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Компанієць К.М. Динаміка концентрації циркулюючих імунних комплексів та їх молекулярного складу у хворих на хронічний некалькульозний
28.05.2014, 17:02

Резюме
Компанієць К.М. Динаміка концентрації циркулюючих імунних комплексів та їх молекулярного складу у хворих на хронічний некалькульозний холецистит у сполученні з ішемічною хворобою серця та хелікобактеріозом при лікуванні еспа-ліпоном та кораргіном.
У хворих на хронічний некалькульозний холецистит у сполученні з ішемічною хворобою серця та хелікобактеріозом мали місце зміни як загального рівня циркулюючих імунних комплексів (ЦІК), так і їх молекулярного складу, які залежали від наявності та ступеня обсіменіння НР. Включення кораргіну та еспа-ліпону до комплексу лікування цих пацієнтів сприяло зменшенню концентрації ЦІК в сироватці крові, так і відновленню їх молекулярного складу.
Ключові слова: хронічний некалькульозний холецистит, ішемічна хвороба серця, хелікобактеріоз, циркулюючі імунні комплекси, лікування, кораргін, еспа-ліпон.
Резюме
Компаниец К.Н. Динамика концентрации циркулирующих иммунных комплексов и их молекулярного состава у больных хроническим некалькулезным холециститом в сочетании с ишемической болезнью сердца и хеликобактериозом при лечении еспа-липоном и кораргином.
У больных хроническим некалькулезным холециститом в сочетании с ишемической болезнью сердца и хеликобактериозом имели место изменения как общего уровня циркулирующих иммунных комплексов(ЦИК), так и их молекулярного состава, которые зависели от наличия и степени обсеменения НР. Включение кораргина и еспа-липона в комплекс лечения этих пациентов способствовало уменьшению концентрации ЦИК в сыворотке крови, так и восcтановлению их молекулярного состава.
Ключевые слова: хронический некалькулезный холецистит, ишемическая болезнь сердца, хеликобактериоз, циркулирующие иммунные комплексы, лечения, кораргин, еспа-липон.
Summary
Kompaniets K.N. Dynamics of concentration of circulatory immune complexes and their molecular composition at patients with chronic noncalculous cholecystitis, combined with ischemic heart disease and helicobacteriosis at treatment of espa-lipon and korargin.
At patients chronic noncalculous cholecystitis, combined with ischemic heart disease and helicobacteriosis troubl the changes of both general level of circulatory immune complexes(CIC) and their molecular composition took place, that depended on a presence and degree of semination of НР. Including of espa-lipon and korargin in the complex of treatment of these patients assisted decline of concentration of CIC in the serum of blood and renewal of their molecular composition.
Key words: chronic noncalculous cholecystitis, ischemic heart disease, helicobacteriosis, circulatory immune complexes, treatments, espa-lipon, korargin.
Рецензент: д.мед.н., проф. І.В. Лоскутова

УДК 616.366-002+616.12-008.331.1]-08-053.81

ДЗ «Луганський державний медичний університет»

ГЗ «Луганский государственный медицинский университет»

91045, кв. 50-летия Обороны Луганска, 1 г, Луганск, Украина

State Establishment "Lugansk State Medical University"

91045,50 Rokyv Oborony Luganska Block, 1G, Lugansk,Ukraine

propedevtika2011@yandex.ru

Introduction. The presence of united pathology is characteristic for a modern patient that results in the origin of independent process in  organism that has its pathogenetic mechanisms and clinical symptoms [3,8]. Nowadays it is registered the incidence rate [9] including in Ukraine on 42,3% [2], in 7,5-14% cases CUC (chronic uncalculary cholecystitis) proceeds  in combination with coronary heart disease (CHD) including one of its forms stable effort angina that remains the issue of the day of modern medicine [4]. The role of infection of Helicobacter  pylori (НР) at the united  biliary and cardiac pathology is remained as not enough  investigated that is not only the factor of origin of  erosive ulcerative defeats of gastroduodenal zone but it is observed in  bilis and mucous membrane of gall bladder (GB) and has influence on development of CHD [10]. Research of immune mechanisms will allow to work out the pathogenetic reasonable ways of treatment optimization  for  improvement of life quality   of patients with CUC in combination with CHD and helicobacteriosis. In this context possibility of using in treatment   combination of home medicinal agents  that contain arginine - donator NO (сorargine) and  lipoic acid attracts attention .

Connection of the work with  scientific programs, plans, themes

The work is accomplished in accordance with the basic plan of research works (RW) of  government facility "Lugansk State Medical University"  and it is a fragment of themes of RW of the department of  propedeutic and internal medicine where a candidate is a participant: "Medical rehabilitation of patients with united pathology"(№ state registration 0109U004608).

The  aim of the research   is investigation of dynamics concentration of circulatory immune complexes and their molecular composition for patients with  chronic uncalculary cholecystitis in combination with coronary heart disease and helicobacteriosis at treatment of espa-lipon and сorargine.

Materials and research methods

It was examined 269 patients with CUC in combination with  CHD that were treated on the bases of department of  propedeutic and internal medicine  ( 82 men -  30,5%; 187 women - 69,5%) middle age of the patients was  42,5±4,5 years old,  with duration of united pathology  from 1 to 12 years, among whom 187 persons had CUC in combination with CHD and helicobacteriosis (I group). The indexes of clinical, laboratory and instrumental researches for these patients were compared with analogical ones of group ІІ that consisted of 82 patients ( men - 32,7%, women - 67,3%) with  CUC in combination with CHD without helicobacteriosis (middle age 41,6±4,4 years old). Later on it was formed two randomized groups of patients from group I depending on facilities of treatment by gender, age and duration of united pathology:  basic (110 persons) and comparison (77 persons). The concentration of circulatory immune complexes (CIC) was studied by the method of precipitation  in the solution of  polyethyleneglycol (PEG) with molecular mass of 6000 dalton; molecular composition  of CIC was studied by differentiated precipitation in 2%, 3,5% and  6% solutions of PEG [6]. It was considered that according to the level of CIC especially the most pathogenic (midmolecule and small molecule  fractions) it was possible to judge about evidence of  immune toxicosis syndrome  [7].

Verification of CUC was carried out according to the  Order of the Ministry of Healthcare of Ukraine № 271 "About approval of protocols of  medical aid  provision  specialty "Gastroenterology""  (13.06.2005); CHD (the stable angina of ІІ FC) - the  Order of the Ministry of Healthcare of Ukraine № 436 "About approval of protocols  of  medical aid  provision  specialty "Cardiology"(03.07.2006) and also on the basis of recommendations of the Ukrainian association of cardiologists(2011).

The treatment of the examined patients was carried out according to the  Order of the Ministry of Healthcare of Ukraine № 271(2005) and  the  Order of the Ministry of Healthcare of Ukraine № 436(2006). The patients were prescribed  standard therapy of CHD that included β-blocators,  ACE inhibitors, aspirin, nitrates of necessity , statins; standard therapy of CUC included antibacterials of necessity, spasmolytics,  cholekinetics, antihistaminics, enzymic preparations, herbal brews with  antiinflammatory and  choleretic action, physical therapy procedures and helicobacteriosis - carrying out of "triple" antihelicobacteriosis therapy during 14 days with control of eradication efficiency. The patients of basic group got corargine (per os before meal  1 pill 3 times per twenty-four hours during three weeks) additionally. The effect of that was conditioned by stimulant influence on  synthesis of NO and  inhibitory one on activity of freely-radical processes [1] and modern medicinal product  espa-lipon (0,9 g one dose in the morning during 2 months) that is one of major components of the system of antioxidant defense of organism, assists supporting of balance in the system of  glutathione and  ubiquinone, prevents the damage of  mitochondria, releases of cytochrome  and cell death that is conditioned by the action of  cytokinins , has a positive  lipotropic action, subdues the sizes of atherosclerotic atherosclerosis plaque  [5].

Statistical data processing of the got results was produced on the base of computer center of the V. Dahl East-Ukrainian national university   using the packages of the licensed softwares of Microsoft Office 2000, Microsoft Excel and Statistica  6.1/ prof.

Obtained results and discussions

While studying the content of CIC in the  blood serum   it was set  that examined patients had reliable changes of  general level of CIC and its molecular composition that depended on the presence and degree of semination НР.

As a result of conducted researches it was set that  all examined patients had the  increase of general concentration of CIC  in the blood serum and at the same time the most expressed were changes in the Іst group (infection НР). So the level of CIC in this group increased on the average in 1,7 and formed 3,19±0,09 g/l ( while the norm is1,88±0,12 g/l; р<0,001) however in the ІІnd group the repetition factor of difference with a norm was 1,25 and general content of CIC was equal  2,35±0,05 g/l (р<0,05). Let notice that the repetition factor  of difference of general level of CIC between groups was1,36 times(р<0,01). While analysing the general concentration of CIC for patients with the different degree of semination  НР it was set that at a high degree it formed 4,25 g/l that was on the average in 2,26 times higher than norm (р<0,001), at  moderate semination it was 3,17 g/l (the repetition factor of difference  with a norm 1,69; р<0,01) and at weak it was 2,44 g/l that was higher than norm in 1,3 times (р<0,05) and at the same time belower than indexes at  high and moderate degree of semination in 1,74(р<0,05) and 1,3(р<0,05) times accordingly. Thus it is evident the dependence of general level of CIC  in the blood serum   from the degree of semination  НР.

The research of molecular composition of CIC for patients with CUC in combination with CHD and helicobacteriosis allowed to reveal that the increase of level of CIC took place mainly due to the most  toxigenic  fractions: midmolecule  (11S-19S) and small molecule (<11S) (table.1).

Table 1

Concentration of CIC and their molecular composition in examined patients with CUC in combination with CHD and helicobacteriosis in

dependence of degree of semination  НР(M±m)

Immunological measure

Norm

Groups of patients

High degree of semination

Moderate degree of semination

Low degree of semination

CIC

г/л

1,88±0,09

4,25±0,21

Р1<0,001

3,17±0,13

Р1<0,01

Р2<0,05

2,44±0,10

Р1<0,01

Р3<0,05

Big molecule fractions

%

44,5±2,3

30,12±2,0

Р1<0,05

33,44±1,6 Р1<0,05

Р2<0,05

35,25±1,7 Р1<0,05

Р3<0,05

g/l

0,84±0,04

1,28±0,09

Р1<0,05

1,06±0,07

Р1<0,05

Р2<0,001

0,92±0,06

Р1<0,01

Р3<0,001

Midmolecule  fractions

%

30,5±2,0

38,59±2,6

Р1<0,05

36,59±2,2

Р1<0,05

Р2<0,001

39,75±2,1

Р1<0,05

Р3<0,001

g/l

0,57±0,04

1,64±0,09

Р1<0,001

1,16±0,07

Р1<0,01

Р2<0,05

0,97±0,06

Р1<0,01

 

Small molecule  fractions

%

25,0±1,6

31,29±2,1

Р1<0,05

29,97±1,7

Р1<0,05

Р2<0,001

25,0±2,1

Р1<0,05

Р3<0,001

g/l

0,47±0,03

1,33±0,06

Р1<0,001

0,95±0,06

Р1<0,01 Р2<0,05

0,61±0,05

Р1<0,01

Р3<0,05

 

Note: Р1 is probability of difference concerning the norm; Р2 is probability of difference between indexes for patients with  high and moderate degree of semination  НР; Р3 is probability of difference between indexes for patients with  moderate and low degree of semination  НР.

Thus increase of content of CIC in the blood serum of patients especially with  high degree of semination  НР  took place mainly due to an accumulation of the most  toxigenic  fractions that  was probably related to suppression of phagocytic activity of monocytes (PAM) that belonged a basic role   in  elimination of CIC from blood.

As a result of immunological research it was set that  all examined patients had the increase of general concentration of CIC  in the blood serum  (table 2).

Table 2

The level of CIC and their molecular composition for patients with CUC in combination with CHD and helicobacteriosis

at the  beginning of treatment(M±of m)

Immunological measure

Norm

Groups of patients

Р

basic

(n=110)

comparison

(n=77)

CIC,         g/l

(>19S),    %

               g/l 

1,88±0,09

3,12±0,09***

3,02±0,12***

>0,05

44,5±2,3

33,0±1,9**

34,7±2,0*

>0,05

0,84±0,04

1,02±0,06*

1,05±0,06*

>0,1

(11S-19S), %  

               g/l 

30,5±2,0

39,9±2,1*

38,5±2,1**

>0,1

0,57±0,04

1,24±0,07***

1,15±0,06***

>0,05

 (<11S),      %

             g/l

25,0±1,6

27,1±1,2*

27,4±1,7**

>0,05

0,47±0,03

0,86±0,04***

0,86±0,05***

>0,05

Note: there is possibility of difference concerning the norm * - at Р<0,05, ** - at Р<0,01, *** - at Р<0,001; the column  Р is an index of possibility of differences between a basic group and group of comparison in the tables 2-3 .

 

So the level of CIC in the basic group was increased at the average in 1,7 times and it made 3,12±0,09 g/l   (a norm is 1,88±0,12 g/l; р<0,001), in the group of comparison it was increased at the average in 1,6 times reaching 3,02±0,12 g/l. Research of molecular composition of CIC for patients with CUC in combination with CHD and helicobacteriosis allowed to reveal that the increase of the level of CIC took place mainly due to the  most toxigenic  fractions : midmolecule  (11S-19S) and small molecule  (<11S). So the  total content of these fractions in the period of recrudescence of CUC in the basic  group of patients at the average it was  67±1,6% at the  norm  55,8±0,5р<0,05), in the group of comparison it was 65,9±0,7%. Determination of absolute content of sum of the indicated fractions of CIC allowed to mark their considerable increasing: in the basic group on the average in 2 times, in the group of comparison in 1,9 times(р<0,001).

In connection with the increase of content of  small molecule and midmolecule immune complexes the relative content of big molecule  CIC had a tendency to the decline of specific gravity in a basic group on the average in 1,34 times concerning the index of norm(44,5±2,3 р<0,01) and in the group of comparison  in 1,28 times(р<0,05). At the same time in connection with the increase of general CIC level  next to the increase of concentration of small molecule and midmolecule       fractions it was marked increasing of absolute count of fraction of big molecule complexes though in a less degree: in a basic group  to 1,02±0,06 g/l, that was  in 1,21 times (at a norm 0,84±0,04; р<0,05) and in the group of comparison in 1,25 times(1,05±0,06 g/l; р<0,05). Thus the changes of CIC for the patients of both groups were of the same type (р>0,05).

After ending of treatment in both groups of patients the positive changes of concentration and molecular composition of CIC in the blood serum  were determined . So the multipleness of reduction of  CIC concentration  for the patients of basic group was at the average 1,9 times(р<0,001), in the group of comparison in 1,4 times (р<0,01). The concentration of CIC in the blood serum in a basic group at the moment of ending of treatment for certain did not differ from the index of reference norm; in the group of comparison it exceeded the norm in 1,5 times(р<0,01). The repetition factor of this index between the patients of basic group and group of comparison made 1,3 times(р<0,01).

The analysis of fractious composition of CIC testified that fractious composition of CIC recommenced after ending of treatment for the patients of basic group. In the group of comparison the studied indexes not having regard to a certain positive dynamics remained different from the norm and data of basic group (table.3).

Table 3

Concentration of CIC and their molecular composition for patients with CUC in combination with  CHD and helicobacteriosis

after ending  of treatment(M±of m)

Immunological measure

Norm

Groups of patients

Р2

basic

(n=110)

comparison

(n=77)

CIC

g/l

1,88±0,09

2,1±0,12

2,8±0,16**

<0,01

Big molecule fractions

%

44,5±2,3

43,81±2,40

33,93±2,20**

<0,01

g/l

0,84±0,04

0,92±0,04

0,95±0,06

>0,05

Midmolecule  fractions

%

30,5±2,0

30,48±1,90

36,07±1,82*

<0,05

g/l

0,57±0,04

0,64±0,05

1,01±0,07***

<0,001

Small molecule  fractions

%

25,0±1,6

25,71±1,64

30,0±1,8*

>0,05

g/l

0,47±0,03

0,54±0,04

0,84±0,06***

<0,001

 

Thus the using of corargine and espa-lipon assisted reduction of concentration of CIC in the blood serum and to renewing of their molecular composition for the patients of basic group. At the same time for the patients of group of comparison after ending of treatment the level of CIC was kept increased with predominating of the  most toxigenic midmolecule and small molecule fractions.

Conclusions

  1. For patients with CUC in combination with coronary heart disease and helicobacteriosis increase of CIC content in the blood serum  took place mainly due to  accumulation of the most toxigenic fractions, especially at high  degree of semination  НР.
  2. Positive influence of corargine and espa-lipon on the level of CIC and their molecular composition was expressed in reduction of concentration of CIC in the blood serum   and in proceeding of their molecular composition due to reduction of level of the most pathogenic  midmolecule and small molecule  fractions.
  3. At the same time for the patients of comparison group after ending of treatment the level of CIC was kept increased with predominating of the most toxigenic midmolecule and small molecule  fractions.
  4. In future the study of concentration of CIC is planned in blood of patients with united pathology in the period of clinical supervision with application of the plant-based preparations.

Література

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  2. Степанов Ю.М. Гастроентерологічна допомога населенню України: основні показники здоров’я та ресурсне забезпечення у 2011 р. / Ю.М. Степанов, І.Ю. Скирда [Електронний ресурс] // Гастроентерологія. - 2013. - № 1 (47). – Режим доступу: http://www.mif-ua.com/archive/article/35996
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  6. Фролов В.М. Исследование циркулирующих им­мун­ных комплексов их диагностическое и прогностическое значение / В.М. Фролов, В.Е. Рычнев, Н.А. Пересадин // Лабораторное дело. – 1986. – № 3. – С. 159 – 161.
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