Inflammatory Cell Infiltration (inflammatory + cell_infiltration)

Distribution by Scientific Domains
Distribution within Medical Sciences


Selected Abstracts


Intranasal exposure to a damp building mould, Stachybotrys chartarum, induces lung inflammation in mice by satratoxin-independent mechanisms

CLINICAL & EXPERIMENTAL ALLERGY, Issue 11 2003
M. Leino
Summary Background Stachybotrys chartarum is a damp building mould and a potent toxin producer that has been related to serious cases of respiratory health problems. However, the direct link between exposure and health symptoms has not been established. Objective To examine the mechanism by which exposure to spores of satratoxin producing and non-producing S. chartarum strains induce inflammatory responses in murine lungs. Methods BALB/c mice were intranasally exposed for 3 weeks to spores of a satratoxin-producing and a non-producing S. chartarum strain. Inflammatory cell infiltration was characterized from bronchoalveolar lavage (BAL) fluid. Cytokine and chemokine mRNA expression in lung tissue was measured with real-time PCR. Bronchial responsiveness to methacholine (MCh) was determined by whole-body plethysmography and serum antibody levels by ELISA. Results A dose-dependent increase in monocytes, neutrophils and lymphocytes was observed in BAL fluid after intranasal (i.n.) instillation of S. chartarum spores. There was no difference in the BAL between exposure to the satratoxin-producing and the non-producing strains. Infiltration of inflammatory cells was associated with an induction of pro-inflammatory cytokine (IL-1,, IL-6 and TNF-,) and chemokine (CCL3/MIP-1,, CCL4/MIP-1, and CCL2/MCP-1) mRNA levels in the lungs. Interestingly, CXCL5/LIX was the only chemokine that showed significantly higher mRNA levels after exposure to the satratoxin-producing strain compared with the non-producing strain. MCh-induced bronchial responsiveness was not altered significantly after mould instillation. Moreover, no significant increase in total or specific IgE, IgG2a and IgG1 antibody levels were found after S. chartarum exposure. Conclusion These results indicate that lung inflammation induced by i.n. instillations of S. chartarum spores is regulated by the induction of pro-inflammatory cytokines and leucocyte-attracting chemokines. The data also imply that S. chartarum -derived components, other than satratoxins, are mediating the development of this inflammatory response. [source]


Pulpal responses to bacterial contamination following dentin bridging beneath hard-setting calcium hydroxide and self-etching adhesive resin system

DENTAL TRAUMATOLOGY, Issue 2 2008
Yuichi Kitasako
Class V cavities were prepared on 30 monkey teeth, and the pulps were exposed with a carbide bur through the cavity floor. Each exposed pulp was capped with either DY or 2V. The cavities were restored with a hybrid resin composite. The resin composite was removed at 180 days after capping, and then cavities were left open to the oral environment for 2 weeks to obtain bacteria contamination DY (BDY) and 2V (B2V; n = 10). A non-bacterial-contaminated group capped with DY was used as control. After bacterial challenges, inflammatory cell infiltration, incidence and differentiation of dentin bridges were evaluated histologically. There were significant differences in the presence of inflammatory cell infiltration among all groups (P < 0.05). No moderate or severe inflammatory reaction was found in Group DY. Group BDY showed moderate or severe inflammatory cell infiltration in 50%, and showed four necrotic specimens. Although no statistically significant difference was found in the formation and differentiation of dentin bridges among all groups, tunnel defects in dentin bridges were detected in 70% (DY), 80% (BDY), and 50% (B2V). Group B2V showed a significantly lower presence of inflammatory cell infiltration than Group BDY (P < 0.05). Bonding agent is supposed to seal the exposure site, and the remaining bonding agent on the cavities was effective as the barrier in the dentin bridges after bacterial challenges. [source]


EOSINOPHILIC GASTROENTERITIS ASSOCIATED WITH GIANT FOLDS

DIGESTIVE ENDOSCOPY, Issue 4 2010
Kenji Ishido
We describe a 54-year-old man who presented with right subcostal pain. Minocycline had been prescribed to treat pruritus, and the symptoms resolved. Subsequently, the patient consulted a local physician because of right subcostal pain. Giant folds were found in the greater curvature of the gastric body, and he was referred to the Department of Gastroenterology, Kitasato University East Hospital. Upper gastrointestinal endoscopy revealed markedly enlarged folds in the greater curvature of the stomach, with redness and edematous mucosa in the lesser curvature. Biopsy showed marked inflammatory cell infiltration (mainly eosinophils), but no atypical cells. Blood tests showed marked eosinophilia and elevated immunoglobulin E levels in the serum. The results of various allergic examinations were negative, but the clinical course suggested drug-induced eosinophilic gastroenteritis, and treatment was started. Minocycline was withdrawn without adequate resolution of symptoms. Because the leukocyte and eosinophil counts continued to increase, the patient was given suplatast, an anti-allergic agent. The symptoms and hematological values improved promptly. The patient recovered uneventfully, with no recurrence. [source]


Inhibition of scratching behaviour caused by contact dermatitis in histidine decarboxylase gene knockout mice

EXPERIMENTAL DERMATOLOGY, Issue 3 2005
M. Seike
Abstract:, A neuronal system dedicated to itch consists of primary afferent and spinothalamic projection neurons. Histamine is thought to be one of the main mediators for the transmission of itch sensation. However, there are little available information on the role of histamine in scratching behaviour and sensory transmission of atopic dermatitis and chronic eczema. In the present study, the role of histamine in scratching behaviour and neural conduction of sensation in the chronic eczema model was investigated by using l-histidine decarboxylase (HDC) gene knockout mice lacking histamine. The chronic contact dermatitis was induced with daily application of diphenylcyclopropenone (DCP) on a hind paw of HDC (+/+) and HDC (,/,) mice for 2 months. The observation of scratching behaviour and the hot-plate test were performed in both mice. Histological studies were performed in the skin and spinal cord tissues. Histological examination revealed that both HDC (+/+) and HDC (,/,) mice displayed the similar extent of inflammatory cell infiltration, hyperplastic epidermis and newly spreading of neuronal processes in the skin tissue. Scratching behaviour was exclusively induced in HDC (+/+) mice, whereas it was barely observed in HDC (,/,) mice. The expression of c-Fos was specifically upregulated in HDC (+/+) mice in lamina I of the spinal dorsal horn following repeated DCP application. Scratching behaviour in chronic contact dermatitis in mice was thought mainly mediated with histamine. The afferent pathway of sensation in chronic contact dermatitis model may connect with the central nervous system through lamina I of the spinal dorsal horn. [source]


The nuclear bile acid receptor FXR as a novel therapeutic target in cholestatic liver diseases: Hype or hope?

HEPATOLOGY, Issue 1 2004
Michael Trauner M.D.
Farnesoid X receptor (FXR) is a bile acid,activated transcription factor that is a member of the nuclear hormone receptor superfamily. FXR-null mice exhibit a phenotype similar to Byler disease, an inherited cholestatic liver disorder. In the liver, activation of FXR induces transcription of transporter genes involved in promoting bile acid clearance and represses genes involved in bile acid biosynthesis. We investigated whether the synthetic FXR agonist GW4064 could protect against cholestatic liver damage in rat models of extrahepatic and intrahepatic cholestasis. In the bile duct ligation and alpha-naphthylisothiocyanate models of cholestasis, GW4064 treatment resulted in significant reductions in serum alanine aminotransferase, aspartate aminotransferase, and lactate dehydrogenase, as well as other markers of liver damage. Rats that received GW4064 treatment also had decreased incidence and extent of necrosis, decreased inflammatory cell infiltration, and decreased bile duct proliferation. Analysis of gene expression in livers from GW4064-treated cholestatic rats revealed decreased expression of bile acid biosynthetic genes and increased expression of genes involved in bile acid transport, including the phospholipid flippase MDR2. The hepatoprotection seen in these animal models by the synthetic FXR agonist suggests FXR agonists may be useful in the treatment of cholestatic liver disease. [source]


Iron chelation prevents lung injury after major hepatectomy

HEPATOLOGY RESEARCH, Issue 8 2010
Konstantinos Kalimeris
Aim:, Oxidative stress has been implicated in lung injury following ischemia/reperfusion and resection of the liver. We tested whether alleviating oxidative stress with iron chelation could improve lung injury after extended hepatectomy. Methods:, Twelve adult female pigs subjected to liver ischemia for 150 min, 65,70% hepatectomy and reperfusion of the remnant liver for 24 h were randomized to a desferrioxamine (DF) group (n = 6) which received i.v. desferrioxamine to a total dose of 100 mg/kg during both ischemia and reperfusion, and a control (C) group (n = 6). We recorded hemodynamic and respiratory parameters, plasma interleukin-6 and malondialdehyde levels, as well as liver malondialdehyde and protein carbonyls content. Total non-heme iron was measured in lung and liver. Pulmonary tissue was evaluated histologically for its nitrotyrosine and protein carbonyls content and for superoxide dismutase (SOD) and platelet-activating factor acetylhydrolase (PAF-AcH) activities. Results:, Reperfusion of the remnant liver resulted in gradual deterioration of gas-exchange and pulmonary vascular abnormalities. Iron chelation significantly decreased the oxidative markers in plasma, liver and the lung and lowered activities of pulmonary SOD and PAF-AcH. The improved liver function was followed by improved arterial oxygenation and pulmonary vascular resistance. DF also improved alveolar collapse and inflammatory cell infiltration, while serum interleukin-6 increased. Conclusion:, In an experimental pig model that combines liver resection with prolonged ischemia, iron chelation during reperfusion of the remnant liver is associated with improvement of several parameters of oxidative stress, lung injury and arterial oxygenation. [source]


High salt diets dose-dependently promote gastric chemical carcinogenesis in Helicobacter pylori -infected Mongolian gerbils associated with a shift in mucin production from glandular to surface mucous cells

INTERNATIONAL JOURNAL OF CANCER, Issue 7 2006
Sosuke Kato
Abstract Intake of salt and salty food is known as a risk factor for gastric carcinogenesis. To examine the dose-dependence and the mechanisms underlying enhancing effects, Mongolian gerbils were treated with N -methyl- N -nitrosourea (MNU), Helicobacter pylori and food containing various concentrations of salt, and were sacrificed after 50 weeks. Among gerbils treated with MNU and H. pylori, the incidences of glandular stomach cancers were 15% in the normal diet group and 33%, 36% and 63% in the 2.5%, 5% and 10% NaCl diet groups, showing dose-dependent increase (p < 0.01). Intermittent intragastric injection of saturated NaCl solution, in contrast, did not promote gastric carcinogenesis. In gerbils infected with H. pylori, a high salt diet was associated with elevation of anti- H. pylori antibody titers, serum gastrin levels and inflammatory cell infiltration in a dose-dependent fashion. Ten percent NaCl diet upregulated the amount of surface mucous cell mucin (p < 0.05), suitable for H. pylori colonization, despite no increment of MUC5AC mRNA, while H. pylori infection itself had an opposing effect, stimulating transcription of MUC6 and increasing the amount of gland mucous cell mucin (GMCM). High salt diet, in turn, decreased the amount of GMCM, which acts against H. pylori infection. In conclusion, the present study demonstrated dose-dependent enhancing effects of salt in gastric chemical carcinogenesis in H. pylori -infected Mongolian gerbils associated with alteration of the mucous microenvironment. Reduction of salt intake could thus be one of the most important chemopreventive methods for human gastric carcinogenesis. © 2006 Wiley-Liss, Inc. [source]


Acute febrile neutrophilic dermatosis (Sweet's syndrome) with nodular episcleritis and polyneuropathy

INTERNATIONAL JOURNAL OF DERMATOLOGY, Issue 2 2002
Taizo Kato MD
A 56-year-old Japanese housewife presented with multiple erythematous lesions in association with ocular hyperemia and pain in the right upper and lower extremities, including the hands and feet. These symptoms were preceded by a sore throat with persistent fever higher than 38.5 °C for about 1 week. Dermatologic examination showed tender, dull-red, erythematous lesions, measuring 1,2 cm in diameter, located predominantly on the forehead, cheeks, auricular region, neck, forearm, hands, and feet. A biopsy specimen obtained from an erythematous lesion on the right forearm revealed prominent edema in the papillary dermis and remarkable inflammatory cell infiltration throughout the entire dermis (Fig. 1). The infiltrate predominantly consisted of neutrophils and nuclear dust without signs of vasculitis. In routine examination, the leukocyte count was 15,000/mL (normal range, 4000,8000/mL) with severe neutrophilia (80%). The C-reactive protein (CRP) level was 17.65 mg/dL (normal range, < 0.5 mg/dL) and the anti-streptolysin (ASLO) level was 611 IU/mL (normal range, < 166 IU/mL). In human leukocyte antigen (HLA) testing, HLA-A2, -B39, -B35, -Cw2, and -Cw7 were positive, and HLA-B51, -B54, and -Cw1 were negative. Figure Figure 1 . Histologic picture showing a dermal infiltrate of neutrophils Ocular hyperemia was caused by episcleritis forming a nodule and surrounding congestion of the superficial episcleritic vessels at the central portion of the sclera (Fig. 2). The patient suffered from pain once an hour, continuing for about 3 min, at the lateral portion of the right upper and lower extremities, as well as the right small finger. Neurologic examination demonstrated moderate or slight muscle weakness in the extremities. Hand grasping powers were 9 and 7 kg on the right and left, respectively. The patient was right-handed. Dysesthesia and paresthesia were also observed on the hands and feet. The deep tendon reflexes were preserved, however, even in the distal portion of the upper and lower limbs. In addition, essential tremor localized to the neck was recognized. Magnetic resonance imaging did not show any episodes of transient abnormal signal intensity in the central nervous system. Figure 2. Nodular episcleritis (right eye). Telangiectasia of winding vessels with nodular elevation was observed at the upper portion of the sclera The patient was treated with prednisolone (initial dose of 30 mg/day) and intravenous injection of cefazolin sodium (2 g/day for 5 days). Almost complete regression of the ocular and neurologic manifestations, as well as the skin lesions, was achieved in 2 weeks. Prednisolone was reduced gradually and suspended after 4 weeks. Leukocyte and neutrophil counts, CRP, and ASO returned to normal on suspension of therapy. Slight paresthesia remained in the right small finger even after stopping steroid. There was no recurrence at follow-up 6 months later. [source]


Toothbrushing promotes gingival fibroblast proliferation more effectively than removal of dental plaque

JOURNAL OF CLINICAL PERIODONTOLOGY, Issue 9 2002
Masazumi Horiuchi
Abstract Objectives: Removal of dental plaque is an essential element of periodontal treatment. However, there have also been studies of the effects of the mechanical stimulation provided by toothbrushing on gingival host-defense mechanisms. The aim of the study was to evaluate the effects of toothbrushing on gingival fibroblast proliferation in dogs over time, compared to effects of plaque removal without brushing. Methods: The mouths of six mongrel dogs were divided into four quadrants: two for daily toothbrushing, and two for daily plaque removal with a curette. After 1, 3 and 5 weeks of treatment, histometrical analyses were performed to assess inflammatory cell infiltration, proliferating cell nuclear antigen (PCNA)-positive fibroblasts, procollagen type I-positive fibroblasts in the subepithelial connective tissue of junctional epithelium. Results: Toothbrushing increased the number of PCNA-positive fibroblasts in the first week, increased the number of type I procollagen-positive fibroblasts at the fifth week, and reduced inflammatory cell infiltration at the third week. Conclusion: These findings suggest that mechanically stimulated fibroblasts begin proliferating within a week, and this cell division results in an increased number of fibroblasts at the third week. It takes 5 weeks before differences in collagen synthesis between brushing and plaque removal areas are detectable. Zusammenfassung Die Proliferation der gingivalen Fibroblasten wird durch Zähneputzen wirkungsvoller gefördert als durch Plaqueentfernung Ziele: Die Entfernung von Zahnplaque ist ein essenzieller Bestandteil der Parodontalbehandlung. Es gibt jedoch auch Studien über die Wirkung einer durch Zähneputzen bewirkten mechanischen Stimulation der gingivalen Abwehrmechanismen. Ziel dieser Studie war es, bei Hunden die Wirkung des Zähneputzen auf die Proliferation der gingivalen Fibroblasten über eine gewisse Zeit zu untersuchen und mit der Wirkung einer Plaqueentfernung ohne Zähneputzen zu vergleichen. Methoden: Das Maul von 6 Mischlingshunden wurde in vier Quadranten unterteilt: zwei mit täglichem Zähneputzen und zwei mit täglicher Plaqueentfernung mittels Kürette. 1, 3 und 5 Wochen nach der Behandlung wurden histometrische Analysen durchgeführt um das entzündliche Zellinfiltrat, die proliferierenden Cell-Nuclear-Antigen (PCNA)-positiven Fibroblasten und die Prokollagen-I-positiven Fibroblasten des subgingivalen Bindegewebes des Saumepithels zu bestimmen. Ergebnisse: Zähneputzen erhöhte in der ersten Woche die Anzahl der PCNA-positiven Fibroblasten, erhöhte bis zur fünften Woche die Anzahl der Type-I-Prokollagen-positiven Fibroblasten und reduzierte das entzündliche Zellinfiltrat bis zur dritten Woche. Schlussfolgerung: Diese Ergebnisse lassen annehmen, dass mechanisch stimulierte Fibroblasten während einer Woche zu proliferieren beginnen und diese Zellteilung eine erhöhte Anzahl von Fibroblasten in der dritten Woche zum Ergebnis hat. Es dauert fünf Wochen bevor zwischen den Bereichen mit Zähneputzen und Plaqueentfernung Unterschiede in der Kollagensynthese nachweisbar sind. Résumé Le brossage dentaire favorise la prolifération des fibroblastes gingivaux d'une manière plus efficace que l'enlèvement de la plaque dentaire L'enlèvement de la plaque dentaire est un élément essentiel dans le traitement parodontal. Cependant, des études ont été menées sur les effets de la stimulation mécanique produit par le brossage dentaire sur les mécanismes de défense de l'hôte au niveau gingival. Le but de l'étude présente a été d'évaluer les effets du brossage dentaire sur la prolifération des fibroblastes gingivaux chez les chiens dans le temps, comparés aux effets de l'enlèvement de la plaque dentaire sans brossage. Les bouches de six chiens bâtards ont été divisés en quatre quadrants : deux pour un brossage dentaire journalier et deux pour l'enlèvement journalier de la plaque à l'aide d'une curette. Après une, trois et cinq semaines de traitement, les analyses histométriques ont été effectuées pour évaluer l'infiltration cellulaire inflammatoire, les fibroblastes positifs à l'antigène du noyau cellulaire proliférant (PCNA), les fibroblastes positifs au procollagène-I dans le tissu conjonctif sous-épithélial de l'épithélium de jonction. Le brossage dentaire augmentait le nombre de fibroblastes positifs (PCNA) durant la première semaine, augmentait le nombre de fibroblastes positifs au collagène type-1 à la cinquième semaine et réduisait l'infiltration cellulaire inflammatoire à la troisième semaine. Ces découvertes suggèrent que les fibroblastes stimulés mécaniquement commencent à proliférer en une semaine, et cette division cellulaire abouti en un nombre plus important de fibroblastes à la troisième semaine. Il faut attendre cinq semaines avant que des différences dans la synthèse du collagène entre les zones de brossage et d'enlèvement de la plaque dentaire ne soient détectables. [source]


Hepatic arterial flow becomes the primary supply of sinusoids following partial portal vein ligation in rats

JOURNAL OF GASTROENTEROLOGY AND HEPATOLOGY, Issue 10 2006
Yukihiro Yokoyama
Abstract Background and Aim:, Partial portal vein ligation (PPVL) is a commonly used procedure to induce prehepatic portal hypertension in animal models. The aim of this study was to test the hypothesis that the hepatic arterial flow becomes the primary source feeding the sinusoids in the liver after PPVL. Methods:, Sprague,Dawley rats underwent either sham operation or partial portal vein ligation (PPVL). The number of vessels in the liver at 2 weeks postoperatively was determined by factor VIII immunolocalization and the gene expression of angiogenic factors was assessed by RT-PCR. The total hepatic arterial supply to the liver was measured using the fluorescent microsphere injection technique. To further test the hypothesis, two additional groups of rats underwent hepatic artery ligation (HAL) or PPVL plus HAL (PPHAL). The integrity of hepatic microcirculation was then evaluated in all four groups by intravital microscopy. Results:, At 2 weeks after operation, the number of vessels detected by factor VIII staining was significantly higher in PPVL compared to sham. Densitometric analysis of RT-PCR bands revealed a significant increase of vascular endothelial growth factor gene expression in PPVL compared to sham. Arterial flow to the liver measured by fluorescent microspheres was increased by 190% in PPVL compared to sham. When all four groups were compared, no prominent histological abnormality was observed in sham, HAL, and PPVL groups; however, PPHAL livers showed focal necrosis and inflammatory cell infiltration around the portal triads. Additionally, only the PPHAL livers showed a decreased sinusoidal diameter and significantly lower perfusion index (PPHAL 42.9 ± 6.1; sham 85.7 ± 7.0, PPVL 80.2 ± 6.5, HAL 70.9 ± 4.5). Conclusions:, These results suggest that the hepatic artery flow becomes the primary source for the blood supply of sinusoids and the compensatory change in the hepatic arterial system plays a critical role in maintaining microcirculatory perfusion following the restriction of the portal vein flow by PPVL. [source]


Estrogen as a neuroprotective agent in rat spinal cord injury

JOURNAL OF NEUROCHEMISTRY, Issue 2002
N. L. Banik
Spinal cord injury (SCI) is a neurological problem affecting approximately 11 000 Americans each year. Several treatment agents have been proposed; however, only methylprednisolone has limited efficacy. Estrogen is a multiactive neuroprotectant with antioxidant and anti-inflammatory properties and attenuates calcium (Ca2+) influx following neuronal injury. To examine the neuroprotective effects of estrogen in SCI, we induced SCI (40 g/cm injury) in rats. Treatment groups were sham (laminectomy only), SCI plus vehicle, and SCI plus estrogen. Injured rats were treated with either 4 mg/kg 17 ,-estradiol (estrogen group) or dimethylsulfoxide (vehicle group) at 15 min and 24 h following injury. All rats were killed at 48 h to analyze SCI segments for calpain content and Bax/Bcl-2 ratio by Western blotting. Tissue was also examined using calcium green-2 to measure intracellular [Ca2+], JC-1 to measure mitochondrial membrane potential, and double immunofluorescence for macrophages and calpain. Calpain content in the lesion penumbra, adjacent to the injury, was higher in vehicle than sham and this increase was attenuated in estrogen treated rats. In the lesion penumbra, the Bax/Bcl-2 ratio was increased in vehicle rats as compared to sham. This increase was attenuated in estrogen treated rats. Estrogen treated rats had less Ca2+ influx, less inflammatory cell infiltration, and increased maintenance of mitochondrial membrane potential compared to vehicle treated rats. Our preliminary data suggest that estrogen may be effective in decreasing Ca2+ influx, inflammatory cell infiltration, and Bax/Bcl-2 ratio following SCI. Acknowledgements:, Supported in part by grants from NIH-NINDS and South Carolina Electric and Gas. [source]


Intra-oral Dirofilaria repens infection: report of seven cases

JOURNAL OF ORAL PATHOLOGY & MEDICINE, Issue 8 2003
W. M. Tilakaratne
Abstract Cutaneous dirofilariasis usually affects animals such as cats and dogs which are known to be the natural host of Dirofilaria. Dirofilariasis displays a worldwide distribution. Certain geographic regions account for the majority of reported cases. South-eastern United States, Australia and Europe have been identified as endemic regions (1, 2). However, new endemic areas are arising with increased awareness in African and Asian regions. Out of about 40 different species of Dirofilaria only a few species are commonly known to infect man, namely Dirofilaria immitus, D. tenices and D. repens. Human infection occurs when a human becomes a blood meal of an infected arthropod vector and on accidental entering of the worm. Rarely this zoonotic infection affects the oral mucosa (3). Man is the dead end of this parasite. Since the human body is an abnormal environment for the parasite, the development of the larvae is inhibited by means of retardation of sexual maturity. Lesions are presented as single non-tender subcutaneous nodules, and most patients are asymptomatic. Diagnosis is established by H&E sections prepared from excised nodules. In a majority of the cases, only a single worm either a male or a female could be identified. The worm is usually dead and degenerated with a massive inflammatory cell infiltration. Seven new cases presented as intra-oral nodules with their clinicopathological correlation are discussed. [source]


Mechanisms of protection by melatonin against acetaminophen-induced liver injury in mice

JOURNAL OF PINEAL RESEARCH, Issue 3 2006
Tatsuya Matsura
Abstract:, The present study was performed to determine whether melatonin protects mouse liver against severe damage induced by acetaminophen (APAP) administration and where melatonin primarily functions in the metabolic pathway of APAP to protect mouse liver against APAP-induced injury. Treatment of mice with melatonin (50 or 100 mg/kg, p.o.) 8 or 4 hr before APAP administration (750 mg/kg, p.o.) suppressed the increase in plasma alanine aminotransferase and aspartate aminotransferase activities in a dose- and a time-dependent manner. Melatonin treatment (100 mg/kg, p.o.) 4 hr before APAP administration remarkably inhibited centrilobular hepatic necrosis with inflammatory cell infiltration and increases in hepatic lipid peroxidation and myeloperoxidase activity, an index of tissue neutrophil infiltration, as well as release of nitric oxide and interleukin-6 into blood circulation at 9 hr after APAP administration. However, melatonin neither affected hepatic reduced glutathione (GSH) content nor spared hepatic GSH consumption by APAP treatment. Moreover, pretreatment with melatonin 4 hr before APAP administration did not influence the induction of hepatic heat shock protein 70 (HSP70) by APAP and melatonin alone did not induce HSP70 in mouse liver. These results indicate that exogenously administered melatonin exhibits a potent hepatoprotective effect against APAP-induced hepatic damage probably downstream of the activity of cytochrome P450 2E1, which works upstream of GSH conjugation in the pathway of APAP metabolism, via its anti-nitrosative and anti-inflammatory activities in addition to its antioxidant activity. [source]


Reduction expression of thrombomodulin and endothelial cell nitric oxide synthase in dermatomyositis

NEUROPATHOLOGY, Issue 4 2007
Guang-li Shen
Dermatomyositis (DM) is a systemic microvasculitis predominantly involving the capillaries. We investigated the expression of thrombomodulin (TM) and endothelial cell nitric oxide synthase (eNOS) in microvessels of DM patients. Twelve patients with acute or subacute onset of proximal muscle weakness and erythematous rash over their faces and shoulders were included in this study. Serum creatine phosphokinase was elevated in almost all patients. Electromyograph showed a myopathic pattern in all patients. Muscle biopsies were performed in all patients and 10 non-DM controls and studied with histological, enzyme histochemical and immunohistochemical staining. von Willebrand factor, TM and eNOS antibodies were used as the primary antibodies. Perifascicular degeneration and inflammatory cell infiltration in the perimysium were noted in almost all patients. Non-special esterase staining was markedly positive in capillary and microvascular endothelium. Marked reduction in TM and eNOS staining was noted in DM patients in perimysium microvessels and perifascicular area capillaries. Vascular lesions in DM were not only limited to capillaries. The low expression of TM and eNOS in microvessels suggests the anticoagulation and vasodilation functions of vascular endothelium is reduced. DM is an inflammatory vascular endothelial disease. [source]


Blood,brain barrier impairment with enhanced SP, NK-1R, GFAP and Claudin-5 expressions in experimental cerebral toxocariasis

PARASITE IMMUNOLOGY, Issue 10 2008
C.-W. LIAO
SUMMARY Infection by Toxocara canis in humans may cause cerebral toxocariasis (CT). Appreciable numbers of T. canis larvae cross the blood,brain barrier (BBB) to invade the brain thus causing CT. In the present studies, we evaluated the BBB permeability and BBB injury as assessed by the cerebral Evans blue (EB) concentration as well as by pathological changes and glial fibrillary acidic protein (GFAP) expression in T. canis -infected mice monitored from 3 days (dpi) to 8 weeks post-infection (wpi). The vasodilation neuropeptides, the expressions of substance P (SP) and its preferred binding neurokinin-1 receptor (NK-1R) as well as claudin-5 of tight-junction proteins associated with BBB impairment were also assessed by Western blotting and reverse-transcriptase polymerase chain reaction. Results revealed that BBB permeability increased as evidenced by a significantly elevated EB concentration in brains of infected mice. BBB injury appeared due to enhanced GFAP protein and mRNA expressions from 4 to 8 wpi. Leukocytes might have been unrelated to BBB impairment because there was no inflammatory cell infiltration despite T. canis larvae having invaded the brain; whereas markedly elevated SP protein and NK-1R mRNA expressions concomitant with enhanced claudin-5 expression seemed to be associated with persistent BBB impairment in this experimental CT model. [source]


Immunohistochemical characterization of glomerular inflammatory cells and expression of adhesion molecules in anti-glomerular basement membrane (anti-GBM) glomerulonephritis induced in WKY rats with monoclonal anti-GBM antibodies of different subclasses

PATHOLOGY INTERNATIONAL, Issue 2 2006
Tadashi Kado
According to previous report, adhesion of CD8-positive cells and macrophages to glomerular endotherial cells through the lymphocyte function-associated antigen-1 (LFA-1)/intercellular adhesion molecule-1 (ICAM-1) pathway is crucial for the initiation and subsequent progression of anti-glomerular basement membrane (anti-GBM) antibody-induced glomerulonephritis (anti-GBM nephritis) in WKY rats. In the present study glomerular inflammatory cell infiltration and LFA-1/ICAM-1 expression were examined in anti-GBM nephritis induced in WKY rats with monoclonal anti-GBM antibodies of different subclasses: IgG1, IgG2a, and IgG2b. The IgG2a and IgG2b subclasses induced significant proteinuria from day 3 as compared with the IgG1 subclass. Glomerular infiltration of macrophages and CD8-positive cells after administration of IgG2a and IgG2b subclass antibodies was significantly elevated compared to that for the IgG1 subclass. The intensity of glomerular ICAM-1 immunostaining by the IgG2a and IgG2b subclass antibodies tended to be stronger than that by the IgG1 subclass. Glomerular LFA-1-positive cell infiltration by the IgG2a and IgG2b subclasses was significantly higher than that of the IgG1 subclass. These results demonstrate that monoclonal antibodies belonging to the IgG2a and IgG2b subclasses strongly induce glomerular infiltration of inflammatory cells and expression of adhesion molecules in rat anti-GBM nephritis. [source]


Role of heat shock protein 47 on tubulointerstitium in experimental radiation nephropathy

PATHOLOGY INTERNATIONAL, Issue 5-6 2002
Diange Liu
The molecular mechanisms of fibrosis in radiation nephropathy have received scant attention. Heat shock protein 47 (HSP47), a collagen-binding stress protein, helps in the intracellular processing of procollagen molecules during collagen synthesis. We investigated the role of HSP47 in the progression of radiation nephropathy using experimental radiation nephropathy. Experimental rat groups were as follows: (i) group I, sham operated (n = 12); (ii) group II, single doses of irradiation, either 7, 15 or 25 Gy to left kidney (n = 60); and (iii) group III, a similar irradiation procedure as group II after right nephrectomy (n = 60). The rats were followed up until 9 months after renal exposure to radiation. Renal dysfunction (as determined by serum creatinine and blood urea nitrogen) and hypertension were noted in group III rats, along with inflammatory cell infiltration and interstitial fibrosis (as determined by increased deposition of collagens). Compared to control rat kidneys, an increased expression of HSP47 was noted in kidneys obtained from irradiated rats. By double immunostaining, HSP47-expressing cells were identified as ,-smooth muscle actin-positive myofibroblasts and vimentin-positive tubular epithelial cells. Increased expression of HSP47 was closely associated with increased deposition of collagens in the widened interstitium of irradiated rats. Overexpression of HSP47 by phenotypically altered tubulointerstitial cells might play a role in excessive assembly/synthesis of collagens and could contribute to tubulointerstitial fibrosis in radiation nephropathy. [source]


Suppression of experimental lupus nephritis by aberrant expression of the soluble E-selectin gene

PATHOLOGY INTERNATIONAL, Issue 3 2002
Satoru Takahashi
Circulating leukocytes, particularly neutrophils and monocytes, are important effector cells in the induction of many forms of glomerulonephritis. Adhesion molecules, especially selectins, are also thought to be critical for the development of this disease. We examined the possible suppressive effect of soluble E-selectin on the development of experimental lupus nephritis induced by the injection of a hybridoma clone (2B11.3) derived from an MRL/MpJ- lpr/lpr lupus mouse. This clone produces IgG3 antibodies that induce severe proliferative glomerulonephritis resembling lupus nephritis when injected into normal mice. Transgenic mice with a soluble E-selectin gene were injected intraperitoneally with the hybridoma cells and histopathologically examined on day 15. As a result, the development of glomerulonephritis was significantly suppressed. This suppression was characterized by fewer inflammatory cell infiltrates, compared with non-transgenic litter mates, despite the fact that there were no remarkable differences in immunoglobulin deposits or expression of E-selectin between the two groups. These findings suggest that by controlling inflammatory cell infiltration, soluble E-selectin plays a preventative role in the development of a particular type of lupus nephritis. [source]


Histologic changes in channel catfish, Ictalurus punctatus Rafinesque, fed diets containing graded levels of gossypol,acetic acid

AQUACULTURE NUTRITION, Issue 4 2010
J.J. EVANS
Abstract A study was performed to evaluate the histologic changes among fingerling channel catfish, Ictalurus punctatus Rafinesque, fed purified diets containing gossypol from gossypol,acetic acid. The catfish were maintained on diets with 0, 300, 600, 900, 1200 or 1500 mg gossypol kg,1 diet for 12 weeks, and histologic samples from the stomach, proximal and distal intestines, pancreas, liver, and spleen were obtained from fish in all groups. Stomach sections exhibited significant gastric gland necrosis in fish fed 600 mg gossypol kg,1 diet or higher. Non-existent-to-mild enterocyte vacuolization loss, inflammatory cell infiltration, and hyperplastic lamina propria were noted in the intestinal sections from gossypol-fed fish, but no significant differences in severity scores were noted. The pancreas from fish fed doses of gossypol above 600 mg gossypol kg,1 diet exhibited significant mild-to-severe necrosis, and livers from fish fed 900 and 1500 mg gossypol kg,1 diet exhibited significantly higher pigment deposition. No other significant histologic differences were observed in the fish fed diets containing gossypol,acetic acid. The data in this study indicates that at least 600,900 mg gossypol kg,1 purified diet can cause statistically significant histologic changes in fingerling channel catfish, suggesting that gossypol should remain at concentrations below 600 mg gossypol kg,1 diet. [source]


GATA-3 protects against severe joint inflammation and bone erosion and reduces differentiation of Th17 cells during experimental arthritis

ARTHRITIS & RHEUMATISM, Issue 3 2009
Jan Piet van Hamburg
Objective Rheumatoid arthritis is associated with the infiltration of T helper cells into the joints. It is unclear whether interferon-, (IFN,),producing Th1 cells or the novel T helper subset, interleukin-17 (IL-17),producing Th17 cells, are the pathogenic mediators of joint inflammation in chronic nonautoimmune arthritis. Therefore, this study was aimed at examining whether the Th2-specific transcription factor GATA-3 can regulate arthritis, in an experimental murine model, by modulating Th1 and/or Th17 cell polarization. Methods Arthritis was induced with methylated bovine serum albumin (mBSA) in both wild-type and CD2 T cell,specific GATA-3 (CD2,GATA-3),transgenic mice. At days 1 and 7 after the induction of arthritis, knee joints were scored macroscopically for arthritis severity and for histologic changes. Single-cell suspensions were generated from the spleens, lymph nodes, and inflamed knee joints. Cytokine expression by CD4+ T cells was determined using flow cytometry, and IL-17 expression in the inflamed knee joints was determined by enzyme-linked immunosorbent assay. Analyses of gene expression were performed for Th17-associated factors. Results Wild-type mice developed severe joint inflammation, including massive inflammatory cell infiltration and bone erosion that increased significantly over time, reaching maximal arthritis scores at day 7. In contrast, only mild joint inflammation was observed in CD2,GATA-3,transgenic mice. This mild effect was further accompanied by systemic and local reductions in the numbers of IL-17+IFN,, and IL-17+IFN,+, but not IL-17,IFN,+, CD4+ T cells, and by induction of Th2 cytokine expression. Moreover, GATA-3 overexpression resulted in reduced gene expression of the Th17-associated transcription factor retinoic acid,related orphan receptor ,t. Conclusion These results indicate that enforced GATA-3 expression protects against severe joint inflammation and bone erosion in mice, accompanied by reduced differentiation of Th17 cells, but not Th1 cells, during mBSA-induced arthritis. [source]


Beneficial effect of galectin 9 on rheumatoid arthritis by induction of apoptosis of synovial fibroblasts

ARTHRITIS & RHEUMATISM, Issue 12 2007
Masako Seki
Objective To compare the expression of galectin 9 (Gal-9) in synovial tissue (ST) from rheumatoid arthritis (RA) patients and osteoarthritis (OA) patients and to evaluate the effects of Gal-9 on fibroblast-like synoviocytes (FLS) in these patients. Methods The expression of Gal-9 in ST and FLS was compared using immunohistochemical techniques. Apoptotic cells in RA and OA ST samples were detected by TUNEL assay. Apoptosis of FLS was analyzed by the sub-G1 method in vitro. The in vivo suppressive effects of Gal-9 on collagen-induced arthritis (CIA) in a mouse model were also elucidated. Results The percentage of Gal-9,positive cells in ST samples and the amount of Gal-9 in synovial fluid samples were significantly higher in patients with RA than in patients with OA, suggesting the involvement of Gal-9 in the development of RA. Compared with the 2 wild-type Gal-9 forms, stable Gal-9, a mutant protein resistant to proteolysis, significantly induced apoptosis of FLS from RA patients. In contrast, other galectins, such as Gal-1, Gal-3, and Gal-8, did not induce apoptosis or suppress the proliferation of human RA FLS. Stable Gal-9 preferentially induced apoptosis and suppressed the proliferation of RA FLS in vitro. It also induced apoptosis of cells in RA ST implanted into SCID mice in vivo. In a mouse model of CIA, apoptotic cells were detected in the joints of stable Gal-9,treated mice, but not phosphate buffered saline,treated mice, and suppressed CIA characterized by pannus formation with inflammatory cell infiltration and bone/cartilage destruction. Conclusion Gal-9,induced apoptosis of hyperproliferative RA FLS may play a critical role in the suppression of RA. [source]


Histopathologic changes at "synovio,entheseal complexes" suggesting a novel mechanism for synovitis in osteoarthritis and spondylarthritis

ARTHRITIS & RHEUMATISM, Issue 11 2007
Michael Benjamin
Objective To determine the extent to which different entheses form part of a "synovio,entheseal complex" (SEC) and whether such SECs are commonly associated with the presence of inflammatory cells and evidence of enthesis microdamage. Methods Specimens from 49 cadaveric entheses were processed for histologic study, and all soft tissue components of the entheses or enthesis organs were examined. To exclude articular cartilage degeneration as a triggering factor for synovitis, the selected entheses included 17 that were not immediately adjacent to such cartilage. Results An SEC was present at 82% of entheses. These included 47% of the attachments not adjacent to articular cartilage, where the synovium was that of bursae or tendon sheaths. One or more of a wide variety of degenerative changes were noted on the soft tissue side of every enthesis; the most common changes were cell clustering and/or fissuring (in 76% of entheses). Synovial villus formation or inflammatory cell infiltration was seen in 85% of entheses, and in 73% of attachments there were also inflammatory cells in the enthesis organ itself. The changes included synovial invasion (pannus formation) of the enthesis. Conclusion Entheses are frequently juxtaposed to synovium, thus forming SECs. They are also often associated with both degenerative and inflammatory changes, and the latter may involve the immediately adjacent synovium. These findings suggest a novel mechanism by which synovitis could develop in both degenerative joint disease and spondylarthritis. [source]


Preliminary evaluation of in vivo reflectance confocal microscopy features of discoid lupus erythematosus

BRITISH JOURNAL OF DERMATOLOGY, Issue 6 2007
M. Ardigò
Summary Background, Discoid lupus erythematosus (DLE) can simulate other inflammatory diseases both clinically and histologically. In vivo reflectance confocal microscopy (RCM) is a noninvasive, reproducible imaging technique already reported to be useful in the evaluation of several inflammatory skin conditions such as contact dermatitis, psoriasis and Darier disease. Objectives, The aims of our study were to define RCM features of DLE and to evaluate its feasibility in biopsy site selection. Methods, Discoid lesions were selected for RCM evaluation from 10 patients with an established diagnosis of DLE. Subsequently, a 4-mm punch biopsy of the same areas evaluated with RCM was rendered for histopathological examination. Results, A series of RCM features of DLE was identified and shown to correlate well with histopathological evaluation. Interface changes, as well as epidermal, dermal and adnexal inflammatory cell infiltration, were identified with RCM in a high percentage of the lesions. A limitation of RCM examination besides imaging depth was the inability to distinguish lymphocytes from other white blood cells. Conclusions, The utility of RCM as a diagnostic tool for DLE awaits further evaluation, although it appears to be promising for biopsy site selection. [source]


Ibudilast: A Non-selective PDE Inhibitor with Multiple Actions on Blood Cells and the Vascular Wall

CARDIOVASCULAR THERAPEUTICS, Issue 3 2001
Yukio Kishi
ABSTRACT Ibudilast (3-isobutyryl-2-isopropylpyrazolo[1,5-a]pyridine) is a nonselective inhibitor of cyclic nucleotide phosphodiesterase (PDE). It is widely used in Japan for improving prognosis and relieving symptoms in patients suffering from ischemic stroke or bronchial asthma. These clinical applications are based on the properties of ibudilast that inhibit platelet aggregation, improve cerebral blood flow and attenuate allergic reactions. The inhibition of platelet aggregation and vasodilatation by ibudilast may be due to synergistic elevation of intracellular cyclic nucleotides and release of nitric oxide (NO) or prostacyclin from endothelium, rather than direct inhibition of PDE5 or PDE3. Another important property of ibudilast is its antiinflammatory activity possibly associated with potent inhibition of PDE4. Combined with its relaxing effects on bronchial smooth muscle, antiinflammatory actvity of ibudilast could favorably influence pathophysiology of asthma by antagonizing chemical mediators triggering asthmatic attacks. Ibudilast was also reported to significantly attenuate inflammatory cell infiltration in the lumbar spinal cord in an animal model of encephalomyelitis. Future investigations should include effects of ibudilast on inflammatory reactions between endothelium and blood cells, which may initiate the development of atherosclerosis. [source]


4131: Pathologic epithelial and anterior corneal nerve morphology in congenital aniridic keratopathy

ACTA OPHTHALMOLOGICA, Issue 2010
P FAGERHOLM
Purpose To document corneal morphology in Swedish families with congenital aniridia. Methods Detailed ophthalmic examinations were conducted in a number of affected and unaffected members. Digital slit lamp photography, anterior segment optical coherence tomography (ASOCT) and in-vivo confocal microscopy (IVCM) examinations were performed bilaterally to document corneal morphology. Results Affected family members presented with different stages of aniridic keratopathy, with a corneal appearance varying from totally transparent to opaque and highly vascularised. Increased corneal thickness in affected members, particularly those with severe keratopathy, was noted by ASOCT. By IVCM, opaque corneas were characterized by active vessels and dense inflammatory cell infiltration. In corneas with milder keratopathy, pathologic epithelial findings included epithelial pleomorphism, focal epithelial opacities, and an absence of limbal epithelial crypts and focal stromal projections at the limbus. Nerves of the anterior cornea exhibited several distinct features, including an unusually close association of subbasal nerves with epithelial cells, an unusually high subbasal nerve density with highly branched nerves, and a prominent whorl region. Additionally, abnormally dense and tortuous anterior stromal nerves, attached to stromal keratocytes, were noted in unaffected members. Conclusion Altered epithelial morphology and a vigorous innervation of the anterior cornea were the most pronounced corneal findings in family members with milder forms of aniridic keratopathy. Further findings confirmed the known increase in corneal thickness and limbal stem cell abnormality in aniridia. [source]


Mechanisms and clinical implications of glucocorticosteroids in the treatment of allergic rhinitis

CLINICAL & EXPERIMENTAL IMMUNOLOGY, Issue 2 2009
M. Okano
Summary Allergic rhinitis is a common airway disease characterized by hypersensitivity, exudation, hypersecretion, inflammatory cell infiltration and remodelling. Intranasal glucocorticosteroids are the most effective drugs for controlling the inflammation caused by allergic rhinitis. Glucocorticosteroids exert anti-inflammatory effects through at least two pathways: the transactivation pathway and the transrepression pathway. Glucocorticosteroids also exert regulatory functions by inducing regulatory cytokines and forkhead box P3 (FoxP3+) regulatory T cells. Evidence suggests that intranasal glucocorticosteroids control not only nasal symptoms but also ocular symptoms. In contrast to sedating H1 receptor antagonists, intranasal glucocorticosteroids can improve impaired performance symptoms, such as daytime sleepiness, associated with allergic rhinitis. Recent studies suggest that intranasal glucocorticosteroids might also be useful for the prophylactic treatment of pollinosis; this possibility is supported by the molecular mechanism of the anti-inflammatory action of glucocorticosteroids. These findings suggest that intranasal glucocorticosteroids might be positioned as first-line drugs for the treatment of both perennial and seasonal allergic rhinitis. [source]


A New Technique for Reconstruction of the Atrophied Narrow Alveolar Crest in the Maxilla Using Morselized Impacted Bone Allograft and Later Placement of Dental Implants

CLINICAL IMPLANT DENTISTRY AND RELATED RESEARCH, Issue 2 2008
Per Holmquist DDS
ABSTRACT Background: In cases when the alveolar crest is too narrow to host an implant, lateral augmentation is required. The use of autogenous bone blocks harvested from the iliac crest is often demanded. One disadvantage is the associated patient morbidity. Purpose: The purpose of this study was to clinically and histologically evaluate the use of morselized impacted bone allograft, a novel technique for reconstruction of the narrow alveolar crest. Materials and Methods: Two patients with completely edentulous maxillae and one partially edentulous, with a mean age of 77 years (range 76,79 years) were included in the study. The alveolar crest width was <3 mm without possibility to place any implant. Bone grafts were taken from a bone bank in Gävle Hospital. Bone from the neck of femur heads was milled to produce bone chips. The milled bone was partially defatted by rinsing in 37°C saline solution. After compression of the graft pieces with a size of 15 mm (height), 30 mm (length), and 6 mm (width), they were then fit to adapt to the buccal surface of the atrophied alveolar crest. One piece was placed to the right and one to the left side of the midline. On both sides fibrin glue was used (Tisseel®, Baxter AG, Vienna, Austria) to stabilize the graft. After 6 months of graft healing, dental implants were placed, simultaneously biopsies were harvested and in one patient two oxidized microimplants were placed. At the time of abutment connection, microimplants were retrieved with surrounding bone for histology. Fixed screw-retained bridges were fabricated in mean of 7 months after implant surgery. Radiographs were taken before and after implant surgery and after 1 year of loading. Results: Sixteen implants with an oxidized surface were placed (TiUnite®, Nobel Biocare AB, Göteborg, Sweden). After 1 year of functional loading, all implants were clinically stable. The marginal bone loss was 1.4 mm (SD 0.3) after 1 year of loading. The histological examination showed resorption and subsequent bone formation on the allograft particles. There were no signs of inflammatory cell infiltration in conjunction with the allograft. The two microimplants showed bone formation directly on the implant surface. Conclusions: This study shows that morselized impacted bone allograft can be used to increase the width of the atrophied narrow alveolar crest as a good alternative to autogenous bone grafts in elderly patients. The histological examination of biopsies revealed a normal incorporation process and no signs of an immunological reaction. Further studies with larger samples are of important to be able to conclude if equal results can be obtained using morselized impacted bone allograft as for autogenous bone graft. [source]


Time-related Histopathologic Changes in Fresh Frozen Carotid Xenografts in a Pig-to-Goat Implantation Model

ARTIFICIAL ORGANS, Issue 10 2009
Ji M. Chang
Abstract We performed an animal experiment with an emphasis on time-related histopathologic changes to evaluate the clinical feasibility of immunologically nontreated xenogenic vascular grafts. Bilateral porcine carotid arteries were harvested, and then, after short-term freezing at ,70°C, interposed into goats' carotid arteries. An antiplatelet agent was administered orally for 3 months postoperatively. The goats were randomly assigned to five periods of observation (1 week, and 1, 3, 6, and 12 months after implantation); two animals were observed at each of these times. Doppler ultrasonography was performed periodically during the observation period. At predetermined times, grafts were explanted and examined using hematoxylin and eosin, and Masson's trichrome stains. Immunohistochemical evaluations were conducted with T-lymphocyte indicator and von Willebrand factor. Two goats died prematurely, one from respiratory problems related to anesthesia and the other from pneumonia. A total of 16 grafts from the remaining eight animals were evaluated. Grafts were all patent except one at 3 months after transplantation. Histologically, xenogenic arterial grafts showed early endothelial cell loss at 1 week. This was followed by a progressive spread of recipient endothelial cells from the anastomotic site, and re-endothelialization was complete at 1 month. The degree of neointimal and medial thickening increased until 3 months, and then decreased. At 12 months, no additional growth of the intimal or medial layers was observed. Adventitial inflammation became severe at 3 months, but was reduced at 6,12 months. The proportions of CD3-positive T-lymphocytes among inflammatory cell infiltrations were very low. Fresh frozen xenogenic arterial grafts showed acceptable patency throughout the 12-month period and showed no evidence of being unduly influenced by rejection reactions. [source]


Protective effect of non-mitogenic human acidic fibroblast growth factor on hepatocyte injury

HEPATOLOGY RESEARCH, Issue 10 2007
Hua Xu
Aim:, To study whether non-mitogenic human acidic fibroblast growth factor (nm-haFGF) has protective effects on H2O2 -induced hepatocyte injury in vitro and CCl4 -induced hepatocyte injury in vivo. Methods:, (i) HL-7702 hepatocytes were incubated with different concentrations of nm-haFGF for 12 h, and then the activity of lactate dehydrogenase (LDH) in culture medium was detected, and genomic DNA electrophoresis analysis was observed after being exposed to H2O2 (8 mmol/L) for 4 h. Proximately, apoptotic rates and protein expressions of Bcl-2 and Bax of HL-7702 cell were detected after being exposed to H2O2 (0.2 mmol/L) for 20 h. (ii) Being injected intraperitoneally with nm-haFGF, mice were treated with CCl4 intraperitoneally to induce hepatic injury. Twenty-four hours later, serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT) were measured and histopathologic changes were evaluated. Results:, (i) In vitro tests: LDH activities and apoptotic rates decreased, the protein expression of Bcl-2 increased and Baxdecreased in nm-haFGF-treated groups at the concentrations of 100 150 and 200 ng/mL, compared with that in the model control group, which was treated with H2O2 alone. The genomic DNA remained nearly intact at the concentrations of 150 and 200 ng/mL. (ii) In vivo tests: serum ALT and AST in nm-haFGF-treated groups (10 ,g/kg and 20 ,g/kg) were much lower as compared to the model control group, which was treated with CCl4 alone. Histological examination showed that nm-haFGF markedly ameliorated hepatocytes vacuolation, cloudy swelling and inflammatory cells infiltration induced by CCl4. Conclusion:, nm-haFGF had protective effects against H2O2 -induced hepatocyte injury in vitro and CCl4 -induced acute liver injury in vivo. [source]


Optimization of pulsed electromagnetic field therapy for management of arthritis in rats

BIOELECTROMAGNETICS, Issue 6 2005
Venkatachalam Senthil Kumar
Abstract Studies were undertaken to find out the effects of low frequency pulsed electromagnetic field (PEMF) in adjuvant induced arthritis (AIA) in rats, a widely used model for screening potential therapies for rheumatoid arthritis (RA). AIA was induced by an intradermal injection of a suspension of heat killed Mycobacterium tuberculosis (500 ,g/0.1 ml) into the right hind paw of male Wistar rats. This resulted in swelling, loss of body weight, increase in paw volume as well as the activity of lysosomal enzymes viz., acid phosphatase, cathepsin D, and ,-glucuronidase and significant radiological and histological changes. PEMF therapy for arthritis involved optimization of three significant factors, viz., frequency, intensity, and duration; and the waveform used is sinusoidal. The use of factorial design in lieu of conventional method resulted in the development of an ideal combination of these factors. PEMF was applied using a Fransleau,Braunbeck coil system. A magnetic field of 5 Hz,×,4 ,T,×,90 min was found to be optimal in lowering the paw edema volume and decreasing the activity of lysosomal enzymes. Soft tissue swelling was shown to be reduced as evidenced by radiology. Histological studies confirmed reduction in inflammatory cells infiltration, hyperplasia, and hypertrophy of cells lining synovial membrane. PEMF was also shown to have a membrane stabilizing action by significantly inhibiting the rate of release of ,-glucuronidase from lysosomal rich and sub-cellular fractions. The results indicated that PEMF could be developed as a potential therapy in the treatment of arthritis in humans. Bioelectromagnetics 26:431,439, 2005. © 2005 Wiley-Liss, Inc. [source]