UDC 615.212.7:616.15–071

The paper presents the results of studies of changes in the biochemical parameters of serum of rats with long-term use of nalbuphine and after its withdrawal. Because long-term use of opioids is known to lead to renal impairment, this study is relevant. There is little data in the literature on the dynamics of renal markers of renal impairment changes at a certain dose and duration and after opioid withdrawal. The aim of the study was to establish some biochemical parameters of the serum of rats with long-term therapeutic doses of nalbuphine and the late withdrawal of the drug. The study material was 45 white sexually mature male rats weighing 180–260 g. The serum determined total protein, urea, creatinine, calcium, phosphorus according to conventional methods. Statistical calculations were performed using RStudio v. 1.1.442 and R Commander v.2.4–4.At six-week administration of therapeutic doses of nalbuphine (subgroup N 6) the serum of rats was 64.40±3.57 g/l, at ten-week administration (subgroup N 10) – 74.90±3.81 g/l, at six-week administration followed by four-week withdrawal (subgroup N 6V4) – 65.60±1.58 g/l. Serum creatinine in subgroup N 6 was 107.90±7.40 μmol/l, N 10–94.28±2.98 μmol/l, N 6V4–96.19±1.26 μmol/l. The serum urea in subgroup N 6 was 7.62±0.73 mmol/l, N 10–8.90±0.90 mmol/l, N 6V4–5.71±0.13 mmol/l. Serum calcium in the subgroup N 6 was 2.39±0.09 mmol/l, N 10–1.98±0.08 mmol/l, N 6V4–2.82±0.08 mmol/l. The serum phosphorus index in subgroup N 6 was 2.11±0.12 mmol/l, N 10–2.04±0.11 mmol/l, N 6V4–2.12±0.07 mmol/l. Thus, prolonged use of nalbuphine leads to impaired nitrogen function of the kidneys and withdrawal of the drug – to partial restoration of this function. At six-week administration of nalbuphine and its subsequent cancellation, disturbance of reabsorption function of a kidney revealed after the tenth week of drug use is not observed.

ABSTRACT 
Aim: To study changes of dental biofilm microbiota composition during experimental opioid exposure, after its withdrawal and when using of complex drug correction.
Materials and Methods: Microbiological studies (48 rats) included microscopic and bacteriological methods, as well as determination of antibiotic susceptibility of microbial isolates. Ceftriaxone and pentoxifylline were used to correction the changes.
Results: The action of opioid for 10 weeks caused considerable changes in the microbiocenosis, which was illustrated by a significant increasing of the opportunistic pathogens quantitative indicators and the emergence of pathogenic microbiota. Changes in the microbiocenosis at 6 weeks of opioid exposure and after its withdrawal for 4 weeks were expressed in the appearance of pathogenic microbiota and the absence of significant differences in quantitative indicators of saprophytic and opportunistic microflora compared to similar indicators in animals with 10 weeks opioid exposure. This indicated a slow progression of dysbiotic changes and the inflammatory process in the oral cavity of rats.
Conclusions: After 10 weeks of experiment with opioid administration for 6 weeks and the use of ceftriaxone and pentoxifylline on the background of 4-week opioid withdrawal, a significant reduction of quantitative indicators of opportunistic bacteria and elimination of pathogenic species of microorganisms was determined. The use of complex drug correction on the background of 10 weeks of opioid exposure led to a significant reduction in the quantitative indicators of opportunistic pathogens and contributed to the elimination of most pathogenic species of microbiota under the action of ceftriaxone.
KEY WORDS: oral cavity, rats, opioid exposure, microbiota, drug correction

UDC 617.55-002.5-07:616.155-097.36-07

Despite the high level of development of modern diagnostics, there is still a problem of diagnosing extrapulmonary and latent forms of tuberculosis. The purpose of the study was to determine the features of the immune status during the Koch immunoprovocation test. Studies were conducted in the venous blood of 50 patients with abdominal tuberculosis before and 72 hours after the Koch skin test. Indicators of cellular immunity were determined by the indirect immunofluorescence method and the content of cytokines by the immunoenzymatic method. The existence of statistically significant differences in the immunogram and in the cytokine profile of the examined patients before and after the Koch test was proved. The Koch immunoprovocation test
exacerbates the pathogenetic manifestations of the chronic inflammatory process, which is manifested by a change in the cytokine spectrum of the blood and makes it possible to clarify the diagnosis of abdominal tuberculosis. Determination of the level of TNFα in the blood serum of patients after the Koch test can be a marker of the latent form of the course of abdominal tuberculosis. Key words: immune system, cytokines, extrapulmonary tuberculosis, Koch test. 

Background. It is known about wide variety of individual reactions to stress explained by genetics factors. On the other hand, it is also known about aerobic fitness variability between individuals. From the above it follows the hypothesis that inter-individual differences in normal conditions determine the characteristics of the body's response to acute stress. The purpose of this study is to test the hypothesis. Material and methods. The experiment is at 58 rats (28 males) Wistar line. Animals were tested for resistance to hypoxic hypoxia and aerobic muscular performance by swimming test. On the basis of the received data two qualitatively equivalent groups in a ratio 10/48 were formed. After a week of recovery over the next 10 days, one animal remained intact and 5 other rats were exposed to water-immersion and restraint stress. The next day after stress, the ECG recorded and some endocrine, metabolic and immune parameters determined as well as erosive-ulcerative lesions of the gastric mucosa evaluated. Results. Four clusters by hypoxic and swimming tests were created retrospectively: normal resistance to hypoxia and muscular endurance (n=11); moderately reduced resistance to hypoxia and normal swimming test (n=25); drastic increased swimming test and normal hypoxic test (n=3); significantly increased resistance to hypoxia and normal swimming test (n=9). Each cluster is characterized by specific (correctness of classification 100%) post-stress changes in 6 neuro-endocrine, 12 immune, 10 metabolic and 2 ECGs parameters, as well as the index of damage to the gastric mucosa. The swimming test determines the post-stress state of the registered parameters by 63,8%, the hypoxic test - by 57,5%, and taken together - by 79,1%. Conclusion. The post-stress neuro-endocrine, immune and metabolic parameters as well as injuries of myocardium and gastric mucosa in rats are determined significantly by innate muscular endurance and resistance to hypoxia.