Clinical Significance of Zinc and Membranolysis Processes in the Course of Acute Pneumonias in School-Age Children

The dissertation is devoted to the study of the clinical significance of zinc and membranolysis processes in the course of acute pneumonias in school-age children. The work examines the role of zinc as a component of more than 300 metalloenzymes, its participation in cellular metabolism, immune system functioning, and membrane-stabilizing capacity. Special attention is given to the relationship between zinc concentration in serum and microvesiculation and lipid peroxidation processes in various forms of acute pneumonia.

The study includes a literature review, a description of clinical material and methods, as well as original results devoted to zinc concentration, characterization of microvesiculation and peroxidation processes in patients. The clinical efficacy of zinc sulfate as a membrane-stabilizing and antioxidant agent in the complex therapy of acute pneumonias in school-age children is considered separately.

Relevance

Over the past ten years, the incidence of respiratory diseases in children has increased by 80%, as a result of which inflammatory lesions of the lungs occupy a high proportion in the structure of morbidity and mortality [7, 20, 129, 137, 148, 165, 190, 220]. Despite the fact that a sufficiently extensive factual material has been accumulated on the issues of pathogenesis, diagnosis, and treatment of acute pneumonias, the relevance of the problem and its social significance remain [166,173, 181, 192].

In recent times, in connection with the completed socio-economic reform, changes in the quality of nutrition, the impact of environmental factors, and the introduction of new school curricula into the educational process, the health status of a large contingent of children, including those of school age, has declined [12, 13, 14, 95, 174, 201]. This has contributed to an increase in the proportion of children with reduced reactivity and to a rise in the frequency of mild forms of the disease [162, 165]. Therefore, an important problem at the present time is the elucidation of new pathogenetic links in the development of the inflammatory process in the lungs and the development of prognostic criteria for the course of acute pneumonias, which will improve the quality of preventive measures aimed at preventing difficult-to-treat, prolonged forms of the disease.

Great significance for the health of a child is attributed to essential trace elements, among which zinc occupies one of the central positions [14, 24, 51, 91, 92, 95, 96, 119, 145, 177, 222]. Being a component of more than 300 metalloenzymes, it plays an important role in cellular metabolism, the functioning of the immune system, and possesses membrane-stabilizing capacity [4, 222, 232, 257, 259, 276, 277]. According to literary data [13, 88, 92, 95, 119, 177, 204, 256], a decrease of zinc in the body is accompanied by an increased predisposition of children to disease. Although a large number of publications have been devoted to the study of the role of zinc in pediatric pathology, this issue is extremely insufficiently addressed in relation to diseases of the respiratory organs.

The connection between zinc deficiency and peroxidation and microvesiculation processes in various forms of inflammatory processes that have a significant impact on the stability of cell membrane structures has not been elucidated. This would make it possible to scientifically substantiate new approaches to the therapeutic correction of identified deviations and to improve the prognosis of inflammatory lung lesions.

Goal of the Study

To study the clinical significance of zinc content in serum in the course of various forms of acute pneumonia in children, to determine the relationship of its indicators with processes of membranolysis, and to develop effective methods of treatment for patients.

Tasks of the Study

To achieve the goal, the following tasks were set:

1. To study the clinical course of acute pneumonia in children depending on zinc content in serum.

2. To investigate indicators of microvesiculation in the dynamics of the course of acute pneumonia in children.

3. To determine the features of lipid peroxidation and antioxidant defense in relation to zinc levels, the state of microvesiculation processes, and forms of inflammatory lesions of lung tissue.

4. To evaluate the efficacy of administering the zinc sulfate preparation in the treatment of various forms of acute pneumonia in children.

Scientific Novelty

For the first time, a comprehensive study of zinc content in serum has been conducted in relation to indicators of peroxidation and microvesiculation in various forms of acute pneumonia in children.

A decrease in zinc concentration in serum has been established in all forms of acute pneumonia, and heterogeneity of zinc indicators depending on the clinical course of the inflammatory process has been noted. In particular, the greatest deficiency of this trace element in the child's body has been identified in cases involving the development of a focal infiltrative process in the lungs.

For the first time, microvesiculation processes have been studied in comparison with zinc concentration. An inverse correlation dependence has been revealed between its content and the level of the cytoplasmic membrane enzyme 5-nucleotidase, which is a marker of cell membrane damage and microvesiculation processes.

For the first time, the features of the course of peroxidation processes in various forms of acute pneumonia against the background of zinc-deficient states in school-age children have been described, and their dynamics during treatment have been reflected.

A close correlation between zinc deficiency in patients with acute pneumonia and indicators of microvesiculation and peroxidation processes has been established.

The inclusion of a zinc-containing preparation — zinc sulfate, possessing antioxidant and membrane-stabilizing action — into the complex of traditional therapy has been scientifically substantiated.

Practical Significance

A differentiated characterization of zinc content depending on the form of acute pneumonia has been provided. Borderline values have been described, at which the inflammatory process tends to follow a prolonged course.

Attention has been drawn to the distinctive course of acute pneumonia in school-age children, manifested by a predominance of focal forms of inflammatory lesions, a blunting of clinical symptoms, and a tendency toward torpid course against the background of low zinc concentration in serum.

Quantitative values of serum zinc parameters, 5'-nucleotidase activity, lipid peroxidation processes, and antioxidant defense may be used for a comprehensive assessment of membranodestructive processes. Given the technical complexities and costly reagents involved in assessing 5'-nucleotidase activity, on the basis of the conducted correlation analysis and the established direct relationship between the indicators of this enzyme and malondialdehyde, an indirect assessment of 5'-nucleotidase by the level of TBC-active compounds has been proposed. An increase in malondialdehyde concentration indicates high activity of the cytoplasmic marker enzyme.

A positive effect of zinc sulfate on clinical parameters and membranolysis processes has been demonstrated, and optimal doses and duration of its administration have been determined.

Implementation of the Work

The results of the work have been implemented in the clinical practice of the pulmonology department of the pediatric inpatient facility of Municipal Clinical Hospital No. 18.

An invention proposal entitled "Method for Predicting the Course of Acute Pneumonia in School-Age Children" (No. 1172/98) was registered at the Kazan State Medical University on March 16, 2002.

Fragments of the work on studying the clinical significance of zinc in serum in the course of various forms of acute pneumonia in children, the relationship of its indicators with the state of cell membranes, and the development of optimal methods of treatment for patients were twice awarded Diplomas of the Union of Pediatricians of Russia for the best scientific research in the field of pediatrics at the IX Congress (2001) and the VIII Congress of Pediatricians of Russia (2003).

The obtained information on the role of zinc in combination with biochemical markers of membranolysis in the pathogenesis of modern mechanisms of acute pneumonia is used in the educational process at the Departments of Pediatric Diseases No. 1 and No. 2 of Kazan State Medical University.

Presentation of the Work

The results of the work have been reported and discussed at the V and VI scientific-practical conferences of young scientists of Kazan State Medical University (2000, 2001); at the IX Congress of Pediatricians of Russia "Children's Healthcare in Russia: Development Strategy," Moscow (2001); at the scientific-practical conference dedicated to the 40th anniversary of the Central Scientific Research Laboratory of Kazan State Medical University, Kazan (2002); at the IX Russian National Congress "Man and Medicine," Moscow, April 8–12, 2002; at the session of the subject-problem commission on the main problems of maternal and child health protection (2000); at the scientific-practical conference: "Application of Zinc Preparations in Pediatrics," Nizhny Novgorod, October 23, 2002; at the Society of Children's Physicians of Kazan: "Modern Preventive Technologies in Pediatrics," Kazan, November 28, 2002; at the VIII Congress of Pediatricians of Russia: "Modern Problems of Preventive Pediatrics," Moscow, February 18–21, 2003.

Main Provisions for Defense

1. In acute pneumonias in school-age children, a deficiency of zinc in serum has been established, the degree of which is closely related to the form of the inflammatory process.

2. The development of acute pneumonia in school-age children is characterized by concomitant changes in the quantitative level of serum zinc, markers of microvesiculation and peroxidation processes, which depend on the phase and form of the inflammatory process in the lungs.

3. The inclusion of zinc sulfate in the complex therapy contributes to a reduction in the duration of clinical manifestations of acute pneumonia, accompanied by the restoration of serum zinc levels and a decrease in the activity of membranodestructive processes.

Publications

Thirteen scientific works have been published on the topic of the dissertation.

Scope and Structure of the Work

The dissertation is presented in 137 pages of typescript and consists of an introduction, a literature review, a description of materials and research methods, results of original research, conclusions, practical recommendations, and a reference list including 203 domestic and 75 foreign sources. The work is illustrated with 18 tables and 16 figures.