Hemosiderin Accumulation Research Articles

Pathological changes of suspected tetrachloro dibenzo--dioxins/tetrachloro dibenzofurans toxication in beef cattle

The contamination of tetrachlorodibenzo- r -dioxins (TCDDs) and tetra chlorinated dibenzofurans (TCDFs) may affect human or animal health such as cancer, reproductive failure, dermaltoxicities and neurologic effects. The present study describes the effects of TCDD/TCDFs contamination in feed to various tissues of beef cattle to which TCDD/TCDFs were detected byGC MS/MS. The results revealed that POPs (DDT, heptachlor, aldrin, dieldrin and endrin) as a precursor for dioxins were detected in all samples except drinking water. The total concentration of OC in soils was Nd – 42.73 m g/kg, grasses (3.30 – 27.66 m g/kg), well water (0.82 – 1.00 m g/kg), feed mill (3.90 m g/kg), sera (Nd – 13.08 m g/kg) and meats (Nd – 100.72 m g/kg). Futhermore, the TEQ residues of TCDDs/TCDFs in beef were 4496.66 - 20642 . 40 pg/g from Yogyakarta, and 717.13pg/g (beef) and 0.037 pg/g (brain tissues) from Solo (Central Java). The concentration of TCDD/TCDFs residues in beef was above the maximum residue limit (MRL) at 2 pg/g. Animal feeds is regarded as the main source of dioxins contamination in meats. Macroscopic changes were general anaemia, cachexia, fibrotic liver, athropic heart, ruminal impaction, constipated intestinal, haemorrhagic kidney, and ptechiae in the brain. Microscopically were depleted spleen vacuolation of interseptum, haemorrhages and accumulation of hemosiderin. Heart shows degeneration, fragmentation and pale cardiac muscle and swollen nuclei. Liver was pale, degeneration of epithelial cells and congestion. Lungs were pneumonia, oedema pulmonum and mild haemorrhage. Intestines showed haemorrhage and infiltration of mononuclear cells, neutrophyls and eosinophyls. Brain was haemorrhage, perivascular cuffs and intranuclear inclusion bodies. The animal was suffering from haemorrhagic enteritis, encephalitis, and hepatic degeneration.

Accuracy of OCT, Grayscale IVUS, and Their Combination for the Diagnosis of Coronary TCFA: An Ex Vivo Validation Study

ObjectivesThis study sought to assess the accuracy of optical coherence tomography (OCT), gray-scale intravascular ultrasound (IVUS), and their combination for detecting thin-cap fibroatheromas (TCFA). BackgroundThe extent to which the imaging characteristics of OCT and IVUS correlate with histologically defined TCFA is unknown. MethodsIVUS and OCT examinations identified focal plaques in 165 coronary arteries from 60 autopsy hearts. A total of 685 pairs of images of OCT and IVUS were compared with histology. By OCT, a TCFA was defined as a signal-poor region with diffuse borders and cap thickness <65 μm. By IVUS, a TCFA was defined by the presence of echolucent zones and/or ultrasound attenuation in areas of positive remodeling. By histology, 12 of 685 focal plaques were classified as TCFAs. ResultsWith histology as the gold standard, the sensitivity, specificity, positive predictive value, negative predictive value, and overall diagnostic accuracy for OCT-derived TCFA were 100%, 97%, 41%, 100%, and 98%, respectively. The corresponding numbers for IVUS-derived TCFA were 92%, 93%, 19%, 99%, and 93%, respectively. The histological findings underlying the false positive diagnoses of OCT for TCFA included large amounts of foam cell accumulation on the luminal surface, large amounts of microcalcifications at the surface, large amounts of hemosiderin accumulation, or organized thrombus. In contrast, histological causes of mischaracterization of TCFA by IVUS were mostly TCFA. When both OCT and IVUS criteria for TCFA were required to be met, the sensitivity, specificity, positive predictive value, negative predictive value, and overall diagnostic accuracy were 92%, 99%, 69%, 99%, and 99%, respectively. ConclusionsIn the present study, neither OCT nor IVUS were optimal to detect TCFA. The combined use of OCT and IVUS may improve TCFA detection accuracy.

Pigment Deposition in the Rat Retina.

Incidental findings in the rat eye are not uncommon in acute and long-term toxicological studies. These findings can be associated with a number of causes unrelated to treatment with the test article, including congenital malformation, trauma, infection, metabolic disease, genetic predisposition, and age-related changes. The occurrence of pigment deposition in the retina of Wistar Hannover (Crl:WI (Han)) rats in a 4-week toxicity study is reported in this communication. The microscopic examination of the eyes in the 4-week toxicity study revealed focal yellow-brown pigment deposits in the retina, mainly located in the ganglion cell layer. The retinal pigment deposits were randomly distributed in the control and treated groups and were considered incidental. The deposits were clearly positive for ferric iron in the Perls' stain but not for lipofuscin by the Schmorl's and Long Ziehl-Neelsen methods. The iron-containing pigment is likely to represent hemosiderin accumulation after retinal micro-hemorrhage or could be indicative of the normal intraretinal iron transport and turnover.

March hemoglobinuria-associated acute tubular injury.

A previously healthy 17-year-old African-American male presented with acute kidney injury after playing basketball without rest for 5–6 h. At presentation, his serum creatinine was 468.5 µmol/L (5.3 mg/dL) with an estimated glomerular filtration rate (eGFR) of 17 mL/min/1.73 m2 calculated by the four-variable modification of diet in renal disease study equation. He had no history of kidney disease and was not taking any medications. Serum creatine kinase was elevated at 2277 U/L (reference range: 9–185 U/L) and his unconjugated bilirubin was 75.2 µmol/L (4.4 mg/dL). Hemoglobin was 133 g/L (13.3 g/dL) and a direct agglutination test was negative. Serum haptoglobin and hemoglobin electrophoresis studies were not done. Due to concern for rhabdomyolysis-associated acute tubular injury/necrosis, a kidney biopsy was performed. Seventeen glomeruli were sampled and were histologically unremarkable. Proximal tubules showed marked attenuation of brush borders and epithelial cell flattening. Granular cast material was identified within distal tubular lumina, which stained weakly by periodic acid–Schiff (PAS) reagent (Figure 1A) and eosinophilic on the hematoxylin and eosin stain (Figure 1B). Immunohistochemical staining for myoglobin was negative (Figure 1C); however, hemoglobin A diffusely and strongly stained the cast material (Figure 1D). A Prussian blue histochemical stain was negative for hemosiderin deposition. No glomerular, tubular basement membrane or interstitial deposits were seen by immunofluorescence or electron microscopy. The biopsy was interpreted as acute tubular injury/necrosis with hemoglobin casts, suggestive of hemolysis-associated acute kidney injury. Fig. 1. By light microscopy, distal tubules show granular cast material, which stains weakly by PAS reagent (A), and eosinophilic on the hematoxylin and eosin-stained section (B). The granular casts were negative upon immunohistochemical staining for myoglobin ... The patient was treated supportively with return to normal kidney function (eGFR > 90 mL/min/1.73 m2) 1 month after presentation. Due to the rapid recovery and absence of persistent hemolysis, it was felt that the hemoglobinuria was a result of exertion-related hemolysis. Renal exposure to excess heme is a known cause of kidney injury and can occur in the setting of intravascular hemolysis (hemoglobinuria) and rhabdomyolysis (myoglobinuria) [1]. Uncommonly, hemoglobinuria can occur as a consequence of physical exertion and subsequent mechanical injury to erythrocytes. This phenomenon, referred to as ‘march hemoglobinuria,’ was first observed in military personnel in the nineteenth century and has since been reported in patients participating in activities with repetitive impact, including runners and percussionists [2–4]. Reports of hemolysis-associated kidney injury have almost exclusively focused on the accumulation of intracytoplasmic hemosiderin (hemosiderosis) within tubular cells, [5] which was absent in our case and is a feature of persistent and/or recurrent bouts of hemolysis and hemoglobinuria. The differential diagnosis of acute tubular injury in the setting of excessive physical exertion includes hypovolemic acute tubular injury, rhabdomyolysis-associated acute tubular injury and hemolysis-associated injury. Hypovolemic acute tubular injury can show intratubular casts formed by the sloughing of cell cytoplasm into the tubular lumina; however, these casts fail to stain for both myoglobin and hemoglobin A. Rhabdomyolysis and hemolysis-associated tubular injury can both demonstrate intratubular hyaline and granular casts, which appear identical on light microscopy. Immunohistochemical staining for myoglobin and hemoglobin A is required to separate these entities pathologically. In summary, acute intravascular hemolysis can rarely occur in the setting of physical exertion and can result in toxic tubular injury with intratubular cast formation.

Posterior Reversible Encephalopathy Syndrome: The Spectrum of MR Imaging Patterns

The aim of this study was to describe lesion patterns, distribution, and evolution in posterior reversible encephalopathy syndrome (PRES) in a larger single-center population. Scans and follow-up, if available, of 50 patients with PRES between 2002 and 2011 were reviewed retrospectively. Lesion patterns, extent, and signal intensity changes were identified and graded on fluid-attenuated inversion recovery (FLAIR) and diffusion-weighted images. Hemorrhagic changes were identified on T2* or susceptibility-weighted images, and gadolinium enhancement on T1-weighted images was identified if available. The most frequently affected regions on FLAIR were the frontal lobes in 54 %, occipital lobes in 34.3 %, and parietal lobes in 31.0 % of cases, thus 65.3 % in the posterior regions. Temporal lobes were affected in 10.6 %, the cerebellum in 6.5 %, and basal ganglia in 1.6 %. Division into vascular supply showed involvement in the anterior circulation in 66.5 % and in the posterior circulation in 33.5 % of cases. On diffusion-weighted imaging (DWI), vasogenic edema was observed in 6.9 %, cytotoxic edema in 9.1 %, and both in 2 % of cases. In 31.9 %, there was shine through, and in 15.9 %, there was shine through as well as cytotoxic or vasogenic edema. Topologic distribution on DWI showed affection of the frontal lobes in 43.5 %, occipital lobes in 25.8 %, parietal lobes in 17.7 %, temporal lobes in 11.3 %, and cerebellum in 1.6 %. T2* or susceptibility-weighted images showed spot-like hemosiderin accumulation in 17.2 % of cases. In 23.1 %, enhancement was seen. Follow-up magnetic resonance imaging showed complete resolution in 66.6 % of patients. The spectrum of imaging findings in PRES is wide. Almost always subcortical and cortical structures are involved. Although posterior changes are prominent in this syndrome, frontal involvement is more frequent than posterior on FLAIR imaging and DWI. On DWI, mixed patterns are not uncommon. Reversibility generally takes place independent of DWI pathology. Hypertension was not a prognostic factor.

Pleomorphic hepatocellular carcinoma following consumption of hypericum perforatum in alcoholic cirrhosis

Hepatocellular carcinoma (HCC) often develops in patients with underlying liver disease, yet HCC with syncytial giant cells (SGCs) is extremely rare. Herein, we report a 55-year-old man with a 6-year history of alcoholic cirrhosis who during his regular checkup presented with marked elevation of alpha-fetoprotein. Clinical examination and imaging analyses revealed a tumor-like lesion in segment 4 of the liver, which was removed by limited wedge resection. Histological analysis by hematoxylin and eosin staining indicated pleomorphic and atypical nodules, with some SGCs, embedded within the boundaries of the neoplastic lesion. The adjacent liver parenchyma showed microvesicular steatosis, pericellular fibrosis, and moderate hemosiderin accumulation (grade 2, as determined by Prussian blue iron stain) in hepatocytes and Kupffer cells but no copper accumulation (as determined by orcein stain). Immunohistochemical analysis showed hepatocyte antigen-positive staining for the neoplastic cells and SGCs. The diagnosis was made for cirrhosis-related HCC with SGCs. The previous reports of pleomorphic HCC have featured osteoclast-like (i.e., mesenchymal type) giant cells, making this case of epithelial type giant cells very rare. The patient's 6-month history of hypericum perforatum/St John's wort self-medication may have prompted the cirrhosis or HCC progression or the unusual SGC manifestation.

Iron laden macrophages in idiopathic pulmonary fibrosis: The telltale of occult alveolar hemorrhage?

RationaleA number of observations suggest that iron accumulates in the lungs of patients with idiopathic pulmonary fibrosis (IPF) with vascular abnormalities, including pulmonary hypertension. ObjectivesThe aim of this study was to determine the prevalence and intensity of accumulation of alveolar epithelial lining fluid (ELF) iron and of alveolar macrophage hemosiderin in IPF and its relationship with disease severity. MethodsForty seven IPF patients and 14 healthy controls were retrospectively evaluated for iron accumulation in the lower respiratory tract using total iron spectrophotometric measures and for hemosiderin accumulation using the Perls' stain with the Golde score. Measurements and main resultsTotal iron levels in ELF were significantly increased in IPF patients compared to non-smoking controls (p < 0.05); there were no differences with healthy smokers (p = 0.2). Hemosiderin accumulation in alveolar macrophages was similar in never smoking and ever smoking IPF patients (p = 0.5), was significantly higher in IPF patients than in both smoking and non-smoking healthy controls (p < 0.05, all comparisons) and was positively correlated with echocardiographic estimates of pulmonary artery systolic pressure (p < 0.05) and with increasing disease severity scores (p < 0.05). ConclusionsThe data show exaggerated accumulation of iron in IPF broncho-alveolar ELF and alveolar cells with no association with tobacco smoke, thus suggesting, occult pulmonary hemorrhage as a likely cause.

Immediate graft histological assay, post pig's liver transplantation

To describe the vascular and tissue histopathological changes in seven sequential experimental liver transplantations in pigs. Fourteen female pigs, Sus domesticus species, with body mass between 5 and 8 kg were utilized. After the end of all anastomoses of the graft implantation in the receptor, the animal was monitored for 30 minutes, and at its end one of the biopsies was collected for histological analysis. The histological criteria utilized were: lytic hepatocyte necrosis, density of septal and portal inflammatory infiltrated, sinusoidal congestion and hemorrhage. The analysis was performed separately for the portal region in zone 1, 2 and 3. Among the structural changes undergone by the graft, those with greater frequency and intensity were vascular congestion and steatosis, which stood out in transplantations 5, 6 and 7. The technique demonstrated vascular alterations represented by vasocongestion, edema and minimum inflammatory reaction. In relation to the parenchyma, was observed macrovacuolar pan-acinar steatosis, focal lytic and occasional hemorrhages, beyond the accumulation of hemosiderin in Kuppfer's cells.

Histopathological changes induced by paraquat on some tissues of gourami fish (Trichogaster trichopterus)

Paraquat is a contact and non-selective herbicide which is used for controlling a wide range of terrestrial weeds and aquatic plants. A long-term contact with this xenobiotic can potentially lead to injuries in fishes as live non-target organisms. Therefore, the current study aimed to investigate the effect of sub-lethal toxicity of paraquat on the pathology of gill, liver, and spleen tissues in gourami fish (Trichogaster trichopterus). In this study, sub-lethal concentration is determined based on lethal concentration (LC50 : 7.16±0.69, 4.46±0.43, 2.19±0.27 and 1.41±0.17 mg/l of paraquat within 24, 48, 72 and 96 hours, respectively). The experiment was done with four varied concentrations of paraquat (0.0, 0.07, 0.15, and 0.3 mg/l equal 0.0%, 5%, 10% and 20% of nominal value of 96 h LC50) during 3 weeks. The exposed ?sh displayed erratic swimming and became lethargic. The changes in gills were characterized by hypertrophy, epithelial, epithelium increase of gill filament, edema and secondary gill lamella. The liver showed hypotrophy of liver cells, cloudy swelling and formation of cytoplasmic vacuoles in the liver tissue of fish treated with 0.15 and 0.3 mg/l concentrations of paraquat. Disorder in the ellipsoid cell and hemosiderin accumulation in melano-macrophage centers was observed in the spleen tissue of fish exposed to 0.15 and 0.3 mg/l of paraquat.

Using magnetic resonance imaging (MRI) for the time course of hemosiderin in bruises

Aim Evaluate the use of MRI to detect the accumulation of hemo-siderin in bruises and assess if this information can be applied to estimate the age of a bruise. Methods A low trauma animal model of a bruise was established for the investigation of hemosiderin deposition. T1 weighted sequence scans were performed on the bruised tissue sections within a 16.4T MRI. The scanned sections were then histologically stained using Perls’ Prussian blue for hemosiderin to compare with the MRI findings. Results Hemosiderin visualised within the Perls’ Prussian blue staining as blue spotting was seen to correspond with dark areas seen within the T1 sequences obtained from the 16.4T MRI. Discussion Hemosiderin is produced from the breakdown of blood in a bruise; it can be readily demonstrated in histological sections using the Perls’ Prussian blue stain and its presence can be used to infer a bruise is not recent. A non-invasive method to investigate this is provided by magnetic resonance imaging (MRI). This study demonstrated that MRI could be used to visualise bruises and that such a technique may have the potential to help estimate the age of a bruise.

Peroxiredoxin II is essential for preventing hemolytic anemia from oxidative stress through maintaining hemoglobin stability

The pathophysiology of oxidative hemolytic anemia is closely associated with hemoglobin (Hb) stability; however, the mechanism of how Hb maintains its stability under oxidative stress conditions of red blood cells (RBCs) carrying high levels of oxygen is unknown. Here, we investigated the potential role of peroxiredoxin II (Prx II) in preventing Hb aggregation induced by reactive oxygen species (ROS) using Prx II knockout mice and RBCs of patients with hemolytic anemia. Upon oxidative stress, ROS and Heinz body formation were significantly increased in Prx II knockout RBCs compared to wild-type (WT), which ultimately accelerated the accumulation of hemosiderin and heme-oxygenase 1 in the Prx II knock-out livers. In addition, ROS-dependent Hb aggregation was significantly increased in Prx II knockout RBCs. Interestingly, Prx II interacted with Hb in mouse RBCs, and their interaction, in particular, was severely impaired in RBCs of patients with thalassemia (THAL) and sickle cell anemia (SCA). Hb was bound to the decameric structure of Prx II, by which Hb was protected from oxidative stress. These findings suggest that Prx II plays an important role in preventing hemolytic anemia from oxidative stress by binding to Hb as a decameric structure to stabilize it.

Diffuse skin hyperpigmentation in CD30+ lymphoproliferation

CD30+ T-cell lymphoproliferative disorders (LD) comprise two main groups of diseases: CD30+ LD of the skin and systemic anaplastic large cell lymphoma (ALCL). The main feature of these disorders is the expression of CD30. We present a patient with an unusual clinical presentation of CD30+ lymphoproliferative disease in a 54-year old Caucasian male who presented with generalized lymphadenopathy and pronounced skin hyperpigmentation. In the lymph nodes and skin, CD30+ lymphoproliferation (ALCL) was diagnosed. The Prussian blue staining identified that the pigment responsible for the skin color was hemosiderin. Chemotherapy was started but the patient’s condition progressively worsened and he died a week after the first cycle. The complete color transformation of the entire skin due to hemosiderin accumulation is, to the best of our knowledge, the first reported observation in a CD30+ lymphoproliferation/ALCL patient. We speculate that hemosiderin-loaded macrophages resulted from the paraneoplastic process by some still unknown mechanism.

A 32-Year-Old Man With Recurrent Kidney Stones and an Abnormal Chest Radiograph

A 32-Year-Old Man With Recurrent Kidney Stones and an Abnormal Chest Radiograph

Cochlear implantation in a patient with superficial siderosis

Superficial siderosis is a rare disease characterized by accumulation of hemosiderin in the leptomeninges, subpial tissue, spinal cord, and cranial nerves. The first clinicopathological description was reported in 1908. Most patients (95%) experience progressive bilateral hearing loss that begins early in the course of disease. The initial management of a patient with hearing loss secondary to superficial siderosis involves sound amplification using hearing aids. However, cochlear implants can be considered in cases where the patient can no longer gain significant benefit from hearing aids. Only 10 studies have described the use of cochlear implants in superficial siderosis and results have been variable. We report the case of a 65-year-old woman with bilateral progressive sensorineural hearing loss caused by superficial siderosis who benefited significantly from cochlear implantation.

The Removal of Post-sclerotherapy Pigmentation following Sclerotherapy Alone or in Combination with Crossectomy

Background Sclerotherapy is a widely used method for the obliteration of blood vessels. Hyperpigmentation is a frequent complication that results from haemosiderin (FeO) accumulation. Hyperpigmentation and changes in the skin can be observed with ultrasound. Objective The aim of this study was to evaluate the efficacy of hyperpigmentation elimination using an intense pulse light generator (IPL) equipped with radio waves (RF) under ultrasonography (US) control. Methods Twenty-one women with permanent hyperpigmentation (after sclerotherapy or crossectomy combined with sclerotherapy) underwent a hyperpigmentation eliminating therapy with the use of IPL + RF and were monitored by using US. The thicknesses of the dermis and the subcutaneous tissue as well as the echogenicities of each layer were assessed. Results As a result of the therapy, a complete regression of hyperpigmentation was achieved in 90.48% of the women, and in 9.52% of the women, the therapy led to a reduction in hyperpigmentation but did not cause its complete disappearance. An increase in dermal echogenicity and a decrease in subcutaneous tissue echogenicity were observed, but there was no change in their thicknesses. After the therapy, the ultrasound images of areas of previous hyperpigmentation corresponded with images that were characteristic of healthy skin. Conclusion IPL + RF therapy is effective for eliminating permanent skin hyperpigmentation after sclerotherapy. US is also useful in this therapeutic method.

Pilot Safety Trial of Deferiprone in 10 Subjects With Superficial Siderosis

Superficial siderosis is a neurodegenerative disease caused by toxic accumulation of hemosiderin on the surface of the brain and spinal cord for which there is no known effective treatment. Oral deferiprone, a lipid-soluble iron chelator with ability to cross the blood-brain barrier, at a dose of 30 mg/kg per day was tested for safety in an open pilot study in 10 subjects with superficial siderosis. Over a 90-day period, deferiprone had no significant adverse effects on hematologic, liver, or neurological function. Ad hoc MRI assessments of the brain indicated a reduction in hemosiderin deposition in some subjects. Deferiprone proved safe in this small population of superficial siderosis subjects. There was MRI evidence of reduced hemosiderin deposition with deferiprone. Prospectively designed efficacy studies are necessary to determine the clinical efficacy of deferiprone in superficial siderosis.

Acute renal failure associated to paroxysmal nocturnal haemoglobinuria leads to intratubular haemosiderin accumulation and CD163 expression

Decreased renal function has been observed in diseases with intravascular haemolysis, including paroxysmal nocturnal haemoglobinuria (PNH). However, the mechanisms via which haemoglobin enhances renal damage in this pathology are not fully known. We report a case of acute renal failure associated to PNH and extensive haemosiderin deposits in tubular cells. Renal biopsy also revealed a strong immunostaining of CD163 (a haemoglobin scavenger receptor expressed in macrophages) and oxidative stress markers (NADPH-p22 phox and haeme oxigenase-1) in areas with deposits of iron. This fact provides evidence for a pathogenic role for free haemoglobin in tubulointerstitial renal injury in human PNH disease.

Superficial Siderosis: A Case Report

Superficial siderosis of the central nervous system is the result of chronic recurrent hemorrhages (e.g., arteriovenous malformations, tumors, or trauma), which leads to the accumulation of cytotoxic hemosiderin and presents with hearing loss, cerebellar dysfunction, and myelopathy. This article presents a clinical case of an 11-year-old boy in whom the diagnosis of medulloblastoma was established. He underwent surgery, and after a few years, he began to complain of hearing loss. Magnetic resonance imaging revealed the cause of the hearing disturbance. The aim of this article is to review the recent literature related to the etiology, clinical and radiologic features of superficial siderosis, emphasizing the role of magnetic resonance imaging.

IκBβ Attenuates Angiotensin II–Induced Cardiovascular Inflammation and Fibrosis in Mice

The development of cardiovascular fibrosis is associated with chronic inflammation, where activation of nuclear factor κB (NF-κB) signaling may play a critical role. NF-κB activation is tightly regulated by the cellular inhibitor of κB (IκB) family of proteins, such as IκBα and IκBβ. IκBα and IκBβ display different regulation kinetics in response to inflammatory stimulation. The present study tested the hypothesis that IκBα and IκBβ may have different roles in modulating cardiovascular inflammation and fibrosis, using a model of angiotensin II infusion-induced hypertension in wild-type mice and IκBβ knock-in mice, in which the IκBα gene is replaced by IκBβ cDNA (AKBI). In WT mice, subcutaneous angiotensin II infusion for 7 days induced increased perivascular and interstitial collagen deposition and fibrotic lesions, associated with myocardial interstitial hemosiderin accumulation and extensive macrophage infiltration. These effects of angiotensin II were dramatically limited in AKBI mice. Replacement of IκBα with IκBβ significantly attenuated angiotensin II infusion-induced expression of interleukin 1β, interleukin 6, monocyte chemotactic protein 1, collagen I and III, fibronectin, and tissue inhibitor of metalloproteinase 1 in the hearts. Furthermore, using cultured vascular smooth muscle cells, we demonstrated that interleukin 1β-induced NF-κB activation and monocyte chemotactic protein 1, vascular cell adhesion molecule 1, and tissue inhibitor of metalloproteinase 1 expressions were suppressed in the AKBI cells because of the replacement of IκBα with IκBβ. These results indicate that NF-κB has an essential role in mediating the cardiovascular inflammatory response to angiotensin II and suggest that targeting the balance of IκBα and IκBβ expression might be a novel therapeutic modality in preventing fibrosis in hypertensive cardiovascular disease.

Repeated blood instillation into the airway of the horse does not cause pulmonary fibrosis

Exercise-induced pulmonary haemorrhage (EIPH) occurs in nearly all strenuously exercising horses. Recent studies have attempted to identify the role of free blood within the airspaces, in the lung fibrosis that develops within the lungs of EIPH horses. Repeated exposure of the equine lung to autologous blood results in lung fibrosis similar to that observed in spontaneous EIPH. Forty ml of autologous blood from the jugular vein was instilled into preselected lung regions of 6 horses one, 2, 3, 4 or 5 times at 2 week intervals, with 40 ml of saline instilled into the contralateral lung serving as a control. The time interval between instillation of the first blood and euthanasia ranged from 2-10 weeks. The lung from each instillation site was harvested, and the histopathology was scored from each region based upon the presence and abundance of blood, haemosiderin and interstitial collagen. Consequently, at the time of euthanasia, the time since instillation of the first blood ranged from 2-10 weeks. Beyond retention of blood, and the accumulation of haemosiderin, there was no visible increase in perivascular and interstitial collagen within the blood-instilled lung sites. In a small number of regions, there were foci of bronchiolitis obliterans organising pneumonia with collagen accumulation within these foci, but no collagen accumulation with the characteristic perivascular and interstitial histological distribution seen in EIPH. Free blood within the airways of horses does not result in a qualitative increase in the amount of interstitial collagen within 8-10 weeks, and is therefore an unlikely aetiological factor in the lung collagen accumulation that occurs in EIPH. This study emphasises the efficiency of the equine lung in clearing blood from the airspaces. Further, it suggests that the aetiopathogenesis of EIPH is not driven by events within the airspace lumen, but rather emanates from within the vasculature and lung interstitium.