G.V.Pavlov, N.V.Nikitin the Scientific edition, Ekaterinburg, 2003

Introduction

Many sections theoretical and applied medicine, in that or other measure connected with functioning in norm and at a system pathology ekzokrinnyh bodies and fabrics, have reached last decades high level developments. The establishment of essential details morfofunktsionalnogo formation became a result of strengthening of interest of theorists and experts to laws ekzosekretsii. In particular, its integration with activity enough known endokrinnoj organism system, as in many glands (podzheludochnaja, salivary, sexual, etc.) was found out The given systems are united not only functionally, but also morfologicheski.

Features of formation ekzokrinnoj systems in antenatalnom the period predetermine not only plural adaptable reactions of a complete organism, but also character patogeneza ekzokrinnyh diseases the adult person, and also can make a basis of possible infringements exchange processes. It is enough to mention ekzokrinnuju system a gastroenteric path, in so considerable degree defining the power balance of an organism, sufficient receipt plastic materials etc. Under digestion is understood difficult process of transformation, and mastering of the accepted food. Depending on an origin of enzymes digestion differs on three types (own, simbiontnoe and autoliticheskoe), from which the own is defined ekskretornoj by activity a gastroenteric path and is the basic type at the higher animals [19]. Synthesis of the enzymes necessary for own digestion is carried out epitelialnymi by cages, salivary glands, podzheludochnoj and glands intestines.

expressiveness Degree as reserve possibilities, and abilities to resist to pathological influence ekzokrinnyh glands and system as a whole it is defined by genetic factors and the circumstances influencing on the further development. Decoding of the reason such universal zkzokrinopatii, as mukovistsidoz (kistofibroz a pancreas) spent in frameworks the global program " the Gene man", has led to an establishment of localisation and to allocation in the pure state not only the gene responsible for formation of an end-product - a secret ekzokrinnyh cages, but also the fiber realising the genetic information. Thereby genetic determination and the control ekzosekretsii has been convincingly shown .

Much earlier was the role ekzogennyh, alimentary, infectious, toxic and so forth the factors promoting infringement of functioning, as selective ekzokrinnyh glands, and ekzokrinnoj systems in whole and leading reversible, sharp, and at times and to irreversible, chronic processes in separate ekzokrinnyh bodies is established.

However the sum of the saved up knowledge in the field of studying and pathologies ekzokrinnoj systems allows to say physiology that in the near future is necessary development of certain uniform schemes korrigirujushchih influences. Naturally, to it certain job on should precede ordering of our knowledge in the field of external secretion.

From the moment of basic fundamental jobs on digestion physiology there has been begun working out of applied problems, in particular problems of pharmacological indemnification of insufficient function of bodies a gastroenteric path, especially ekzokrinnoj pancreas parts, as hopes of its stimulation were not justified. Despite all extending assortment of fermental preparations for replaceable therapy, the correction problem ekzokrinnoj intestines remains to insufficiency of a pancreas and glands still unresolved. However last years the given problem has been advanced thanks to introduction in clinic of new generation enzimnyh the preparations, one of best of which is Kreonj. In the given job we represent the literature review on replaceable therapy intestinalnymi enzimami, and also own data of clinical approbation of preparation Kreon at patients mukovistsidozom.

1. Sketch of evolution of development ekzokrinnoj fabrics

For realisation of own ability to live any cages of an organism and those problems which are shown to it by a complete organism, the given cage should absorb some set of various substances, switch on them in the metabolism and allocate in the extracellular environment for further transformations products of anabolism and (or) katabolizma. In any case to process deducing of these products, named ekstruziej [English extrusion pushing out, expression (Sovr. The dictionary of foreign words, 1992)], precede quite certain processes. However according to tradition we will not recede from the terminology based on Latin roots, and we will use the term secretion (secretio branch), meaning process of education and allocation specialised glands of a human body and animal special active substances. Thus the product developed by gland is meant, that, through vyvodnoj the channel gets to any cavity of an organism or on its surface the secret, and developed by gland which does not have vyvodnogo a channel, and also is called as some fabrics, gets directly to blood or a lymph is called inkret.

to answer a question in what a generality both distinction of secretion and inkretsii is necessary to consider the problem formations ekzo - and endokrinnoj secretions during evolution.

According to A.M.Ugoleva`s theory [18, 19] secretion as that has arisen from nonspecific ekskretsii which existed on the earliest stages of evolution live as one of the general elements of a metabolism between out of - and endocellular environments. Possibility of removal by a cage of products of a metabolism, i.e. ekskretsija should be a necessary condition of such exchange. Realization of it has led to that along with products katabolizma from a cage are allocated in an environment or interkletochnoe space some bolshee or smaller quantity of biologically active molecules (enzimov, hormones, vitamins, mediatorov). On the basis of this " losses" a useful material at corresponding conditions also there is a formation sekretornogo process. With the points of view of utility the evolution course has fixed the raised maintenance in structure secrets and inkretov enough specific products of a metabolism of a cage, corresponding functions of special sets of cages necessary for realisation, become further corresponding bodies. For example, digestive enzymes while concentration of others substances either decreased began to develop a number of cages, or remained at former level.

qualitatively new and rather important acquisition in process evolutions was occurrence of ability of ferruterous cages - gladulotsitov - to to storage in them of a quantity sekretornogo a product in shape sekretornyh granules. Hence, at a corresponding cage has appeared possibility actively and immediately to deduce a little big quantity of a secret in reply to stimulation ekstruzii. The further evolution has ground this process, having created in a cage the mechanism simultaneously and reserving and transport function: there was device Goldzhi education in a kind widely the developed network of densely packed and flattened tanks, each of which has incorporated various sets of enzymes, etc. Thus, first the cage has secured itself against undesirable influence synthesised by it biologically rather active substances. Secondly, differenpirovka the device Goldzhi has given the chance for maturing and secret deposition. And in the third, occurrence of a superfluous product was exposed to destruction in device Goldzhi for the sake of giving more or less stable ur ovnja sekretornogo process.

the processing chain (metabolism) vneshnesekretornogo a product at which has been involved a basic principle of a feedback Thus was gradually formed. There is a general law progressive evolution (oligomerizatsija) according to which there is a consolidation of homogeneous absent-minded cages and their congestions. This position in to a full measure concerns and evolution ekzokrinnyh glands [2].

the higher animals had a division of glands on ekzo - and endokrinnye, and is sharp enough, unlike the lowest. On the other hand, along with processes of consolidation of isolated homogeneous cages, occurs and association of these cages in one body - association. So has occurred with sexual glands, podzheludochnoj, salivary, etc. Such education is enough the compact glands uniting in a single whole ekzo - and endokrinnye a part, creates preconditions for the big variations of thin local regulation of processes secretions ekzokrinnyh parts of these bodies, including with the help parakrinnoj secretions.

Evolution ekzogennoj regulation is connected with evolutionary changes as nervous, and endokrinnoj systems, on the one hand, and retseptornyh devices of cages - with another. L.G.Lejbson [12] has offered a hypothesis about an origin and evolution of receptors of cages according to which special the specific albuminous connections entering in lipidnyj bisloj plasmatic of membranes and other components of cages, become further to play a role receptors, have arisen is not dependent on occurrence of hormones. Retseptornye fibers originally could play not retseptornuju a role, and to regulate a complex physical and chemical processes in a cage. All course of evolution with the advent of a mutation have changed both receptors, and hormones and there was their ability to communicate with each other. Thus, hormones became stimulators for performance by their receptors reguljatornyh functions.

More often hormones are characterised as substance, operating on the remote places of the development - targets to which they are brought by blood - telekrinnaja secretion. It is rather difficult to draw a distinction between types inkretsii, but it is accepted to distinguish parakrinnuju secretion at which biologicheky the effect is reached by local diffusion or autokrinnuju, at which the operating beginnings influence on sekretirujushchie their cages. And if these types secretions, and also ekzosekrety are the products synthesised in a cage, which after allocation in out of do not become structural components a surrounding fabric ekskrety are the substances to which allocation not processes of endocellular synthesis, and in essence being products katabolizma, and rekrety - not changed molecules allocated with a cage and ions (Rice 1 precede).

Rice 1. Classification eliminiruemogo a material and secretion kinds

In turn sekretirujushchie cages differ on types. In those cases when end of process of secretion is accompanied by destruction cages, i.e. all cage finally turns to an amorphous secret, it is accepted to speak about golokrinovoj secretions. For a human body it very much rare type of secretion. A little meets apokrinovyj type when end-product allocation is accompanied by branch apikalnoj parts cages more often. Such type of secretion, in particular, is characteristic for potovyh glands, localised in axillary hollows and in promezhnosti. Most often in an organism takes place merokrinovyj type at which branches of parts of a cage together with a secret do not occur. It defines that circumstance, that at merokrinovoj secretions synthesis and regeneration processes occur enough smoothly, in parallel and continuously.

So, classical representations of cytology draw a picture, according to which sekretornye fibers are synthesised according to genetic the information program of the cage passed through RNK from DNA, on ribosomes, located on membranes so-called granuljarnogo endogogazmaticheskogo retikuluma (GER). The formed predecessor of fiber undergoes respective alterations simultaneously with moving to a place of the realisations. In particular, originally the predecessor of fiber moves in in channels or tanks GER where it is exposed to some transformations, and then is transported to tanks and device Goldzhi membranes. In a complex Goldzhi there is an accumulation sekretornogo the squirrel in condensing vakuoljah, which are gradually condensed and will be transformed in mature sekretornye granules, subjects ekstruzii by ekzotsitoza. Usually this process from the synthesis beginning before allocation of a ready product occupies on the average 1 - 1,5 hours. For the speed allocation of the formed secret influence speed of merge of membranes sekretornyh granules with a plasmatic membrane of a cage, a concentration gradient (concentration of substances in cages and in gleams atsinusov and channels).

it is important to underline, that, most likely, itself glandulotsit it is capable to select different ways of registration and deducing of a secret depending on type and a kind razdrazhitelja, its dose and duration of influence. Besides and all ferruterous cages differ from each other on character developed substrata albuminous, mukopolisaharidnyh, vodno-salt. All it finds reflexion and in a morphological structure glandulotsitov. However the description of these differences already is beyond the given sketch.

2. Mechanisms ekzosekretsii

Thus, at all structural and functional distinctions all sekretirujushchie cages have the general origin, mechanisms education and endocellular transportation of a secret. The nature enough is conservative, that with reference to ekzokrinnym to glands and bodies testifies to unity of many osnovopolatajushchih mechanisms. Hence, at seeming extreme measures in ability to live ekzokriknyh glands between them all spectrum of medical trades - from pediatrics and therapy to urology and gynecology lays.

In many bodies of an organism from the point of view ekzokrinologii epitely the intestines, a bilious bubble, etc., and sekretirujushchy, for example podzheludochnaja, salivary, etc. glands are divided on mainly vsasyvatelnyj, for example. On the other hand, character of an allocated secret allows to divide glands of external secretion on neslizeobrazujushchie, the end-product structure which consists basically from vodnoelektrolitnogo a component (potovye, plaintive, salivary), and slizeobrazujushchie which secret except vodnoelektrolitnogo contains also other substratum - albuminous, mukoproteinovyj, mukopolisaharidnyj (podzheludochnaja, predstatelnaja glands, glands epitelija respiratory grakta and other) .

Thus, it is quite proved, and to that there is a set proofs, to assume similarity of general mechanisms synthetic, transport and other processes in ekzokrinnyh organs and fabrics.

Though till now still there is no full representation about ways of transport and deducing of a secret from cages, and specialisation ekzokrinnyh cages is various, nevertheless, some general mechanisms ekzosekretsii are established. As is known, sekretornyj the answer arises on external stimulus " primary messendzherov" (intermediaries) - nejrotransmitterov, hormones, metabolitov or overwhelming action of any factors. Sekretogennye substances, co-operating with receptors of membranes atsinarnyh cages induce two functionally various stimulation ways - through nervous and hormonal mechanisms. One of them switches on activation ATS which carries out a role secondary messendzhera, located on a membrane inside, level increase tsamf in cages and then activation tsamf-dependent from proteinkinazy - the enzyme consisting from two reguljatornyh and two kataliti cheskih subedinits. Released kataliticheskaja subedinitsa fosforiliruet the albuminous substratum also calls strengthening of secretion [23].

the Friend Oh the mechanism operates through pool mobilisation endocellular calcium. Rather considerable if not predominating, the role in it plays fiber kalmodulin (KM) having four communications with calcium, and for the bill these communications passing in an active status. Penetration of calcium into a cage can go through AGF-DEPENDENT kaltsievye pumps. At concentration increase calcium it contacts Sa2+КМ, and this complex influences on Sa-transporting fiber (carrier). Sodium leaving a cage can exchange on calcium which enters into it.

Results of physiological researches have shown, that in activity regulation mukoznyh glands dominates innervatsija, having holinergichesky and parasympathetic character. However it at all does not exclude participation in secretion sympathetic adrenergicheskih ways of carrying out nervous impulses and, probably, neadrenrgicheskoj neholinergicheskoi innervatsii.

Sekretogennymi the substances starting the mechanism of increase tsamf are sekretin and vazoaktivnyj intestinalnyj peptid (TWISTED), and calling mobilisation of cellular calcium - hastrin and holetsistokinin. And though the initial stages initsiatsii secretions are various, in the subsequent phases they co-operate also additive definitive effect there can be big, than a simple sum of two interactions Sekretornaja activity potovyh, salivary, plaintive, bronchial and others ekkrinovyh glands is under influence not only adrenergicheskoj and holinergicheskoj systems, but also innervatsii peptidnymi fibres.

the Effect of stimulation mukoznyh glands, similar sympathetic nervous, has been received in vitro at influence on glands agonistami and #945;-adrenoretseptorov [11]. Histologic researches have shown, that the nerves containing kateholaminy, settle down both between atsinusami, and in atsinusah between glandulotsitami. The nervous fibres containing small granular vials, on to the character are adrenergicheskimi and at the person settle down close glandulotsitov. Besides, ability to accelerate ferruterous secretion possesses and vazoaktivnyj intestinalnyj peptid (TWISTED) and, possibly, so-called R.Vse`s substance the aforesaid characterises the independent control of secretion slime glandulotsitami.

the Role of hormones as powerful and universal regulators cage abilities to live is studied in detail enough. In particular, in the last years it has been shown, that prolaktin (PL) regulates rezorbtsiju chlorine in ekzokrinnyh glands [32]. prolaktin it is presented in granules so-called diffuznoj epitelialnoj endokrinnoj systems (DEE) cages sekretornogo rings human potovyh cages. Peptidy and other hormones, sekretirovannye parakrinno or autokrinno in cages DEE participate in regulation local cellular activity [38]. Possibly PL modulates concentration of chlorine in a secret through reabsorbtsiju salts in channels on ljuminalnoj to a membrane. Besides, PL can ingibirovat activity fosfolipazy А2 and clearing arahidonovoj acids.

influence of some other mediatorov is much less investigated. In particular, it is experimentally established, that atsinarnye cages have receptors to prostaglandinam and the Pg-mediated effect is realised in suppression fermentoobrazovanija ekzokrinnymi by cages [33].

secret Education develops of two processes of secretion the electrolits expressed however in various glands in unequal degree. For example, isotonic, rich Сl-the secret atsinarnyh cages a pancreas, stimulirovannyj atsetilholinom, holetsistokininom, in different proportions mixes up with the isotonic secret rich NSO3, formed in epitelii channels in reply to sekretin and TWISTED.

the Share enriched Сl-a secret in the general secretion at the person is insignificant. In reply to stimulation m-holinoretseptorov and in smaller to degree a-adrenoretseptorov the secret atsinarnyh pancreas cages on Сl- to structure is similar to plasma. Meanwhile, secretion is mediated by carriers Na +/ Сl-and Na +/H + or their equivalents. It becomes especially clear if to consider, that movement of ions not is end in itself, and it is necessary for moving defined, physiologically justified at present and under these circumstances, quantities of a liquid.

thermodynamics Laws suppose not only chreskletochnoe, but and intercellular moving of a liquid. However the answer becomes obvious in advantage chreskletochnogo water movings at the statement of a question: Whether there can be connecting intercellular complexes and structures are capable to pass a considerable quantity of a liquid and not to admit thus notable for complete an organism of loss of allocated ions?

In turn the understanding of uniform mechanisms of secretion allows to present those mechanisms of a half-ohm which arise at variety pathological statuses and diseases, and on this basis to start to to working out and application in practical activities of some therapeutic complexes.

2.1. Pancreas secretion

One of the most massive ekzokrinnyh bodies is a pancreas, which, besides, sekretiruet and a number of hormones, in particulars insulin. Pancreas hormones sekretirujutsja and #945; - and #946; - and and #948;-cages of islets Langergansa and basically regulate a carbohydrate exchange in an organism. Islets Langergansa are located among cages ferruterous parenhimy, making gland great bulk.

At the person the pancreas for days allocates nearby 1,5-2 litres of juice that means production gland in weight 80-100 g 20 ml on 1 g weights a day. So high efficiency almost has no equal in a human body. Pancreatic juice represents difficult education [colourless izoosmotichnaja to plasma of blood a liquid of alkaline reaction (rn 7,8-8,4), without a smell and with relative density 1007-1009] which conditionally enough can be divided into two components. First, it is its main component - organic substances basically an albuminous origin, most important of which are digestive enzymes: proteazy, lipaza, amilaza, in general complexities to 12 enzymes. From 6-8 digestive enzymes, daily allocated in a gastroenteric path of the person, 4-5 g it is developed by a pancreas [13]. Secondly, it vodoelektrolitnyj a component, containing in number other bicarbonates, microcells, and also slime. Education of a pancreatic secret is the sum of two processes of secretion electrolits. Isotonic, rich С1-the secret formed, apparently, in atsinarnyh cages and liberated under action atsetilholina and holetsistokinina-pankreozimina, in various proportions mixes up with the isotonic secret rich NSO3 which, possibly, is formed in epitelii channels in reply to sekretin and TWISTED [14 with 16]. The share enriched С1- a secret atsinarnyh cages in the general secretion at the person is minimum.

In postnatalnom the period the pancreas starts to develop especially intensively in the period from 6 mes till 2 years that is caused by qualitative and quantitative change of a food. In reply to introduction sekretina the pancreas responds increase in all enzymes at children is more senior 2th years. However gland development proceeds and in more senior age that is traced morfologicheski in gradual occurrence bugristosti and deleting of borders between segments.

Parenhima a pancreas represents separate the trubchato-alveolar segments consisting from epitelialnyh of cages, sekretirujushchih pancreatic juice. Structural unit parenhimy glands - atsinus - consists from 8-12 atsinarnyh the cages, several tsentroatsinarnyh cages, intercellular sekretornyh capillaries and vnutridolkovogo a channel. Atsinarnye cages a pancreas have the form of the truncated cone with the wide basis and contain 22 % rough rough retikuluma, mitohondrii make about 8 %, zimogennye gr anuly - 6,4 % and condensed vakuoli - 0,7 % [9]. In sekretornyh cages distinguish ischerchennyj an external belt and the internal granular. Such in the image, the morphology sekretornyh pancreas cages is typical for the cages developing an albuminous secret. N.K.Permjakov and soavt. [13, с.49] allocate five phases sekretornogo the cycle developed on defined territories of a cage:

Ekzokrinnyj the pancreas device concerns to to glands with merokrinovoj secretion at which mature granules zimogena enter close contact with apikalnoj a cage membrane.

Obrazuemyj atsinarnymi cages juice gipotonichen, therefore water transport in a gleam protokovoj systems occurs passively, under influence osmotic pressure, the juice following from Faterova a dummy in a gut, izotonichen. the Deducing channels of gland gradually merging basically vyvodnoj a channel, vystlany cubic epiteliem. Besides, in a mucous membrane of channels cages, developing an albuminous secret contain bokalovidnye the cages allocating slime, and also. And if the main function atsinarnyh cages is synthesis and secretion of various digestive enzymes function cages protokovoj systems is production of the secret, rich with bicarbonates a liquid necessary for neutralisation of gastric acid in intestines [9, с.49]

nejrogumoralnaja and hormonal regulation of secretion of a pancreas occurs on a duodeno-pancreatic axis by a principle a feedback - the universal mechanism of many vistseralnyh functions an organism. That regulation vneshnesekretornoj pancreas secretions consists in allocation under the influence of hydrochloric acid of a stomach cages a duodenal gut and the top departments of a thin gut of hormones pankreozimina and sekretina. Sekretin stimulates hydrogenetic function, raises the general secretion and the maintenance of bicarbonates. Considering close interaction sekretina with gastric acid, sekretin operates most effectively on an empty stomach and in to a late phase of digestion as at this particular time in duodenal a gut the greatest quantity zabuferennoj acids arrives. Similar action on secretion of bicarbonates though also smaller degree, than sekretin, possesses and TWISTED. pankreozimin possesses ekboliticheskim action: makes active fermentoobrazovatelnuju function atsinoznyh cages. Holetsistokininu attribute the diversified effects, including trophic influence on podzheludochnuju gland and appetite regulation, but its role as a stimulator secretion of pancreatic enzymes [14 is most precisely established, with. 16].

Bombezin it is capable to make stimulating impact on secretion of fiber by gland. On the other hand braking action on ekzosekretsiju a pancreas possess pancreatic polipeptid, somatostatin, enkefalin, nejrotenzin.

Amilolitichesky action of a pancreas is caused by secretion and #945; - and and #946;-amilazy, maltazy, laktazy, invertazy. Secretion amilazy at a fruit practically is absent. After a birth amilaza sekretiruetsja fermentativno active and to age of 1 year its level in duodenal to a gut makes only half of level of the adult person. At its optimum actions at rn 6,7-7,0 amilaza splits the basic carbohydrate components of food - sugar and starch in a duodenal gut and the top departments thin intestines to monosugars.

At newborn children low level activity pancreatic lipazy is defined, that grows out limited of biosynthesis or the lowered secretion. This fact partially explains incomplete vsasyvanie lipidov and frequent steatoreju at children of early age. However to to age of 1 year concentration lipazy sharply increases and exceeds level adults in 2,5 times. Lipaza it is allocated in an inactive status, it is activated by bilious acids and operates in an optimum rn 7,0-8,6. Except lipazy lipolitichesky the complex of pancreatic juice switches on fosfolipazu And and holesterolesterazu. Their basic physiological action - splitting neutral fat to glycerine and fat acids.

proteazy pancreatic juice are presented by variety specialised enzimov: tripsin, himotripsin, a complex eripsina, karbopetidaza, karbonatnaja oksipeptidaza, kollagenaza, elastaza, etc. At newborn children good absorbability and digestion of fibers is provided ekzo - and endopeptidazami as level himotripsina at makes them 50-60 % from level of children is more senior 2th years, karbopeptidazy In - 15-20 %, and tripsina - 90-100 %. Proteolitichesky enzymes are allocated in intestines in an inactive status that has the big biological value as amilaza and lipaza represent, as well as all enzimy, fibers. Thereof their presence at one solution with proteazami could lead to their destruction in an education place - in atsinusah a pancreas. Proteolitichesky enzymes are activated in a duodenal gut duodenazoj, enterokinazoj, providing oshchelachivanie and splitting of a sour mix proteozov, peptonov and partially not changed fiber to peptidov and amino acids.

Everyone atsinarnaja the pancreas cage is capable to make all developed by gland enzimy. It is thus used a universal principle cellular " conveyer", consisting in interchangeability of separate cellular elements. It is promoted by asynchronous activity atsinarnyh cages within one atsinusa and groups atsinusov [48, with 49].

the Pancreas possesses good kompensatornymi possibilities. It is enough to tell, that it is enough for full digestion of fats 2/3 parenhimy gland, fibers - 1/2, carbohydrates - 1/10, and for sufficient digestion - it is considerable its smaller part. The basic clinical displays ekskretornoj insufficiency of a pancreas (steatoreja and kreatoreja) arise at deficiency proteaz and lipazy more than 90 %.

the Practising doctor quite often should deal with a pathology ekzokrinnoj pancreas parts. And insufficiency vneshnesekretornoj functions can be primary or secondary. Most the expressed display ekzokrinnoj insufficiency of a pancreas is reduction or full absence of secretion of enzymes, and also such infringement reologii a secret at which at normal synthesis digestive enzimov owing to disporii they do not reach a place of the realisation. Thereof process of digestion changes and is broken normal mastering of nutrients.

2.2. Enteralnaja secretion

Responding problems of digestion and vsasyvanija food, mucous the intestines cover possesses the whole set of the specialised cages having doubtless signs ekzokrinnoj of secretion. Generally speaking, about mucous to a cover, it is difficult to draw a distinction between actually ekzokrinnymi cages and glands and the cages which do not have those signs.

In mucous duodenal guts digestive juice is developed trubchato-apinoznymi brunnerovskimi by glands. Brunnerovsky glands allocate the dense colourless liquid of alkalescent reaction containing mutsin and pepsinopodobnyj fermeng, activated hydrochloric acid. Besides, enveloping mucous a duodenal gut a dense secret, juice brunnerovskih glands carries out a protective role.

the intestines Mucous membrane is densely covered by fibers, between which settle down intestinal (liberkjunovy) glands or kripty, developing intestinal juice. At the bottom liberkjunovyh jelly z are panetovskie cages in which cytoplasm contain sekretornye granules. Unlike adults, at children of gland Paneta contain not only in thin, but also in thick to a gut. Intestinal juice contains a considerable quantity of digestive enzymes and mukoproteiny. In kriptah a thick gut contain bokalovidnye cages, producing necessary for mucous membrane and education humidifying kala slime.

According to ekskretornoj A.M.Ugoleva`s theories [19] extracellular digestion shares on polostnoe, or distantnoe, and pristenochnoe, or the contact. Secretion of glands of a gastroenteric path provides, before everything, polostnoe on apikalnyh membranes enterotsitov it is possible to present digestion, and education of a fermental layer as evolution morfostaticheskoj ekskretsii. Pristenochnoe digestion is carried out actually intestinal by the enzymes fixed on membranes of microfibers. The given type of digestion most typical for thin intestines. Over apikalnymi membranes enterotsitov the zone glikokaliksa, formed mukopolisaharidnymi is located by threads. Presence of intestinal enzymes in glikokalikse increases a surface pristenochnogo digestion. Over glikokaliksom it is located continuously replaced the layer of slime which also is a product of secretion and rich enzymes.

Complexity of regulation vneshnesekretornoj intestines to the full corresponds to activity by variety sekretiruemyh it of substances. the Status of transport of a liquid is regulated by the maintenance endocellular calcium in cytoashes enterotsitov.

Essential influence on secretion is rendered by levels parakrinnyh inkretov (hormones) of a gastroenteric path. So, gastralnyj ingibirujushchy peptid, enterogljukagon also TWISTED strengthen secretion of a thin gut. From found in extracts of a gut the factors which have been not identified as hormones, duokrinin and enterokrinin possess stimulirujushchimm effect, in particular on brunnerovy glands.

the Spectrum of diseases mucous the intestines, proceeding with defeat sekretirujushchih glands, is rather extensive. And. V.Frolkis [22] all a complex tonkokishechnyh the frustration, all it intestinalnye and ekstraintestinalnye displays, suggests to designate the term " enteralnaja insufficiency". Those whom questions of a pathology of a thin gut interest, we send to the monography of the author with the similar name. Within the limits of the given edition we will tell only, that practically all pathology of intestines requires that or other degree in replaceable therapy by enzymes.

3. Indications to replaceable therapy by enzymes. Oslozhneniya

to Indications for replaceable fermental therapy are the diseases proceeding with full or partial insufficiency podzheludochnoj of gland and glands of intestines [4, 24, 34] (Tab. 1.)

Representations about possible decrease functional activity of a pancreas at long reception enzimnyh preparations, sometimes extended both among patients, and among doctors, have under themselves no any scientific basis and consequently critics maintain. On the contrary, the premature termination of a preparation can eliminate reached therapeutic effect, therefore illness symptoms renew [4].

Other possible error trapping internista, appointing replaceable therapy by enzymes, consists in a dose choice a preparation. In the general view the recommendation concerning a dosage enzimov can be formulated as follows: the preparation dose should get out strictly individually, in compliance with degree zkzokrinnoj insufficiency a digestive path at the concrete patient under the control clinical and paraclinical signs. And, nevertheless, the recommended average dose is appointed from calculation 8000-10000 FIP.u. Lipazy/kg of weight of a body (about activity enzymes in preparations see more low).

Table 1. Indications for replaceable fermentativnoj therapies

Long application of replaceable therapy by enzymes, especially in high doses in some cases can lead to complications. to the Most serious is striktura a thick gut [29]. The development reason striktury consists in long use of highly active means with the maintenance lipazy from above 20000 FEP.u. Thus surplus of enzymes influences in the adverse image on mucous thick intestines, resulting to proof morphological changes. For the sake of justice it is necessary to tell, that the modern generation of enzymes of type Kreonj is deprived the given complication.

Other complication also connected with a high dose of enzymes, development giperurikozemii and in this connection displays artroiatii [31] is. The given complication also is not marked at purpose of the newest generation of fermental preparations.

4. The characteristic enzimnyh preparations

History replaceable enzimnoj therapies ofitsinalnymi has begun preparations with application of an extract of a pancreas (pankreatina) in the form of a powder. Thus at once lacks, low efficiency owing to inaktivatsii enzimov by sour gastric juice, necessity uses of high doses, organolepticheskie properties and dr E di Magno and soavt were found out. (1977 [26] have established, that at reception pankreatina only tripsina and 8 % lipazy reach 22 % of a lean gut in the active form necessary for processing himusa.

Following generation of pancreatic enzymes were preparations in which the operating beginning has been covered by system of covers (Panzinorm, Festal, Digestal and dr). However their application also soon has found out the above-stated lacks and, besides, in each tablet or a dragee there was a ballast that has led to substantial growth of volume of a tablet (more than 3 mm) and to essential restriction for use of the given means in to pediatric practice as tablet fragments injured mucous, and the basic part of a preparation - enzymes - inaktivirovalis gastric contents. Inaktivatsija pancreatic enzymes sour gastric juice has led to necessity of simultaneous purpose antisekretornyh preparations - Н2-blokatorov gistaminovyh receptors, ingibitorov a protonew pomp and others antatsidov.

In the subsequent generation enzimnyh means these lacks managed to be overcome by sharp reduction of volume of a tablet (on the average from 1,2 to 2,0 mm), increases kislotoustojchivosti at the expense of a covering of the operating beginning thin polymeric films. The first preparation of the given generation became offered in the mid-seventies pankr eaza. Later have appeared Кreon®, Prolipase®, Cotazym®, Ultrasa®, Protilase®, Pantsitratj, etc. Thus were on the market variations of the given preparations with various activity - from 4000 to 40000 FIP u have been offered. lipazy. Considering enough the big assortment enzimnyh the preparations delivered by various firms to the doctor it is necessary to be guided in to an estimation of the activity expressed in European and North American units. In tab. 2. Such units and a parity between them are presented.

Table 2. Activity Units of measure pancreatic enzymes

the Abundance of preparations has prompted many researchers on comparative researches in clinic [39]. So, M. Otte et al. (1987 [37] comparing 14 preparations have come to conclusion, that only 3 from them save high activity within 120 minutes inkubatsii at rn 6,6. Thus most preferable means had appeared Кreon®. Comparison of activity Кreon® and Prolipase® has shown advantages of the first: higher percent of liberation lipazy at inkubatsii at rn 5,6 (85,9 and 14,4 %); higher factor vsasyvanija fat (89,98 and 88,95 %) and factor vsasyvanija nitrogen (86,09 and 84,75 %) [28].

Кreon is the microspherical form pankreatina from a pancreas of the pig, optimum balanced on structure lipazy, amilazy and proteaz/Microspheres Кreon® have protective kislotoustojchivoe a covering steady against aggression of gastric juice and are concluded in gelatinous a capsule.

All it has allowed to achieve creation of a high dose of enzymes owing to uniform distribution enzimov in duodenal both thin to a gut and dissolution of a polymeric film only in an optimum rn > 5,5 [5, 39]. Such in the image, it was possible to observe the standard requirements shown to to pharmacological preparations, switching on:

At the same time it has allowed to use the given means, both at adults, and at children of any age group.

At treatment Kreonom trophic function holetsistokinina [25] is saved. As it was possible to establish, proteinazy Pseudomonas aeruginosa do not render ingibirujushchego action on enzymes Kreona, and application of the given means essentially does not influence level ingibitorov proteaz (and #945; 1-ingibitor proteaz and and #945; 2-macroglobulin), on a gain specific antibodies in blood with negative effect for patients [27].

a Fig. 2. The origin abdominalnyh pains at infringements and their knocking over

As was specified to pancreatic secretion above Кгеоn® is deprived such complication, as striktura a thick gut. Besides, purpose Kreona raises level fat-soluble vitamins in an organism [7, 36].

Besides gidroliticheskogo actions (and thanks to it) pancreatic enzymes can stop a painful syndrome that illustrates fig. 1. It is necessary to specify, that purpose of extracts pancreatic enzimov is necessary for spending strictly individually and the preparation dose should correspond to degree vneshnesekretornoj to insufficiency of gland unlike traditional srednevozrastnyh doses.

Clinical experience of application Kreona has found out it analgezirujushchee action, partially because pancreatic extracts activate opioidnye peptidy, partially at the expense of ability tripsina to reduce level holetsistokinina in blood plasma [26, 34].

Recently experts of company SOLVAY PHARMA create new modern forms of fermental preparations of a pancreas, containing minimikrosfery (Kreon 10000 and Kreon 25000) which are considered as preparations of the first choice in fermental therapy. At new process manufactures began possible to reduce the size of a gelatinous capsule considerably. So, the size of a capsule of preparation Kreon 10000 containing minimikrosfery, in two time is less than size of capsule Kreon which contains microspheres. New forms preparation Kreon 10000 and Kreon 25000 meet all requirements shown to to a modern fermental preparation.

5. Application of preparation Kreonj at mukovistsidoze

Mukovistsidoz represents system multiorgannoe the disease of hereditary character having in the basis defeat ekzokrinnyh of glands of an organism. Now from more 250 described hereditary illnesses of a metabolism in evropeoidnoj populations more often meets mukovistsidoz at 1 of 2000-2500 newborns.

Mukovistsidoz - polymorphic on clinic (expressiveness, severity levels, etc.) diseases, i.e. defect is predetermined till a birth the child. However we managed to establish, that is far not at all disease began with a birth, at many patients the clinical picture has undergone certain evolution in the form of transformation of clinical forms of illness, change severity levels. Hence, except genetic factors on an illness current set of factors of environment On the basis of these reasonings influences it is possible to construct the hypothetical formula illustrating a parity of genetic and ecological factors:

Fm = and #931; (НMi + СMi) - and #931; (HNj + CNj), where Fm - a phenotype by sign mukovistsidoza; НMi - hereditary factors mukovistsidoza; СMi - sredovye adverse factors (a diet, a pneumonia, an infection etc.) ; HNj - hereditary favorable factors, CNj - sredovye favorable factors (a diet, treatment, prophylactic medical examination etc.).

From the given model follows, that if and #931; (НMi + СMi) > and #931; (HNj + CNj) disease display is available and if in given equation to put a sign = or <, patients will be fenotipicheski if and are not healthy then to have an easy current of disease. This the formula, by the way, can explain and clinical polymorphism mukovistsidoza. With the practical point of view for the doctor it is important to solve questions of reduction of factors CMi and strengthenings of factors СMi. And now there was a strategist icheskaja possibility to reduce pressure of factor НMi for the bill molekuljarno-genetic methods and prenatalnoj diagnostics.

Total infringement of activity of ionic channels of membranes cages ekzokrinnyh bodies leads to change reabsorbtsii sodium and chlorine, that in turn promotes decrease in volume of a water component of a secret glands and, as consequence, disporii - to difficulty of outflow and stagnation of secrets ekzokrinnyh glands in vyvodnyh channels which directly is connected with infringement reologii.

Infringement of digesting function of a gastroenteric path at mukovistsidoze define the whole complex of deviations of some systems and functions: vitamin insufficiency, damage of systems of a homeostasis, krovetvornoj, etc. Together with infringement of splitting and vsasyvanija fats mastering fat-soluble vitamins decreases.

the Basic defect mukovistsidoza calls various, at times rather considerable changes in activity of a gastroenteric path at patients as the given system is centre ekzokrinnoj fabrics. it is Enough to name such glands and bodies, as salivary and podzheludochnaja glands, a stomach and a liver, mucous thick and thin intestines. The given system represents the anatomic and functional unity subordinated uniform of the purpose - to maintenance of recycling of food substances and homeostasis regulation.

pancreas Dysfunction is secondary and caused by corking vyvodnyh channels and atsinusov a viscous secret. At 75 % of patients the maintenance tripsina in blood whey corresponded chronic to a pancreatitis, at 10 % sharp, and increase lipazy depended on weight pathological process. Patients mukovispidozom have a decrease secretions by a sodium pancreas, kalija, chlorides and water. Reduction leads to secretion of bicarbonates inaktivatsii pancreatic enzimov and pretsipitatsii bilious salts on a gut surface, that in turn breaks soljubilizatsiju lipidov [36].

At mukovistsidoze decrease in fat acids not only in blood, but also in fabrics (a liver, lungs, heart) is revealed. To the greatest degree digestion of fats at the expense of decrease in level pancreatic lipazy suffers. Deficiency tripsina and himotripsina define infringement vsasyvanija the squirrel. At it activity decrease enterokinazy, carrying out the basic role in transformation tripsinogena, himotripsina and prokarbopeptidazy in their active forms is revealed. All it leads disbalansu amino acids in blood (sum increase zamenimyh on 11 % and decrease in the sum irreplaceable on 27 %). Inadequate digestion and absorption of proteins and soluble vitamins in fats leads to level decrease transferrina and prealbumina.

On a status of acidity and fermentativnoj activity gastric juice can consider, that ability of a stomach to food digestion is not broken, except decrease in volume gastric and duodenalnogo juice with presence a slime considerable quantity.

Steatoreja conducts to loss of calcium with a chair which is allocated in the form of soap as in intestines takes place omylenie calcium not adsorbed fat acids. Thereof can develop gipokaltsiemija, and sometimes and tetanija [17].

thus, infringement of activity of glands digestive systems at mukovistsidoze defines variety of secondary changes digestion and vsasyvanija foodstuff.

the Clinical picture mukovistsidoza rather polimorfna and develops of symptoms of defeat of various bodies and the systems expressed in unequal degree. At the analysis of proportions of patients it was found out weak development of a hypodermically-fatty layer, increase in a circle of a thorax, growth decrease. Development of a dystrophy in patients directly is connected with infringement activity of system of digestion, thus that gipotrofija develops against normal or even the raised appetite is characteristic. Though the muscular weight at patients mukovistsidozom is lowered, absolute speed degradations of muscular fibers is not changed.

At sick children with classical kratinoj mukovistsidoza characteristic appearance - the doll person, the expanded, quite often deformed thorax, the big blown up stomach (the umbilical hernia is quite often marked), thin finitenesses with deformation trailer phalanxes of fingers of hands and feet in a kind " is early enough formed; drum-type sticks", dry, serovato-earthy colour a skin. From other general symptoms it is possible to specify on accompanying dysfunction of a pupil of an eye, and also defeat of eyes as night blindnesses with the characteristic changes of an eye bottom liquidated by purpose of vitamin A.

the Clinical picture of a respiratory syndrome develops from combinations of some symptoms: cough to which at an aggravation bronholegochnogo process a short wind and tsianoz, intolerance physical loadings and a short wind, presence listened damp and dry rattles in lungs, as a rule, accompany constantly or often, even out of an aggravation bronholegochnogo process.

Studying of a clinical picture mukovistsidoza at adults and has shown teenagers, that with the years there is a demonstration smoothing illnesses, the quantity of rare displays of disease and complications thus increases. We managed to register the symptoms peculiar only to teenagers and the adults. Basically it concerns reproductive system: a delay of sexual development, barreness, a chronic prostatitis., in our opinion, postulation of that position is rather important, that symptoms mukovistsidoza adults develop not only of cases resulting of early children`s age, but also has probably begun clinical displays in much later age. Degree of expressiveness of changes physical working capacity correlates with weight of a body.

the Clinical picture of defeat of a gastroenteric path at mukovistsidoze is defined by change of physical and chemical structure of secrets digestive glands and the syndrome connected with it malabsorbtsii and maldigestii.

Indirect display of an intestinal syndrome is decrease weights of a body, and the more considerably, than more low level intestinalnyh enzymes. Characteristic for mukovistsidoza it is considered development gipotrofii against normal or even the raised appetite. The given supervision can be useful at carrying out of differential diagnostics with others enteropatijami.

Test with d-ksilozoj has allowed us to estimate degree vsasyvanija carbohydrates as in a lean gut (a portion 1), and in distalnyh departments thin guts (a portion 2). At the patients surveyed by us the total average index tests with d-ksilozoj has appeared lowered - 22,61±3,1 % at the expense of infringement vsasyvatelnoj functions and initial (12,68±1,9 %) and distalnyh departments (9,93±3,4 %) thin intestines.

At a part of patients pains in a stomach at the expense of a congestion gases in intestines were marked. The phenomena meteorizma define at fizikalnom inspection - the increased stomach, one of which reasons is the hypotonia of muscles.

In our supervision we have met three cases late ileusa (an equivalent mekonialnogo ileusa), that was shown in a kind invaginatsii in an interval between 1st and 2nd years of a life and has led surgical to intervention with a resection of a part of a gut.

In these cases in intestines gleam the weight of type mekonija is found out zamazkoobraznaja. It is characteristic, that the given patients before development late ileusa did not accept some pancreatic enzymes that could be an immediate cause of development of an equivalent mekonialnogo ileusa.

One of starting symptoms of an intestinal syndrome at mukovistsidoze is chair infringement. It is considered the most typical fat, plentiful, fetid, zamazkoobraznyj grey colour a chair. Rather unpleasant the smell of excrements is connected wit h presence of products of disintegration of fibers and at times happens is intolerable other members of a family. At the moment of diagnostics mukovistsidoza steatoreja it has been found out in 87,5 %, and nitrogenous losses at 1 9,1 % of patients.

Considerable steatoreja it is shown by occurrence on diapers and the linen is difficult otstiryvaemyh stains, bad washing off kala from walls of a pot or even visible approximately fat droplets. A congestion of a viscous sticky secret of glands intestines and good vsasyvanie waters lead to consolidation kalovyh weights and define at a part of patients propensity to locks or, that happens more often, especially at sick senior age groups, to alternation of locks and an unstable chair, disappearing independently, but, as a rule, repeating again.

Owing to such infringements defekatsii, and also meteorizma, decrease in a tone of muscles promezhnosti, can arise secondary anorektalnye complications: analnye cracks and rectum loss - at 19 % patients. As we managed to note selection of an adequate dose of enzymes led to gradual disappearance of this symptom. Hence, it can relieve the patient of unjustified surgical intervention.

At all patients mukovistsidozom with an intestinal syndrome it is defined assotsiirovannyj intestines dysbacteriosis in a combination with low activity enterokinazy and SHCHF in kale, that specifies in synthesis infringement enzymes in a thin gut.

As a rule, the dystrophy at mukovistsidoze is accompanied by various displays poligipovitaminoza, basically fat-soluble vitamins; at 25 % of patients with a heavy current of an intestinal syndrome develops secondary tseliakija and disaharidaznaja insufficiency.

Radiological research reveals a gas congestion in loops of a thin gut, a hypotonia and a hypomotor dyskinesia in various departments, a slime congestion in gut gleams, sometimes " washing off" a relief and folds a mucous membrane. The relief of a duodenal gut rough, chaotic, is more rare cellular, in the form of honeycombs filled with slime, kistoznyj pnevmatoz thick than guts, izjazvlenie thin intestines [1].

Ehografichesky research of a pancreas has allowed to reveal changes at 42-74 % of patients with mukovistsidozom from which at 90,5 % has been received strengthened ehosignal; at 3,6 % were found out kisty and in 1,4 % of patients expansion of channels of gland [30]. In our series supervision (51 patients) to find out makrokisty in a pancreas increase ehosignala at 18, increase in gland at 7 of 51 surveyed patients was possible at 5 patients.

power consumption Studying in rest at patients from 8 till 35 years has shown its increase correlating with decrease of function of lungs and level of fat of a body. Level of power inputs at patients has made 876-950 kcal in comparison with 758 kcal in control group healthy, that is on the average on 25 % above. Hence, at mukovistsidoze the increase in requirement for energy is marked, the last in turn influences a food status.

From what there is an infringement of balance of energy at patients mukovistsidozom?

Any disease which leads to destruction or loss bolshej parts parenhimy a pancreas can cause development a diabetes. Such diseases concerns and mukovistsidoz. It is noted, that risk of development of a diabetes at patients mukovistsidozom in 10 times above, than at healthy [14, with 16].

Other prominent aspect of metabolic complications mukovistsidoza is infringement of functional activity thyroid glands. Interest to studying of its function is caused also by that circumstance, that defeat of glands of a gastroenteric path can lead to belkovo-high-calorie insufficiency as nedopostuplenie enzymes a pancreas causes insufficient mastering of food substances. At belkovo-high-calorie insufficiency in an organism are marked defined changes of levels of hormones of a thyroid gland: level Т3 decreases at increase reversible Т3 and Т4 [21]. We had been spent studying of function of a thyroid gland by means of definition of levels Т3, Т4, TGG and TSG in whey of blood by RIA method. As have shown results, patients had an essential decrease in levels Т4 on to comparison with control group of healthy children of similar age (97,8±6,3 and 161,63±12,98 nmol/l accordingly, р< 0,01) and Т3 (1,3±0,04 and 1,98±0,12 nmol/l, р< 0,05). Concentration TTG, on the contrary, has been raised to 9,72 ME/ml against norm - 4,27±0,7, р< 0,001). Maintenance TSG has appeared in limits standard fluctuations - 18,8 mkg/ml (18-21).

Thus, the carried out research has shown, that at patients mukovistsidozom there is a change of functional activity a thyroid gland which can be regarded as biochemical gipotireoz. it is possible, the mechanism of reduction of conversion Т4 in Т3, intended for protection of an organism from superfluous metabolic stimulation in this case takes place, and noted changes it is possible to regard as biologically expedient reaction for preservation of hormonal balance at these patients. It becomes clear in the light of the received data on restriction a power consumption in rest.

As it was specified above, one of regulators of allocation of salts with then is prolaktin. M Robertson et al. [38] consider increase activity PL at patients mukovistsidozom as a consequence of its strengthened production in DEE cages as in cages epitelija easy patients the quantity of granules PL has been increased. S. Wiersbitzky et al. [40] suppose some possibilities realisations PL in patogeneze mukovistsidoza, including: increase PL in to blood whey; abnormal structure PL; change of Pl-receptors; change endocellular processing (metabolism) PL; indirect influence PL on kalmodulin.

the research carried out by us syvorotochnogo level PL at patients with mukovistsidozom has established its raised concentration - 402,1±10,3 mU/ml in comparison with standard level. Thus the correlation analysis has shown, that there is a communication between levels PL in blood and chlorides in sweat (r=0,51, р< 0,02). It is obviously possible to us to consider increase PL and as one from the moments patogeneza infringements of electrolits at mukovistsidoze. Received results show, that PL plays a role not only as a lactation regulator, but also as a regulator of transport chlorine