Endothelial Cell Swelling Research Articles

Paeonol Protects Rat Heart by Improving Regional Blood Perfusion during No-Reflow

No-reflow phenomenon, defined as inadequate perfusion of myocardium without evident artery obstruction, occurs at a high incidence after coronary revascularization. The mechanisms underlying no-reflow is only partially understood. It is commonly caused by the swelling of endothelial cells, neutrophil accumulation, and vasoconstriction, which are all related to acute inflammation. Persistent no-reflow can lead to hospitalization and mortality. However, an effective preventive intervention has not yet been established. We have previously found that paeonol, an active extraction from the root of Paeonia suffruticosa, can benefit the heart function by inhibiting tissue damage after ischemia, reducing inflammation, and inducing vasodilatation. To further investigate the potential cardioprotective action of paeonol on no-reflow, healthy male Wistar rats were randomly divided into four groups: sham, ischemia-reperfusion (I/R) injury (left anterior descending coronary artery was ligated for 4 h followed by reperfusion for 8 h), and I/R injury pretreated with paeonol at two different doses. Real-time myocardial contrast echocardiography was used to monitor regional blood perfusion and cardiac functions. Our data indicated that paeonol treatment significantly reduces myocardial infarct area and no-reflow area (n = 8; p < 0.05). Regional myocardial perfusion (A·β) and cardiac functions such as ejection fraction, stroke volume, and fractional shortening were elevated by paeonol (n = 8; p < 0.05). Paeonol also lowered the serum levels of lactate dehydrogenase, creatine kinase, cardiac troponin T, and C-reactive protein, as indices of myocardial injury. Paeonol exerts beneficial effects on attenuating I/R-associated no-reflow injuries, and may be considered as a potential preventive treatment for cardiac diseases or post-coronary revascularization in which no-reflow often occurs.

Maintenance of vascular integrity by pericytes is essential for normal kidney function.

Pericytes are tissue-resident mesenchymal progenitor cells anatomically associated with the vasculature that have been shown to participate in tissue regeneration. Here, we tested the hypothesis that kidney pericytes, derived from FoxD1+ mesodermal progenitors during embryogenesis, are necessary for postnatal kidney homeostasis. Diphtheria toxin delivery to FoxD1Cre::RsDTR transgenic mice resulted in selective ablation of >90% of kidney pericytes but not other cell lineages. Abrupt increases in plasma creatinine, blood urea nitrogen, and albuminuria within 96 h indicated acute kidney injury in pericyte-ablated mice. Loss of pericytes led to a rapid accumulation of neutral lipid vacuoles, swollen mitochondria, and apoptosis in tubular epithelial cells. Pericyte ablation led to endothelial cell swelling, reduced expression of vascular homeostasis markers, and peritubular capillary loss. Despite the observed injury, no signs of the acute inflammatory response were observed. Pathway enrichment analysis of genes expressed in kidney pericytes in vivo identified basement membrane proteins, angiogenic factors, and factors regulating vascular tone as major regulators of vascular function. Using novel microphysiological devices, we recapitulated human kidney peritubular capillaries coated with pericytes and showed that pericytes regulate permeability, basement membrane deposition, and microvascular tone. These findings suggest that through the active support of the microvasculature, pericytes are essential to adult kidney homeostasis.

Scanning and transmission electron microscopy of the cells forming the hepatic sinusoidal wall of rat in acetaminophen- and Escherichia coli endotoxin-induced hepatotoxicity

Drugs and xenobiotics as well as bacterial endotoxins may reach the liver either systematically or after intestinal absorption. Therefore, cells lining the sinusoidal wall form the last barrier before blood constituents get in contact with the parenchymal cells. In this work, the ultrastructure of the cells forming the sinusoidal wall was studied after acetaminophen and Escherichia coli endotoxin treatments. Rats received acetaminophen at a dose of 1000mg/kg body weight by intraperitoneal injection once in acute and four times with a 1-week interval in chronic treatments, and E. coli endotoxin at a dose of 5mg/kg of body weight by intraperitoneal injection once in acute and four times with a 1-week interval in chronic treatments. Tissue samples were collected for scanning and transmission electron microscopy. Swelling of sinusoidal endothelial cells was noticed in both acute intoxicated groups with narrowing of the fenestrae, whereas large gaps were formed in chronic toxicity. Activation of Kupffer cells was a prominent common feature between the four toxicity groups. Interestingly, hepatic stellate cell activation was evident in both chronic acetaminophen and chronic endotoxin groups. Large amounts of collagen fibers were seen surrounding the hepatic stellate cells and in Disse space.

Glomerulopathy with distinctive fibrillar deposits but lacking glomerular deposition of type III collagen.

A 62-year-old woman with nephrotic syndrome underwent a renal biopsy. Under light microscopy, the biopsy findings included lobulation and enlargement of glomeruli, occasional thickening of glomerular capillary walls, and narrowing of the capillary lumen by swollen endothelial cells. Congo red staining was negative for amyloid. No significant intraglomerular fibrin deposition was found by phosphotungstic acid hematoxylin staining. Immunofluorescence microscopy showed no deposition of immunoglobulin G, A, or M; no κ or λ light chains; and no C3 or C1q. Electron microscopy revealed distinctive subendothelial and mesangial fibrillar deposits, mesangial cell interposition, and swelling and vacuolization of endothelial cells resulting in capillary lumen narrowing. Although some curvilinear fibrillar deposits mimicked the bundles of type III collagen fibers seen in collagenofibrotic glomerulopathy, neither glomerular deposition of type III collagen nor elevation of serum procollagen III peptide was noted. This glomerulopathy does not fulfill any known disease entities with non-amyloid non-immunoglobulin-derived organized glomerular deposits.

Role of the PTEN/PI3K/VEGF pathway in the development of Kawasaki disease.

Kawasaki disease (KD) is a disease of unknown etiology and the leading cause of childhood acquired heart disease. In this study, the significance of the phosphatase and tensin homolog (PTEN)/phosphoinositide 3-kinase (PI3K)/vascular endothelial growth factor (VEGF) pathway in the development of KD was investigated in a rabbit model. Rabbits were divided into the control group, which received saline injection, and the experimental group, which was treated with bovine serum albumin to induce arthritis and KD. After 1, 7 and 30 days the animals were sacrificed, and the white blood cell count, serum VEGF, and serum creatine kinase (CK) levels were measured. The coronary artery was examined histologically as well as immunohistochemically for PTEN and PI3K. After the induction of arthritis, coronary artery of the rabbits showed endothelial cell swelling, osteoporosis, necrosis and inflammatory cell infiltration. PTEN expression in these rabbits increased with the increasing number of modeling days. The expression of PI3K showed a decreasing trend. The number of white blood cells in rabbits after KD modeling were significantly higher than those in the controls. One day and 7 days after modeling the serum VEGF level in KD rabbits was significantly higher than that in the control group after 1 and 7 days followed by a decrease by 30 days. There was no significant change in serum CK on the day after the modeling, and the serum CK level was significantly higher after 7 and 30 days. In conclusion, the expression of PTEN/PI3K was altered at different stages of KD. PTEN expression gradually increased with the disease progression, while the expression of PI3K gradually decreased. Serum markers indicated that the PTEN/PI3K/VEGF signaling pathway is important in the vascular injury in KD.

Morphological Changes in Myocardial Blood Microvessels in Experimental Craniocerebral Injury

Aim of the research is to evaluate the structure changes of the capillaries, arterioles, venules and intra and extravascular alterations in myocardium of rats after traumatic brain injury (TBI). Material and methods. Experiments were performed in 18 white male noninbred rats. Midline thoracotomy was performed, and the heart excised under intraperitoneal anesthesia (sodium thiopental) on 3, 7 and 12 days after TBI. Myocardial tissue of the left ventricle was examined under light and electron microscopy. The results showed that following brain trauma there were changes of microvascular wall characterized by alterations of permeability, paracellular oedema, outgrowths of vessel endothelium, swelling, edema, and thinning of endothelial cells, intussusceptions, vacuolization of cytoplasm with fragmentation within the myocardium of the rats with TBI. Intravascular changes were manifested by the formation of hyaline thrombi, microaggregates and sludge of red blood cells in the lumen, altered vascular membrane structures, bubbles or even complete absence of circulation in capillaries (noreflow). Alterations outside of the vascular wall were manifested by the formation of diapedetic hemorrhage and development of a strongly pronounced perivascular edema. The injury of microvessels and the microrelief of the luminal surface of endothelial cells appeared to be important factors of activation of vascularplatelet mechanism of hemostasis. Conclusion. Treatment of traumatic disease should consider the need in timely correction of nonspecific alter ations associated with TBI to optimize the restructuring of cytoskeleton of endothelial cells, abrogate endothelial dysfunction and prevent microcirculatory complications.

CHANGES IN THE CONTRACTILE CARDIOMYOCYTES AND HEMOMICROCIRCULATORY BED IN PREGNANT RATS AND THEIR PUPS EXPOSED TO HEMIC HYPOXIA

The performed analysis of the morphology of cardiomyocytes and myocardial vascular bed in 12 pregnant rats and 16 newborn pups exposed to the hemic hypoxia induced by NaNO 2 revealed some similar degenerative and destructive changes which were more pronounced in pups. The main morphological characteristics of hypoxic myocardial damage in pregnant and newborn rats were presented in the form of phenomena of mixed dystrophy, swelling and destruction of endothelial cells and contractile cardiomyocytes along with the lysis of myofibrils, perivascular edema, capillary hyperemia, emptiness and spasm of the arterioles and contracture changes. Revealed pathological changes in the myocardium reflect the development of the myocardiodystrophy processes in pregnant rats and newborn pups.

HISTOPATHOLOGICAL EFFECTS OF GLYPHOSATE HERBICIDE ON DIFFERENT ORGANS OF MALE AND FEMALE ALBINO RATS

The effect of major herbicide used worldwide glyphosate was studied on some organs of mature male and female albino rats (Rattus norvegicus). The LC50 was determined for glyphosate was 9.7% as crushed maize bait.Animals were fed on bait treated with (12 LC50) for 15 days. The organs were collected two weeks after treatment and fixed in 10% formalin saline. The results revealed that the liver of male showed necrosis of some hepatocytes with infiltration of mononuclear inflammatory cells, while the liver of females showed necrosis of some hepatocytes and dilation of blood vessels surrounded by fibrin with activation of vankopfer cells. Hemorrhage, infiltration of mononuclear inflammatory cells and necrosis of cells lining renal tubes were observed in the kidney of male, while in female ,granular degeneration changes of cells lining renal tubes with infiltration of mononuclear inflammatory cells and hyper cellularity of glomeruli with thrombosis of some blood vessels were recorded . The lung of male showed congestion of blood vessels and thickening of its wall, hyper proliferation of cells lining bronchial, infiltration of mononuclear inflammatory cell and thickening of interstitial wall, whereas hemorrhage, swelling of endothelial cells lining blood vessels, infiltration of mononuclear inflammatory cells and emphysema were observed in the lung of female.

Histologic Features of Intestinal Thrombotic Microangiopathy in Pediatric and Young Adult Patients after Hematopoietic Stem Cell Transplantation

High-risk transplantation-associated thrombotic microangiopathy (TMA) can present with multisystem involvement and is associated with a poor outcome after hematopoietic stem cell transplantation (HSCT), with < 20% 1-year survival. TMA may involve the intestinal vasculature and can present with bleeding and ischemic colitis. There are no established pathologic criteria for the diagnosis of intestinal TMA (iTMA). The goal of our study was to identify histologic features of iTMA and describe associated clinical features. We evaluated endoscopic samples from 50 consecutive HSCT patients for 8 histopathologic signs of iTMA and compared findings in 3 clinical groups based on the presence or absence of systemic high-risk TMA (hrTMA) and the presence or absence of clinically staged intestinal graft-versus-host disease (iGVHD): TMA/iGVHD, no TMA/iGVHD, and no TMA/no iGVHD. Thirty percent of the study subjects had a clinical diagnosis of systemic hrTMA. On histology, loss of glands, intraluminal schistocytes, intraluminal fibrin, intraluminal microthrombi, endothelial cell separation, and total denudation of mucosa were significantly more common in the hrTMA group (P < .05). Intravascular thrombi were seen exclusively in patients with hrTMA. Mucosal hemorrhages and endothelial cell swelling were more common in hrTMA patients but this difference did not reach statistical significance. Patients with hrTMA were more likely to experience significant abdominal pain and gastrointestinal bleeding requiring multiple blood transfusions (P < .05). Our study shows that HSCT patients with systemic hrTMA can have significant bowel vascular injury that can be identified using defined histologic criteria. Recognition of these histologic signs in post-transplantation patients with significant gastrointestinal symptoms may guide clinical decisions.

Clinicopathologic analysis of acroangiodermatitis: 12 case reports

Objective To investigate the clinicopathologic features and differential diagnosis of acroangiodermatitis (AM). Methods Clinical and pathological data on 12 patients with AM were retrospectively reviewed. Results Clinical manifestations of AM consisted of circumscribed brown to violaceous macules, plaques, nodules and ulceration. Lesions were located in bilateral legs in 6 patients, and in unilateral legs in the other 6 patients. Histopathological examination revealed an increased number of lobular or clump - shaped capillaries and small veins whose lumens were round and regular, swelling of vascular endothelial cells, and different degrees of erythrocyte extravasation, hemosiderin deposition, dermal fibrosis and sparse infiltrates of inflammatory cells. The lesions were histologically located in the superficial dermis in 3 cases, in the upper and middle dermis in 8 cases, and in the entire dermis in 1 case. Immunohistochemical studies showed that vascular endothelial cells stained positive for CD31 and CD34, while perivascular cells stained negative for CD34. Conclusions AM has specific clinical and pathological manifestations, and pathological examination is essential for the diagnosis of AM. Key words: Sarcoma, Kaposi; Disease attributes; Pathology; Diagnosis; Acroangiodermatitis

From Glomerular Endothelium to Podocyte Pathobiology in Preeclampsia: a Paradigm Shift.

Preeclampsia is a pregnancy-specific syndrome characterized by renal dysfunction and high blood pressure. When evaluated with light microscopy, the renal lesion of preeclampsia is marked by endothelial cell swelling and the appearance of bloodless glomeruli. However, regarding the pathobiology of renal damage in preeclampsia, attention recently has shifted from the glomerular endothelial cells to the podocytes. The angiogenic imbalance in preeclampsia plays a key role in the development of both podocyte and endothelial damage in the glomerular filtration barrier. Here, we review the latest studies on the role of podocytes in the development of renal damage in preeclampsia and on podocytes as potential targets for diagnosis, treatment, and prevention of long-term complications of preeclampsia.

Superficial fibrin thrombi … and other findings: a review of the histopathology of human scabietic infections.

Cutaneous infection with the mite Sarcoptes scabiei var. hominis is associated with epidermal and dermal changes. After noting superficial fibrin thrombi in two biopsies with scabies mites, we comprehensively reviewed the histopathologic findings in scabietic infections to determine the frequency of this finding. Twenty five biopsies of scabies infection were retrieved from the archives of our institution; only cases containing scabietic mite parts or scybala were included. The microscopic features were documented. Nearly half (40%) of the cases showed fibrin thrombi within vessels of the superficial dermis. Other frequent findings included dermal eosinophils (88% of cases), epidermal spongiosis (76% of cases), lymphocyte atypia (64%), a superficial and deep infiltrate (52% of cases), dermal neutrophils (52%) and endothelial cell swelling (52%). Half of the cases contained polarizable mite elements. Less commonly encountered features included extravasated erythrocytes (44%), dermal edema (32%), pink 'pigtails'(28%), intraepidermal pustules (24%), plasma cells (20%) and vasculitis (4%). The pathologic characteristics of scabietic infection are wide-ranging. Spongiosis, superficial and deep inflammation, and dermal eosinophils and neutrophils are seen in the majority of cases. Superficial fibrin thrombi are not uncommon in scabietic infection, and may provide a helpful diagnostic clue when mites are not visible on initial sections.

Morphology of contractile cardiomyocytes and vessels in pregnant rats and their pups exposed to hemic hypoxia

Zadnipryany I. V., Tret'yakova O. S., Sataieva T. P., Zukow W. Morphology of contractile cardiomyocytes and vessels in pregnant rats and their pups exposed to hemic hypoxia. Journal of Education, Health and Sport. 2015;5(4):72-80. ISSN 2391-8306. DOI: 10.5281/zenodo.16595 http://ojs.ukw.edu.pl/index.php/johs/article/view/2015%3B5%284%29%3A72-80 https://pbn.nauka.gov.pl/works/553142 http://dx.doi.org/10.5281/zenodo.16595 Formerly Journal of Health Sciences. ISSN 1429-9623 / 2300-665X. Archives 2011 – 2014 http://journal.rsw.edu.pl/index.php/JHS/issue/archive Deklaracja. Specyfika i zawartośc merytoryczna czasopisma nie ulega zmianie. Zgodnie z informacją MNiSW z dnia 2 czerwca 2014 r., ze w roku 2014 nie bedzie przeprowadzana ocena czasopism naukowych; czasopismo o zmienionym tytule otrzymuje tyle samo punktow co na wykazie czasopism naukowych z dnia 31 grudnia 2014 r. The journal has had 5 points in Ministry of Science and Higher Education of Poland parametric evaluation. Part B item 1089. (31.12.2014). © The Author (s) 2015; This article is published with open access at Licensee Open Journal Systems of Kazimierz Wielki in Bydgoszcz, Poland and Radom in Radom, Poland Open Access. This article is distributed under the terms of the Creative Commons Attribution Noncommercial License which permits any noncommercial use, distribution, and reproduction in any medium, provided the original author(s) and source are credited. This is an open access article licensed under the terms of the Creative Commons Attribution Non Commercial License (http://creativecommons.org/licenses/by-nc/3.0/) which permits unrestricted, non commercial use, distribution and reproduction in any medium, provided the work is properly cited. This is an open access article licensed under the terms of the Creative Commons Attribution Non Commercial License (http://creativecommons.org/licenses/by-nc/3.0/) which permits unrestricted, non commercial use, distribution and reproduction in any medium, provided the work is properly cited. The authors declare that there is no conflict of interests regarding the publication of this paper. Received: 20.01.2014. Revised 27.02.2015. Accepted: 15.03.2015. UDC 611.08: 611: 611.12 + 611.16 morphology of contractile cardiomyocytes and vessels IN PREGNANT rats AND their pups exposed to HEMIC HYPOXIA I. V. Zadnipryany, O. S. Tret'yakova, T. P. Sataieva , W. Zukow Medical Academy named after S.I. Georgievskiy Federal State Autonomous Educational Institution of H igher Education Crimean Federal University Kazimierz Wielki University, Bydgoszcz Summary The performed morphological analysis of cardiomyocytes and myocardial vessels in 12 pregnant rats and 16 newborn pups exposed to the hemic hypoxia induced by NaNO 2 revealed some similar degenerative and destructive changes which were more pronounced in pups. The main morphological characteristics of hypoxic myocardial damage in pregnant and newborn rats were presented in the form of phenomena of mixed dystrophy, swelling and destruction of endothelial cells and contractile cardiomyocytes along with the lysis of myofibrils, perivascular edema, capillary hyperemia, emptiness and spasm of the arterioles and contracture changes. Revealed pathological changes in the myocardium reflect the onset of myocardiodystrophy processes in pregnant rats and their newborn pups. Keywords: hemic hypoxia, cardiomyocytes, vessels, myocardium, pregnant rats, pups.

Pulmonary microvascular dysfunction and pathological changes induced by blast injury in a rabbit model.

Vascular leakage has been proven to play a critical role in the incidence and development of explosive pulmonary barotrauma. Quantitatively investigated in the present study was the severity of vascular leakage in a gradient blast injury series, as well as ultrastructural evidence relating to pulmonary vascular leakage. One hundred adult male New Zealand white rabbits were randomly divided into 5 groups according to distance from the detonator (10 cm, 15 cm, 20 cm, 30 cm, and sham control). Value of pulmonary vascular leakage was monitored by a radioactive 125I-albumin labeling method. Pathological changes caused by the blast wave were examined under light and electron microscopes. Transcapillary escape rate of 125I-albumin and residual radioactivity in both lungs increased significantly at the distances of 10 cm, 15 cm, and 20 cm, suggesting increased severity of vascular leakage in these groups. Ultrastructural observation showed swelling of pulmonary capillary endothelial cells and widened gap between endothelial cells in the 10-cm and 15-cm groups. Primary blast wave can result in pulmonary capillary blood leakage. Blast wave can cause swelling of pulmonary capillary endothelial cells and widened gap between endothelial cells, which may be responsible for pulmonary vascular leakage.

Pathological investigation of the mortality in captive Grasscutter (Thryonomys swinderianus) colonies in Accra, Ghana

Hepatorenal syndrome and clinical signs of heart failure occurred sporadically in 3-to 12-month-old Grasscutter(Thryonomys swinderianus) in captive colonies originally derived from in-bred male and female littermates. Macroscopic lesions in severely affected animals included subcutaneous edema, cervical swelling, pneumonia and hepatomegaly. 43 Grasscutters that were found dead and or were euthanatized because of dyspenia and lethargy were necropsied and representative blocks of tissues from heart, lungs, kidneys, liver and neck examined microscopically. Myocardial lesions were present in all rats and consisted of multifocalcardiac myocyte necrosis, and mononuclear inflammatory cell infiltration. 60% of the dead Grasscutters had chronic pulmonary congestion, and microscopically, livers showed chronic passive congestion. The kidneys showed tubular cell damage that appeared to be the central event in the pathogenesis of renal dysfunction and injury in Grasscutter, as evidenced by endothelial cell swelling, detachment, and accumulation of cast in the renal tubules. Swelling of the neck in these colonies of Grasscutter appeared to have resulted predominantly from unknown reasons possibly caused by stasis of venous blood secondary to right heart failure associated with a heritable cardiomyopathy.

Degos Disease Associated with Behçet's Disease.

Dear Editor: Degos disease (DD) is a rare, thrombo-occlusive vasculopathy that primarily affect the skin, gastrointestinal tract, and central nervous system1. The cutaneous lesions present as characteristic papules with porcelain-white central atrophy and an erythematous raised border. Behcet's disease (BD) is a systemic vasculitis characterized clinically by recurrent oral aphthous and genital ulcers, cutaneous lesions, and iridocyclitis/posterior uveitis2. DD can be found as an apparent idiopathic disease or as a surrogate clinical finding in some connective tissue diseases. Here, we report a patient with cutaneous manifestation of DD, associated with mucocutaneous and systemic BD lesions. A 45-year-old woman had asymptomatic erythematous papules with central, porcelain-white colored umbilication on the trunk and both extremities for 20 years, and some of the lesions had healed to leave atrophic scars (Fig. 1A, B). She also had recurrent oral and genital ulcers for 20 years (Fig. 1C). She had been treated with prednisolone, dapsone, and colchicine for 2 years, but the cutaneous lesions did not improve with BD treatments. Fig. 1 (A, B) Erythematous to brownish papules with porcelainwhite central atrophy. (C) Recurrent oral aphthous ulcer. Histopathologic examination of a typical lesion showed a cell-poor, wedge-shaped area of dermal necrosis with vessel occlusion as well as dermal edema. Occluded vessels with thrombosis and vascular endothelial cell swelling were observed at the base of the wedge-shaped lesion, and the area was surrounded by lymphocytic infiltration (Fig. 2). Copious mucin deposition was visible in the dermis, which also showed positive staining for Alcian blue (data not shown). The laboratory findings for antinuclear antibody, lupus anticoagulant, anticardiolipin antibodies, and antiphospholipid antibodies were all negative. The results of the pathergy test were positive. The patient also had non-erosive asymmetric arthritis, and a 99m Tc-HDP 3-phase bone scan showed hot uptake. She had a scarring change on the retina due to recurrent chorioretinitis. Colonoscopy showed no specific findings for DD or BD. The patient was diagnosed with DD associated with BD. The cutaneous lesions, which were not responsive to BD treatment, improved after 4 months of treatment with aspirin and dipyridamole. Fig. 2 Histopathologic finding showing a wedge-shaped dermal infarct with a broad base toward the epidermis. An occluded dermal vessel is visible at the base of the dermal infarct area, and a lymphohistiocytic inflammatory infiltrate is visible at the lateral ... While the etiology of DD is unknown, evidence suggests a primary vaso-occlusive process. Vascular coagulopathy, endothelial cell damage, and an autoimmune process are considered the major pathogenic mechanisms3,4. In BD, an immune-mediated occlusive vasculitis is found in most sites of the active disease, and the endothelium appears to be the primary target5. The cutaneous lesions of the present patient were characteristic of DD and did not respond to BD treatments. This indicates that, while DD can be associated with BD, it is a distinct disease entity to BD. To the best of our knowledge, although Sweet's syndrome and pyoderma gangrenosum in BD have been reported in association with BD, our patient represents the first reported case of DD associated with BD. With the underlying vaso-occlusive process of both DD and BD, it is reasonable for an association between DD and BD to exist. Whether this patient had the same underlying mechanisms or the findings were coincidental is yet to be determined. We suggest that DD and BD are distinct disease entities but that DD can be associated with BD.

Interobserver agreement on histopathological lesions in class III or IV lupus nephritis.

To treat lupus nephritis effectively, proper identification of the histologic class is essential. Although the classification system for lupus nephritis is nearly 40 years old, remarkably few studies have investigated interobserver agreement. Interobserver agreement among nephropathologists was studied, particularly with respect to the recognition of class III/IV lupus nephritis lesions, and possible causes of disagreement were determined. A link to a survey containing pictures of 30 glomeruli was provided to all 360 members of the Renal Pathology Society; 34 responses were received from 12 countries (a response rate of 9.4%). The nephropathologist was asked whether glomerular lesions were present that would categorize the biopsy as class III/IV. If so, additional parameters were scored. To determine the interobserver agreement among the participants, κ or intraclass correlation values were calculated. The intraclass correlation or κ-value was also calculated for two separate levels of experience (specifically, nephropathologists who were new to the field or moderately experienced [less experienced] and nephropathologists who were highly experienced). Intraclass correlation for the presence of a class III/IV lesion was 0.39 (poor). The κ/intraclass correlation values for the additional parameters were as follows: active, chronic, or both: 0.36; segmental versus global: 0.39; endocapillary proliferation: 0.46; influx of inflammatory cells: 0.32; swelling of endothelial cells: 0.46; extracapillary proliferation: 0.57; type of crescent: 0.46; and wire loops: 0.35. The highly experienced nephropathologists had significantly less interobserver variability compared with the less experienced nephropathologists (P=0.004). There is generally poor agreement in terms of recognizing class III/IV lesions. Because experience clearly increases interobserver agreement, this agreement may be improved by training nephropathologists. These results also underscore the importance of a central review by experienced nephropathologists in clinical trials.

Radioprotective effects of valproic acid, a histone deacetylase inhibitor, in the rat brain.

Radiotherapy is commonly used in the treatment of brain tumors but can cause significant damage to surrounding normal brain. The radioprotective effects of valproic acid (VPA) on normal tissue in the rat brain were evaluated following irradiation. Male Wistar rats were used in the present study and 48 rats were randomly divided into four groups consisting of 12 rats each. The whole-brain irradiation (WBI) was delivered by X-ray and the rats received the following treatment once a day for 5 days. The control group (sham-exposed group) received sham irradiation plus physiological saline. The VPA group received sham irradiation plus 150 mg VPA/kg. The X-ray group received WBI plus physiological saline. The combined group received WBI plus 150 mg/kg intraperitoneally VPA. A total of 6 months post-irradiation, the rats were sacrificed and the brains were harvested. Cell apoptosis in the cortex was determined by immunohistochemistry 24 h post-irradiation using an antibody for protein caspase-3. Transmission electron microscope (TEM) analyses were used to assess the effects of VPA on the radioprotection of rat normal brain cells 6 months post-irradiation. The weights of the animals in the TEM group measured over the two weeks after the first injection of VPA were also observed. Histological findings demonstrated that apoptosis occurred on the cortex 1 day after treatment, peaking in the X-ray group. The cells of the combined group showed a moderate caspase-3 staining compared to the X-ray group. There was a trend towards a lower body weight of the X-ray group following irradiation compared to either no-irradiation or rats of the combined group, although there was no significant difference in the average weight between the combined group and irradiated rats. Mild swelling of the capillary endothelial cells in the irregular lumen was observed in the combined group, whereas the X-ray group showed a severe structural disorder. In conclusion, VPA supplementation during radiotherapy may be beneficial for radioprotection following WBI by reducing normal brain cell injury.

Time course of pulmonary burden in mice exposed to residual oil fly ash.

Residual oil fly ash (ROFA) is a common pollutant in areas where oil is burned. This particulate matter (PM) with a broad distribution of particle diameters can be inhaled by human beings and putatively damage their respiratory system. Although some studies deal with cultured cells, animals, and even epidemiological issues, so far a comprehensive analysis of respiratory outcomes as a function of the time elapsed after exposure to a low dose of ROFA is wanted. Thus, we aimed to investigate the time course of mechanical, histological, and inflammatory lung changes, as well as neutrophils in the blood, in mice exposed to ROFA until 5 days after exposure. BALB/c mice (25 ± 5 g) were randomly divided into 7 groups and intranasally instilled with either 10 μL of sterile saline solution (0.9% NaCl, CTRL) or ROFA (0.2 μg in 10 μL of saline solution). Pulmonary mechanics, histology (normal and collapsed alveoli, mononuclear and polymorphonuclear cells, and ultrastructure), neutrophils (in blood and bronchoalveolar lavage fluid) were determined at 6 h in CTRL and at 6, 24, 48, 72, 96, and 120 h after ROFA exposure. ROFA contained metal elements, especially iron, polycyclic aromatic hydrocarbons (PAHs), and organochlorines. Lung resistive pressure augmented early (6 h) in the course of lung injury and other mechanical, histological and inflammatory parameters increased at 24 h, returning to control values at 120 h. Blood neutrophilia was present only at 24 and 48 h after exposure. Swelling of endothelial cells with adherent neutrophils was detected after ROFA instillation. No neutrophils were present in the lavage fluid. In conclusion, the exposure to ROFA, even in low doses, induced early changes in pulmonary mechanics, lung histology and accumulation of neutrophils in blood of mice that lasted for 4 days and disappeared spontaneously.

Erythropoietin protects against hemorrhagic blood–brain barrier disruption through the effects of aquaporin-4

Erythropoietin (EPO) has protective effects against many neurological diseases, including intracerebral hemorrhage (ICH). Here, we aimed to test EPO's effects on blood–brain barrier (BBB) disruption morphologically and functionally following ICH, which has not been well investigated. We also examined whether the effects were dependent on aquaporin-4 (AQP4). We detected the expression of perihematomal AQP4 and EPO receptor (EPOR) induced by EPO injection at 1, 3 and 7 days after ICH. We also examined the effects of EPO on BBB disruption by ICH in wild-type mice, and tested whether such effects were AQP4 dependent by using AQP4 knock-out mice. Furthermore, we assessed the related signal transduction pathways via astrocyte cultures. We found that EPO highly increased perihematomal AQP4 and EPOR expression. Specifically, EPO led to BBB protection in both types of mice by functionally reducing brain edema and BBB permeability, as well as morphologically suppressing tight junction (TJ) opening and endothelial cell swelling, and increasing expression of the TJ proteins occludin and zonula occluden-1 (ZO-1). Statistical analysis indicated that AQP4 was required for these effects. In addition, EPO upregulated phosphorylation of C-Jun amino-terminal kinase (JNK) and p38-mitogen-activated protein kinase (MAPK) as well as EPOR and AQP4 proteins in cultured astrocytes. The latter was inhibited by JNK and p38-MAPK inhibitors. Our data suggest that EPO protects BBB from disruption after ICH and that the main targets are the TJ proteins occludin and ZO-1. The effects of EPO are associated with increased levels of AQP4, and may occur through activation of JNK and p38-MAPK pathways after binding to EPOR.