen is supported during entire experiment duration during 10-12 days.
EFFECT: method makes it possible to obtain adequate model of said pathology due to combined influence of factors, which lead to development of morphological and patho- physical malfunctions, most closely reflecting essence of obstructive purulent cholangitis.
SUBSTANCE: invention can be used both for studying mechanisms of development of paroxysmal states with progredient course (epilepsy) and for screening (selection) of novel medications, possessing potential anti-epileptic activity. For this purpose, rats are given fractional injections of convulsant 1.5-pentamethylentetrazole (pentylenetetrazole) with 15 minute interval in dose 10 mg/kg in volume 0.1 ml solution per 100 g of body weight until fist generalised convulsive seizure develops. After that calculated is threshold dose of convulsant reflecting base level of CNS excitability for each animal. When sessions are repeated, dynamics of change of initial dose of pentylenetetrazole is taken into account, interval between sessions of pentylenetetrazole titration can constitute from 24 and more than 168 hours.
EFFECT: method ensures high accuracy of evaluation of change of seizure development threshold due to the fact that expression of modelled progredient state can be changed at any stage of carrying out chronic research without application of special methods of examination.
1 tbl, 2 dwg
SUBSTANCE: in order to correct endothelial dysfunction white male rats of Wistar line have endothelial dysfunctions modelled by intro-peritoneum introduction of N-nitro-L-arginine methyl ether in dose 25 mg/kg daily, for seven days. Degree of dysfunction development is estimated by ratio of indices of endothelium-independent and endothelium-dependent vasodilation. Correction of endothelial dysfunction is carried out by intra-peritoneum introduction of medicine "Etoxydol" in dose 25 mg/kg one time per day, for 7 days in the morning.
EFFECT: correction of endothelial dysfunction by novel derivative of 3-oxypyridine in specially developed for this purpose dose and mode of medication introduction.
2 tbl, 1 ex
SUBSTANCE: to study etiology and pathogenesis of periodontitis, and in order to define tactics of treating periodontitis in case, when evident symptoms of periodontitis exacerbation are absent carried out is modelling of periodontitis on dogs by introduction in gum around neck of upper and lower incisors of ethanol in concentration 65-75% or corticosteroid medication in amount 0.3-0.4 ml per injection.
EFFECT: increase of model credibility of disease, similar in pathomorphological menifestations to periodontitis in humans, reduction of model obtaining terms.
SUBSTANCE: for modelling of syncytial bonds between cells in vitro nervous cells, separated by known methods from ganglions of mollusc Lymnaea stagnalis are fused, after taking off their connective-tissue capsules and glial membranes. Nervous cells are placed in culture medium, centrifuged, left for 2 days.
EFFECT: method makes it possible to model and study mechanisms of multinuclear nervous cells formation and their physiological properties without fusing means and increasing medium temperature.
SUBSTANCE: invention refers to medicine, namely to purulent surgery, and can be used for treating patients with critical ischemia of lower extremities. For this purpose, standard medical therapy is additionally combined with single-step wound layered infiltration of soft tissues by Perftoran at 3 cm from wound edges in dose 10-15 ml if the wound is localised on a feet, and 40-50 ml if the wound is localised on a leg or a hip every second day in amount 8-10 procedures.
EFFECT: method allows reducing length of treatment and managing pain syndrome, accelerating wound cleansing and healing in higher intensity of repair processes ensured by constant maximally effective active Perftoran concentration in the wound zone.
FIELD: medicine, pharmaceutics.
SUBSTANCE: invention refers to chemical-pharmaceutical industry, and concerns creation of a pharmaceutical composition with a wide spectrum of pharmacological activity, namely exhibiting antihypoxic, neuroprotective and antiamnestic activity, and also showing an ergogenic nature. The declared pharmaceutical composition contains semax and choline. The outcome of experiments proves that the offered pharmaceutical composition containing semax and choline, mutually intensifies an effect of each of them.
EFFECT: composition can find application in creation of the new drug preparations exhibiting neuroprotective activity in a combination with antihypoxic and antiamnestic activity and the ergogenic nature and used for treatment of various pathologies of the central nervous system.
12 tbl, 4 dwg
SUBSTANCE: invention refers to a therapeutic and diagnostic agent used in treatment or diagnostics of a cerebral disease caused by a mitochondrial dysfunction, or in a method for prevention within a surgical intervention and an intravascular surgery, and also to a diagnostic technique for cerebral diseases. The therapeutic agent contains an iron compound and δ-aminolevulinic acid or its salt by formula R2R1NCH2COCH2CH2COR3 (1) where each R1 and R2 independently represents hydrogen atom, and R3 represents a hydroxyl group or C1-24 alkoxy group. The diagnostic agent contains 8-aminolevulinic acid or its salt by formula specified above. The diagnostic technique for the cerebral disease caused by mitochondrial dysfunction, involves a stage of introduction of the specified diagnostic agent followed by a stage of exposure of a diagnosed brain region to light, capable to excite protoporphyrin IX, accompanied by emission of red light, and a stage of diagnostics of the involved brain by the detected emission of red light.
EFFECT: higher diagnostic efficiency.
7 cl, 4 dwg, 2 ex
FIELD: medicine, pharmaceutics.
SUBSTANCE: invention relates to medicine, in particular, to pharmacy. As medical substance composition contains therapeutically effective quantity of trimetazidine dihydrochloride, as prolonging agent - interpolymer complex of polyacrylic acid and polyethylenglucol. As additional substances composition includes: bibasic calcium phosphate, monocrystalline cellulose, basic calcium carbonate, group of sliding substances - stearic acid and/or its salts. Composition can be made in form of pills, covered with coating, contains optimal quantity of additional substances, makes it possible to sufficiently release medical substance and ensures its high bio-availability.
EFFECT: obtaining prolonged pharmaceutical composition, which has antianginal action.
16 cl, 6 tbl, 6 ex, 2 dwg
SUBSTANCE: pharmaceutical compositions containing at least one compound of formula (IIIa) or (IIIb) or (IVa) or (IVb), where -X- and Y are described in the claims, or pharmaceutically acceptable salts, esters or amides thereof and a pharmaceutically acceptable carrier, which can be used in processes with modulation or E- and P-selectin expression.
EFFECT: obtaining low-molecular non-glycoside and non-peptide compounds, capable of creating antagonism to selectin-mediated processes.
11 cl, 38 ex, 3 tbl
FIELD: medicine, pharmaceutics.
SUBSTANCE: claimed invention relates to field of pharmaceutics and medicine and pharmaceutical composition for treatment of reperfusion disorders, which contains inert auxiliary substances and as active component compounds of general formula I-Iva.
EFFECT: obtaining pharmaceutical composition for treatment of reperfusion disorders.
SUBSTANCE: invention relates to novel flavonoid compounds of formula 1 where R1-R5 assume values given in the description. The invention also relates to a pharmaceutical composition based on said compounds and a treatment and prevention method. Such compounds and corresponding pharmaceutically acceptable derivatives and/or salts are used in pharmaceutical, veterinary and nutraceutical fields.
EFFECT: compounds and compositions have antioxidant properties and are especially effective in treating ischemic and reperfusion injury.
39 cl, 19 dwg
FIELD: medicine, pharmaceutics.
SUBSTANCE: invention refers to medicine, and concerns an injection dosage form for treating an acute ischemic stroke and a craniocereberal injury characterised by the fact that as an active ingredient, it contains a therapeutically effective amount of heptapeptide Met-Glu-His-Phe-Pro-Gly-Pro, and at least one substance chosen from a group of antioxidants.
EFFECT: invention provides high neuroprotective effect in acute severe CNS affections associating various models of the stroke and the craniocereberal injury, as well as high stability and prolonged use.
12 cl, 13 ex, 2 dwg, 5 tbl
FIELD: medicine, pharmaceutics.
SUBSTANCE: invention refers to an ester presented by formula  where R1' represents 1) C1-C6 alkyl which is optionally substituted by one or more identical or different halogens, or 2) -CO-C1-C6 alkoxy; R2' represents 1) hydrogen or 2) C1-C6 alkyl, R3', R4' and R5' are identical or different, and each represents 1) hydrogen, 2) halogen, 3) C1-C6 alkyl which is optionally substituted by one or more identical or different halogens, 4) C1-C6 alkoxy, 5) -COR13' where R13' represents (a) hydroxy, (b) C1-C6 alkyl, (c) C1-C6 alkoxy which is optionally substituted by one or more identical or different substitutes selected from (1) hydroxy, (2) C1-C6 alkoxy which is optionally substituted by phenyl, (3) -NR11'CO-C1-C6 alkyl where R11' represents hydrogen, (4) -CONR8'R9' where R8' and R9' are identical or different, and each represents C1-C6 alkyl, (5) -CO- C1-C6 alkoxy optionally substituted by phenyl, (6) phenyl optionally substituted by one or more identical or different substitutes selected from halogen, C1-C6 alkoxy and -CO-C1-C6 alkoxy, and (7) a heterocycle selected from pyridyl, thienyl and which all can be substituted by one or more identical or different C1-C6 alkyl groups, or (d) -OR19' where R19' represents a group or a group or piperidyl which is optionally substituted by -CO-C1-C6alkyl, 6) a heterocycle selected from oxadiazolyl and tetrazolyl, and said heterocycle is optionally substituted by C1-C6 alkyl optionally substituted by one or more identical or different substitutes selected from -CONR8'R9' (R8' and R9' have the same values as defined above) and -CO-aralkyloxy, or 7) nitrile; R6' and R7' are identical or different, and each represents 1) C1-C6 alkyl or 2) a nitrogen-containing 5 or 6-members saturated heterocycle containing a monocycle formed when R6', R7' and a neighbouring nitrogen atom are taken together, and optionally including oxygen as a heteroatom; Y1, Y2, Y3 are identical or different, and represent, 1) all carbon atoms, or 2) one of Y1, Y2, Y3 represent a nitrogen atom, and the others are carbon atoms; Y4 represent a carbon or nitrogen atom ;-X- represents 1) -(CH2)1 where 1 represents an integer 1 to 3, 2) -CH2-NR18'-CH2- where R18' represents C1-C6 alkyl, or 3) or to its pharmaceutically acceptable salt.
EFFECT: compounds presented by formula are effective as agents for treatment or prevention hyperlipidemia, arteriosclerosis, coronary artery disease, obesity, diabetes and hypertension or similar diseases since they are withdrawn very quickly and exhibit excellent MTP inhibitory activity.
23 cl, 32 tbl, 137 ex
SUBSTANCE: invention relates to aminophosphate derivatives of general formula (1a), pharmaceutically acceptable salts or hydrates thereof, which can be used in medicine as S1P (sphingosine-1-phosphate) receptor modulators,
where R3 is a straight alkyl group containing 1-3 carbon atoms; X is an oxygen or sulphur atom and n equals 2 or 3.
EFFECT: obtaining novel biologically active compounds with high S1P receptor modulating action.
9 cl, 59 ex, 1 tbl
SUBSTANCE: application involves a combination of AMN107 and PKC412 tyrosine kinase inhibitors for preparing a therapeutic agent for treating systemic mastocytosis (SM), including associated with oncogenic mutation KIT-D816V. The use of the invention enables higher clinical effectiveness of treating SM due to synergetic mast cell growth inhibition under action of the AMN107 and PKC412 combination.
EFFECT: higher efficacy of the composition.
3 cl, 3 tbl, 17 dwg, 2 ex