Perivascular Sclerosis Research Articles

Macrophage hyperfunction as a cellular trigger for fibroplastic changes in internal organs in pneumoconiosis among miners

Introduction. The significant prevalence of anthracosilicosis and silicosis, characterized by the rapid development of pneumofibrosis in coal mine workers, is a serious socially significant problem worldwide. A key component of the pathogenesis of pneumoconiosis is the macrophage reaction to fibrogenic dust, which is a complex immunological response, with prolonged and intense exposure leading to chronic inflammation in various organs and systems, fibrosis and a progressive decrease in their functions. A deep understanding and evaluation of the macrophage reaction as a potential biomarker for the diagnosis of lung damage in miners will allow us to develop more effective strategies to combat dust damage to organs and systems. The study aims to consider macrophage hyperfunction as a trigger mechanism for fibroplastic changes in internal organs in pneumoconiosis in miners. Materials and methods. Using light microscopy, specialists conducted extended cytological, histological and immunohistochemical studies of bronchial smears and autopsy material (fragments of bronchi, lungs, heart, liver and kidneys) of 50 miners of Kuzbass coal enterprises who died simultaneously as a result of a man-made disaster. Morphometric analysis of histological structures with measurement of linear dimensions was used for a comprehensive assessment of pathomorphological changes. Results. There was a sharp increase in the number and size of actively phagocytic alveolar macrophages loaded with dust particles in the lungs of miners. Pathological changes in internal organs were characterized by pronounced fibrosis in the peribronchial and perivascular zones, stroma with deposition of dust particles and a pronounced macrophage reaction. In a group of miners with more than 15 years of experience in the central and distal parts of the lungs, in the intermuscular zones of the myocardium, the portal tracts of the liver, and the central segments of the kidneys, there was a constant increase in the expression of immunohistochemical markers CD14, CD34, actin and vimentin, which can be used as diagnostic markers for the identification of macrophage inflammation and fibrosis, will allow to assess the degree of severity of the pathological process. A characteristic feature of the miners' long experience of dust exposure was the presence of progressive pronounced perivascular sclerosis extending beyond the vascular histione. Experts found fibroblastic cells with positive expression of CD14, CD31 and CD34 in the sclerotic zones. Limitation. The absence of cytogenetic and electron microscopic examination, which is expected in the future in conjunction with the expansion of the range of immunohistochemical research methods. Conclusion. The results of extended pathomorphological and cytological studies emphasize the importance of an integrated approach to the diagnosis of occupational diseases in the coal industry. The use of a combination of these methods will allow timely detection of macrophage inflammation and fibrous process in dust pathology, specific changes at the cellular and tissue levels, as well as to assess the severity of the pathological process. Ethics. The study of autopsy material was based on a secondary examination of blocks and ready-made histological micro-preparations (glasses) of the material of the Bureau of Forensic Medical examination of Novokuznetsk, Osinniki, Prokopyevsk. The studies of pathomorphological material were carried out strictly on the basis of Federal Law No. 323-FZ dated 11/21/2011 "On the Basics of Protecting the Health of Citizens in the Russian Federation", in particular Article 67 "Conducting pathological anatomical autopsies", Federal Law No. 8-FZ dated 12.01.1996 "On Burial and Funeral Business" (Article 5, pp. 1, 2), as well as in accordance with the Order of the Ministry of Health of the Russian Federation dated 06.06.2013 No. 354n "On the procedure for conducting pathological anatomical autopsies", Order of the Ministry of Health of the Russian Federation dated 03/24/2016 No. 179n "On the Rules for conducting pathological anatomical studies".

CLINICAL AND PATHOHISTOLOGICAL MANIFESTATIONS OF ACUTE KIDNEY INJURY AMONG PATIENTS WITH ACUTE DRUG POISONING (OVERDOSE).

The aim: To investigate clinical and pathohistological manifestations of acute kidney injury among patients with drug poisoning (overdose). Materials and methods: A cohort retrospective analysis of medical data of 86 patients treated in 2017-2021 with a diagnosis of "acute drug poisoning" com¬plicated by the development of acute kidney injury syndrome was conducted. A forensic medical examination of deceased patients (7 persons) was carried out. Histological samples were examined using an microscope OPTON Axioskop (Germany) in transmitted light, at magnifications of 100 and 400 times. Statistical analysis of the obtained data was carried out using the IBM SPSS Statistics 29.0.0.0 program, Pearson's correlation analysis was used, p≤0.05. Results: Acute renal failure in drug poisoning occurs under the influence of prerenal (hypoxia, r=0,66, р=0,0021; hypovolemia, r=0,61, р=0,0333) and renal factors (toxic effect of chemical components of the drug and rhabdomyolysis, r=0,743, р=0,0034). In the tissue samples, erythrocyte stasis in the capillaries, general fullness of blood vessels, signs of the sludge effect and small diapedesis hemorrhages were found; vasculitis and perivascular sclerosis are noted; foci of mononuclear infiltration of the stroma, focal edema, necrosis and interstitial fibrosis; desquamation, degenerative-dystrophic changes of the nephrothelium, tubular atrophy were found; hyaline casts in separate tubules; focal glomerular changes with segmental increase of the mesangial matrix and proliferation of endothelial cells, atrophy and hyalinosis of individual glomeruli were noted. Conclusions: The multifactorial effect of opioids is confirmed by microcirculation disorders, vascular, interstitial, tubular and glomerular changes in the kidneys.

MO130: Effect of Long-Term Low Protein Diet Use at Myocardium Remodelling in Rats With Experimental Decrease of Working Nephrons Weight

Abstract BACKGROUND AND AIMS Cardiovascular disturbances are the most frequent cause of death in patients with chronic kidney disease (CKD). Various options of low protein diets (LPD) are widely used in CKD treatment. However, their role in cardioprotection at CKD is understudied. The aim was to study the features of myocardium remodelling in Wistar rats for a long period post-nephrectomy (NE), who received LPD that included 10% of the complex of indispensable amino acids and their keto analogues. METHOD The study was carried out on adult (2.5–3 months) Wistar male rats. The control group (C) consisted of 9 sham operated (SO) rats; the second group consisted of 8 animals, in whom the resection of 5/6 kidney tissue (NE) was performed with the purpose to create the renal dysfunction model. The rats from these two groups received the standard feed, containing 20.16% of animal protein. The rats from the third group (n = 12) received LPD that included 10% of the complex of indispensable amino acids and their keto analogues (Ketosteril, Fresenius Kabi, Germany) after 5/6 NE. Four months after NE, blood pressure (BP, mm Hg) was measured in the animals. The left ventricular muscle mass index (LVMMI) was calculated as a ratio of LV weight/body weight (mg/g). The morphological changes of the myocardium were evaluated by quantitative morphometry using VideoTest 5.2. Results are presented as mean ± SD. The Student's t-test and the Mann–Whitney test were used for statistical analysis. RESULTS In 4 months, the average BP level in the C group was 130 ± 5 mm Hg; in rats with NE on the standard diet, it was 158.7 ± 11.0 mm Hg, and in animals on LPD 130 ± 12.8 mm Hg (P < .001). In rats with NE on the standard diet, LVMMI (2.72 ± 0.11) was higher than in the C group (2.35 ± 0.09, P < .01). In rats with NE that received LPD, there was no significant change in this indicator versus the C group (P > .05). In rats with NE against LPD administration, the cardiocytes thickness (9.5 ± 1.9 µm) and the cardiocytes nuclei area (26.6 ± 4.7 µm2) decreased, the ratio of cardiocytes nuclei area and cardiocytes thickness (0.38 ± 0.14) versus animals at the standard diet (14.19 ± 0.08, µm; 34.1 ± 8.1 µm2; and 0.23 ± 0.03; P < .001 in all cases) increased. In the NE group on LPD, the number of polynuclear cardiocytes was less than (0.3%) versus the NE group on the standard diet (1%). The connective tissue area indicator was 2837.6 ± 1263.1 µm2 versus 4008.1 ± 2185.7 µm2 (P = .061) in rats that received common feed. The decrease in ratio of capillaries area (%)/cardiocytes area (%) in rats on LPD, more than two times versus the NE group on standard diet, was noted. This is mostly conditioned by decrease in area occupied by connective tissue to 12% (2837.60 ± 1263.19 µm2) and decrease in total capillaries cross section up to 5% (1061.1 ± 78.3 µm2) in rats with LPD. The decrease of perivascular fibrosis degree in animals on LPD was determined. However, the vessel wall thickness in the NE groups (NE + LPD and NE on standard diet 29.9 ± 7 µm and 26.4 ± 17.6 µm; р = 0.211, respectively) increases versus C group (17.6 ± 5.1; P = .03). CONCLUSION The use of LPD in rats with NE has a cardioprotective effect, inhibiting the BP increase and the LVMMI index growth. In terms of histology, this was expressed through the decrease of cardiocyte hypertrophy degree, decrease in nuclei area, decrease of nucleoplasmic ratio, diffuse and perivascular sclerosis area.

Prolonged Inhalation Exposure to Coal Dust on Irradiated Rats and Consequences.

The purposes of this study were to research immune system changes and liver and lung tissues in irradiated rats after prolonged exposure to coal dust. A study was carried out on 30 male Wistar rats that were divided into 3 groups: group I, intact animals; group II, exposure to coal dust and 0.2 Gy γ-irradiation; and group III, combined exposure to 6 Gy γ-irradiation and coal dust. The combination of a low and sublethal dose of γ-irradiation with coal dust leads to a significant change in immunity at the remote period. Particularly, the increase in radioactivity at the combined effect causes weakening of phagocytosis, and reduction in T lymphocytes by a factor of 2, immunoglobulin imbalance, and cytokine dysfunction develop secondary immune failure. During prolonged inhalation with coal dust of irradiated animals with the dose of 0.2 Gy, fibrosis and perivascular sclerosis of the bronchial wall of the lungs are formed, and perivascular fibrosis is formed in the liver. The increase in exposure dose up to 6 Gy in combination with coal, in the distant period, caused pulmonary hypertension amid hypertrophy of light arterial vessels and fibrous changes in arteriole, and destructive changes and collection necrosis develop in liver parenchyma. In the case of dust radiation synergy, the increase in doses leads to a significant immune deficiency, which occurs according to the “dose effect” principle; increases damage to animal tissues; and leads to liver tissue necrosis, pulmonary fibrosis, and pulmonary hypertension.

Changes in the histostructure of the lungs of old rats under conditions of persistent hyperhomocysteinemia

To date, homocysteine has been found to be an important biomarker of bronchopulmonary pathology, including COPD. The increase in its concentration in the blood plasma causes the start of free radical processes and the production of reactive oxygen species, which activate lipid peroxidation in lung tissue. In addition, the activation of endoplasmic reticulum stress with increasing homocysteine levels is the main reason for triggering apoptosis of alveolocytes. The aim of the research is to study the features of lungs histostructure in old rats under conditions of hyperhomocysteinemia. The experimental study was performed on 20 white nonlinear old (24-26 months) male rats. During the experiment, the animals were divided into two groups – control and experimental. Simulation of the state of persistent hyperhomocysteinemia was achieved by administering to rats of experimental group thiolactone homocysteine at a dose of 200 mg/kg body weight intragastrally for 60 days. Histological specimens were studied using an SEO CCAN light microscope and photo-documented using a Vision CCD Camera with an image output system from histological specimens. In elderly animals under conditions of experimental hyperhomocysteinemia develop severe destructive-degenerative changes in the lungs. Significant remodeling of the vascular bed, bronchi, inflammatory manifestations, enlargement of dis- and atelectasis and emphysematically altered alveoli of the respiratory lungs, violation of the alveolar walls, with the release of blood cells into the alveolar space and the formation of small diapedetic hemorrhages. The development of perivascular, peribronchial and interstitial sclerosis is characteristic.

Organ-specific pathomorphological changes during COVID-19

COVID-19 is an acute respiratory infection caused by SARS-CoV-2 coronavirus causing pneumonia, lesions in the cardiovascular system and other organs, high mortality risk, especially in geriatric patients. Due to the great relevance, this study was aimed at describing the case of severe COVID-19 with development of multiple organ failure. Materials and methods. Available accompanying medical documentation (outpatient charts, medical history) was analyzed. Clinical and morphological analysis was carried out by providing description of macro- and micropreparations; histological methods (hematoxylin and eosin staining, Lee reaction) were used. Results. Female patient K.G., 69 years old, was hospitalized to the therapeutic department diagnosed with coronary heart disease. Acute coronary syndrome with ST segment elevation was made on 04/20/2020. A competing diagnosis: severe community-acquired bilateral multi-segmental pneumonia. The patient’s condition was aggravated wile applying therapy followed by biological death occurred. An autopsy revealed bilateral subtotal hemorrhagic pneumonia. Macroscopic lung examination demonstrated “lungs filled with red fluid”. In the brain — perivascular and pericellular edema, hyalinosis, blood stasis and sludge, marked dystrophic and necrotic neuronal changes. Cardiomyocyte fragmentation, areas of perivascular sclerosis with inflammatory infiltrates as well as erythrocytic sludge are found in the heart and blood vessels, respectively. A weak positive reaction according to Lee method was observed. Such clinical and morphological case demonstrates along with lung damage involvement of the heart resulting in acute coronary syndrome (morphologically manifested by ischemic myocardial dystrophy) and the brain. Thus, premorbid background in elderly patients results in developing acute pulmonary heart failure, pulmonary and cerebral edema.

Characteristic morphological signs of the brain damage during chronic hepatitis C virus infection identified in autopsy samples

Background: The central nervous system damage is one of the most common extra hepatic manifestations of chronic hepatitis C viral (HCV) infection, with the prevalence of up to 50% of the infected cases. Previous studies have identified the main clinical, pathogenetic and neurometabolic features of this pathology, which make it possible to suggest its definite nosological independence. However, the morphological pattern of brain lesions in chronic HCV infection remains virtually unexplored, significantly limiting the possibility of comprehensive pathological diagnosis of the disease. Aim: To study morphological patterns and to identify typical and diagnostically significant pathological signs of brain involvement in chronic HCV infection. Materials and methods: This was a retrospective descriptive cross-sectional study performed with a range of immunohistochemical (IHC) and pathomorphological techniques in the autopsy brain samples from patients who died of chronic HCV infection (40 cases) and those who died without any signs of past mental and infectious disorders (the control group, 15 cases). Results: The сharacteristic morphological signs of HCV-associated brain injury are IHC expression of the NS3 viral marker, an increase in CD68-positive microglial cell count, white brain matter microgliosis, perivascular and diffuse round cell inflammatory infiltration, degeneration and loss of neurons, neurophagy, demyelination, axonal degeneration, perivascular sclerosis, fibrous cell gliosis, small perivascular hemorrhages, focal hemosiderosis and calcification. The parameters of the identified abnormalities differ significantly depending on the brain region (p < 0.001). The identification of the HCV NS3 marker in the nervous tissue has the definitive diagnostic value. Conclusion: The body of histopathological abnormalities found in various parts of the brain from the infected patients represents the morphological equivalent of the clinical and functional manifestations of HCV-associated cerebral dysfunction. The results obtained can be used to improve the pathological diagnostics of brain lesions in chronic HCV infection; their implementation is feasible in routine pathological practice.

A NOVEL MUTATION IN A PATIENT WITH PULMONARY VENO-OCCLUSIVE DISEASE MASQUERADING AS PULMONARY ARTERIAL HYPERTENSION

A NOVEL MUTATION IN A PATIENT WITH PULMONARY VENO-OCCLUSIVE DISEASE MASQUERADING AS PULMONARY ARTERIAL HYPERTENSION

МОРФОЛОГІЧНІ ЗМІНИ СЕРЦЯ У ТВАРИН З ЕКСПЕРИМЕНТАЛЬНИМ СИСТЕМНИМ ЧЕРВОНИМ ВОВЧАКОМ

Патологія серця при системному червоному вовчаку (СЧВ) належить до найбільш частих проявів захворювання і багато в чому визначає його прогноз, а морфологічні зміни уражень міокарда, ендокарда та коронарних судин залишаються вивченими недостатньо. Гістологічна оцінка окремих кардіальних структур проводиться на природних моделях СЧВ у лінійних мишей.Мета і задачі роботи: вивчити в експерименті на тваринах (щурах) з моделлю СЧВ ступінь ушкодження міокарда, ендокарда й судин серця, зіставивши отримані результати з даними гістологічного дослідження тканин тимусу та селезінки.Матеріал і методи. Моделювання СЧВ виконано на 53 білих безпородних щурах (34 самиці і 19 самців) з використанням уведень повного адъюванта Фрейнда, селезінкової дезоксирібонуклеїнової кислоти великої рогатої худоби, циклофосфаміду, азиду й дезоксирібонуклеїнату натрію, вигодовуванням тварин з додаванням в їжу сульфату кадмію, оксибутирату літію і молібдату амонію. Гістологічні препарати серця забарвлювали гематоксиліном та еозином, альціановим синім (рН=2,6), за ван Гізоном, ставилась PAS-реакція.Результати. Експериментальний СЧВ супроводжується розвитком кардіопатії у усіх тварин з гіпертрофією, дистрофією і некрозом кардіоміоцитів, морфологічними ознаками склерозу коронарних судин, строми міокарда, ендокарда та клапанів серця, проліферацією судинного ендотелію, яка має дисперсійні й прямі кореляційні зв'язки зі ступенем лімфомакрофагальної інфільтрації інтерстицію, периваскулярною і клапанною гістіоцитарною клітинною інфільтрацією, а характер ушкоджень ендотелію судин щільно пов'язаний з наявністю в стромі міокарда хмарних клітин, визначається некрозом ендокарда та колагенолізом клапанів, зменшенням лімфоїдної тканини в селезінці, а також клітин в мозковому шарі і телець Гассаля в тимусі.Висновки. При експериментальній вовчаковій кардіопатії спостерігається закономірне ураження усіх структур серця, причому в їх патогенетичних побудовах беруть участь імунні порушення, на що вказують ушкодження відповідних структур імунокомпетентних органів – тимусу і селезінки.

ХАРАКТЕР ТА ОСОБЛИВОСТІ МОРФОЛОГІЧНИХ ЗМІН У ПІДНЕБІННИХ МИГДАЛИКАХ У ХВОРИХ НА ХРОНІЧНИЙ ТОНЗИЛІТ ЗАЛЕЖНО ВІД РІВНЯ АПОПТОЗУ ЛІМФОЦИТІВ

При зіставленні стану апоптозу і некрозу в лімфоцитах піднебінних мигдаликів і периферійної крові за результатами морфологічних досліджень у хворих на хронічний тонзиліт встановлено залежність морфологічних змін від стану апоптозу.Мета дослідження – встановити рівень апоптозу і його співвідношення з некрозом у лімфоцитах і нейтрофілах гомогенату піднебінних мигдаликів та у периферійній крові хворих на хронічний тонзиліт і зіставити отримані дані з результатами морфологічних досліджень.Матеріал і методи. Проведено обстеження хворих на хронічний тонзиліт після тонзилектомії з визначенням стану апоптозу і некрозу в лімфоцитах та нейтрофілах гомогенату піднебінного мигдалика і у периферійній крові на проточному цитофлюориметрі. Крім того, всім пацієнтам проводилося морфологічне дослідження видалених піднебінних мигдаликів.Результати. При хронічному тонзиліті в лімфоцитах апоптоз переважає над некрозом. Таке переважання характерне для бактерійного ураження мигдаликів, на відміну від вірусного, при якому воно проявляється у нейтрофілах. Причому кратність цього переважання корелює із морфологічними змінами у самих мигдаликах.По мірі наростання патоморфологічних змін наростає і кратність співвідношення апоптоз/некроз. При співвідношенні, кратному 2–3, патоморфологічна картина представлена лише помірними судинними реакціями у вигляді посилення васкуляризації із збільшенням кількості та розширенням просвіту дрібних артерій і артеріол з одночасним зниженням пропускної спроможності артерій середнього калібру. Це, разом із морфологічним станом слизової оболонки, сполучнотканинної капсули і фолікулів дає підстави вважати, що захворювання ще перебуває у стадії компенсації і підлягає консервативному лікуванню.При співвідношенні апоптоз/некроз, кратному 4–6, були зареєстровані судинні зміни дилатаційного характеру. До них приєднувалися морфологічні зміни у вигляді стоншання слизової оболонки, потовщення сполучнотканинної капсули і зменшення розмірів фолікулів та їх просвітлення, що, разом із явищами метаплазії і гіперкератозу епітелію слизової оболонки, може бути підтвердженням субкомпенсації патологічного процесу.Виявлені ж при кратності співвідношення апоптоз/некроз в 7 разів і більше морфологічні зміни у вигляді подальшої деградації епітелію слизової, проліферації сполучної тканини як у капсулі, так і проникнення її у паренхіму разом із вираженим периваскулярним склерозом, деструктивними змінами із макрофагальною реакцією у значно зменшених за розмірами лімфоїдних фолікулах, наявністю скупчень білкового детриту та відповідними судинними реакціями є ознаками декомпенсації захворювання і необхідності його оперативного лікування.Висновки. При співвідношенні апоптоз/некроз у лімфоцитах гомогенату піднебінних мигдаликів і периферійній крові, кратному 2–4, морфологічні зміни у самих мигдаликах відповідають захворюванню у стадії компенсації, при співвідношенні 4–6 за даними морфологічних досліджень процес можна вважати субкомпенсованим і при співвідношенні 7 і більше – декомпенсованим.

The effect of the complex antidiabetic composition on the histostructure of the pancreas in rats under the conditions of dexamethasone-induced diabetes

Researchers of the National University of Pharmacy (NUPh) have developed a pharmaceutical composition based on glibenclamide and metabolitotropic substances with the proven antioxidant, membrane-protective and hypolipidemic action. Aim. To study the effect of a new antidiabetic composition (NAC) on the pancreatic histological structure in rats under experimental dexamethasone-induced diabetes. Materials and methods. The experimental diabetes mellitus in rats was induced by dexamethasone in the dose of 150 mg/kg for 5 weeks against the background of a high-calorie diet. Rats were divided into the following groups: Group 1 – control pathology (n=10); Group 2 receiving the NAC in the dose of 4.0 mg/kg (n=10); Group 3 receiving the reference drug glibenclamide in the dose of 0.25 mg/kg (n=10). All data obtained were processed using methods of variation statistics. The microscopic examination was carried out under a Granum light microscope, photographing of microscopic images was performed with a Granum DSM 310digital video camera. Photos were processed on a Pentium 2.4 GHz computer using the Toup View program. Results. In animals of the control pathology group introduction of dexamethasone against the background of a hypercaloric diet led to a marked decrease in the optical density of pancreatic islets in the microslide (up to 11.4 ± 1.0), their uneven distribution in the lobes, and redistribution of the percentage ratio between the islets. The percentage of large islets increased by 2.4 times, the islets themselves were hypertrophied, often had an elongated shape. Pancreatic islets in the middle practically disappeared. Although not significantly, the share of small islets increased by 26.61 %. There were mosaic lesions of pancreatic islets. There were hypertrophic, dystrophic changes in some of them, or beta-cells in the state of necrosis. The widening of the lumen of the excretory ducts, and focal expressive perivascular sclerosis were observed. Introduction of the NAC against the background of the experimental dexamethasone-induced diabetes significantly inhibited destruction of the pancreas compared to the control pathology. The volume density of pancreatic islets increased (by 57.89 %), their shape was much more common. The share of large islets decreased by a factor of 4.4. The share of medium (by the number of beta cells) pancreatic islets was restored to the intact level. At the same time, small islets still occupied a rather high share – 37.5 %. Morphologically, the beta cells in islets were more complete. There no «budding» of small islets from the mother one, and the membrane between the islets. The signs of hypertrophy of islets were clearly reduced. There was no sclerosis in the interlobar connective tissue layers, perivascular sclerosis, and dilatation of ductula. Introduction of the reference drug glibenclamide in the dose of 0.25 mg/kg to a lesser degree normalized the histological structure of the pancreas than the NAC. Although the state of pancreatic beta cells in a significant number of islets was normal, some of them had signs of vacuolization. Some islets were not too clearly separated from the acinar parenchyma; there was necrobiosis of some beta cells. The morphometric analysis of islets showed that the relative proportion of small islets still remained elevated compared to the intact control and even higher than in the control pathology group (by 20 %) although not significantly. The bulk density of pancreatic islets in microslides increased by 61.40 %. Conclusions. A new antidiabetic composition based on glibenclamide and metabolitotropic substances has a corrective effect on the state of the endocrine apparatus of the pancreas of female rats, it leads to a marked increase in the total number of islets (primarily small and medium ones) compared to the control pathology, a visualized increase in morphologically more complete insulin cells. The NAC exhibits a significant protective effect on pancreatic cells.

PATHOGENETIC ASPECTS OF DEVELOPMENT OF ARTERIAL HYPERTENSION IN COAL WORKERS

We carried out gistomorphometrical researches of vessels of the small circle of blood circulation in the pulmonary tissue of 17 miners which had worked under dust conditions on the average 14,1±0,5 years. They were considered as healthy according to the results of dynamic observation and they perished due to technogenic catastrophe. The results showed that the thickening of the endothelial layer, the hypertrophy of smooth muscle structures and the development of perivascular sclerosis are happened in the vessels of the lungs of miners. Changes of the structure of the vessel wall lead to its thickening and reduction the lumen of the vessel, that creates conditions for the development of pulmonary hypertension. The hypertrophy of smooth muscle structures is considered as one of the manifestations of systemic coniotic processes which occur in the wall of the pulmonary vessels and consequently causes a further increase in blood pressure that has secondary character. The obtained results dictate the need to develop methods of early monitoring of the cardiovascular system in coal workers to detect latent and the initial stages of pulmonary hypertension.

Morphological and functional characteristics of tubulointerstitium in IgA-nephropathy

Objective. The aim of this study was to investigate the vessels and stroma in renal tubulointerstitium in IgAnephropathy. Design and methods. The coefficient of arterial obstruction was assessed. The laboratory and pathological studies (including immunohistochemistry CD31 and quantitative/semi-quantitative assessment of pathohistopathological changes: atrophy of tubules, local sclerosis, perivascular sclerosis, sclerosed glomeruli, the coefficient of obstruction of the arteries with a diameter greater than 100 microns) were performed. Results. The serum creatinine level inversely correlated with the obstruction coefficient (r = –0,83, p < 0,05), and positively— with perivascular sclerosis (r = 0,64, p < 0,05). There was a statistically significant positive correlation between CD31+ and creatinine (r = 0,60, p < 0,05), and between CD31+ and arterial obstruction coefficient (r = –0,75, p < 0,05). Conclusion. The results suggest that the changes in the vascular structure, and therefore the hemodynamic in renal parenchyma may be responsible for fibrosis in the tubulointerstisium in IgA-nephropathy.

Pathological tortuosity of the internal carotid artery: morphological characteristics

Aim. Pathological tortuosity of the internal carotid artery (PT ICA) is one of the leading causes of extracranial cerebral circulation disorders. Despite considerable progress in methods of diagnosis and increasing number of operations etiology, pathogenesis and morphogenesis of PT ICA remain unclear. In order to study pathological changes in PT ICA material of 26 patients was studied using routine methods of light microscopy and histochemical methods.Methods and results. It was established that among patients middle aged women predominated. For PT the characteristic type of deformation was coiling (21 cases out of 26); elongation, combined tortuosity and double kinks were met rarely. In pathomorphologic study of carotid arteries hyperplasia of intima with proliferation of smooth muscle cells, irreversible changes in elastic fibers of media with the growth of fibrous connective tissue, dystrophy of collagen fibers and smooth-muscle cells, perivascular sclerosis without cell infiltration in adventitia were revealed.Conclusion. This indicates expressed fibrogenesis processes in all the layers of the vessel wall providing the irreversibility of circulatory deformation.

Extracellular matrix remodeling myocardium of the left ventricle rats with experimental heart failure after perindopril and melatonin administration

The aim of the study was to examine the reorganization of extracellular matrix left ventricular myocardium (LVM) rats (n = 38) with experimental heart failure (EHF) as affected by perindopril and melatonin administration. Rats LVM was studied using the methods of light microscopy, immunocytochemistry and morphometry. At day 14 of EHF, marked mosaic staining cardiomyocytes acid dyes, manifest hemodynamic disturbances: venous and capillary congestion, lymphostasis, perivascular and interstitial edema, there was a increase the volume density (OD) stroma, high activity of MMP-1 and TIMP-1. After modeling the EHF to 28 days in LVM, a further increase of hemodynamic met, cardiosclerosis areas and perivascular sclerosis, a significant increase OD stroma, observed decrease in the expression of MMP-1 and TIMP-1. In rats given perindopril and melatonin for 14 days, there was a regression of pathological changes in the balance was maintained MMP-1/TIMP-1 ratio close to the group of intact rats. Cardioprotective effects of perindopril and melatonin on extracellular matrix LVM of rats with EHF is discussed.

Morphofunctional analysis of the prostate exposed to chemical manufacture factors.

The structural characteristics of the prostate and the blood flow in the organ were studied in chemical plant workers suffering from chronic prostatitis. The prostate echostructure was characterized by vast zones of fibrosis and calcinosis, the hemodynamic ultrasonic parameters were low. Degenerative changes in the acinar structures and stromal fibrosis predominated in the biopsy specimens, these shifts were the most pronounced in the peripheral and transitory zones. Foci of common and small-acinar degeneration of the glands, abundant concrements, and significant collagenization with periglandular and perivascular sclerosis without or with slight inflammatory infiltration were detected. We hypothesize that long exposure to adverse factors of sulfuric acid manufacture contributed to the development of pathological changes in the prostate.

Hyalin Perivascular Arcs and Rings in Sclerosing Atypical Fibroxanthomas

To the Editors: Several variants of atypical fibroxanthoma (AFX) are split based on cytomorphology, for example, clear cell, granular cell, and spindle cell nonpleomorphic types.1 Nine cases of an unusual variant of AFX with keloidal tumoral sclerosis were presented by Kim and McNiff,2 following in from an anecdotal report3 and series of “keloidal” AFX. In several cases, “the keloidal collagen also formed ring-shaped structures surrounding CD31-positive vascular structures.” This report conveys our research on the perivascular sclerosis in a subset of 10 AFX examples with collagenous arcs and rings (Table 1).TABLE 1: 10 Prospectively Selected Cases of Sclerosing AFXThis curious arc and ring pattern of hyalinized collagen in some AFXs is morphologically similar to the always superficially located perivascular linear and tubular sclerosis in a minority of dermatofibromas. It is cautioned that the keloidal collagen associated with atypical fibrohistiocytic cells in AFX may erroneously lead to the diagnosis of “keloidal dermatofibroma.4” Interesting in this regard, it has been said that the spectrum of fibrous histiocytoma (a diagnostic term utilized as a synonym for dermatofibroma) can be viewed somewhat more broadly, with dermatofibroma (DF) at one pole and with its “malignant analogue” AFX at the other.5 In both entities, AFX and DF, a sparse central component of CD31-positive cells in the sclerotic arcs and rings deemed endothelial cells led to our initial hypothesis that the “keloidal collagen” is actually vascular basement membrane material of effete capillaries. Laminins, nidogens, and perlecans are arranged into highly organized supramolecular architectures by vascular basement membranes.6 We proposed the adherence of these elements likely explained the homogeneous (hyalinized) appearance of this material by obscuring its fibrillar texture (Figs. 1, 2). However, reactions for collagen type IV (specific for vascular basement membrane material)7 were negative for the morphologically similar curvilinear and circular material in both our AFX and DF examples. Also unreactive were the coarse hyalinized collagen bands of a common keloid, which like dermal collagen, are predominantly collagen type I.8FIGURE 1: Atypical fibroxanthoma. A, Hyalin rings surround small vessels in lower right of this AFX overlain by impetiginized parakeratosis (×400). B, Pleomorphic histology includes the usual tumor giant cells (×200). C, Dual immunohistochemical reaction: central endothelial cells label red for CD31 and rest upon an actin-positive (brown) pericyte layer (×700).FIGURE 2: Dermatofibroma. A, Sclerotic arcs and rings surround central cells in effete vessels; hemosiderin is the brown pigment (×700). B, A dual immunohistochemical reaction labels central endothelial cells red for CD31 although actin-positive pericytes are decorated brown as they layer against the external sclerotic ring (×700). C, A collagen IV reaction labels a thin endothelial basement membrane brown that lies between the endothelial cells and pericytes; the thick sclerotic collagenous rind around the vessel is nonreactive, that is, not thickened endothelial basement membrane (×1000).Pericytes are actin-positive cells situated in the basement membranes outside the endothelium of capillaries and venules. During the onset of angiogenesis the intramural pericytes leave the microvascular wall and enter the perivascular space, where they become collagen producing stromal cells. Sundberg et al9 identified 4 stages of pericyte migration/progression from the endothelium to a collagen-synthesizing fibroblast in the interstitium. Pericytes have been identified in the wound-healing process via their expression of platelet-derived growth factor, a moiety which enhances neoformation of collagen and is associated with a collagen-rich dense tumor stroma, and have been shown to differentiate into collagen-producing cells during liver fibrosis.10 Double immunohistochemical reactions in our AFXs and DFs alike display concentric pattern: luminal CD31-positive endothelial cells within a ring of actin-positive pericytes that face the external rim of sclerotic material (Figs. 1C, 2B). Lesional cells of both DF and AFX show no consistent propensity to border the sclerotic material, discounting any role they might have in producing it. This leaves the pericyte stimulated to differentiate into fibroblasts when in a proliferative “fibrohistiocytic” environment, as the sole architect because it is consistently found within the rings as expected. Sclerotic hyalin rings similar to the material under discussion have been illustrated in hemangiopericytomas.10 The consistent localization of the pericyte to within the hyalin rings of the 10 sclerosing AFXs in this series supports the hypothesis that this material is synthesized by pericytes, a proposition that should be tested by more sophisticated studies. Larisa M. Lehmer, MA Bruce D. Ragsdale, MD Western Dermatopathology with Central Coast Pathology and Santa Barbara Pathology Laboratory, San Luis Obispo, CA 93401

Results pathomorphologic study of musculocutaneous tissue samplings with people who subject to influence a little doses of ionizing radiation

To study the influence of small doses of ionizing radiation on microvasculature, the skin-muscular biopsy in the lower leg region was performed in 33 liquidators or clean-up workers at the Chernobyl Nuclear Power Plant and 7 workers of a typical research nuclear reactor (RNR).A histological feature in the liquidators was the presence of the disseminated productive panvasculitis with pronounced lymphocytary infiltration of the vessel wall and sclerosis outcome in most microvasculature vessels, perivascular sclerosis. Changes in vessels of RNR workers increased with the increase а total doses from productive panvasculitis with involvement from few to most microvasculature vessels, formation of perivascular fibrosis and perivascular sclerosis. The revealed changes may be significant in the observed somatic pathology.

Functionally-morphological kidneys condition in patients with rheumatoid arthritis

The aim of the investigation was to study the functional-morphological state of kidney in patients with rheumatoid arthritis (RА). Examination was performed on 75 patients with RA and 25 healthy subjects. In addition to complete clinical and instrumental examination accepted in specialised clinic, biopsy of kidney was conducted. At 62 patients changes in an urinary deposit are taped. According to 25 nephrobiopsies in 12 cases took place mesangioproliferative variant of a chronic glomerulonephritis, the amyloidosis was detected at 5 patients, in 8 cases - vascular changes, the weak and moderate phenomena of a productive vasculitis of arterioles, the capillaries, accompanied by a focal perivascular sclerosis. Nephroprotective effect of basic therapy of RА was found.

Final Report on the Safety Assessment of Sodium p -Chloro- m -Cresol, p -Chloro- m -Cresol, Chlorothymol, Mixed Cresols, m -Cresol, o -Cresol, p -Cresol, Isopropyl Cresols, Thymol, o -Cymen-5-ol, and Carvacrol1

Sodium p-Chloro-m-Cresol, p-Chloro-m-Cresol (PCMC), Mixed Cresols, m-Cresol, o-Cresol, p-Cresol, Isopropyl Cresols, Thymol, Chlorothymol, o-Cymen-5-ol, and Carvacrol are substituted phenols used as cosmetic biocides/preservatives and/or fragrance ingredients. Only PCMC, Thymol, and o-Cymen-5-ol are reported to be in current use, with the highest concentration of use at 0.5% for o-Cymen-5-ol in perfumes. The use of PCMC in cosmetics is restricted in Europe and Japan. Cresols can be absorbed through skin, the respiratory tract, and the digestive tract; metabolized by the liver; and excreted by the kidney as glucuronide and sulfate metabolites. Several of these cresols increase the dermal penetration of other agents, including azidothymidine. In acute oral toxicity studies, LD50 values were in the 200 to 5000 mg/kg day-1 range across several species. In short-term studies in rats and mice, an o-Cresol, m-Cresol, p-Cresol or m-Cresol/p-Cresol mixture at 30,000 ppm in the diet produced increases in liver and kidney weights, deficits in liver function, bone marrow hypocellularity, irritation to the gastrointestinal tract and nasal epithelia, and atrophy of female reproductive organs. The no observed effect levels (NOEL) of o-Cresol was 240 mg/kg in mink and 778 mg/kg in ferrets in short-term feeding studies, with no significant dose-related toxicity (excluding body weight parameters). In mice, 0.5% p-Cresol, but neither m-Cresol nor o-Cresol, caused loss of pigmentation. Short-term and subchronic oral toxicity tests performed with various cresols using mice, rats, hamsters, and rabbits resulted in no observed adverse effect levels (NOAELs) for mice of 625 ppm and rats of 50 mg/kg day-1, although the NOEL was 2000 ppm in a chronic study using rats. In rabbits, < or =160 mg/kg PCMC was found to produce irritation and erythema, but no systemic effects. Hamsters dosed with 1.5% p-Cresol in diet for 20 weeks had a greater incidence of mild and moderate forestomach hyperplasia as compared to the control. Acute inhalation toxicity studies using rats yielded LC50 values ranging from >20 mg/m(3) for o-Cresol to >583 mg/m(3) for PCMC. No deaths were recorded in mice given o-Cresol at 50 mg/m(3). Cats exposed (short-term) to 9 to 50 mg/m(3) of o-Cresol developed inflammation and irritation of the upper respiratory tract, pulmonary edema, and hemorrhage and perivascular sclerosis in the lungs. Rats exposed (subchronic) to o-Cresol at 9 mg/m(3) had changes in leukocytes, spinal cord smears, nervous activity, liver function, blood effects, clinical signs, and neurological effects. In guinea pigs, exposure to 9 mg/m(3) produced changes in hemoglobin concentrations and electrocardiograms (EKGs). Rats exposed (subchronic) to 0.05 mg/m(3) Mixed Cresols by inhalation exhibited central nervous system (CNS) excitation, denaturation of lung protein, and decreased weight gain. All cresols appear to be ocular irritants. Numerous sensitization studies have been reported and most positive reactions were seen with higher concentrations of Cresol ingredients. Developmental toxicity is seen in studies of m-Cresol, o-Cresol, and p-Cresol, but only at maternally toxic levels. In a reproductive toxicity study of a mixture of m-Cresol and p-Cresol using mice under a continuous breeding protocol, 1.0% caused minimal adult reproductive and significant postnatal toxicity in the presence of systemic maternal toxicity. The o-Cresol NOAEL was 0.2% for both reproductive and general toxicity in both generations. Cresol ingredients were generally nongenotoxic in bacterial, fruit fly, and mammalian cell assays. Thymol did not induce primary lung tumors in mice. No skin tumors were found in mice exposed dermally to m-Cresol, o-Cresol, or p-Cresol for 12 weeks. In the trypthan blue exclusion assay, antitumor effects were observed for Thymol and Carvacrol. Clinical patch testing with 2% PCMC may produce irritant reactions, particularly in people with multiple patch test reactions, that are misinterpreted as allergic responses. o-Cresol, p-Cresol, Thymol, Carvacrol, and o-Cymen-5-ol caused no dermal irritation at or above use concentrations. In two predictive patch tests, PCMC did not produce a sensitization reaction. Overall, these ingredients are not significant sensitizing or photosensitizing agents. The Cosmetic Ingredient Review (CIR) Expert Panel noted some of these ingredients may increase the penetration of other cosmetic ingredients and advised cosmetic formulators to take this into consideration. The CIR Expert Panel concluded that the toxic effects of these ingredients are observed at doses higher than would be available from cosmetics. A concentration limitation of 0.5% was chosen to ensure the absence of a chemical leukoderma effect. For p-Cresol and Mixed Cresols (which contain p-Cresol), the Panel considered that the available data are insufficient to support the safety of these two ingredients in cosmetics. Studies that would demonstrate no chemical leukoderma at concentrations of use of p-Cresol and Mixed Cresols, or would demonstrate a dose response from which a safe concentration could be derived, are needed.