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14Serum lactate already a proven marker for intestinal ischemia was found to be elevated in this ischemic group with a mean of 34.93mg/dl and 23.41mg/dl in the non-ischemic group with a significant P value of 0.015. The sensitivity of serum lactate was 87% and specificity was 41%. Serum Intestinal Fatty Acid Binding Protein (IFABP) was significantly elevated in the ischemic group with a mean of 673.53pg/ml versus 65.94pg/ml in the non-ischemic group with a P value of 0.0002.
Of the 56 patients diagnosed with ischemia, 55 were operated on. One patient had radiographic signs of ischemia, received anticoagulants, and was discharged. Diagnostic laparotomy was performed in 55 patients, ischemic or gangrenous segment of the intestine was resected and sent for histological examination. All histopathological results corresponded to gangrene or ischemia.
There were 14 patients had ischemia of the jejunum (25.5%), ileum in 19 patients (34.5%), jejunum and ileum in 9 patients (16.5%), colon in 7 patients (13%), colon and ileum in 4 patients (7%) and jejunum, ileum and colon in 2 patient (3.5%). Mortality in the ischemic group was 13 patients (23.7%) and non-ischemic group was 1 patient (1.8%).
Conclusion.
Intestinal ischemia is a surgical emergency and warrants immediate surgical intervention. Quicker diagnosis aided by serum I-FABP levels will enable us to intervene in such patients quickly reducing morbidity and mortality among patients. Author concluded that serum I-FABP is a specific, sensitive, quick and cost-
effective indicator of intestinal ischemia. It can identify ischemic changes in bowel at an early stage which will enable us to intervene early and reduce morbidity and mortality. If bowel ischemia is detected earlier, there may be a scope to preserve the bowel by removal of the offending agent, however, this analysis is beyond the scope of present study.
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2. Dayton MT, Dempsey DT, Larson GM, Posner AR. New paradigms in the treatment of small bowel obstruction. Current Prob Surg. 2012;49:642-717.
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4. Dunphy JE. Abdominal pain of vascular origin. Am J Med Sci. 1936;192:109-13.
5. Elliot JW. The operative relief of gangrene of intestine due to occlusion of the mesenteric vessels. Ann Surg. 1895;21(1):9-23.
6. Lange H, Jackel R. Usefulness of plasma lac-tate concentration in the diagnosis of acute abdominal disease. Euro J Surg. 1994;160(6-7):381-4.
7. Ozden N, Gurses B. Mesenteric ischemia in the elderly. Clin Geriatric Med. 2007;23(4):871-87.
8. Wilson C, Imrie CW. Amylase and gut infarction. Brit J Surg. 1986;73(3):219-21.
MATERNAL TOXIC HEPATITIS, STRUCTURAL AND FUNCTIONAL FORMATION OF THE LEAN INTESTINE OF THE OFFSPRING IN THE DYNAMICS OF EARLY POSTNATAL
ONTOGENESIS
KhasanovB.
Bukhara State Medical Institute, Department of Histology, Cytology and Embryology,
Bukhara, Uzbekistan
Abstract
There was investigated the effect of toxic heliotrinic hepatitis in female rats on the formation of the lean intestine of the offspring in the dynamics of early postnatal ontogenesis. It was established that the negative effect of chronic toxic hepatitis in females, leading to a lag in the formation of the lean intestine in the period of early postnatal ontogenesis, progressing to the transition of rat pups to mixed and definitive nutrition.
Keywords: intestine, formation, lactation, chronic hepatitis, ontogenesis, offspring.
It is known that the neonatal period is especially important for the development of the body, since after birth, babies are immediately exposed to a large number of microorganisms. The high rates of morbidity and mortality observed in the first months of life due to infectious diseases such as otitis media, upper and lower respiratory tract infections, gastroenteritis, sepsis and meningitis are caused, among other things, by significant quantitative and qualitative deficiencies in various components of the immune system. To compensate for this immunological immaturity inherent in the period of the fetus and newborn, as well as the first months of life, nature has developed mechanisms of adaptive protection provided by the mother, represented by trans
placental transmission of antibodies, anti-infectious resistance factors in the amniotic fluid, and after birth, in colostrum and milk. However, this whole system of harmonious genetically determined processes inherent in the physiological course of pregnancy ceases to work in the event of the influence of unfavorable factors, infectious effects and extra genital pathology of the mother. Particularly, it was found that the effect of alcohol and chronic hepatitis of pregnant women has an adverse effect on the offspring - it delays its physical development, reduces resistance, inhibits the development of structural and cytochemical properties of the stomach, intestines, kidneys [6,7,9,10]. At the same time, the question: what effect does maternal hepatitis
have on the formation of the lean intestine in developing offspring, in the dynamics of early postnatal ontogenesis, remains poorly understood.
Due to this, the purpose of our research was to study the structural and functional features of the formation of the lean intestine of the offspring of rats born to mothers with toxic hepatitis during breastfeeding.
Materials and research methods
The experiments have been carried out on 120 sexually mature white outbred rats - females weighing 175-220 g. The rodents were kept on a standard food ration in a vivarium. A model of heliotrinic hepatitis was obtained by weekly administration of 0.05 mg of heliotrin per gram of animal weight for 6 weeks [1]. 10 days after the last inoculation, the rats were mated to produce offspring. The experimental group consisted of rat pups born to mothers with HTH. The control was rat pups born to mothers, instead of heliotrin, were injected with an appropriate amount of isotonic solution at the same time. The rodents were kept in separate cages, for the reliability of the results obtained; the litter was left at the rate of eight pups per lactating female. Rats were killed simultaneously from both the control and experimental groups on the first, third, 7th, 14th, 21st and 30th days of postnatal life. After decapitation, the abdominal cavity was opened to the animal, then the lean intestine was separated, and samples of the jejunum of the lean intestine were used for morphological examination. To carry out morphological and morphometric research, samples of the lean intestine of rat pups were fixed in a 10% solution of neutral formalin. The pieces were dehydrated in an increasing concentration of alcohol and chloroform, and then they were embedded in paraffin. Histological sections 5-8 ^m thick were stained with hematoxylin and eosin. The morphometric research was carried out on serial sections using an eyepiece micrometer. The Styudent's and Fischer's method with the calculation of the arithmetic mean (M), the mean error of the mean (m) and reliability indicators (P) processed all data statistically.
Results
The results of our research showed, the lean intestine of newborn rat pups has characteristic features. The intestines of rat pups on day 1 after birth have a thin wall, in which the mucous membrane, submucosa, inner and outer muscular membranes are clearly distinguished. The inner muscle layer of the latter is more developed than the outer one, covered with a serous membrane. The mucous membrane of the jejunum is formed by villi, which at different stages of formation can be triangular, finger-like, and filamentous. With lengthening, their epithelial layer on them becomes single-row. The forming villi retain a multi-row arrangement of nuclei in the basal part of epithelial cells. The crypts in the jejunum are just being laid. Formed villi of the correct finger-like shape, without wrinkling on the lateral surfaces. The characteristic relief of the mucous membrane increases its surface and creates favorable conditions for digestion and absorption.
Hereinafter, on days 3 -7 of postnatal development, significant changes in the mucous membrane of the jejunum occur due to an increase in its thickness, as well as the thickness of the muscle layer, the growth of the
formed villi and crypts, the redistribution of their relative number depending on the linear parameters, a sharp decrease with time in low villi and shallow crypts.
On the 15th day of postnatal development, all structures of the jejunum in pups of the control group are practically formed (see Fig. 1.). Their morphomet-ric indicators are presented in the table. The limb epithelial cells covering the villi had a highly prismatic shape, their brush border appeared in the form of a thin, clearly visible, brightly oxyphilic strip. The oval nuclei, with a clearly manifested structure, were located very compactly at the same level, closer to the basal pole. Chromatin of nuclei is small lumpy, evenly distributed over the karyoplasm. One or two nucleoli were clearly visible, usually located in the center. It was noticed that the nuclei, like the epithelial cells themselves, decreased in the direction of the tops of the villi, the cytoplasm underwent micro vacuolization, its oxyphilic properties decreased, which indicated the physiological renewal of the epithelium.
By the transition of rats to definitive nutrition, that is, on the 21-30th day after birth, the morphological structure of the mucous membrane of the lean intestine is almost similar to that of sexually mature animals. This increases the length and diameter of the lean intestine. While maintaining the general architectonics of the mucous membrane, this causes a proportional increase in the number of villi and crypts and, consequently, the digestive-absorbing surface of the organ, the same sensitivity to the stimulating effect of food. An even greater development of the structural components of the jejunum occurs on the 30th day of postnatal development.
Conducted research of the lean intestine in offspring born from females with chronic toxic hepatitis showed that, although at first glance, there were no pronounced morphological changes that would sharply contrast with the lean intestines of rat pups in the control group. However, the morphometric research carried out indicate that in the offspring obtained from the females of the experimental group, during the period of early postnatal ontogenesis, there is a delay in the formation of the jejunum. Particularly, it was found: a decrease in the average number of villi on the transverse section of the intestine, a decrease in the height of the villi, a decrease in the average number of enterocytes (EC) on a transverse section of the crypt, a decrease in the thickness of the mucous and musculocutaneous membranes up to 15 days and only a decrease in the height of the EC in the middle third of the crypts to 7 days of development of rat pups. There is also a decrease in the average number of ECs on the longitudinal section of the villus, the height of ECs in the middle third of the villus, the number of ECs on the longitudinal section of the crypt, the depth of crypts, and a decrease in the number of mitotically dividing cells up to 21 days of development. Along with this, an increase in the relative number of goblet cells of the villi of the jejunum of rat pups born and fed by females with chronic toxic hepatitis up to 21 days of development should be noted (see Table).
While researching the structural and functional features of the jejunum of 15-day-old rat pups born and
fed by females with chronic tosic hepatitis, a delay in the development of the jejunum was observed (see Figure 2). The wall thickness is less than in the control, the villi differed in polymorphism and lower height, and the crypts looked like short tubes and were located more rarely. The limb epithelial cells lining the villi are lower, the oxyphilic properties of the cytoplasm are reduced, and the brush border is thinned and difficult to see. The nuclei of epithelial cells of a rounded shape, smaller in size, were located, in contrast to the control, at a greater distance from each other. Bowel-shaped cells are numerous, cylindrical in shape with weakly basophilic cytoplasm. The stroma of the villi is slightly edematous with insignificant leukocyte infiltration. Tissue basophils were found somewhat more often than in the control. Hemocapillaries are moderately dilated. Loosely located underdeveloped crypts are observed. They looked like short tubular formations lined with epithelial cells that are smaller in height than in the control. The nuclei are reduced in size, slightly basophilic.
In the next 21-30 days of development, the stabilization of the structural components of the jejunum of the experimental group rat pups is characteristic.
Discussion
Analyzing the results obtained, it is necessary to point out that for the full development of the baby, starting from the first day after childbirth, protein components are needed: "the main plastic material", and, of course, easily digestible carbohydrates of the mother's milk. In addition, a certain dynamics of the level of hormones in milk is revealed, associated with their participation in the process of metabolic adaptation of new-borns to extra uterine existence and causing the restructuring of protein, carbohydrate and fat metabolism in the postnatal period. Colostrum and milk enzymes that enter the body of a newborn during breastfeeding also have a beneficial effect on the processes of its adaptation, affecting the metabolism of proteins and carbohydrates in the intestine [2]. It was found that in the offspring of rats with chronic hepatitis, there is a steady decrease in body weight gain, and a lag in the structural and functional development of the lean intestine [4, 5]. Perhaps one of the reasons for these changes during the
period of lactotrophic nutrition is the previously discovered decrease in the amount of protein, carbohydrates and enzymatic activity of milk. A decrease in cellular components, apparently, is one of the factors characterizing a decrease in the immunomodulatory function of milk. In addition, a decrease in the number of macrophages, monocytes and lymphocytes, which, on the one hand, contribute to the violation of the transfer of adoptive immunity. In addition, as indicated in our previous research, the intake of lysosomes, lipid droplets present in these cells, is significantly reduced. As a result, the trophic influence and immunobiological properties of breast milk are significantly reduced, allowing the child to adapt and survive in the "world of microbes", where it enters immediately after childbirth [11].
Along with the above, with hepatitis, profound changes in metabolic processes occur, including a violation of protein metabolism, which, of course, affects the hormonal balance, and, consequently, the development of the placenta and mammary gland, as well as the developing offspring. It is also necessary to take into account the immunodeficiency state of the mother with hepatitis; it becomes clear the reason for the lag in the development of the digestive and immune systems of the offspring, established by many researchers [8]. In addition, it has been shown that the process of chronic heliotrin hepatitis is accompanied by profound morphological changes in the body's immune system. These changes lead to an imbalance between the T and B systems of the immune system and the development of an autoimmune process [11]. Summarizing all the above causal relationships, we can assume that they could contribute to morphological changes in the lean intestine of the offspring of mothers with chronic toxic hepatitis.
Thereby, it can be concluded that toxic hepatitis of the mother during breastfeeding has a negative effect on the development of the lean intestine of rat pups, which is expressed in the lagging behind the formation of the jejunum during the period of early postnatal ontogenesis, progressing to the transition of rat pups to mixed and then to definitive nutrition.
Fig. 1. The lean intestine of a 15 day old rat of the control group. Hematoxylin-eosin staining. Magnification: x 100.
Fig. 2. The lean intestine of a 15 day old rat in the experimental group. Hematoxylin-eosin staining. Magnification: x 100.
Table 4
Structural and functional formation of the lean part of the small intestine of offspring born to females rats with _chronic toxic hepatitis in the dynamics of early postnatal ontogenesis_
Investigated parameters A Rat pups age (in days)
group of animals 1 3 7 15 21 30
The number R 25,4±0,72 28,3±0,86 31,5±0,78 38,2±0,65 46,7±2,4 50,8±1,76
of villi on a
transverse section of E 21,6±0,67 24,8±0,56 26,3±0,75 32,8±0,87 42,4±1,41 48,8±1,66
the intestine
Number of R 47,2±0,24 51,2±1,88 65,2±2,48 73,2±2,62 78,5±3,62 91,4±4,82
ECs. on 1 side of the longitudinal section of the villi E 31,4±0,24 34,8±1,36 41,6±1,46 60,8±1,38 67,0±2,56 88,6±3,65
The height R 292,5±3,35 302,4±3,11 361,0±2,82 444,2±6,13 461,4±4,12 485,3±11,33
of villus E 265,6±2,26 273,4±2,12 318,2±4,18 363,5±3,54 452,6±4,22 472,5±9,33
ECs height R 21,5±0,95 22,0±0,82 22,3±0,94 23,8±0,93 26,1±0,43 37,6±0,62
(^m) in the middle third of the E 18,4±0,65 18,8±0,65 19,3±0,62 20,5±0,82 21,8±1,11 36,6±1,43
villi
Refers to the number R 1,6±0,06 5,8±0,18 7,6±0,26 9,1±0,17 10,8±0,19 14,4±0,26
of goblets. cl. on the villi (per 100 cells)
E — 10,0±0,18 13,2±0,21 14,6+0,21 13,9±0,23 23,5±0,28
The number R 45,2±0,98 49,2±1,34 59,6±1,45 84,3±3,90 126,4±6,20 135,4±9,32
of crypts on
a transverse section of E 38,6±0,81 43,2±0,91 50,1±1,28 72,7±1,86 118,9±8,45 131,1±6,55
the intestine
Number of R 6,7±0,61 7,5±0,33 9,2±0,43 12,2±0,45 35,8±1,23 42,2±0,86
ECs of the longitudinal section of E 4,8±0,14 5,2±0,21 6,0±0,12 10,2±0,43 29,8±1,30 41,7±0,65
the crypt
Number of ECs on the cross section of the crypt R 7,7±0,61 8,9±0,11 14,6±0,93 19,4±0,92 20,1±1,32 21,7±0,65
E 5,6±0,13 6,4±0,12 9,9±0,15 15,9±0,75 18,7±0,94 19,9±0,34
Depth of crypts R 21,5±0,21 28,4±0,22 43,8±0,62 74,1±0,55 189,3±3,33 202,4±4,06
E 16,4±0,12 22,8±0,56 32,4±1,08 65,3±0,62 148,3±2,65 196,2±3,13
Height (^m) in the middle third of crypts R 16,2±0,31 16,1±0,65 16,0±0,51 15,6±1,05 15,7±1,30 17,3±0,95
E 13,0±0,26 13,1±0,32 13,3±0,43 13,9±0,95 14,6±1,25 16,8±0,23
The number of mitoses (per 1000 cells) R 14,4±0,43 21,6±0,78 23,4±0,98 26,4±0,83 21,6±0,62 18,4±0,92
E 10,4±0,28 13,6±0,61 14,4±0,52 14,2±0,48 16,2±0,37 15,9±0,38
Mucosal thickness R 306,4±4,11 318,2±2,13 375,6±9,46 462,4±11,34 498,8±16,22 507,6±13,85
E 288,4±2,56 293,6±3,44 346,2±4,18 383,6±7,06 473,2±13,11 505,3±15,18
Serous-muscular thickness R 76,2±1,45 82,3±2,45 94,5±4,32 116,4±3,82 124,6±5,65 136,6±7,55
E 68,2±1,66 72,8±2,21 77,4±3,22 103,2±3,21 114,8+4,54 125,4±6,65
Note: 1) Gr. an. - a group of animals; ECs - enterocytes; goblet. - Goblet; cl. - cells. 2) The values where the differences are significant relative to the control at P <0.05 are highlighted in bold.
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