Thrombi In Blood Vessels Research Articles

Dental pulp stones and their correlation with metabolic diseases.

Dental pulp calcifications or pulp stones are calcified structures found in dental pulp, mostly around or enclosing a blood vessel. The formation of these calcifications begins with concentric layers of calcified tissue within which remnants of necrotic and calcified cells may be present. The calcifications of thrombi in blood vessels, called phleboliths, may also serve as nidi for denticles. In metabolic diseases such as diabetes, hypertension or poor periodontal health, there are obvious changes in blood vessels and vascularization. In our study, we observed histopathological sections of dental pulp and correlated systemic diseases such as diabetes and hypertension with poor periodontal health and dental pulp stones. The aim of our study was to evaluate the histopathology of dental pulp stones, their distribution among various age groups and sexes and to identify any correlations between pulp stone formation and systemic diseases such as type II diabetes and hypertension. Samples from 100 patients with metabolic diseases such as type II diabetes and hypertension were collected. The pulp was extirpated from the teeth that were undergoing root canal treatment, and the teeth were extracted. The collected pulp sample was fixed in 10% formaline neutral buffer, subjected to routine histopathological procedures and stained with haematoxylin and eosin. The pulp of teeth extracted for orthodontic treatment was considered a control for patients with no metabolic disease. There was a definite relationship between increased pulp stones and metabolic diseases such as type II diabetes and hypertension; likewise, poor periodontal health was significantly related to pulp stones.

PRODUCTION OPTIMIZATION, PARTIAL PURIFICATION, AND THROMBOLYTIC ACTIVITY EVALUATION OF PROTEASE OF Bacillus cereus HSFI-10

Cardiovascular disease is the primary cause of mortality in the world due to the formation of blood clots or thrombi in blood vessels. Bacterial proteases commonly function as thrombus dissolver agents in the pharmaceutical industry. Bacterial isolate HSFI-10 (Holothuria scabra Fermented Intestine-10) previously isolated from Rusip fermented sea cucumber had demonstrated thrombolytic activity. This study aimed to produce crude protease of HSFI-10 strain at an optimized incubation time and determine the thrombolytic activity of crude and dialysate proteases on A, B, AB, and O blood types. Isolate HSFI-10 was first molecularly identified and found to be Bacillus cereus with a homology level of 99.80% with Bacillus cereus strain ST06. The optimum crude enzyme was obtained after 48-h incubation with an activity of 222.52 U/mL, which increased to 438.84 U/mL after ammonium sulfate precipitation and dialysis. Clot lysis activity of crude enzymes was measured based on the gravimetry method on blood in the ABO system, showing results that ranged from 68.99% to 69.76%, while the dialysate ranged from 81.16% to 82.52%. In conclusion, partial purification of bacterial protease could increase both its specific and thrombolytic activities on human blood in the ABO system, with only 1% activity variability between A, B, AB, and O blood types.

Polysaccharide extracted from Morchella esculenta inhibits carrageenan-induced thrombosis in mice

MCP prevented carrageenan-induced thrombosis in mice by reducing platelets activation, oxidative stress and monocytes adhesion to damaged endothelial cells. MCP has great potential to develop into a natural antithrombotic drug. Our study suggests a new application of Morchella esculenta , which can be used as food supplements and nutraceuticals to benefit human health. • Morchella esculenta Polysaccharide reduces thrombi formed in in mouse tissues. • Morchella esculenta Polysaccharide attenuates platelet activation. • Morchella esculenta Polysaccharide inhibits oxidative stress in platelets and endothelium cells. • Morchella esculenta Polysaccharide inhibits adhesion of monocytes to endothelium cells. Thrombosis is one of the leading causes of death worldwide and is associated with inflammation and oxidative stress. This study aims to investigate the effect of Morchella esculenta Polysaccharide (MCP) on thrombosis. Our results showed that MCP inhibited thrombi in blood vessels of mouse tail, liver and lung, which was contributed by the inhibition of collagen accumulation, tumor necrosis factor-α and P-selectin expression. In vitro , human platelet clot retraction test indicated that MCP inhibited platelet activation, which was related to inhibition of platelet receptors, AKT and ERK1/2 pathways. Additionally, MCP inhibited oxidative stress by inducing anti-oxidative enzymes in human platelets and human umbilical vein vascular endothelium cells (HUVECs). Moreover, MCP inhibited oxidized low-density lipoprotein or LPS-induced adhesion of monocytes to HUVECs by reducing adhesion molecules expression. Taken together, these data demonstrate MCP exhibits antithrombotic properties, indicating Morchella esculenta can be used as food supplements and nutraceuticals against thrombosis.

TAKE DIVERSION ǃ - A PERIODONTIST POINT OF VIEW ON MUCORRMYCOSIS.

A new recently emerged complication of COVID-19 is a rare fungal infection also called the black fungus caused by a group of fungi called mucormycetes. These group of fungi commonly appear throughout the environment, particularly in association with decaying organic matter and in the soil. Oral health is essential to general health and greatly inuences the quality of life. Mucormycosis is a rapidly progressive fungal infection characterized by endothelium invasion and the development of thrombi in blood vessels resulting in necrosis. Mucormycosis localized to the periodontal tissues (i.e., gingiva and alveolar bone) is exceedingly rare. The clinical manifestation of mucormycosis also overlaps with the dental ndings of periodontal abscess, due to which it is misdiagnosed as lesion of periodontal origin. Early diagnosis is crucial in order to promptly initiate therapeutic interventions necessary for preventing progressive tissue invasion and its devastating sequelae and improving outcome and survival. Diagnosis of mucormycosis remains challenging. Clinical approach to diagnosis has a low sensitivity and specicity, it helps however in raising suspicion and prompting the initiation of laboratory testing. Successful management of mucormycosis is based on a multimodal approach, including reversal or discontinuation of underlying predisposing factors, early administration of active antifungal agents at optimal doses, complete removal of all infected tissues, and use of various adjunctive therapies. Another emerging imaging technique, which may eventually aid in the diagnosis and management of mucormycosis is the Cone Beam computed tomography(CBCT). Periodontal disease is not a fatal disease, but it can lead to any systemic or life threatening complications, which can be avoided by accurate diagnosis.

Magnetoimpedance Thin Film Sensor for Detecting of Stray Fields of Magnetic Particles in Blood Vessel.

Multilayered [FeNi (100 nm)/Cu (3 nm)]5/Cu (500 nm)/[Cu (3 nm)/[FeNi (100 nm)]5 structures were used as sensitive elements of the magnetoimpedance (MI) sensor prototype for model experiments of the detection of magnetic particles in blood vessel. Non-ferromagnetic cylindrical polymer rod with a small magnetic inclusion was used as a sample mimicking thrombus in a blood vessel. The polymer rod was made of epoxy resin with an inclusion of an epoxy composite containing 30% weight fraction of commercial magnetite microparticles. The position of the magnetic inclusion mimicking thrombus in the blood vessel was detected by the measurements of the stray magnetic fields of microparticles using MI element. Changes of the MI ratio in the presence of composite can be characterized by the shift and the decrease of the maximum value of the MI. We were able to detect the position of the magnetic composite sample mimicking thrombus in blood vessels. Comsol modeling was successfully used for the analysis of the obtained experimental results and the understanding of the origin the MI sensitivity in proposed configuration. We describe possible applications of studied configuration of MI detection for biomedical applications in the field of thrombus state evaluation and therapy.

Possible antithrombotic properties of propolis

The formation of thrombi in blood vessels results in thrombosis that is responsible for considerable morbidity and mortality because it is associated with arterial diseases such as myocardial infarction, stroke and peripheral occlusive disease in addition to venous thromboembolic disorders. Pharmaceutical agents such as anticoagulant agents and antiplatelet agents are applied at the prevention of the recurrence of thrombotic disorders. However, the use of these pharmaceuticals can result in side effects such as bleeding, as well as renal and hepatic disorders. The prevention and treatment of diseases using functional foods and alternative medicines has recently attracted attention. Functional foods and alternative medicines with possible antithrombotic properties that have been used for many years are now receiving significant focus in terms of the treatment and prevention of thrombosis. Because they have already been used for so long, they are likely to be safe. Propolis is a hive product comprising resinous materials collected by bees from plants and it includes various chemical compounds. Various biological activities of propolis have been indicated and propolis is used as folk medicine and health supplement worldwide. This report reviews the possibility of using propolis as an antithrombotic agent.

MON-202 EVALUATION OF SURROGATE PREDICTORS OF MORTALITY DUE TO SNAKE ENVENOMATION AND RENAL HISTOPATHOLOGICAL CORRELATION

To evaluate the surrogate predictors of mortality due to venomous snake bite and to study the spectrum of histopathological changes of kidney in death due to venomous snake bite. One year Descriptive, Observational, Cross-sectional, Hospital and Mortuary based study. During autopsy, detailed external and internal examination was done to find the macroscopic changes at the local area of bite, kidneys. The slices of tissue from Kidneys were taken from selected cases in such a way that a slice contains all the physiological layers of the organ including diseased and normal (as seen on naked eye examination) portions with intervening transitional zone. Stained slides were examined under microscope to identify any pathological changes in kidney tissues. The findings of histopathological study were compared with that of the normal tissues. Thus the pathological process as identified in respect to the tissue involved. Macroscopic features on autopsy shows 4.1% with only congestion, congested with focal medullary haemorrhage in 36.7%, congested with patchy corticomedullary haemorrhage in 8.2%, congested with diffuse haemorrhage in 51.02%. Renal histopathological findings shows the predominant feature is Tubular Necrosis found in 57.1% of cases. 8.2% of cases shows Cortical Necrosis. Thrombi in blood vessels were found in 14.3% of cases. Of the Tubular Necrosis cases 20.4% of cases presented with dilated tubules lined by flattened epithelium & tubules shows hyalinised material in its lumen; 8.2% of cases shows small tubules containing proteinetious material in their lumen. All the cases shows features of congestion and inflammation. Haemorrhage is seen in 95.9% of cases. The predominant feature is Tubular Necrosis found in 57.1% of cases. 8.2% of cases shows Cortical Necrosis. Thrombi in blood vessels were found in 14.3% of cases. Of the Tubular Necrosis cases 20.4% of cases presented with dilated tubules lined by flattened epithelium & tubules shows hyalinised material in its lumen; 8.2% of cases shows small tubules containing proteinetious material in their lumen. All the cases shows features of congestion and inflammation. Haemorrhage is seen in 95.9% of cases. Multivariate analysis shows only number of AVS (0.020), duration of hospital stay/period of survivability (0.024), bleeding manifestations (0.000), shock/hypotension (0.000) & DIC (0.000) are positively correlated with Tubular Necrosis. With Cortical Necrosis, there is correlation with DIC (0.026) only. Whereas, only shock/hypotension (0.013) gives positive correlation with the presence of thrombi in blood vessels The prognosis for snakebite depends on factors besides hospital treatment: whether first aid is given immediately after the bite, early initiation of appropriate treatment, and the type of snake involved along with amount and severity of venom. Histopathological changes, especially in renal tissue can aid in differentiating between the nature of snake and the damage it causes.

Organic Semiconducting Nanoparticles as Efficient Photoacoustic Agents for Lightening Early Thrombus and Monitoring Thrombolysis in Living Mice.

Acute venous thrombosis is prevalent and potentially fatal. Accurate diagnosis of early thrombus is needed for patients in timely clinical intervention to prevent life-threatening conditions. Photoacoustic imaging (PAI) with excellent spatial resolution and high optical contrast shows more promise for this purpose. However, its application is dramatically limited by its signal-off effect on thrombus because of the ischemia in thrombus which lacks the endogenous photoacoustic (PA) signal of hemoglobin. To address this dilemma, we herein report the feasibility of using organic semiconducting nanoparticles (NPs) for contrast-enhanced PAI of thrombus in living mice. An organic semiconducting NP, self-assembled by amphiphilic perylene-3,4,9,10-tetracarboxylic diimide (PDI) molecules, is chemically modified with cyclic Arg-Gly-Asp (cRGD) peptides as a PA contrast agent (cRGD-PDI NPs) for selectively lightening early thrombus. cRGD-PDI NPs presents high PA intensity, good stability in light and serum, and sufficient blood-circulating half-life. In living mice, PA intensity of early thrombus significantly increases after tail vein injection of cRGD-PDI NPs, which is 4-fold greater than that of the control, blocking, and old thrombus groups. Pathological and immunohistochemical findings show that glycoprotein IIb/IIIa abundant in early thrombus is a good biomarker targeted by cRGD-PDI NPs for distinguishing early thrombus from old thrombus by PAI. Such a lightening PAI effect by cRGD-PDI NPs successfully provides accurate information including the profile, size and conformation, and spatial distribution of early thrombus, which may timely monitor the obstructive degree of thrombus in blood vessels and the thrombolysis effect.

Diagnoses of Ovine Infection by the Serotype-4 Bluetongue Virus on Minas Gerais, Brazil

Background: Bluetongue (BT) is a viral disease transmitted by hematophagous vectors of the genus Culicoides. In Brazil, the identifcation of antibodies against the virus has been held for over thirty years, however clinicopathological diagnosis of the disease are scarce. The frst reported case occurred in the state of Paraná in 2001, confrmed by isolation and identifcation of serotype 12 of BTV. In the state of Rio Grande do Sul, in 2009, two outbreaks confrmed and was identifed the serotype 12. Serotype 4 was isolated during an outbreak in the state of Rio de Janeiro in 2013. This study describes the Diagnoses of ovine infection by the serotype-4 bluetongue virus in Minas Gerais, Brazil. Case: In a farm in the Southern region of the state of Minas Gerais, a group of 28 male sheep, was sent for necropsy at the Setor de Patologia Veterinária of Universidade Federal de Lavras (SPV-UFLA). In a flock of 80 male sheep 28 died with clinical signs of respiratory distress, whereas other showed signs of anemia and hypoproteinemia, cough, sneezing, prostration, fever, mucopurulent nasal discharge, anemia and submandibular edema. At necropsy, the main changes observed were cranioventral pulmonary consolidation, hemorrhage at the base of the pulmonary artery and ulcerating lesions in the hard palate mucosa, rumen and reticulum. The histological changes consisted of bacterial bronchopneumonia, papillary necrosis associated with bacterial structures, multifocal vasculitis in the submucosa and thrombi in blood vessels of the serosa in the rumen and reticulum, hyaline and flocculate necrosis in esophageal muscle, skeletal and cardiac muscle fbers were also observed, associated with moderate mononuclear inflammatory infltrate between fbers and around blood vessels. Discussion: The diagnosis of BT was confrmed by the identifcation of nucleic acids of the virus in blood samples and from tissues of animals from the herd by RT-PCR and by the detection of antibodies against Bluetongue virus with the agar gel immunodiffusion (AGID) test using serum samples from the remaining herd animals. Serotype 4 was identifed in three of the samples inoculated into KC cells. The hemorrhage at the base of the pulmonary artery, one characteristic fndings, was found in three of the necropsied sheep. The pulmonary lesions observed in the present study strongly suggest the occurrence of pneumonia caused by opportunistic bacteria, especially Mannheimia haemolytica, which is commonly associated with pneumonia in sheep infected with BTV. This work is the frst in the state of Minas Gerais and the fourth in Brazil to report an outbreak of the disease with clinical signs. The economic impact of bluetongue results not only from the direct losses of animals to the disease, but also to the correlation among BTV infection and other problems including pneumonia, abortion and verminoses. In a study focused on the characteristics of ovine farming in Minas Gerais, farmers from the center-southwest reported that abortion and pneumonia were among their main problems. Thus, further epidemiological studies on BTV may improve the level of identifcation of infected herds and may help promote prophylactic measures. Necropsies and histopathology exams constitute crucial tools for diagnosis, because most cases present at a sub-clinical stage or in association with other, concomitant diseases. Keywords: BTV 4, viral diseases, sheep, RT-PCR e IDGA

Expression and activity evaluation of reteplase in Escherichia coli TOP10

Reteplase is a part of tissue Plasminogen Activator (t-PA) used for theremoval of thrombi in blood vessels. In the present study we express the reteplase genein Escherichia coli TOP10 and then its thrombolytic activity was measured. The recombinant plasmid pBADgIIIA was transformed into the competent Escherichia coli TOP10 and then transformed bacteria was seeded into bioreactor containing 1.5 L LB medium and induced by 0.02% L-Arabinoseat 37°C, pH 7, and 180 rpm until OD 600 of 0.6 was reached.Samples were analyzed by SDS-PAGE and western blotting andthe expression of reteplase was examined. Finally the activity of this recombinant protein was evaluated using Chromogenic Activity Assay Kit. The presence of reteplase in transformed Escherichia coli TOP10 wasexamined by western blotting which revealed that the target protein in form inclusion body was expressed as a unique band at39 and the refolded reteplase was 66KDa. The amount of protein produced was 90.5µg/mL and its activity was determined as 0.8 units. In this study, the expression of reteplase in Escherichia coli TOP10 wasscaled up under optimum condition. Furthermore we earned reteplase with partially suitable thrombolytic activity.

Effect of Mori Folium Extract on Improvement of Blood Flow in Ferric Chloride-Induced Carotid Artery Damage Rat Model

In a previous study, we have shown that mulberry leaves (Mori Folium) extract MFE) and its compounds have the antioxidant effect in human red blood cells. However, the possible effect of MFE and its compounds on improvement of blood flow were not reported. Therefore, the aim of this study is to investigate the effects of MFE and its compounds on improvement of blood flow in a rat model of topical ferric chloride (FeCl₃)-induced carotid artery damage. The FeCl₃ treatment seriously damaged the carotid artery: the walls of the artery, blood flow rate, blood vessel diameter, blood vessel area and blood flow amount. However, administration of MFE or its compound has ameliorated the blood flow and suppressed thrombus in blood vessels. Moreover, the concentrations of serum total cholesterol, triglycerides, and LDL cholesterol in the MET and its compound groups were remarkably reduced in comparison to the control group, and HDL cholesterol concentration was higher in the MET and its compound groups than in the control group. These results suggest that MFE and its compounds ameliorate the thrombosis against blood vessel damage.

The biotechnological potential of fibrinolytic enzymes in the dissolution of endogenous blood thrombi.

Formation of endogenous thrombi in blood vessels is one of the leading causes of death in our modern life. According to data provided by the World Health Organization (WHO) in 2000, heart diseases are responsible for 29% of the total mortality rate in the world. For this, a tremendous amount of research has been done in the area of prevention and treatment of these diseases. The classical therapy of these thrombi relies upon the use of antiplatelets, anticoagulants, or even surgeries. Relatively recently, the fibrinolytic enzymes produced by microorganisms, snakes, earthworms, insects, plants, and other organisms are being successfully used in the treatment of blood clots, especially with regard to the direct dissolving action on fibrin in tandem with less cost and side effects in comparison with the first-generation thrombolytic agents, streptokinase and urokinase. Furthermore, recombinant DNA technology has succeeded in improving and decreasing the undesirable effects of the first generation of enzymes. Recombinant PAs or rt-PAs like alteplase, retelase, saruplase, tenecteplase, lanoteplase, and desmoteplase became available in the drug markets with advantages of less binding loci with PAI-1 to avoid degradation while providing faster and more complete reperfusion in a greater number of patients with less risk of bleeding and intracranial hemorrhage. This review is the first to cover all the natural and recombinant thrombolytic agents used in enzyme therapy.

남항(Vitis romaneti) 유래 포도잎 추출물과 Resveratrol의 항산화 및 혈행개선 효과

The purpose of this study is to investigate the effects of 80% ethanol grape leaf extract (VGLE) and resveratrol (VGLR) from Vitis romaneti on antioxidant of red blood cells (RBC) of rat and efficacy of blood flow improvement in a rat model of topical ferric chloride (FeCl3)-induced carotid artery damage. RBC oxidative hemolysis and plasma lipid peroxidation induced by the aqueous peroxyl radical generator 2,2-azobis(2-amidinopropane) dihydrochloride were significantly suppressed by VGLE or VGLR in a dose-dependent manner. The FeCl₃ treatment seriously damaged the carotid artery: the walls of the artery and blood flow. However, VGLE or VGLR administration has ameliorated the blood flow and suppressed thrombus in blood vessels. These results suggest that VGLE or VGLR ameliorates the oxidative stress of RBC and thrombosis against blood vessel damage.

Coil Type Ultrasonic Motor for Vascular Endoscope

IVUS (Intravascular Ultrasound) is a useful medical device to observe the thrombus in blood vessels, and such a micro motor less than 1.0mm in outer diameter is desired to apply IVUS in narrow brain vessels. In our previous works, ultrasonic motor consisting of a wire coil type stator, a waveguide, a cylindrical rotor, an ultrasonic vibrator has been developed. This motor is rather easy to miniaturize because of its simple structure. However, this motor behavior is unstable rotate. To improve these problems, a foil type stator has been applied in stead of a wire coiled stator. An ultrasonic motor with 0.05mm thick foil type stator was manufactured and tested their performances. It was able to verify that this ultrasonic motor with a foil type stator has the right quality. So, simplified IVUS system using ultrasonic motor with a foil type stator was manufactured and tested their fundamental performances. In order to expand development of new application, ultrasonic motor with a shortened waveguide and ultrasonic motor integrated driving unit with a stator was developed.

Theoretical approach on vein graft survival: simulation on vein graft

Artery reconstruction in upper extremities is rare performed compared to artery reconstruction in lower extremities. Primary vascular repair was performed in many cases. An interposition vein graft or venous bypass grafting were applied in order to alleviate thrombus in blood vessel. However, one or more of the applied vein graft are blocked or severely narrowed due to the mismatched internal diameter failure on vein graft. The objective of this study is to investigate the blood flow influence on vein graft with the mismatched internal diameter failure. The applied three dimension computational fluid dynamic was employed to determine velocity, pressure gradient, resistances of blood flow and wall shear stress on the kinked vein graft. We expect that velocity, pressure gradient, resistance of blood flow and wall shear stress on the mismatched internal diameter of vein graft model to behave non-hydraulically compared to an ideal straight graft. Furthermore, longitudinal impedance modulus (ZL) is expected to be insufficient due to the mismatched internal diameter failure on vein graft.

Enteritis and Septicemia in a Horse Associated With Infection by Escherichia fergusonii

This report presents a clinical case of enteritis and septicemia with subsequent death of an adult horse associated with Escherichia fergusonii, in Germany. The patient died within 24 hours after onset of clinical signs, including fever and erosive stomatitis. Major pathologic findings were severe, acute, fibrinous, and necrotizing enteritis; severe, acute, fibrinous endocarditis; as well as multiple, hyaline thrombi in blood vessels. E fergusonii and Escherichia coli were isolated in moderate to high amounts from the intestine, the tricuspid valve, and the liver. This article represents the first case report of lethal enteritis and septicemia associated with E fergusonii infection in a horse.

Study of blood flow impact on growth of thrombi using a multiscale model

An extended multiscale model is introduced for studying the formation of platelet thrombi in blood vessels. The model describes the interplay between viscous, incompressible blood plasma, activated and non-activated platelets, as well as other blood cells, activating chemicals, fibrinogen and vessel walls. The macroscale dynamics of the blood flow is represented by the continuous submodel in the form of the Navier–Stokes equations. The microscale cell-cell interactions are described by the stochastic Cellular Potts Model (CPM). Simulations indicate that increase in flow rates leads to greater structural heterogeneity of the clot. As heterogeneous structural domains within the clot affect thrombus stability, understanding the factors influencing thrombus structure is of significant biomedical importance.

Iron Medication–Associated Gastric Mucosal Injury

An endoscopic antral biopsy specimen was taken from a 48-year-old, white woman with iron deficiency anemia who was currently taking ferrous sulfate, 250-mg tablets, twice a day. Microscopic examination of the biopsy specimen revealed oxyntic and transitional mucosa with marked crystalline, brown-pigmented material deposited in the superficial mucosa (Figure 1, original magnification 364). Mucosal injury was apparent, including pyknotic nuclei and distortion of the epithelium associated with encrustation of iron material. In addition, focal luminal acute inflammatory exudates and mucosal erosion were evident. An iron stain (Gomori method) confirmed that the brown pigment material was crystalline iron (Figure 2, original magnification 364). The iron stain also highlighted hemosiderin pigment accumulation in the deep fundic glands. No Helicobacter pylori organisms or intestinal metaplasia were identified on special stains (Giemsa and periodic acid‐Schiff/Alcian blue). Oral iron medication has been widely used for prevention and treatment of anemia. It is well recognized that iron overdose can cause severe corrosive injury to the upper gastrointestinal (GI) tract, which includes mucosal necrosis, ulceration, and ischemia. Although mucosal injury that results from iron tablet ingestion at the therapeutic level has been rarely reported, 1,2 it can be seen in approximately 1% of biopsy specimens taken from the upper GI tract, including the esophagus, stomach, and duodenum, during endoscopic examinations. 1 Ferrous sulfate is the most common iron medication associated with the pathologic findings. The diagnosis of iron deposition in the mucosa is straightforward. Material from iron tablets has a characteristic brown crystalline and clumpy fibrillar appearance. It represents oxidized inorganic iron and is refractile but not polarizing. Most of the iron is extracellular. It can be luminal, lying adjacent to the surface epithelium and admixed with luminal fibrinoinflammatory exudates. In addition, crystalline iron is often seen in the lamina propria or granulation tissue or forming iron-containing thrombi in blood vessels. 1,2 The crystalline iron can be easily distinguished from hemosiderin pigments despite positive staining by iron for both substances. The latter is intra

COLONIC ULCERATION - A PREVIOUSLY UNREPORTED ADVERSE EFFECT OF MYCOPHENOLATE MOFETIL

584 Gastrointestinal (GI) side effects, especially diarrhea are among the most common adverse effects of mycophenolate mofetil (MMF). GI hemorrhage secondary to gastric and duodenal ulceration has been described, but colonic ulceration has not previously been reported. In this communication we report four patients who developed colonic ulceration and lower GI bleeding following commencement of MMF. None of the patients were on any drugs known to cause colonic ulceration. Demographic data is given in the following table:Findings on colonoscopy ranged from a solitary ulcer in the cecum to multiple punched out ulcers in the ascending and transverse colon (Patient#1). Patient #1 had recurrent lower GI bleeding. MMF was discontinued after the third episode of hematochezia and follow-up colonoscopy 1 month later showed complete healing of the ulcers with no scarring. Histological features common to all four patients were the presence of large irregular cells with prominent nuclei in the lamina propria. Patient #1 also had fibrin thrombi in blood vessels in the lamina propria. Immunohistochemical stains for Cytomegalovirus and Herpes Simplex virus were negative in all four patients. None of the patients have had recurrence of GI bleeding following discontinuation of MMF with a follow-up period of 15 to 516 days. In summary, we report four patients who developed lower GI bleeding temporally related to commencement of MMF. This adverse effect of MMF has not been previously described.

COLONIC ULCERATION - A PREVIOUSLY UNREPORTED ADVERSE EFFECT OF MYCOPHENOLATE MOFETIL.

584 Gastrointestinal (GI) side effects, especially diarrhea are among the most common adverse effects of mycophenolate mofetil (MMF). GI hemorrhage secondary to gastric and duodenal ulceration has been described, but colonic ulceration has not previously been reported. In this communication we report four patients who developed colonic ulceration and lower GI bleeding following commencement of MMF. None of the patients were on any drugs known to cause colonic ulceration. Demographic data is given in the following table:Findings on colonoscopy ranged from a solitary ulcer in the cecum to multiple punched out ulcers in the ascending and transverse colon (Patient#1). Patient #1 had recurrent lower GI bleeding. MMF was discontinued after the third episode of hematochezia and follow-up colonoscopy 1 month later showed complete healing of the ulcers with no scarring. Histological features common to all four patients were the presence of large irregular cells with prominent nuclei in the lamina propria. Patient #1 also had fibrin thrombi in blood vessels in the lamina propria. Immunohistochemical stains for Cytomegalovirus and Herpes Simplex virus were negative in all four patients. None of the patients have had recurrence of GI bleeding following discontinuation of MMF with a follow-up period of 15 to 516 days. In summary, we report four patients who developed lower GI bleeding temporally related to commencement of MMF. This adverse effect of MMF has not been previously described.