Method of preventing toxic lead effect on experiment animals with chronic poisoning
SUBSTANCE: invention concerns experimental medicine, particularly experimental toxicology, and can be applied in prevention of toxic lead effect on experiment animals. Method involves daily subcutaneous injection of acyzol in amount of 30 mg/kg simultaneously with lead acetate introduction to stomach through gastric tube in amount of 40 mg/kg.
EFFECT: efficient prevention of toxic lead effect during chronic poisoning due to dosage-dependent effect control.
1 ex, 4 tbl, 2 dwg
The invention relates to ecology, medicine, toxicology, experimental biology and can be used in the study of methods of prevention of chronic toxic effects of heavy metals, particularly lead, on the functional state of the kidneys.
One of the urgent problems of modern medicine and Nephrology is the study of the influence of heavy metals in the organs of the urogenital system of the population. In the last years highlights the increase in the frequency of renal pathology in the population living in ecologically unfavorable regions. (Ermachenko A.B., Sawtooth V.I. 1985; Ansary R.A. et al., 1991). As the major organ of excretion of many metals from the body, the kidneys have an increased toxic load, and therefore serve as a target of toxicity. Lead is especially inherent ability to hit the tubular epithelium of the kidneys, so the kidneys are one of the critical organs of intoxication in General (Kireeva, H.E., 2007).
Due to environmental degradation and progressive increase in the concentration of lead in the environment, the search for effective means of preventing its toxic action on the human body is one of the urgent problems of medicine.
There are plenty of detoxicants able to prevent or reduce toxic is some effect of heavy metals on the body. These include thiol compounds - unithiol, sodium thiosulfate, succimer, various chelating agents - pentatsin, the disodium salt of ethylenediaminetetraacetic acid, deferoxamine, and others (Mashkovsky PPM Medicines: in 2 volumes. Vol.2. - Kharkov "Torching", 1998. S-220). But along with therapeutic effect they can cause various side effects: gastrointestinal disorders, allergic reactions, leukopenia, thrombocytopenia, etc. Also they are able to excrete minerals and essential ions like iron, calcium, etc. and cause a violation of metabolic processes, which makes them long and prophylactic use.
As a detoxifier preference was given to azizoglu. Aziza is a comprehensive tsinkorganicheskih connection. The chemical structure of bis (1-vinylimidazole) cindicates. Azizol was developed as an antihypoxic agent in carbon monoxide poisoning and is the only drug for the prevention and life-saving at the specified defeat. Azizol unique product of its pharmacological properties and breadth of use that do not have a toxic action on the organism of man and animal, has no side effects. Azizol fills the concentration of zinc in enzyme systems, helps to optimize the promotion of tissue respiration, improves oxygen-dependent properties of the blood, due antihypoxant and antioxidant action azizol has lipoic property.
Previously azizol was used as hepatoprotector, means for treatment of psoriasis, antidote for poisoning by carbon monoxide, adaptogene, coronary-active antiischemic and antiarrhythmic agent.
Closest to the claimed method is prevention of toxic effects of lead with the use of sodium Selenite, taken as a prototype (Galacian S.M., however F.K. New technologies in reducing the toxic effects of lead with the help of sodium Selenite //Vladikavkaz biomedical journal. - 2003. - T4. - Vol.5-6. - P.64-67), namely, that animals received lead acetate daily with food dose of 30 mg/kg weight of the animal. Simultaneously with this, the animals received twice a week with food sodium Selenite at a dose of 0.4 mg/kg weight of the animal. The duration of the experiment 6 months.
The disadvantage of the prototype is that the lead acetate and sodium Selenite are used as nutrition in the diet, which reduces the accuracy of the control dose-dependent effect.
The claimed invention is directed to the solution of this problem involves the development of a way to prevent the toxic effects of lead in experimental animals etc is chronic poisoning.
The solution to this problem provides a significant reduction in the toxic effects of lead in chronic poisoning in experimental animals by optimizing tissue respiration, improve oxygen-dependent properties of blood. One of the main pathophysiological mechanisms of toxic action of lead on the body as a whole is its inherent ability to negatively affect the processes of tissue respiration. Respiration is a combination of redox processes in cells, tissues and organs, proceeding with the participation of molecular oxygen. Respiration is an important part of metabolism and energy in the body. The intensity of tissue respiration is highest in tissues of the kidneys, perhaps that is why the kidneys are highly sensitive to the toxic effects of heavy metal. Arizol in turn helps to optimize tissue respiration, improving oxygen-dependent properties of the blood, thereby reducing the disturbance of processes of tissue respiration, contributing to stabilization of the pathological process.
To achieve this, the technical result of the claimed invention, a method of preventing the toxic effects of lead in experimental animals with chronic poisoning, including simultaneous introduction of antidote and acetate of lead, as de is oxycanta apply azizol, administered to the animals daily subcutaneous dose of 30 mg/kg, along with a daily injection of lead acetate through a tube into the stomach at a dose of 40 mg/kg
The proposed method differs from the prototype in that, first, is dosed introduction of lead acetate and alzola that facilitates precise control of the dose-dependent effect, and secondly, for the first time applied pharmacological drug - azizol prevention of chronic toxic nephropathy.
Between the features of the proposed method and the result is the following causality, azizol, contributing to stabilization of the processes of tissue respiration, reducing the toxic effects of lead on the body, has a preventive effect.
Prophylactic administration of alzola, subcutaneously at a dosage of 30 mg/kg, every day, at the same time with intragastric introduction of a solution of lead acetate at a dose of 40 mg/kg for 16 days reduces the manifestations of toxic nephropathy, recovery of kidney function. The inventive method is efficient, cost effective and easily reproducible.
According to the authors the information set of essential features that characterize the essence of the claimed invention, is not known, which allows to make a conclusion about conformity of the invention, the criterion of "novelty".
On mn is the authors, the essence of the claimed invention should not be for experts explicitly known level of medicine, since it is not detected above the possibility of obtaining a way to prevent the toxic effects of lead acetate in experimental animals with chronic poisoning, including subcutaneous administration of alzola every day, along with daily injection of solution of acetate of lead through noninvasive probe into the stomach for 16 days, which allows to conclude that the criterion of "inventive step".
The set of essential features that characterize the invention, in principle, can be repeatedly used in medicine with the result, consisting in an effective and easily reproducible method of prevention of toxic effects of lead, by reducing the pathological effects of heavy metal, that allows to make a conclusion about conformity of the invention, the criterion of "industrial applicability".
This method is as follows.
To obtain toxic substances lead acetate dissolved in sterile distilled water so that per unit of solution, 0.2 ml, have 8 mg of lead (in terms of metal). For every 100 g weight rats injected with 0.1 ml toxic solution that is not extremely durable, the volumetric water load on the organism of experimental animals. The solution alzola prepared in such a way that each solution of 1 ml for 30 mg alzola. The solution alzola for each injection is prepared daily before the introduction. The solution of lead acetate is injected through noninvasive probe into the stomach at a dose of 40 mg/kg, daily 1 time per day for 16 days, two groups of animals (No. 1 and No. 2). At the same time, from the first day of the introduction of lead acetate, the group # 2 every day subcutaneously injected arizol in the dosage of 30 mg/kg using an insulin syringe for single use only.
After the time of the experiment (16 days) investigated the functional state of the kidneys, which included the determination of urine output (ml/HR/100 g), glomerular filtration rate (ml/HR/100 g), tubular reabsorption of water (%), osmolarity urine excretion of sodium, potassium, and protein.
Rats were scored with the use of thiopental. The results obtained in group 2 compared with the control group (gr. No. 1) and background indicators intact group.
For histological examination of tissue samples (kidney) were fixed in 10% neutral formalin, and then was subjected to fill in paraffin and subsequent preparation of slices of a thickness of 7-8 microns. Sections were stained with hematoxylin and eosin. The study sections were performed in transmitted light using a microscope Micmed-1 under magnification 80·200·400.
The method you is by morphologically, which figure 1 in the experimental group identified expressed alterative, necrobiotic and necrotic changes in the tissues of the kidney were noted: hemorrhage in the glomerulus (a); the extension of the lumen of tubules (b), necrosis of individual groups of tubules (b), necrobiosis all tubules (g) on the background of their solid hydropic dystrophy (d). In the glomeruli revealed a pronounced swelling, degenerative changes, there are small hemorrhages in the stroma. Figure 2 histological examination of the kidneys in group No. 2 revealed less pronounced dystrophic and necrobiotic changes in the tissues of the kidney: the regeneration of tubules (a), a moderate expansion of the ducts tubules (b), lymphohistiocytic infiltration of stroma (C), which is an indicator of the regeneration process.
Example. Two groups of male rats Wistar rats weighing 200-300 g were injected through noninvasive probe into the stomach of a solution of lead acetate at a dose of 40 mg/kg every day for 16 days. At the same time, from the first day of the introduction of lead acetate group No. 2 every day subcutaneously administered arizol in the dosage of 30 mg/kg Over 16 days examined renal function in conditions 6-hour spontaneous diuresis, conducted definition: volume of diuresis, glomerular filtration rate by endogenous creatinine, tubular reabsorption of water excretion with urine sodium ions, potassium and calcium excretion in the tree with urine, the osmolarity of the urine.
Sodium, potassium in plasma and urine was determined by the method of breeding photometry, using tribal analyzer liquids PAGE-1, the concentration of calcium and creatinine was determined spectrophotometrically (SF-26) using sets of "Calcium-Arsenazo-agate", "Creatinine-agate", "company" Agat-Honey", Moscow, Russia). The protein concentration was determined spectrophotometrically (SF-26) by the method of Lowry. The osmolarity of the urine was determined using Osmomat-300. The results of all series of experiments processed statistically with the use of the criterion of "t" student test on a PC Pentium-3 using Prizma 2.2.
The results showed (table 1 and 2)that in rats with chronic intoxication with lead acetate (group 1) was significant increase in 6-hour spontaneous diuresis (p<0,05), despite a significant reduction in glomerular filtration rate (GFR) (p<0,05). Politicheskaya reaction was caused by the reduction of reabsorption of water (p<0,05), while there was an increase in Na excretion (p<0,05) (p<0.05), and Sa (p<0.05), the content of protein in the urine (p<0,05), there was a decrease of urine osmolarity (p<0,05), indicating a violation of concentrating kidney function. On the background of the simultaneous introduction of alzola in group No. 2 was significant reduction in 6-hour spontaneous diuresis (p<0,5) compared with group # 1 with isolated introduction of lead acetate, due to the significant increase in tubular reabsorption of water (p<0,05) despite the increase in GFR (p<0,05). Compared with group # 1 were observed significantly lower values of Na excretion (p<0,05) (p<0.05), and Sa (p<0,05). At the same time was increased urine osmolarity (p<0.05), and therefore the use of alzola helps prevent changes concentrating kidney function. The use of alzola contributed to the reduction in the degree of proteinuria (p<0,05) in rats with chronic toxicity of lead acetate.
Toxic effects of lead acetate after intragastric administration caused changes in the electrolyte composition of blood plasma (table 3). The lower sodium levels (p<0,05) associated with a high loss of sodium in the urine due to an earlier defeat tubular apparatus of the kidneys and decrease tubular reabsorption of cations (p<0,05), (table 4). The use of arizola on the background of the toxicity of lead acetate significantly reduced the severity of changes in the electrolyte composition of the blood (p<0,05).
The influence of arizola on the basic processes of urine formation and excretion of protein in urine in rats in conditions 6-hour spontaneous diuresis, on the background of intragastric administration of lead acetate 40 mg/kg (M±m).
|Conditions of experience||Stat. show.||The processes of urine formation||Protein excretion mg/hour/100 g|
|Diuresis, ml/HR/100 g||GFR, ml/HR/ 100 g||EOC, %|
|16 days lead acetate (40 mg/kg) + azizal (30 mg/kg)||M±M||0,11±50,0014||16,49±0,092||99,31±0,0072||1,906±0,028|
|16 days lead acetate (40 mg/kg)||M±M||0,136±0,0025||14,72±0,11||99,07±0,02||2,795±0,042|
|Note: (*) - significant (p<0.05) change compared with the background.|
List of abbreviations:
• GFR - glomerular filtration rate;
• EOC - the tubular reabsorption of water.
The influence of arizola on the excretion of electrolytes and osmolarity of urine in rats in conditions 6-hour spontaneous diuresis on the background intragastric administration of lead acetate at a dose of 40 mg/kg (M±m).
|Conditions of experience||Stat. show.||Excretion of electrolytes µmol/hour/100 g||The urine osmolarity (OSM/l)|
|16 days lead Acetate (40 mg/kg) + azizal(30 mg/kg)||M±m||7,695±0,154||11,76±0,327||0,185±0,0042||1,416±0,0573|
|16 days lead Acetate (40 mg/kg)||M±m||8,54±0,194||13,53±0,53||0,205±0,0081||0,9254±0,031|
|Note: (*) - significant (p<0.05) change compared with the background.|
The influence of arizola on the concentration of electrolytes in the blood plasma background intragastric administration of lead acetate at a dose of 40 mg/kg of body weight (M±m).
|Conditions of experience||Stat. show.||The concentration of electrolytes in the blood plasma (mmol/l).|
|16 days lead acetate (40 mg/kg) + azizal (30 mg/kg)||M±m||2,240±0,0209||140,6±0,503||5,017±0,056|
|16 days lead acetate (40 mg/kg)||M±m||2,054±0,0221||138,0±0,478||5,59±0,114|
|Note: (*) -significant (p<0.05) change compared with the background.|
The influence of arizola on the reabsorption of calcium, sodium under conditions of 6-hour spontaneous diuresis on the background intragastric administration of lead acetate at a dose of 40 mg/kg (M±m)
|Conditions of experience||Stat. show.||The reabsorption (%)|
|16 days lead acetate (40 mg/kg) + azizal (30 mg/kg)||M±m||99,23±0,0194||99,47±0,0148|
|16 days lead acetate (40 mg/kg)||M±m||98,96±0,0407||99,30±0,0273|
|Note: (*) - significant (p<0.05) change compared with the background.|
From the foregoing it follows that the use of alzola is an effective way to prevent the toxic effects of lead in chronic poisoning.
The way to prevent the toxic effects of lead in the experiment is lnyh animals in chronic poisoning, involving the simultaneous introduction of antidote and acetate of lead, characterized in that as a detoxifier used azizol, administered to the animals daily subcutaneously at a dose of 30 mg/kg, along with a daily injection of lead acetate through a tube into the stomach at a dose of 40 mg/kg
SUBSTANCE: invention concerns experimental medicine, particularly experimental nephrology, and can be applied in chronic nephropathy modeling. To achieve the effect, lead acetate is introduced to stomach through gastric tube daily once in a day in amount of 40 mg per kg of animal weight rated in metal equivalent, where 8 mg of lead corresponds to 0.2 ml of solution.
EFFECT: emulation of adequate model of irreversible chronic toxic nephropathy due to obtainment of optimal maximum toxic dosage.
1 ex, 4 tbl, 1 dwg
SUBSTANCE: invention refers to experimental medicine, namely to thyrotoxicosis simulation ensured by endogastric introduction of Thyreotom in weekly graded doses 25 mkg/kg to 200 mkg/kg within 6 weeks followed by evaluation of functional activity of thyroid gland.
EFFECT: method provides creation of such thyroid gland pathology ensuring a clinical presentation of hyperfunctioning thyroid gland in blood and peripheral organs, and simulating colloid goitre pathology in thyroid parenchyma.
SUBSTANCE: invention relates to medical models. Method includes visualisation of anatomic structures. For its realisation natural anatomical object is used, in which with latex mass, dyed to imitate blood colour, injection of artery and venous systems of brain vessel system is performed separately. Successively, skin flap, muscle-fascial structures and aponeurosis are moved apart above trepanation site. Mill hole of occipital and temporal bones is formed from which squama is resected. By means of semicircular cut is opened and drawn aside. Sections of cerebellum hemispheres substance are made detachable.
EFFECT: obtaining possibility to model close to real situation aimed at development of manual skills of neurosurgeons.
SUBSTANCE: invention relates to experimental medicine, namely to experimental gastroenterology and can be used for modelling autoimmune gastritis in rats. For this purpose water-salt antigen, containing mixture of homogenate of allogenic mucous membrane of stomach in physiological solution and complete Freund's adjuvant, with component ratio 1:4, is introduced to animal. Method ensures possibility of obtaining model on rats, what results in decrease of research work cost.
EFFECT: ensuring possibility of obtaining model on rats, what results in decrease of research work cost.
2 dwg, 6 cl
SUBSTANCE: invention relates to experimental medicine. Bioimpedancemetry (BIM) is carried out three times in the region of the apex of the heart at different points on an area of 5 mm2. The average value (Z avg.), and if the Z avg. is more than 220 Ohm, it speaks of the presence of anthracyclonic cardiomyopathy. The method is simple and makes it possible to reliably diagnose anthracyclonic cardiomyopathy in an experiment.
EFFECT: developing of a simple, objective method for diagnosing anthracyclonic cardiomyopathy in an experiment.
2 tbl, 1 ex
SUBSTANCE: invention relates to medicine, namely to experimental surgery and concerns prevention of post-resection hyperglycaemia after pancreatectomy in experiment. For this purpose 96 hours before pancreatectomy suspension containing twenty-four-hour culture of pancreatic island cells of newborn piglets in concentration 2×106 in 1 ml of medium is introduced into iliac region once.
EFFECT: method ensures complete insulin-independence of experimental animal after pancreatectomy due to selection of optimal number of introduced cells as well as time and place of their introduction.
SUBSTANCE: combination therapy for chronic limb ischemia is ensured by revascularisation osteomyoplasty performed on the laboratory animal with experimental limb on 7th day after modelling. It is followed with intraperitoneal introduction of L-arginine once a day assuring effective circulation management.
EFFECT: higher clinical effectiveness.
1 ex, 1 tbl
SUBSTANCE: invention refers to experimental medicine, particularly to experimental cardiopharmacology and can be used for endothelium dysfunction correction. For this purpose dysfunction is modelled by intraperitoneal introduction of L-nitro-arginine-methyl ester dosed 25 mg/kg daily during 7 days to rats. This therapy is combined with endogastric introduction of macrolide agent Josamycin dosed 10 and 30 mg/kg singly a day.
EFFECT: method provides correction in any antioxidant profile.
1 ex, 1 tbl
SUBSTANCE: invention concerns medicine and medical equipment namely bracing of a knee joint of laboratory rabbits. The method of calculation of the individual form of an internal circle of a pressing pelot on a knee joint of laboratory rabbits consists that on the roentgenogram of a knee joint executed in a direct projection, the whirlbone is divided in lines of 12 equal to 30 degrees of angles. Construction of the form of the pressing pelot is spent on points of crossing of beams with a whirlbone circle, having receded on two millimetres from it.
EFFECT: calculation of the form of internal circle of pressing pelot on knee joint of laboratory rabbits.
SUBSTANCE: invention concerns experimental medicine, namely to experimental rheumatology and can be used for pseudorheumatism modelling. For this purpose 4 mg of an ovalbumin into 1 ml of full Freund's adjuvant (FFA) in the knee joint area are entered subcutaneously. After ovalbumin introduction in FFA, intravenously a papain in a dose of mass of a body of 8-10 mg/kg is entered. Then for 12 days from the beginning of formation of model 5 mg of an ovalbumin is entered into a cavity of a knee joint, thus enter an ovalbumin in FFA unitary.
EFFECT: reduction of quantity of stages and terms of modelling of pseudorheumatism, formation of more expressed system inflammatory reactions in an organism that allows to spend approbation of complex ways of treatment with use not only locally - but also is system operating preparations.
FIELD: medicine, experimental abdominal surgery.
SUBSTANCE: as experimental animals one should apply mongrel dogs of 12-17 kg body weight. Under general anesthesia one should conduct superior-median laparotomy, introduce 3.0 ml 70%-ethanol solution under pancreatic capsule and then laparotomic wound should be sutured up. Manipulation should be performed once. The method provides modeling adequate acute pancreatic inflammation at no side effects being very simple in implementation.
EFFECT: higher efficiency.
FIELD: medicine; medical engineering.
SUBSTANCE: method involves studying transverse longitudinal and rotation stiffness characteristics. The studies are carried out step-by-step from the first order units to complete external fixation apparatus structure. The device has frame and is provided with calibration loads, wire rope, displacement indicators, strip for fastening to loading end of bone imitator fragment, beam for fixing displacement indicators, beams having unit for modeling longitudinal and transverse loadings. The frame is manufactured as parallelepiped. The fixing panel has openings for bone imitator, for fixing external fixation apparatus and yoke connection union and is fixed in end face part of the frame. Beam for fixing displacement indicators has longitudinal slit for fixing the indicators and arranging them on lateral slots in frame base. The beams having unit for modeling rotational, longitudinal and transverse loadings are arranged on lateral frame sides on lateral slots in base.
EFFECT: high vision acuity without applying spectacle-based correction; accelerated treatment course.
2 cl, 16 dwg, 1 tbl
FIELD: experimental medicine.
SUBSTANCE: the present innovation deals with modeling urinary calculosis in rats due to injecting intraperitoneally 60%-glucose solution at 1 ml/100 g animal body weight twice daily for 2 mo. The method is very simple and enables to achieve lithogenesis in 25% experimental animals.
EFFECT: higher efficiency of experimental modeling.
2 dwg, 2 ex, 4 tbl
SUBSTANCE: method involves using Hann diode crystal with proper frequencies of pathogenic microorganisms and cells during their death period or during the stimulating factors action period being applied.
EFFECT: enhanced effectiveness of treatment; wider range of biophysical action types.
3 cl, 1 tbl
FIELD: medicine, experimental physiology.
SUBSTANCE: hypoxia with hypercapnia should be modeled due to creating a closed system of inhaled air circulation. Air enters lungs out of hermetically sealed reservoir and at expiration returns back. The process of recirculation is supplied with an apparatus of artificial pulmonary ventilation. The innovation suggested provides steadiness in development of hypoxia with hypercapnia excluding the development of stressor reaction. Conditions should be created to carry out any manipulations with an animal in the course of an experiment.
EFFECT: higher efficiency of modeling.
5 dwg, 1 ex
FIELD: medicine, stomatology.
SUBSTANCE: the present innovation should be carried out for the purpose to study ethiology and pathogenesis of parodontitis. One should affect with emotional stress in experimental animals (mature rats) due to placing 10-11 experimental animals into the cage at area of 0.018 sq. cm/animal. Before placing into the cage one should create artificial dental plaque around the cervix of the upper and lower incisors with the help of stomatological cement for every experimental animal. In the course of modeling all experimental animals should eat paste-like food. The method enables to shorten terms for obtaining the model desired and increase its similarity with pathomorphological manifestations of human parodontitis.
EFFECT: higher efficiency of investigation.
FIELD: medical equipment.
SUBSTANCE: device has input first variable resistor, capacitor and permanent resistor. Permanent resistor is connected to arm second and third variable resistors. Second ends of variable resistors are connected with motionless contacts of polarized relay. Movable contact of relay is connected to common bus. Input of device is connected to amplifier which has output connected with control wiring of polarized relay. Second end of wiring is connected with common bus. Device is intended for electrical modeling of balanced and misbalanced conditions of acupuncture point at electropunctural action with unlike-poled signals due to liquidation mutual errors at any circuit of opposite arms of the device. Values of active resistances can be installed independently at any arm of device.
EFFECT: increased precision.
FIELD: experimental medicine.
SUBSTANCE: laboratory animals should be once injected intraperitoneally or intravenously with phenylhydrazine at the dosage of 100-150 mg/kg.
EFFECT: higher efficiency.
1 cl, 4 ex, 2 tbl
FIELD: medicine, experimental biology, ecology, toxicology.
SUBSTANCE: at studying the mechanisms of heavy metals toxic action, in particular, cadmium upon renal function, it is suggested to introduce cadmium sulfate solution into stomach once daily for 2 mo at the dosage of 0.5 mg/kg, on conversion to metal, where cadmium corresponds to 0.5 mg per 1 ml solution. The present innovation enables to study the pathology in dynamics of development and elaborate and searching preparations for treating and preventing chronic toxic nephropathy.
EFFECT: higher efficiency.
1 ex, 3 tbl
SUBSTANCE: method involves exposing cell or cell group to external power source. At least two electrodes are introduced before treating the cells. One of electrodes is set on cytoplasmatic external cell membrane surface and the other one cell membrane and membrane potential value is measured. External electric voltage source is connected to the introduced electrodes oppositely in polarity with cell membrane potential difference value being not less than cell membrane potential.
EFFECT: enhanced effectiveness in building cell damage model by means of energy burst and death.