e16196 Background: Microsatellite instability (MSI), as an acquired feature of malignant tumors, is a predictive and prognostic marker. The less aggressive nature of MSI-positive tumors has been associated with high immunogenicity. In the present study, MSI was assessed in NET samples of different localizations. Methods: The sample included 50 patients with a diagnosis of pancreatic NET (G1-G3) and NET of colon (G2-G3). MSI was analyzed by fragment analysis of five microsatellite loci (Bat25, Bat26, NR21, NR24, NR27). The level of MLH1 methylation was detected by pyrosequencing. Results: MSI was noted in 25.8% cases of the NET of colon and in 13.3% cases of the NET of the pancreas. In the case of pancreatic NET, only MSI low level was identified (instability at 1/5 loci), while in the case of NET of colon, most cases were classified as MSI high level. The incidence of MSI of pancreatic NET was consistent with literature data for small intestinal NET (14%), unlike MSI NET and BRAF V600 mutated adenocarcinomas of colon, MSI-positive pancreatic NET were not associated with hypermethylation of the MLH1 promoter. MSI was more often detected in women over 60 years old, at stages of the tumor process without distant metastases (p = 0.49). The sample size did not allow us to determine significant differences in the studied clinical and pathological groups of NETs, however, we note that in all cases of an unfavorable course of the disease (progression, death), was noted MSS status of tumors. Conclusions: Thus, MSI-positive NET of colon resembles MSI-positive adenocarcinomas of colon in frequency and pathogenetic mechanisms, while in terms of the identified frequency of MSI in pancreatic NET resembles the NET of the small intestine.
Пурины-это многофункциональные соединения, по уровню которых можно судить о степени гипоксического повреждения тканей и сохранности генетического материала клеток. Цель-изучить особенности пуринового метаболизма в корковом веществе почек у молодых самцов крыс в зависимости от продолжительности ишемии одной из них. На 60 самцах была исследована динамика аденина (А), гуанина (Г), ксантина (К), гипоксантина (ГК) и мочевой кислоты (МК) в корковом веществе почек: ишемизированной и контрлатеральной-после ишемии одной из них в течение 5, 10, 15, 20 и 25 мин, контроль-интактные крысы. Метод определения-прямая спектрофотометрия водного раствора термокоагулянта лизатов клеток почек. Установлено, что в ишемизированной почке через 5-10 мин ишемии количество пуринов, кроме МК, увеличивалось в среднем в 1,2 раза (р<0,05), а через 25 мин ишемии-уменьшалось: количество Г и ГК восстанавливалось до нормы, а уровни А и К становились в 1,5 раза (р<0,05) меньше значений в интактных почках. Концентрация пуринов в контрлатеральной почке возрастала через 15 мин ишемии в среднем в 1,4 раза (р<0,05). Содержание всех пуринов, кроме МК, максимально уменьшалось через 25 мин, при этом в ишемизированной почке содержалось меньше А и Г, чем в контрлатеральной. Таким образом, установлено, что у молодых самцов обе почки «отвечают» одинаковой динамикой пуриновых метаболитов в корковом веществе на ишемию одной из них, при этом в ишемизированном органе изменения возникают раньше и в большей степени, что надо учитывать при проведении оперативных вмешательств на почках у людей. Ключевые слова: пурины, ишемия, почки, крысы, самцы.
592 Background: Our purpose was to study the dynamics of cortisol (C) and aldosterone (A) in the blood plasma in patients receiving surgery with the epidural block (EB) for local kidney cancer. Methods: 58 patients aged 56.5±8.7 years underwent partial nephrectomy with warm ischemia for 15-20 minutes (EB – 35 patients, standard anesthesia (SA) - 23 patients). EB involved catheterization of the epidural space at Th10-L1 with the following infusion of a mixture of ropivacaine 2 mg/ml and epinephrine 2 μg/ml at 6-10 ml/hr using a syringe doser, intraoperatively and within the first three postoperative days. The levels of C and A were studied by radioimmunoassay in the blood plasma of patients before the surgery (b/s), 40 min after the start of the surgery (40' s/s) and on days 1 and 3 after the surgery (a/s). Results were compared to the levels in the blood plasma of 32 healthy donors (N). Results: C and A exceeded N in all patients b/s (p < 0.01). C increased by an order of magnitude 40' s/s only in SA (p < 0.001), while A increased in all patients, compared to the levels b/s. C decreased by 1.5 times in EB on day 1 a/s; C in SA was similar to the levels b/s; A decreased to similar levels in all patients but was still higher than N by 1.4 times on average (p < 0.01). The C levels remained stable in all patients on day 3; A levels became normal in EB only, while in SA they were 2.1 times lower which caused the loss of salts and fluid. Conclusions: SA affected the regulation of the adrenal function by the central nervous system and urine formation processes in the kidney. In SA, abnormal C and A levels preserve for a longer period of time enhancing the water and salt imbalance in the body. Significant decrease of C and the normalization of A in EB indicate the preservation of the adrenal function influencing urine formation processes in the kidney. In local kidney cancer, it is advisable to use epidural block instead of standard anesthesia as the latter blocks regulatory functions of the central nervous system.
593 Background: The purpose of the study was to reveal the effect of the epidural block (EB) on the dynamics of the main universal inhibitors in the blood plasma and urine of patients with local kidney cancer. Methods: 58 patients aged 56.5±8.7 years underwent partial nephrectomy with warm ischemia for 15-20 minutes (EB – 35 patients, standard anesthesia (SA) - 23 patients). EB involved catheterization of the epidural space at Th10-L1 with the following infusion of a mixture of ropivacaine 2 mg/ml and epinephrine 2 μg/ml at 6-10 ml/hr using a syringe doser, intraoperatively and within the first three postoperative days. α2-Macroglobulin (α2M) and α1-proteinase inhibitor (α1PI) were studied by ELISA and spectrophotometry in the blood plasma and urine of patients before the surgery (b/s), 40 min after the start of the surgery (40' s/s) and on days 1 and 3 after the surgery (a/s). Results were compared to the levels in the blood plasma and urine of 29 healthy donors (N). Results: α2M and α1PI in the blood plasma and urine of all patients b/s were lower than N (p < 0.05). α2M in the blood plasma of all patients 40' s/s was similar to N. Normal α2M levels were maintained in the blood plasma in EB on days 1-3 a/s, while in SA they increased by 2.8 times on day 1 and decreased by 3.4 times on day 3, compared to the previous measurement results. α1PI in EB began to increase since 40' s/s with its normalization by the day 3 a/s; α1PI in SA was decreased in the blood plasma and urine during the whole study period. The urine/blood plasma ratio for α2M (α2Mu/α2Mb) was increased b/s in all patients, with its normalization on days 1-3 in EB and its decrease by 9.5-3.1 times on days 1 and 3 in SA. The α1PIu/α1PIb ratio was increased b/s on average by 2.1 times in all patients, with its normalization 40' s/s in EB, and remained similar to N by the day 3. Normalization was not observed in SA; α1PIu/α1PIb was decreased since 40' s/s to the day 3 by 1.8-1.4 times (p < 0.05), compared to N. The results showed that in SA, the proteolysis was not controlled in the kidney due to the inhibitor deficiency. Conclusions: The epidural block contributes to the restoration of the activity of α2M and α1PI universal endogenous inhibitors during and after surgery, in contrast to the standard anesthesia.
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