By M. Elber. Sweet Briar College. 2019.
Intrinsic clearance is the maximal ability of the liver to eliminate drug in the absence of any blood flow limitations order copegus 200 mg otc. Smoking is known to increase the enzymes responsible for theophylline metabolism (a drug with a low hepatic extraction) purchase copegus 200 mg. Would a patient with a history of smoking likely require a higher cheap copegus 200mg otc, lower, or equivalent theophylline total daily dose compared to a nonsmoking patient? Consequently, the total daily dose of lidocaine may need to be decreased in a patient with heart failure who has a myocardial infarction. Which of the following types of metabolism do drugs with a high extraction ratio undergo to a significant extent? For a drug that is totally absorbed without any presystemic metabolism and then undergoes hepatic extraction, which of the following is the correct equation for F? Route of administration, extraction ratio, and protein binding are all factors that should be considered when trying to assess the effect of disease states on plasma concentrations of drugs eliminated by the liver. Will drugs that inhibit the hepatic cytochrome P450 system likely increase or decrease the plasma clearance of theophylline? For aminoglycosides, the terminal elimination rate constant can be estimated from the creatinine clearance by which of the following equations? Smoking raises the concentrations of enzymes that also metabolize theophylline, so more theophylline would beW metabolized, requiring a higher theophylline dose. F represents the fraction of drug that reaches the systemic circulation; E is the extraction ratio. Theophylline is a low-extraction drug and its clearance is roughly equal to intrinsic hepatic clearance (Cl ), so the effect of cytochrome P450 enzyme induction isi likely to decrease intrinsic and overall clearance. Highly ionized drugs do remain in the urine because ionized forms of drugs do not cross membranes well. Glomerular filtration rate does not account for tubular secretion or reabsorption. Aminoglycosides undergo little if any extra-renal elimination and therefore the y-intercept value should be close to zero. The answer should represent the approximate fraction of drug excreted per hour, and this value should be less than one. Research the metabolism of primidone and discuss the clinical significance of its metabolites. Select several drugs whose prescribing information indicates that the dose should be decreased with hepatic impairment. Research the pharmacokinetics of carbamazepine and discuss its metabolism when given alone and when given with other enzyme inhibitors or inducers. Specifically, how would you begin a patient on carbamazepine and how would you monitor and adjust its dose? Research the various oral fluoroquinolones to determine which can affect the metabolism of theophylline and to what extent. Describe situations in which alteration of urine pH with urine acidifier or alkalinizing agents can be used to enhance the clinical response of other drugs. Look up and compare the various equations that can be used to calculate the elimination rate constant for gentamicin, tobramycin, and amikacin. Explain the various biopharmaceutic processes that can result in nonlinear pharmacokinetics. Use the t90% equation to estimate the time required for 90% of the steady-state concentration to be reached. This is the case only when drug elimination processes are first order (as described in previous lessons). When these linear relationships are present, they are used to predict drug dosage. For example, if a 100-mg daily dose of a drug produces a steady-state peak plasma concentration of 10 mg/L, we know that a 200-mg daily dose will result in a steady-state plasma concentration of 20 mg/L. Therefore, such drugs are said to follow nonlinear, zero-order, or dose-dependent pharmacokinetics (i. Just as with drugs following linear pharmacokinetics, it is important to predict the plasma drug concentrations resulting from a drug dose. In this lesson, we discuss methods to characterize drugs that follow nonlinear pharmacokinetics. Nonlinear pharmacokinetics may refer to several different processes, including absorption, distribution, and renal or hepatic elimination (Table 10-1). Even though absorption and distribution can be nonlinear, the term nonlinear pharmacokinetics usually refers to the processes of drug elimination. When a drug exhibits nonlinear pharmacokinetics, usually the processes responsible for drug elimination are saturable at therapeutic concentrations. These elimination processes may include renal tubular secretion (as seen with penicillins) and hepatic enzyme metabolism (as seen with phenytoin). When an elimination process is saturated, any increase in drug dose results in a disproportionate increase in the plasma concentrations achieved because the amount of drug that can be eliminated over time cannot increase. This situation is contrary to first-order linear processes, in which an increase in drug dosage results in an increase in the amount of drug eliminated over any given period. Of course, most elimination processes are capable of being saturated if enough drug is administered. However, for most drugs, the doses administered do not cause the elimination processes to approach their limitations. Clinical Correlate Many drugs exhibit mixed-order pharmacokinetics, displaying first-order pharmacokinetics at low drug concentrations and zero-order pharmacokinetics at high concentrations. It is important to know the drug concentration at which a drug "order" switches from first to zero. Phenytoin is an example of a drug that switches order at therapeutic concentrations, whereas theophylline does not switch until concentrations reach the toxic range. For a typical drug having dose-dependent pharmacokinetics, with saturable elimination, the plasma drug concentration versus time plot after a dose may appear as shown in Figure 10-3. After a large dose is administered, an initial slow elimination phase (clearance decreases with higher plasma concentration) is followed by a much more rapid elimination at lower concentrations (curve A). However, when a small dose is administered (curve B), the capacity of the elimination process is not reached, and the elimination rate remains constant. At high concentrations, the elimination rate approaches that of a zero-order process (i. At low concentrations, the elimination rate approaches that of a first-order process (i.
Note that α must be greater than β copegus 200mg online, indicating that drug removal from plasma by distribution into tissues proceeds at a greater rate than does drug removal from plasma by eliminating organs (e cheap copegus 200mg on-line. Plasma drug concentrations with a two-compartment model after an intravenous bolus dose buy generic copegus 200mg. For a one-compartment model (Figure 6-8), we know that the plasma concentration (C) at any time (t) can be described by: -Kt Ct = C0e (See Equation 3-2. The equation is called a monoexponential equation because the line is described by one exponent. The two-compartment model (Figure 6-9) is the sum of two linear components, representing distribution and elimination (Figure 6-10), so we can determine drug concentration (C) at any time (t) by adding those two components. Therefore: -αt -βt Ct = Ae + Be This equation is called a biexponential equation because two exponents are incorporated. For the two-compartment model, different volume of distribution parameters exist: the central compartment volume (Vc), the volume by area (Varea, also known as Vβ), and the steady-state volume of distribution (Vss). As in the one-compartment model, a volume can be calculated by: For the two-compartment model, this volume would be equivalent to the volume of the central compartment (Vc). The Vc relates the amount of drug in the central compartment to the concentration in the central compartment. If another volume (Varea or Vβ) is determined from the area under the plasma concentration versus time curve and the terminal elimination rate constant (β), this volume is related as follows: This calculation is affected by changes in clearance (Cl). The Varea relates the amount of drug in the body to the concentration of drug in plasma in the post-absorption and post-distribution phase. Although it is not affected by changes in drug elimination or clearance, it is more difficult to calculate. One way to estimate Vss is to use the two-compartment microconstants: or it may be estimated by: using A, B, α, and β. Because different methods can be used to calculate the various volumes of distribution of a two- compartment model, you should always specify the method used. When reading a pharmacokinetic study, pay particular attention to the method for calculating the volume of distribution. Clinical Correlate Here is an example of one potential problem when dealing with drugs exhibiting biexponential elimination. Recall that A steeper slope equals a faster rate of elimination resulting in a shorter half-life. If a terminal half-life is being calculated for drugs such as vancomycin, you must be sure that the distribution phase is completed (approximately 3-4 hours after the dose) before drawing plasma levels. Plasma drug concentrations with a one-compartment model after an intravenous bolus dose (first-order elimination). Plasma drug concentrations with a two-compartment model after an intravenous bolus dose (first-order elimination). The plasma drug concentration versus time curve for a two- compartment model is represented by what type of curve? For a two-compartment model, which of the following is the term for the residual y-intercept for the terminal portion of the natural- log plasma-concentration versus time line? The equation describing elimination after an intravenous bolus dose of a drug characterized by a two-compartment model requires two exponential terms. A patient is given a 500-mg dose of drug by intravenous injection and the following plasma concentrations result. K12 represents the rate constant for drug transfer from compartment 1 (central) to compartment 2 (peripheral). The y-intercept associated with the residual portion of the curve (which has a slope of -α) is A. One for distribution phase and the other for elimination or post- distribution phase. Describe situations for which it would be better to use a two-compartment model rather than a one-compartment model. What is the minimum number of plasma-concentration data points needed to calculate parameters for a two-compartment model? Definitions of symbols and key equations are provided here: K = elimination rate constant C0 = plasma drug concentration just after a single intravenous injection e = base for the natural log function = 2. Forty-eight hours after beginning the infusion, the plasma concentration is 12 mg/L. If we assume that this concentration is at steady state, what is the theophylline clearance? As we know V and K, what would the plasma concentration be 10 hours after beginning the infusion? If the infusion is continued for 3 days and then discontinued, what would the plasma concentration be 12 hours after stopping the infusion? If the infusion is continued for 3 days at 40 mg/hour and the steady-state plasma concentration is 12 mg/L, what rate of drug infusion would likely result in a concentration of 18 mg/L? After the increased infusion rate above is begun, how long would it take to reach a plasma concentration of 18 mg/L? If this patient is assumed to have an "average" V of 15 L and a normal half-life of 3 hours, what will be the peak plasma concentration at steady state? After the fifth dose, a peak plasma concentration (drawn at the end of the infusion) is 5 mg/L and the trough concentration (drawn right before the sixth dose) is 0. For this patient, what dose should be administered to reach a new steady-state peak gentamicin concentration of 8 mg/L? To calculate the plasma concentration with a continuous infusion before steady state is reached, the following equation can be used: where t = 10 hr. If the continuous intravenous infusion is continued for 3 days, steady state would have been reached, so the plasma concentration would be 12 mg/L. When the infusion is stopped, the declining drug concentration can be described just as after an intravenous injection: -Kt Ct = Csse where: Ct = plasma concentration after infusion has been stopped for t hour, Css = steady-state plasma concentrations from continuous infusion, and K = elimination rate constant. Then remember that at steady state: Css = K0/Clt or, rearranged: Css × Cl =t K0 If the desired Css equals 18 mg/L, then: k0 = 18 mg/L × 3. Whenever the infusion rate is changed to a new rate (increased or decreased), it will take approximately five half-lives to achieve a new steady state.
Likewise order copegus 200mg, intestinal microfora appears to be dependent upon the presence of metabolize acemannan to smaller compounds by the anthraquinone fraction purchase copegus 200 mg without prescription, in particular aloe- cleavage of the β-1→4 linkages generic copegus 200mg amex. Aloe vera did not display any treatment-related patholog- gel, decolorized gel, or decolorized whole leaf). Aloe-emodin also contains a benzylic bacterial assays for mutagenesis and/or other hydroxy moiety that has the potential to undergo assays for genotoxicity. Tese data suggest that the Te impact of this increased production is pres- neoplastic response observed with Aloe vera is a ently not clear. Although the mechanism by consequence of the conversion of the anthrone which Aloe vera whole leaf preparations induce C-glycosides to aloe-emodin, which by itself or intestinal neoplasms in rats is not fully under- in combination with other Aloe vera components stood, it is clear that the molecular pathways is responsible for the development of adenomas observed in the intestinal neoplasms induced in and carcinomas in the large intestine. Summary of Data Reported mice did not develop adenoma or carcinoma of the large intestine, which may be due to the fact 5. Te leaves contain two types of liquids: a shorter gastrointestinal tracts and faster gastro- yellow bitter latex under the skin, and a viscous intestinal transit times than rats, which could gel in the inner section. Commercial products are contribute to the lack of a tumour response in made from processed leaves. Decolorization removes emodin cream on the photocarcinogenic activity pigments and anthraquinones from the whole of simulated sunlight in female mice based on leaf extract. Te dried latex has medicinal uses an increase in the multiplicity of squamous as a laxative. Te other forms are used in foods, cell papilloma, carcinoma or carcinoma in situ dietary supplements, beverages, and cosmetic (combined). Exposure data, where they exist, do not efect of the whole leaf extract cream or decol- identify the nature of products containing Aloe orized whole leaf extract cream on the photocar- vera used by consumers. In contrast, aloe-emodin has signifcantly increased incidence of any type genotoxic activity. Tese data suggest that the of tumours in males or females given drink- neoplastic response observed with Aloe vera is a ing-water containing whole leaf extract of Aloe consequence of the conversion of the anthrone vera. C-glycosides to aloe-emodin, which by itself or In a study of photo-co-carcinogenesis with in combination with other components of Aloe simulated sunlight, four articles were studied by vera is responsible for the adenomas and carci- skin application in hairless mice: three test arti- nomas in the large intestine of rats. Mutagenicity of anthraqui- Tere is sufcient evidence in experimental none and benzanthrone derivatives in the Salmonella/ animals for the carcinogenicity of whole leaf microsome test: activation of anthraquinone glyco- extract of Aloe vera. Frameshif mutagenicity of certain naturally occurring phenolic Whole leaf extract of Aloe vera is possibly compounds in the ‘Salmonella/microsome’ test: acti- vation of anthraquinone and favonol glycosides by gut carcinogenic to humans (Group 2B). Aloe Vera S0008-6215(00)83936-1 Leaf, Aloe Vera Leaf Juice, Aloe Vera Inner Leaf Juice. Isolation of a human intestinal bacterium capable of Akao T, Che Q-M, Kobashi K, Hattori M, Namba T transforming barbaloin to aloe-emodin anthrone. Toxicology and carcinogenesis studies of a Cosmetic Ingredient Review Expert Panel (2007). Final noncolorized whole leaf extract of Aloe barbadensis report on the safety assessment of AloeAndongensis Miller (Aloe vera) in F344/N rats and B6C3F1 mice Extract, Aloe Andongensis Leaf Juice,aloe Arborescens (drinking water study). Natl Toxicol Program Tech Rep Leaf Extract, Aloe Arborescens Leaf Juice, Aloe Ser, 577(577):1–266. Clear evidence of carcinogenic Extract, Aloe Barbadensis Leaf Juice,aloe Barbadensis activity by a whole-leaf extract of Aloe barbadensis Leaf Polysaccharides, Aloe Barbadensis Leaf Water, miller (aloe vera) in F344/N rats. Toxicol Sci, 131(1):26– Aloe Ferox Leaf Extract, Aloe Ferox Leaf Juice, and Aloe 39. Int J Toxicol, 26(1):Suppl 2: Brandin H, Viitanen E, Myrberg O, Arvidsson A-K 1–50. Studies in the feld of drugs and 10,10′-bianthrone derivatives by human intes- containing anthraquinone derivatives. Genotoxicity Determination of the anthraquinones aloe-emodin of aloeemodin in vitro and in vivo. Strasbourg, France: European aloenin, a bitter glucoside constituent of Aloe arbo- Directorate for the Quality of Medicines & HealthCare. Te infuence of long-term Aloe vera ingestion on 68 Aloe vera age-related disease in male Fischer 344 rats. Carbohydr Res, Jiao P, Jia Q, Randel G, Diehl B, Weaver S, Milligan G 86(2):247–57. Characterization of the Journal of Environmental, Agricultural and Food genotoxicity of anthraquinones in mammalian cells. Nesslany F, Simar-Meintières S, Ficheux H, Marzin D Mass spectrometry-based metabolite profling and (2009). Rhein induces apoptosis through induction treatment of diabetes mellitus and dyslipidemia. Am J of endoplasmic reticulum stress and Ca2+-dependent Health Syst Pharm, 67(21):1804–11, 1806, 1808 passim. Products that contain active ingredient - analysis of commercial “Aloe vera” materials and Aloe vera. Natl Toxicol thin-layer chromatographic urine screen for laxative Program Tech Rep Ser, 553(553):7–33, 35–97, 99–103 abuse. Te of high-performance liquid chromatographic and thin- Merck Index - An Encyclopedia of Chemicals, Drugs, layer chromatographic methods for determination of and Biologicals. Toxicologic assessment of a commer- whole leaf extract-induced large intestinal tumors in cial decolorized whole leaf aloe vera juice, lily of the F344 rats share similar molecular pathways with human desert fltered whole leaf juice with aloesorb. Analysis of 13 phenolic compounds in Aloe lized aloe vera gel supplement drink in mice. Safety of purifed decolorized (low anth- etary high-purity aloe vera inner leaf fllet prepara- raquinone) whole leaf Aloe vera (L) Burm. Inhibition of cytochrome P450 enzymes Yokohira M, Matsuda Y, Suzuki S, Hosokawa K, by rhein in rat liver microsomes. J Chromatogr B Analyt Ulbricht C, Armstrong J, Basch E, Basch S, Bent S, Technol Biomed Life Sci, 796(1):113–9. Exposure Data Common names: Hydrastis; Golden seal; Yellow Indian plant; Yellow seal Goldenseal (Hydrastis canadensis L.
A full draft of the guidelines was circulated for comment to members of the Guideline Development Groups and the external peer review group order copegus 200 mg without prescription. A total of 21 Guideline Development Group members and 12 peer reviewers declared membership of pharmaceutical industry or other advisory panels or receipt of consulting fees cheap copegus 200 mg on line, and 23 Guideline Development Group members and 13 peer reviewers declared pharmaceutical industry fnancial support through grants for research buy copegus 200mg with mastercard. There was also a further declaration at the Guideline Development Group meeting of the involvement of members as investigators in key trials and studies. The broad range of constituencies represented on the different Guideline Development Group panels was also noted, and that the majority of members had no declared interests. All individuals with declared interests therefore proceeded to participate fully in the Guideline Development Group meetings or to act as peer reviewers. The proposed recommendations were then considered, informed by a standardized decision-making table for each topic (Box 3. The Guideline Development Groups discussed both the proposed wording of the recommendations and the rating of its strength (strong or conditional). All decisions were reached by discussion and consensus on the recommendations, including their strength and, where appropriate, the conditions to be attached to the recommendations. Disagreements were resolved through e-mail discussions, teleconferences and redrafting recommendations and rationale. Early drafts of sections of the guidelines were circulated to Guideline Development Group members, and a full draft of the guidelines was circulated to Guideline Development Group members and peer reviewers for comment. The extensive comments from more than 100 reviewers were addressed where possible and incorporated into the revised guidelines. The quality of evidence is defined as the confidence that the reported estimates of effect are adequate to support a specific recommendation. Observational studies are initially rated as low-quality evidence but may be upgraded if the magnitude of the treatment effect is very large, if multiple studies show the same effect, if evidence indicates a dose–response relationship or if all plausible biases would underestimate the effect (10). The higher the quality of evidence, the more likely a strong recommendation can be made. The strength of a recommendation reflects the extent to which the Guideline Development Group was confident that the desirable effects of following a recommendation outweigh the potential undesirable effects. The strength is influenced by the following factors: the quality of the evidence, the balance of benefits and harms, values and preferences, resource use and the feasibility of the intervention (Table 3. A strong recommendation is one for which the Guideline Development Group was confident that the desirable effects of adhering to the recommendation outweigh the undesirable effects. A conditional recommendation is one for which the Guideline Development Group concluded that the desirable effects of adhering to the recommendation probably outweigh the undesirable effects but the Guideline Development Group is not confident about these trade-offs. The reasons for making a conditional recommendation include the absence of high- quality evidence; imprecision in outcome estimates; variability in the values and preferences of individuals regarding the outcomes of interventions; small benefits; applicability in all settings versus specific settings; and benefits that may not be worth the costs (including the costs of implementing the recommendation). The more that the benefts outweigh the risks, the more likely that a strong recommendation will be made. Values and If the recommendation is likely to be widely accepted or highly valued, a preferences strong recommendation will probably be made. If there are strong reasons (acceptability) that the recommended course of action is unlikely to be accepted, a conditional recommendation is more likely to be made. Costs and fnancial Lower costs (monetary, infrastructure, equipment or human resources) implications or greater cost–effectiveness will more likely result in a strong (resource use) recommendation. Feasibility If an intervention is achievable in a setting where the greatest impact is expected, a strong recommendation is more probable. This applies to specific topics in Chapter 9, including retention across the continuum of care, but this did not lead to formal recommendations. Structured discussions were held among Guideline Development Group members regarding setting priorities for key clinical recommendations in various epidemic scenarios (settings with generalized and concentrated epidemics and with low, moderate and high ArT coverage). A short version will summarize key new and existing recommendations for easy reference. A library of all supporting documentation and evidence will also be made available on the web site. Assistance will be provided to Member States to adapt the guidelines to their national contexts. An evaluation of how users have implemented the guidelines has been developed to assess the uptake of the recommendations and the barriers to effective implementation. Interim technical and programmatic updates may be developed if important new evidence becomes available. These include existing recommendations that have been updated, where a new evidence review was undertaken as part of this guidelines process. They are presented in the following format to reflect the full evidence review and discussion held within the Guideline Development Group for new recommendations. When the recommendation relates to a specific population, the key issues for that population may be briefly summarized. The new evidence on which the recommendation is based and other key operational and programmatic considerations that informed the development of the recommendation are summarized. In some cases, key clinical implementation issues specific to the recommendation are listed. For several key recommendations, discussion of implementation considerations relevant to programme managers is presented in Chapter 10. In some cases, critical issues requiring further research are briefly described or listed, where these are integral to the recommendations. The references relating to each section are listed at the end of the guidelines by chapter number. In general, these are presented in the following format: Background; Source(s) for recommendation(s); Additional guidance (where appropriate); and Existing recommendation(s). The populations relevant to each recommendation are clearly specifed and also marked by an appropriate symbol for quick reference. The tables highlight selected topics that are particularly relevant to the respective populations. However, the topics listed are not exhaustive and many of the recommendations and other guidance are relevant across different populations.
Due to the peculiarities of the discharge mechanism of the hollow cathode discharge are present in the spectrum of the arc and spark lines as the main gas and cathode material cheap 200mg copegus with amex. Results and discussion: Usually atomic absorption spectrometer contains multiple light sources copegus 200mg without a prescription, selectable using a stepper motor buy 200mg copegus amex. The disadvantage of such structures is a significant increase in lamp size and partial diaframirovannie emission cathodes distant. Additionally, you must rebuild the optical system control device for the removal of various cathodes. It is proposed to use a coaxial cylindrical hollow cathode instead of the cathode for the creation of a multi-element light source for spectral analysis. Along the axis of the cathode cavity accommodate 5 -6 bars of equal length cathodes made of different materials. The diameter of the rods must be minimal, but to a certain size so that it does not lead to the heating 284 and deformation of the rods. The radius of the circle on which the rods must be located advisable to take equal to half the radius of the cathode polosti. Eto due to the fact that the bars do not extend beyond the region of negative glow that can reduce the radiation intensity. Accommodation close to the axis of the rods leads to mutual screening rods from the ions coming from the negative glow, which can also reduce the intensity of the radiation. The current density of the rod of the cylinder can exceed the current density of the order. Therefore rod sprayed more intensively than the cylinder, hence at small discharge currents will occur in the spectrum lines of the material web and the cylinder are fixed line material. Thus, a compound of one of the cylinder rods to the cathode leads to a source line in the spectrum of radiation material rod. To change the form of the spectrum is only necessary to connect to the cathode corresponding rod Conclusions: The proposed design of the light source it is possible to control the intensity of the emission spectra of different elements at a constant discharge current by applying the rod of a building. The proposed multi -element light source can be used in devices for multi-atomic absorption analysis. Economic theory, the provisions of which are used in the selection of regressors, is not perfect. So often in the econometric model includes factors that should not be there, and do not turn on the factors that must be present there. Proper specification of the econometric model indicates that • choose the right function for the relationship between the independent and dependent variables; • excluded from the model covariates insignificant and unimportant; • the model includes all relevant and significant covariates. Violation of the last of these conditions leads to very unpleasant consequences: • estimation of the regression parameters are biased and unfounded; • checking the quality of the model hypotheses and the construct confidence intervals for the parameter estimates are incorrect. The test is based on the auxiliary regression of the dependent variable on factors x1, x2 of the original model and power functions of the estimated values variable ŷ: 2 3 = 0 + 1 1 + 2 2 + 1 + 2 + ⋯ + + Further, it is necessary to check a hypothesis by the corresponding F-test: 0: 1 = 2 = ⋯ = = 0 If value of statistics is more critical, then the zero hypothesis is rejected, and the specification of model is recognized incorrect. The considered scheme of testing of the specification of econometric model is realized in many software products, in particular in the program environment R. R is distributed free of charge, and now it is the de facto standard for statistical computing. Usage: resettest(formula, power = 2:3, type = c("fitted", "regressor", "princomp"), data = list()) Arguments: A symbolic description for the model to be tested (or a fitted formula "lm" object). A vector of positive integers indicating the powers of power the variables that should be included. A string indicating whether powers of the fitted response, the regressor variables (factors are left out), or the first principal type component of the regressor matrix should be included in the extended model. The studies in theoretical immunology on the basis of mathematical models are considered nowadays as a priority direction in the investigations of complex systems in biological sciences which is supported by the European Science Foundation and the European Society of Mathematical and Theoretical Biology. Understanding of regularities in immune response provides the researchers and clinicians new powerful tools for the stimulation of the immune system and for increasing its efficiency in the struggle against antigen invasion. In this connection the construction of mathematical models of immune response to an antigen irritant is considered as the only right tactics in the cognition of the above regularities. The aim of the work is to develop the simple mathematical model of subclinical form of infectious disease on the basis of an equilibrium relation for each component that participates in an immune response (antigen, antibody, plasma cell, and degree of damage of an organ subjected to antigen attack). The mathematical model must adequate represent the immunological models based on theoretical and experimental conceptions on the defense system of organism. Indeed, in designing the simplest model of immune defense we have used the main conception of immunology: an antibody binds an antigen and forms antibody-antigen complexes. In proportion to the quantity of these complexes, plasma cells are formed in an organism in a time t which carry out the mass production of antibodies. The quantity of plasma cells forming in response to antigenic stimulation depends on the viability of the affected organ: the more severe is the damage to this organ the less is the quantity of plasma cells because of the deficiency arising that affects the immune defense activity. It is seen that many details are missing in this model; however, all the essential components of the immune defense mechanism are taken into account. The basic acting factors of an infectious disease are: 1) concentration of pathogenic multiplying antigens, V(t); 2) concentration of antibodies, F(t); 3) concentration of plasma cells, C(t); 4) relative characteristic of affected organ, m(t). So, the simple mathematical model of infectious disease is represented as the system of nonlinear differential equations: 288 dV (β γF)V dt dC ξ(m)αV(t - τ)F(t- τ)- μC (C C*) dt . Subclinical form of infectious disease is usually latent and is not connected with physiological disorder of an organism. It is usual contact of an organism with a familiar antigen, and the organism has the resources sufficient to suppress the antigen: specific immunoglobulin, lymphocytes, interferon, macrophages, and other components of the immune system. In this case the proliferating population of viruses or bacteria is suppressed by available resources and the antigen is destroyed before it reaches the concentration level that provokes noticeable immune and physiological reactions of the organism. Antigen concentration dynamics in case of subclinical form of disease The simple mathematical model of subclinical form of infectious disease, of course, is extremely approximate and requires further detailed elaboration. However, even in this form it allows one to include in the system various essential factors of infectious disease dynamics. Realization of simple mathematical model of subclinical form of infectious disease with the help of spreadsheet LibreOffice Calc allows computing the main parameters of disease and representing them graphically. This model is useful for exploration of general picture of a disease course and for explanation of some results of observations. Some theoretical results may be used in searching for effective methods of treatment. When violations of cerebral circulation the most important pathogenetic significance insufficient blood flow to the tissues of the brain in the pool stenotic or occluded artery and the failure or delay of venous outflow. Venous stasis in the brain is the most common form of venous disorders of cerebral circulation in a number of organic diseases of the brain.