Structural Changes in Rat Hepatocyte Nucleolus under Nucleolar Stress Caused by Hypothermia.

Structural changes in rat hepatocyte nucleoli were studied during deep hypothermia simulated by immersion in water at 5°C for 40 min (ambient air temperature 7°C). In comparison with the control, phenomena of nucleolar stress occurred in rats during hypothermia: the number of fibrillar centers (FC) per nucleus (by 1.7 times) and per nucleolus (by 1.6 times), nucleolonemal nucleoli per nucleus (by 2.8 times), and the relative content of nucleolonemal nucleoli per nucleus (by 2.6 times) significantly decreased (p=0.0000001); the number of FC per nucleolonemal nucleolus also decreased by 1.4 times (p=0.01). In the hepatocyte nuclei, we observed an increase in the relative content of transitional type nucleoli per nucleus (by 1.3 times; p=0.01), the number of FC per transitional type nucleolus (by 1.4 times; p=0.003), the content of free FC per nucleus (by 3 times; p=0.00004), and the percentage of free FC per nucleus (by 3.5 times; p=0.00004). These changes can be considered as compensatory and adaptive reactions, and transitional type nucleoli can be attributed to the "reserve" nucleolar pool.

Experience of Using Tripeptide Leu-Ile-Lys for Experimental Therapy of Chronic 16-Week Oxalate Nephrolithiasis in Rats.

We studied the effect of tripeptide Leu-Ile-Lys on the course of chronic 16-week oxalate nephrolithiasis in rats modeled by administration of 1% ethylene glycol solution in drinking water for 16 weeks. The tripeptide Leu-Ile-Lys obtained by chemical synthesis (sample purity ≥98%) was administered intragastrically through a probe in a dose of 11.5 mg/kg in 1 ml saline. It was found that during tripeptide Leu-Ile-Lys significantly alleviated the course of experimental pathology, which was confirmed by characteristic biochemical and morphological indicators. We observed a decrease in the concentration of calcium ions by 4.4 times, weakening of oxidative stress in the renal tissue due to a decrease in the total prooxidant activity by 1.2 times, normalization of increased catalase activity, and reduction of superoxide dismutase activity by 2.4 times relative to disease control. Histological signs of nephrolithiasis were recorded in 9% cases (vs. 75% cases in disease control).

Effect of Tripeptide Leu-Ile-Lys on the Course of Experimental Nephrolithiasis.

We studied the effect of Leu-Ile-Lys tripeptide on the course of experimental oxalate nephrolithiasis modeled in rats by administration of 1% ethylene glycol solution instead of drinking water for 6 weeks. The Leu-Ile-Lys tripeptide obtained by chemical synthesis (purity ≥98%) was administered through a gastric tube (11.5 mg/kg in 1 ml saline). Administration of Leu-Ile-Lys tripeptide against the background of experimental oxalate nephrolithiasis significantly alleviated the course of experimental pathology, which was confirmed by typical biochemical and morphological changes: decrease in urinary activity of γ-glutamyltransferase (by 2.1 times in comparison with the initial level) and intensity of oxidative stress (the content of TBA-reactive products decreased by 1.3 times in comparison with that in untreated animals) and increase in glutathione peroxidase activity by 1.8 times; no histological signs of nephrolithiasis were found in animals treated with the tripeptide.

Relationship between Cooling Medium and Hepatocyte Ploidometric Parameters in Albino Rats.

Relationship between the method of hypothermic exposure and ploidometric characteristics of hepatocyte nuclei of rats were studied immediately after hypothermic exposure and during the posthypothermic period. The following cooling modes were used: single submersion into 5°C water (until rectal temperature drop to 20-25°C; deep hypothermia) and single exposure at air temperature of -25°C (until rectal temperature drop to 30°C; moderate hypothermia). A manifest destructive effect of deep hypothermia on rat liver was detected: the exposure caused manifest alteration of hepatocytes (alteration index increased 81-fold immediately after the exposure and remained 16-fold higher than normally after 14 days) and an increase of DNA accumulation index with predominance of hepatocytes with 5c-8c nuclei (60% of the population) during the entire period of observation, which indicated intensification of the compensatory and adaptive processes in the liver with predominating high-ploid population of hepatocytes. Hepatocyte alteration processes in response to moderate hypothermia were less intense (hepatocyte alteration index increased 19-fold immediately after the exposure and remained 3-fold higher than normally after 14 days). The DNA accumulation index increased moderately immediately after the exposure and returned to normal after 14 days, with emergence of 2c hepatocytes and an increase in the level of 4c hepatocytes (51% of the population), which indicated realization of a different strategy of liver regeneration - recovery of the cell population intrinsic to intact animals.

Morphological Evaluation of the Influence of the Peptide Complex from Tissue of Porcine Kidneys on the Experimental Urolithiasis.

We performed morphological analysis of the effect of the peptide complex from porcine kidneys on the course of experimental urolithiasis modeled in rats by treatment with 1% ethylene glycol solution (in drinking water) for 6 weeks. The peptide complex obtained by acetic acid extraction was administered in a dose of 15 mg. Administration of the peptide complex to animals with experimental kidney stone disease leads to 100% destruction of large and medium stones to the "dust" granularity.

Mast Cells in Renal Cancer: Clinical Morphological Correlations and Prognosis.

Morphofunctional activity of mast cells in renal cancer is studied on specimens from the center of the tumor, peritumorous zone (with an obligatory fragment of the pseudocapsule), and from renal tissues maximally distant from the tumor. The counts and areas of tumor cells were maximum in the peritumorous zone in comparison with intact kidney tissue and central zone of the tumor. Analysis of correlations revealed a direct correlation between the tumor cell count in the peritumorous zone and some clinical morphological parameters of the tumor (anaplasia degree, size, presence of invasion and metastases, and angiogenesis). The count of mast cells in the renal peritumorous zone inversely correlated with 5-year survival: 100% cumulative 5-year survival in patients with mast cell count <6.7±1.6 per field of view.

[Renal morphological changes in experimental oxalate nephrolithiasis]. / Morfologicheskie izmeneniia pochki pri éksperimental'nom oksalatnom nefrolitiaze.

AIM: Тo evaluate renal morphological changes in the early stages of lithogenic processes and during urinary correction of urine with oxalate-chelating compounds (sodium citrate). MATERIAL AND METHODS: An experimental model of oxalate nephrolithiasis was performed on 80 male Wistar rats weighing 180 to 250 g. Rat kidneys were morphologically and ultrastructurally studied. Immunohistochemical techniques were applied to study the features of development of endoplasmic reticulum stress. RESULTS: There were histotopographic changes in the renal tissue elements in the early stages of development of lithogenic processes accompanied by characteristic ultrastructural changes in the epithelium of the renal tubules and collecting ducts: by expansion of elements in the granular endoplasmic network, by mitochondrial damage with formation of large, ampullary extended cristae, and by emergence of autolysosomes. Signs of development of endoplasmic reticulum stress with activation of protein GADD153 were found, which deteriorated the cell lining of the nephron tubules and collecting ducts. CONCLUSION: In the early stages of development of lithogenic processes, there are stereotypic ultrastructural and histotopographic changes in the epithelium of the nephron tubules and collecting ducts, which contribute to the progression of stone formation processes and to the disruption of cellular homeostasis with activation of endoplasmic reticulum stress, synthesis impairment, or post-translational modifications in modulator proteins of lithogenesis.

Development of Endoplasmic Reticulum Stress during Experimental Oxalate Nephrolithiasis.

Morphological and ultrastructural study of the kidney was performed in rats with oxalate nephrolithiasis. Specific features of endoplasmic reticulum stress were evaluated during nephrolithiasis and treatment with α-tocopherol. We observed the signs of endoplasmic reticulum stress with activation of proapoptotic pathways and injury to the cell lining in nephron tubules and collecting ducts. Ultrastructural changes were found in the organelles, nuclei, and cell membranes of epitheliocytes. A relationship was revealed between endoplasmic reticulum stress and oxidative damage, which developed at the early state of lithogenesis.

[Experimental study of the wound-healing effect of new drug compositions intended for the therapy of esophageal burns].

The anti-inflammatory and wound-healing effects of new formulations for the treatment of esophageal burns have been studied in Chinchilla rabbits with model chemical burns of skin. The healing process was evaluated according to the clinical and morphological criteria on the 3rd, 7th, 10th, 14th, and 21st day. It is established that the new drugs accelerate the regeneration of skin tissue in comparison to that in the control and reference groups of animals. At the late stage of skin regeneration, this is manifested by reliable differences in the degrees of cicatrization and tissue collagenization. Two hydrophilic polymer-based drug compositions, which are successively applied in accordance with the burn process development, exhibit pronounced anti-inflammatory and skin-regenerative effects. These formulations can be recommended for the therapy of esophageal burns.

[Surgical-drug therapy aspects of the treatment of patients with obliterating thromboangiitis of the lower limbs]. / Operativno-medikamentoznye aspekty lecheniia bol'nykh obliteriruiushchim trombangiitom nizhnykh konechnostei.

Standard operative interventions (thromboendarterectomy, (autovenous shunt) in patients with thromboangiitis obliterans of the lower limbs produce a poor effect. This is explained both by a poor initial condition of the draining channels and by advancement of the primary thromboangitic affection of the vascular wall in the zone of the intervention with its development into a stenotic-occlusive process. The use of some technical (operative) innovations, particularly postoperative arterial infusion of suspended forms of immunosuppresive agents (hydrocortisone, Kenalog), increased essentially the efficacy of restorative operations on the vessels with a high level of limb preservation and patency of the vessels which had been operated on.