Connective Tissue Growth Research Articles

Adrenal glands: morphofunctional reorganization based on the influence of exogenous and endogenous factors

The adrenal glands are the subject of many researches in biology and medicine. They have unique histoarchitectonics of the parenchyma and structure of the bloodstream. They also perform a number of important functions necessary for the normal vital activity of the body under stress. A large number of scientific papers are devoted to the study of changes in the structural organization of this organ at the micro- and submicroscopic levels under the influence of various external and internal factors. Morphofunctional changes in the gland after experimental thermal burns of the skin remain poorly understood, which requires further experimental studies in this area.The purpose of this study was to review the scientific literature on the effects of factors of different origins on the morphofunctional structure of the adrenal glands.The article analyzes scientific publications devoted to the study of the effects on the adrenal morphology of stress factors, heavy metals, drugs and toxic substances, alcohol, smoking, starvation, hypergravity, physical exercises, hypothermia, poisoning, dehydration, drugs, diabetes, and viral infections. It was found that the factors we mentioned cause the reorganization of the structural components of the adrenal glands, violations of their histoarchitectonics, in particular microcirculatory bed, at the micro- and submicroscopic level. In most cases, there were phenomena of pericellular and perivascular edema, focal hemorrhage, connective tissue growth, thickening of the connective tissue capsule of the organ with signs of edema, vacuolation and edema of the cytoplasm, and the appearance of pyknotic nuclei. In the long term that followed after the experiment, the stabilization of morphofunctional elements of the gland and the microcirculatory bed was recorded, but complete restoration of the structural integrity of the organ did not occur.

Zika virus promotes CCN1 expression via the CaMKIIα-CREB pathway in astrocytes

ABSTRACT Zika virus (ZIKV) infection in the human central nervous system (CNS) causes Guillain–Barre syndrome, cerebellum deformity, and other diseases. Astrocytes are immune response cells in the CNS and an important component of the blood–brain barrier. Consequently, any damage to astrocytes facilitates the spread of ZIKV in the CNS. Connective tissue growth factor/Nephroblastoma overexpressed gene family 1 (CCN1), an important inflammatory factor secreted by astrocytes, is reported to regulate innate immunity and viral infection. However, the mechanism by which astrocyte viral infection affects CCN1 expression remains undefined. In this study, we demonstrate that ZIKV infection up-regulates CCN1 expression in astrocytes, thus promoting intracellular viral replication. Other studies revealed that the cAMP response element (CRE) in the CCN1 promoter is activated by the ZIKV NS3 protein. The cAMP-responsive element-binding protein (CREB), a transacting factor of the CRE, is also activated by NS3 or ZIKV. Furthermore,a specific inhibitor of CREB, i.e. SGC-CBP30, reduced ZIKV-induced CCN1 up-regulation and ZIKV replication. Moreover, co-immunoprecipitation, overexpression, and knockdown studies confirmed that the interaction between NS3 and the regulatory domain of CaMKIIα could activate the CREB pathway, thus resulting in the up-regulation of CCN1 expression and enhancement of virus replication. In conclusion, the findings of our investigations on the NS3-CaMKIIα-CREB-CCN1 pathway provide a foundation for understanding the infection mechanism of ZIKV in the CNS.

Morpho-biochemical and immunohematologic features of calves infected with the agent of viral diarrhea

Тhe key direction of scientific research is considered to be the study of the characteristics of the course and manifestation of the disease, as well as the determination of virulent properties of pathogens. Calves infected with the agent of viral diarrhea were chosen as a model for study of the infectious process. The study summarizes the pathogenetic mechanisms of development and expression of viral diarrhea. Clinical, biochemical, and immunehematologic features of the disease were specified. data on morphological changes in parenchymal organs of diseased animals were found. Changes in protein, lipid, mineral metabolism, and electrolyte balance indices associated with increased activity of lactate dehydrogenase are considered to be metabolic features of VD. Immunologic research showed a shift in the process of lymphocyte differentiation with activation of the b-cell link of immunity and a decline in the phagocytic index. Calves infected with VD revealed signs of structural immunodeficiency, which is morphologically confirmed by the decrease of most of the lymphoid follicles of the spleen. The lungs displayed signs of catarrhal and purulent bronchitis, manifested by hyperplasia of the bronchial epithelium, desquamation of the epithelium and accumulation of exudate in the bronchial lumen and peribronchial edema. Evidence of serous lymphadenitis were registered in the lymph nodes associated with reduction of subcapsular lymphoid follicles, both in the subcapsular and central sinuses. They were accompanied by the growth of connective tissue in the stroma of the organ.

Патоморфологічні зміни в окремих трубчастих і паренхіматозних органах перепелів за еймеріозу

The work is devoted to the study of pathologic-anatomical and microscopic changes in tubular (duodenum, jejunum, cecum) and parenchymal (liver, lungs, spleen, kidneys) organs of quails for eimeriosis caused by E. tenella, E. necatrix, E. acervulina. The work was carried out on the basis of the pathomorphological laboratory of the Department of anatomy and histology of Zhytomyr national agroecological University (Zhytomyr, Ukraine). Average invasion intensity after E. tenella, E. necatrix, E. acervulina was 4,3, 6,1 and 4,3 oocytes in 1 g of dung. The generally accepted classical methods of pathomorphological studies were used. It is established that the development of the pathological process in the body of quails with eimeriosis has a multi-organ character. The main pathologic-anatomical and microscopic changes were revealed in the cecum - serous catarrhal and hemorrhagic inflammation, necrosis of mucosal structures, the presence of Eimeria of different stages of development at the base of the villi and around the crypts of the mucosa, among the components of serous and hemorrhagic exudate in the lumen of the intestines. Lesions of the duodenum and jejunum were manifested by catarrhal mucous inflammation. Regarding parenchymal organs, granular and fatty dystrophy of hepatocytes, venous hyperemia, necrosis, infiltration of the parenchyma by lymphocytes were registered in the liver; in lungs-stagnant hyperemia and edema; in spleen-hypoplasia of lymphoid nodules, growth of connective tissue, infiltration of parenchyma by lymphoid cells; in kidneys-hyperemia and hemorrhages, granular dystrophy of epithelial cells of renal tubules, proliferative intracapillary glomerulonephritis. Pathomorphological changes in the studied organs of quails infested with E. tenella, E. necatrix, E. acervulina. Eimeria species are established, expand the available information on the pathogenesis of eimeriosis in birds and can be used as tests of differential diagnosis and in the development, organization of scientifically based therapeutic and preventive measures in quail farms of Ukraine.

Morphofunctional changes in the digestive organs of pigs under the influence of soy processing product-okara

Okara obtained by processing soy grown in the Amur region contains twice as much raw and digestible protein as the product produced in the Western regions of our country. According to zootechnical analysis, it contains a mass fraction of crude protein of 29.58% and the amount of digested protein of 266.22 g. Its unnormalized use as a protein Supplement during intensive fattening of pigs causes fatty dystrophy of acinar cells and infiltrative growth of adipose and connective tissue, degenerative degeneration of the endocrine part of the glandular epithelium of the pancreas. Observed in liver cirrhotic transformation and protein-fatty degeneration of hepatocytes In 12-duodenum of piglets us were diagnosed with moderate diffuse chronic atrophic duodenitis, which manifests as thinning of the mucosa, flattening of surface epithelium, reducing the number of crypts and villi. The results of histological studies of the main digestive glands (pancreas and liver), as well as the small intestine allow us to conclude that soy Okara from Amur producers has a negative effect on the morpho-functional state of the digestive system, and as a result, a decrease in the digestibility and digestibility of nutritional components of the feed.

PATHOMORPHOLOGICAL STRUCTURE OF INTRAHEPATIC DUCTS AND CHOLEDOCH IN PATIENTS WITH ACUTE AND CHRONIC CHOLANGITIS.

Abstract. The morphological status of bile duct cells was studied in patients with acute and chronic cholangitis at different terms of the disease.All patients (32) were divided into 4 groups: up to 5 days, 12-14 days, 28-30 days and 10-12 months. The control group included 12 patients without clinical manifestations of choledocholithiasis. Acute cholestasis is registered in the intrahepatic bile ducts, the maximal severity of which is on first two weeks. In the period of 28-30 days the residual phenomena of acute cholangitis and the growth of connective tissue in the duct walls and around them are registered. In patients with cholangitis, the largest changes in the wall of the choledochus are recorded in 3-5 days from the onset of the disease in the form of edema-desquamative and epithelium necrosis. On 12-14 days marked "attenuation" and demarcation of the inflammatory process, and on 28-30 there’s the appearance of connective tissue in the wall of the choledoch. Patients operated on for chronic recurrent cholangitis for 1 year are documented on the background of the development of choledoch stricture, cholestasis, cholangiosclerosis, and biliary cirrhosis, as a complication.

ABOUT THE BASICS OF COMPREHENSIVE GERIATRIC ASSESSMENT

The article covers the principles of comprehensive geriatric assessment — an interdisciplinary diagnostic procedure aimed at developing a plan of treatment, long-term monitoring and support of an elderly person. The components of a comprehensive geriatric assessment, including the determination of physical, functional, psychological and social status of the subject, are reflected. During the process of analyzing the patient’s physical status, the age-related features of the functioning of various organs and systems, knowledge of which is necessary for the development of a targeted geriatric care strategy, should be taken into account. Involution of the respiratory organs is characterized by a decrease in the respiratory surface, atrophic processes in the mucous and lymphoid tissues, and an increased risk of developing bronchoobstructive syndrome. Degenerative sclerotic changes in the cardiovascular system contribute to the development of circulatory failure, sinus node dysfunction, increased sensitivity to stress factors, orthostatic hypotension, etc. With age, the secretory function of the gastrointestinal tract decreases, and the functional ability of the liver is limited. Reducing the reserve capacity of the kidneys provokes the development of inflammatory processes and contributes to the dehydration of the body. In older people, the risk of developing diabetes, hypothyroidism and hyperparathyroidism increases. The growth of connective tissue in the blood-forming organs limits the functionality of the blood system. Age-related changes in the musculoskeletal system are characterized by a decrease in muscle mass and the development of osteoporosis. Drug therapy is also being analyzed, since polypharmacy in the elderly is associated with a particularly high risk of developing side effects of the drugs. Assessment of the functional status implies the determination of the self service ability and the degree of a person’s independence from the help of others by his/her ability to perform basic functions, activities in everyday life and instrumental activity. The psycho emotional status is judged by the emotional background of the patient and his/her cognitive functions. Social and household status is estimated by the living conditions of an elderly person. Based on the results of a comprehensive geriatric assessment, an individual management plan is drawn up, the implementation of which is possible with the combined efforts of the geriatrician and a team of medical specialists, relatives, and social workers.

KARACİĞER HEMOSTAZINDA YENİ BİR BİTKİSEL İLAÇ: DENEYSEL BİR HAYVAN ÇALIŞMASI

<pre><!--block-->Objective: Bleeding is one of the major complications of surgical procedures. Severe bleeding can be seen after liver injury. Various methods have been described in the literature for stopping liver bleeding such as compression, Pringle maneuver, and other hemostatic agents have been used. In this study, the use of anti-inflammatory, antioxidant, antimicrobial, analgesic, and anticoagulant agents described in the literature were evaluated for hemostatic efficacy following liver injuries. Materials and Methods: In this study 28 Wistar albino female / male rats from out-bred production were used. Animals were divided in 4 groups. After liver damage model creation, various herbal substances were applied to the liver. Hematocrit and platelet counts were measured. In addition, for histopathologic changes in the liver parenchyma, the rats were sacrificed, and the liver was resected. Results: The amount of bleeding (p:0.001) and the preoperative and postoperative hematocrit changes (p:0.009) were statistically significant between the groups. There was no significant difference in connective tissue growth (p:0.065) and necrosis (p:0.062). There were significant differences in inflammation and without karyorrhexis (p:0.003). Discussion: Histopathological examinations showed that the groups using active agents had more connective tissue and karyorrhexis. Therefore these tissues could help to stop bleeding. </pre>

Mechanistic analyses in kidney transplant recipients prospectively randomized to two steroid free regimen-Low dose Tacrolimus with Everolimus versus standard dose Tacrolimus with Mycophenolate Mofetil.

Calcineurin inhibitors (CNI), the cornerstone of immunosuppression after transplantation are implicated in nephrotoxicity and allograft dysfunction. We hypothesized that combined low doses of CNI and Everolimus (EVR) may result in better graft outcomes and greater tolerogenic milieu. Forty adult renal transplant recipients were prospectively randomized to (steroid free) low dose Tacrolimus (TAC) and EVR or standard dose TAC and Mycophenolate (MMF) after Alemtuzumab induction. Baseline characteristics were statistically similar. EVR levels were maintained at 3–8 ng/ml. TAC levels were 4.5±1.9 and 6.4±1.5 ng/ml in the TAC+EVR and TAC+MMF group respectively. Follow up was 14±4 and 17±5 months respectively and included protocol kidney biopsies at 3 and 12 months post-transplantation. Rejection-rate was lower in the TAC+EVR group. However patient and overall graft survival, eGFR and incidence of adverse events were similar. TAC+EVR induced expansion of CD4+CD25hiFoxp3+ regulatory T cells as early as 3 months and expansion of IFN-γ+CD4+CD25hiFoxp3+ regulatory T cells at 12 months post-transplant. Gene expression profile showed a trend toward decreased inflammation, angiogenesis and connective tissue growth in the TAC+EVR Group. Thus, greater tolerogenic mechanisms were found to be operating in patients with low dose TAC+EVR and this might be responsible for the lower rejection-rate than in patients on standard dose TAC+MMF. However, further studies with longer follow up and evaluating impact on T regulatory cells are warranted.

PSME3 Promotes TGFB1 Secretion by Pancreatic Cancer Cells to Induce Pancreatic Stellate Cell Proliferation.

Pancreatic cancer is a highly malignant disease that is associated with poor prognosis. One hallmark of pancreatic cancer is excessive desmoplasia, characterized by fibrous or connective tissue growth and altered tumor stroma. Pancreatic stellate cells (PSCs) comprise a mesenchymal cell type that contributes to pancreas fibrosis and cancer progression. PSME3 is a regulatory subunit of the proteasome that is expressed in various cancers such as breast, ovarian, and pancreatic. Notably, PSME3 modulates lactate secretion in pancreatic cancer, suggesting a potential function in regulating pancreas fibrosis. However, the role of PSME3 in pancreatic cancer cell (PCC)-PSC interactions remains unclear. The current study, for the first time, explored the mechanism involved in PSME3-mediated PCC-PSC interactions. IHC showed that PSME3 is highly expressed in PCCs, and this was found to correlate with tumor differentiation. RNA interference (RNAi) indicated that PSME3 is involved in PCC apoptosis. PCR array and cell co-culture experiments suggested that conditioned culture medium (CM) from PSME3-knockdown PCCs could suppress PSC proliferation by down-regulating TGFB1 secretion. Transcription factor (TF) activation assays showed that PSME3 regulates TGFB1 production by inhibiting activation protein-1 (AP-1). Together, these data demonstrate that PSME3 interacts with AP-1 to regulate TGFB1 secretion in PCCs and promote PSC proliferation. Our results indicate a novel PSME3-regulated association between PSCs and PCCs and provide a promising therapeutic strategy for this malignancy.

A case report of bioprosthetic valve dysfunction after tricuspid valve replacement in a preschool patient: the contribution of pannus and calcification

Aim. To assess the contribution of pannus and calcification to the development of bioprosthetic valve dysfunction after tricuspid valve replacement in a pediatric patient.Materials and methods. A 3-month-old patient presented with tricuspid valve dysplasia and grade 4 tricuspid insufficiency underwent tricuspid valve replacement with the bioprosthesis «PeriCor» (ZAO «NeoKor», Russian Federation). The patient at the age of 6 years required a redo tricuspid valve replacement 5 years 8 months after initial surgery. Degenerative changes of the dysfunctional bioprosthetic valve explanted from the tricuspid position were assessed using macroscopic description and light microscopy. Cellular composition, the presence of bacteria, colocalization of calcifications with recipient cells were analyzed. The distribution of calcifications and their volume in the biomaterial tissue were estimated using microcomputer tomography imaging (micro-CT).Results. Bioprosthetic valve dysfunction was mainly caused by the pannus formation which was shown to encapsulate the anterior leaflet, resulting in its total failure and severe stenosis (reduced effective orifice area). There were no signs of ruptures and perforations in the valve tissues found. All leaflets were shown to contain predominantly fibroblastic cells and single blood cells, mainly located in the surface layers of the leaflets in the regions without any signs of calcification. Bacteria staining was negative for all types of the studied biomaterials. Calcifications were present in all xeno-tissue elements of the explanted bioprosthesis (i.e. leaflets, aortic segment, and pericardium). In addition, calcifications were also found in pannus growing during a functioning bioprosthetic valve. Calcifications were predominantly located in the co-optation and commissure zones of the leaflets. Importantly, massive calcifications were observed around the bioprosthetic stent frame. The total volume of calcification accounted for 1/3 of the biological component of the bioprosthesis (729 mm3).Conclusion. According to the data obtained in this study, we may conclude that the primary cause of the bioprosthesis failure was the growth of connective tissues, resulting in pannus-related dysfunction, rather than severe calcification of all bioprosthetic components. One may assume that bioprosthetic dysfunction is related to the peculiarity of the inflammatory response of the preschool patient. However, this typeof dysfunctions requires further investigation.

Catabolic effects of fibroblast growth factor-1 on chondrocytes through matrix metalloproteinase-13 and connective tissue growth factor/CCN2: possible role in osteoarthritis

Catabolic effects of fibroblast growth factor-1 on chondrocytes through matrix metalloproteinase-13 and connective tissue growth factor/CCN2: possible role in osteoarthritis

ПРЕДОТВРАЩЕНИЕ АТРОФИИ ТЕНОТОМИРОВАННОЙ КАМБАЛОВИДНОЙ МЫШЦЫ КРОЛИКА ПРИ ДЕНЕРВАЦИИ. НЕЙРОТРОФИЧЕСКОЕ ВЛИЯНИЕ

In the 1930—1940s R. G. Leibson and A. G. Ginеtsinsky with colleagues carried out the experiments were it was shown that the changes in tenotomized rabbit soleus muscle are completely eliminated if the nerve is cut at the same time. The authors concluded that atrophy from inactivity is not a passive process, but it is an active result of neural influences which are carried out by the ventral roots of sciatic nerve. The nature of these influences has not been studied and nervous control is not clear. The present study was carried out on 2-month old Californian rabbits to confirm the described phenomenon and to investigate the assumed neurotrophic mechanisms. The morphological signs of atrophy and degeneration of tenotomized rabbit muscles, muscle fiber death of and growth of connective tissue were eliminated on day 11 of exposure by simultaneous Achilles tenotomy. The effect of colchicine application on the tenotomized muscle was almost the same as denervation (10 mM solution was applicated at the sciatic nerve for 10 min), but in the case of colchicine the degenerative changes were more pronounced. Denervation of the tenotomized muscle or colchicine application maintained the fast fiber cross-sectional area at the level of intact control. Sciatic nerve denervation or colchicine application prevented the rise in soleus muscle TrkB and TrkС expression and altered some neurotrophin expression. Denervation with tenotomy decreased TrkB mRNA expression by 3.4 times (p < 0.05), TrkC — by 3.2 times (p < 0.05), NT3-by 3.4 times (p < 0.05) compared with the tentotomized contralateral limb, colchicine with tenotomy — by 3.6 and 2.9 times respectively (p < 0.05).

Morphological characteristics of fetal testes in chronic intrauterine hypoxia in different gestation periods

To study the morphological characteristics and expression of vascular endothelial growth factor (VEGF) in the fetal testes exposed to chronic intrauterine hypoxia during pathological pregnancy in different gestation periods. The testes from 48 male fetuses that had died in the antenatal or early neonatal period in mothers with pathological pregnancy were morphologically evaluated. Chronic intrauterine hypoxia was shown to be a powerful damaging factor and leads to delayed gonadal development. Histological examination of testicular tissue showed a significant reduction in the number of tubular cells per vision field, a decrease in tubular diameter and area, with the simultaneously increased area of the stroma and a larger number of vessels. Immunohistochemical study revealed the pronounced cytoplasmic expression of VEGF in testicular tissue in different gestation periods in the spermatogenic epitheliocytes, vessels, Leydig interstitial cells, while the maximal expression of this receptor was observed at 19-25 weeks' gestation, the degree of expression decreased at 26-29 weeks' gestation. Intrauterine hypoxia has a destabilizing effect on the processes of proliferation and differentiation of the spermatogenic epithelium, interstitial endocrinocytes, activates the processes of angiogenesis and the growth of connective tissue. All this can involve not only gonadal dysgenesis, but also future reproductive dysfunction. Hypoxia stimulates the expression of VEGF, whose receptors are present in almost all testicular cell populations. It can be assumed that VEGF can act as a paracrine regulator of Leydig cell activity, also as an inducer of angiogenesis, and thus play a certain role in the development of male fertility.

MicroRNA-27a Suppresses Detrusor Fibrosis in Streptozotocin-Induced Diabetic Rats by Targeting PRKAA2 Through the TGF-β1/Smad3 Signaling Pathway

We examined the effects of microRNA-27a (miR-27a) on detrusor fibrosis in streptozotocin (STZ)-induced diabetic rats. Eighty healthy Sprague-Dawley (SD) rats were randomly allocated into control, diabetic, miR-27a mimics, mimics control, miR-27a inhibitors, inhibitors control, siRNA-PRKAA2 (siPRKAA2) and inhibitors + siPRKAA2 groups (the latter 7 groups were established as STZ-induced diabetic rat models and treated in different manners). Detrusor cell apoptosis in bladder tissues was determined through terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling assay (TUNEL) staining. Detrusor cells were assigned to the blank, miR-27a mimics, mimics control, miR-27a inhibitors, inhibitors control, siPRKAA2 and inhibitors + siPRKAA2 groups. Flow cytometry determined the cell cycle stage and apoptosis. Quantitative reverse transcription polymerase chain reaction (qRT-PCR) and western blotting (WB) were used to assess the expression of miR-27a, PRKAA2, TGF-β1, Smad3, p-Smad3, fibronectin (FN), connective tissue growth (CTGF), and collagen-I (COL-I) in tissues and cells. Compared with the control group, the diabetic, miR-27a mimics, and siPRKAA2 groups showed reduced weight and PRKAA2 expression, but elevated blood glucose, serum creatinine (sCr), blood urea nitrogen (BUN), cell apoptosis, and expression of TGF-β1, Smad3, FN, COL-I, CTGF, and p-Smad3. The opposite trend was observed in the miR-27a inhibitors group. PRKAA2 is a target gene of miR-27a. Compared to the blank group, the miR-27a mimics and siPRKAA2 groups indicated markedly increased TGF-β1, Smad3, FN, COL-I, CTGF and p-Smad3 expression; decreased PRKAA2 expression; and increased cell apoptosis. The miR-27a inhibitors group showed the opposite trend. These results indicate that miR-27a may contribute to detrusor fibrosis in STZ-induced diabetic rats by targeting PRKAA2 via the TGF-β1/Smad3 signaling pathway.

Galectin-3 Inhibition by a Small-Molecule Inhibitor Reduces Both Pathological Corneal Neovascularization and Fibrosis.

PurposeCorneal neovascularization and scarring commonly lead to significant vision loss. This study was designed to determine whether a small-molecule inhibitor of galectin-3 can inhibit both corneal angiogenesis and fibrosis in experimental mouse models.MethodsAnimal models of silver nitrate cautery and alkaline burn were used to induce mouse corneal angiogenesis and fibrosis, respectively. Corneas were treated with the galectin-3 inhibitor, 33DFTG, or vehicle alone and were processed for whole-mount immunofluorescence staining and Western blot analysis to quantify the density of blood vessels and markers of fibrosis. In addition, human umbilical vein endothelial cells (HUVECs) and primary human corneal fibroblasts were used to analyze the role of galectin-3 in the process of angiogenesis and fibrosis in vitro.ResultsRobust angiogenesis was observed in silver nitrate–cauterized corneas on day 5 post injury, and markedly increased corneal opacification was demonstrated in alkaline burn–injured corneas on days 7 and 14 post injury. Treatment with the inhibitor substantially reduced corneal angiogenesis and opacification with a concomitant decrease in α-smooth muscle actin (α-SMA) expression and distribution. In vitro studies revealed that 33DFTG inhibited VEGF-A–induced HUVEC migration and sprouting without cytotoxic effects. The addition of exogenous galectin-3 to corneal fibroblasts in culture induced the expression of fibrosis-related proteins, including α-SMA and connective tissue growth factor.ConclusionsOur data provide proof of concept that targeting galectin-3 by the novel, small-molecule inhibitor, 33DFTG, ameliorates pathological corneal angiogenesis as well as fibrosis. These findings suggest a potential new therapeutic strategy for treating ocular disorders related to pathological angiogenesis and fibrosis.

The features of structural remodeling of rat testicles at poststrumectomic hypothyroidism.

Introduction. The lack of thyroid hormones leads to the decrease in basal metabolism and violation of the functional state of different organs and systems. One of the leading places is occupied by the cardiovascular disorders which affect the state of gonads. Objective - to determine the nature of morphofunctional reorganization of rat testicles and features of their bloodstream remodeling after the strumectomy. Methods. The experiments were conducted on mature white male rats which underwent the strumectomy. The material for histology were taken after 1, 3, 7, 14 and 28 days after the surgery. Histological sections stained with hematoxylin and eosin, by Van Ghison method. Results. In 1 day after the strumectomy the arterial and venous plethora was observed, which was combined with stromal edema. 3 days after the surgical intervention the morphological signs of organ circulatory disorders were partially reduced. However, the stromal edema remained and was accompanied by reduce in number of cell layers in spermatogenic epithelium with the increasing of intervals between them and their detachment from the basement membrane. In seven days morphological manifestations of vascular responses became more obvious. One could observe the narrowing of the orifices of side branches of the small arteries from the trunks. Identified changes progressed up to 14 days. Arteries with particularly thick walls and narrowed lumen were often detected. In tubules the signs of fibrous transformation were detected. On the 28th day of experiment the signs of disorders of blood circulation and nourishment of testicles were further compounded. Seminiferous tubules looked devastated. Their fibrous transformation was observed with the growth of connective tissue in the interchannel intervals. Conclusion. After the strumectomy in the rat testicles it was observed the significant circulatory disorders of organ leading to the degenerative changes in the stroma and parenchyma. The progression of degenerative changes leads to the reduction of spermatogenic epithelium, fibrous transformation of seminiferous tubules with the growth of connective tissue in the interstices.

Antibacterial activity and biocompatibility of three-dimensional nanostructured porous granules of hydroxyapatite and zinc oxide nanoparticles—an in vitro and in vivo study

Ceramic scaffolds are widely studied in the bone tissue engineering field due to their potential in regenerative medicine. However, adhesion of microorganisms on biomaterials with subsequent formation of antibiotic-resistant biofilms is a critical factor in implant-related infections. Therefore, new strategies are needed to address this problem. In the present study, three-dimensional and interconnected porous granules of nanostructured hydroxyapatite (nanoHA) incorporated with different amounts of zinc oxide (ZnO) nanoparticles were produced using a simple polymer sponge replication method. As in vitro experiments, granules were exposed to Staphylococcus aureus and Staphylococcus epidermidis and, after 24 h, the planktonic and sessile populations were assessed. Cytocompatibility towards osteoblast-like cells (MG63 cell line) was also evaluated for a period of 1 and 3 days, through resazurin assay and imaging flow cytometry analysis. As in vivo experiments, nanoHA porous granules with and without ZnO nanoparticles were implanted into the subcutaneous tissue in rats and their inflammatory response after 3, 7 and 30 days was examined, as well as their antibacterial activity after 1 and 3 days of S. aureus inoculation. The developed composites proved to be especially effective at reducing bacterial activity in vitro and in vivo for a weight percentage of 2% ZnO, with a low cell growth inhibition in vitro and no differences in the connective tissue growth and inflammatory response in vivo. Altogether, these results suggest that nanoHA–ZnO porous granules have a great potential to be used in orthopaedic and dental applications as a template for bone regeneration and, simultaneously, to restrain biomaterial-associated infections.

Histologic Examination of Teeth with Necrotic Pulps and Periapical Lesions Treated with 2 Scaffolds: An Animal Investigation

IntroductionTraditional pulp regeneration procedures that use a blood clot as a scaffold have produced histologic evidence of bone, cementum, and connective tissue growth within the root. Platelet-rich plasma (PRP) is a bioactive scaffold containing growth factors that enhance wound healing. AimThe aim of this study was to histologically compare the tissues generated when PRP or a blood clot is placed into teeth with preexisting necrotic pulps and periapical lesions. MethodsTwenty-four canine teeth from 6 immature ferrets were used. Two ferrets served as positive controls. Sixteen experimental canine teeth from 4 ferrets were infected, debrided, treated with a triple antibiotic paste, and randomly distributed to the following groups: group 1 (blood clot/Gelfoam), group 2 (PRP), and group 3 (no scaffold). At 3 months, the ferrets were sacrificed, and the tissues were evaluated histologically. Data were analyzed by using the Fisher exact test (P < .05). ResultsIn 3 of 6 teeth in the PRP group, 2 of 6 teeth in the blood clot group, and 1 of 4 teeth in the no scaffold group, an ingrowth of hard tissues was observed in the apical third of the roots. When using PRP or a blood clot as a scaffold, we found significantly more apical narrowing and hard tissue deposition in comparison to not using a scaffold (P < .05). ConclusionsThe use of PRP or blood clots as scaffolds results in the ingrowth of bone-like, cementum-like, and connective tissue in the apical third of the roots at inconsistent rates.

Evaluation of Fibrogenic Potential of Industrial Multi-Walled Carbon Nanotubes in Acute Aspiration Experiment

Local inflammatory response in the lungs and fi brogenic potential of multi-walled carbon nanotubes were studied in an acute aspiration experiment in mice. The doses were chosen based on the concentration of nanotubes in the air at a workplace of the company-producer. ELISA, fl ow cytometry, enhanced darkfield microscopy, and histological examination showed that multi-walled carbon nanotubes induced local inflammation, oxidative stress, and connective tissue growth (fibrosis). Serum levels of TGF-β1 and osteopontin proteins can serve as potential exposure biomarkers.