Organotypic endothelial adhesion molecules are key for Trypanosoma brucei tropism and virulence.

Trypanosoma brucei is responsible for lethal diseases in humans and cattle in Sub-Saharan Africa. These extracellular parasites extravasate from the blood circulation into several tissues. The importance of the vasculature in tissue tropism is poorly understood. Using intravital imaging and bioluminescence, we observe that gonadal white adipose tissue and pancreas are the two main parasite reservoirs. We show that reservoir establishment happens before vascular permeability is compromised, suggesting that extravasation is an active mechanism. Blocking endothelial surface adhesion molecules (E-selectin, P-selectins, or ICAM2) significantly reduces extravascular parasite density in all organs and delays host lethality. Remarkably, blocking CD36 has a specific effect on adipose tissue tropism that is sufficient to delay lethality, suggesting that establishment of the adipose tissue reservoir is necessary for parasite virulence. This work demonstrates the importance of the vasculature in a T. brucei infection and identifies organ-specific adhesion molecules as key players for tissue tropism.

Frequency of detection and load of amastigotes in the pancreas of Leishmania infantum-seropositive dogs: clinical signs and histological changes.

BACKGROUND: Zoonotic visceral leishmaniasis is caused by the protozoan Leishmania infantum and is highly lethal in humans and dogs if left untreated. The frequency of this parasite and associated histological changes in the pancreas of dogs are poorly studied. Therefore, the objectives of this study were to evaluate the frequency of detection and load of amastigotes in the pancreas of L. infantum-seropositive dogs and to identify the clinical signs and histological changes associated with parasitism of this organ. METHODS: One hundred forty-three dogs from an endemic area in Brazil that tested seropositive for L. infantum were studied. The dogs were clinically examined, killed, and necropsied between 2013 and 2014. One fragment of the pancreas was randomly collected for histopathology and immunohistochemistry, and spleen and bone marrow were collected for culture. RESULTS: Leishmania amastigotes were detected in the pancreas of 22 dogs (15.4%) by immunohistochemistry, all exhibiting L. infantum parasitism in the spleen and/or bone marrow. Poor body condition and cachexia were only associated with infection of the pancreas with Leishmania spp. (p = 0.021) and were found in 40.9% of dogs with pancreatic infection. Anorexia, vomiting, and/or diarrhea were observed in 9.2% of dogs with pancreatitis. The median parasite load in the pancreas was 1.4 infected macrophages/mm2. Pancreatic histological changes and their frequencies were: granulomatous pancreatitis (28.0%), lymphoplasmacytic pancreatitis (23.8%), acinar cell degeneration (6.3%), fibrosis (5.6%), hemorrhage (2.1%), eosinophilic pancreatitis (0.7%), suppurative pancreatitis (0.7%), and necrosis (0.7%). CONCLUSIONS: The present results demonstrate that L. infantum is one of the etiological agents of chronic pancreatitis in dogs; however, the frequency of detection and parasite load are low in this organ. The lack of an association of poor body condition and cachexia with pancreatitis and the low frequency of clinical signs commonly associated with pancreatitis suggest that a significant portion of the organ is not affected by this parasite. On the other hand, the association of poor body condition and cachexia with concomitant infection of the pancreas, spleen, and/or bone marrow with this parasite suggests that these manifestations are the result of a more advanced stage of canine visceral leishmaniasis.

[Combined left hemihepatectomy for multiple organ alveococcosis]. / Kombinirovannaya levaya gemigepatektomiya v lechenii mul'tiorgannogo al'veokokkoza.

Advanced multiple organ parasitic invasion is reported in the article. A thorough assessment of pathological process, surgical anatomy and preoperative examination resulted radical surgery despite multiple organ disease. Surgical procedure included extended left-sided hemihepatectomy, atypical resection of S6liver segment and pancreas, removal of themediastinal parasite with partial excision of parietal pleura and pericardium.

A pathological study of Leishmania infantum natural infection in European rabbits (Oryctolagus cuniculus) and Iberian hares (Lepus granatensis).

In this study, we describe the pathology of Leishmania infantum infection in naturally infected wild Leporidae and compare diagnosis of infection using histopathology, direct fluorescent antibody (DFA) assay, immunofluorescence antibody test (IFAT) and quantitative real-time PCR (qPCR). Tissues were analysed from 52 European rabbits (Oryctolagus cuniculus) and 7 Iberian hares (Lepus granatensis) from the Community of Madrid (Spain). Our results show that L. infantum infection is associated with only minimal histopathological lesions and that L. infantum amastigotes can be detected by DFA assay in all tissues types tested, including skin. These results were confirmed by qPCR on fresh frozen tissues in 13% of rabbits and 100% of hares. However, L. infantum DNA could not be detected by qPCR on paraffin-embedded tissue obtained by laser capture microdissection. Using the DFA assay to diagnose L. infantum, infection may provide further insights into this disease in wild animals and may allow the precise tissue localization of L. infantum, thereby guiding follow-up tests with more accurate qPCR.

A rare case of the simultaneous location of Echinococcus multilocularis in the liver and the head of the pancreas: case report analysis and review of literature.

BACKGROUND: Echinococcosis multilocularis (Hydatid Disease - HD) is a zoonotic disease caused by the larval form of Echinococcus multilocularis (EM). The main sites for this zoonosis are the Middle East, China, India, Alaska, and Siberia. It is rather rare in Europe. In Poland, the Warmian-Masurian Province is the endemic region for Echinococcus multilocularis. The clinical manifestation of the disease is dependent on the location, the size of the cyst and the development stage of the parasite. Considering the uncommon character of echinococcosis in Central Europe, especially such located in the areas outside the liver and lungs, the authors would like to present a case of coexistence in one patient of two EM foci in the liver and the head of the pancreas. CASE PRESENTATION: We present a clinical case of a 32-year-old man who was diagnosed with a cystic lesion with septa and calcification in the sixth segment of the liver and a suspicious change in the head of the pancreas. ELISA Em 2 plus test was positive, Western Blot method - the P-5 pattern showed an image that is characteristic of an EM infection. The sixth liver segment with a tumour and a tumour from the head of pancreas were excised by means of laparotomy. On the 6th day after the surgery the patient was discharged from hospital without complications and in good condition. Currently, he is under the control of a parasitic and zoonotic clinic. He takes an 800 mg daily dosage of Albendazole. CONCLUSIONS: The presented clinical case shows that if we have a patient with cystic / tumour change in the pancreas and positive immunological tests, CT and MRI of the abdominal cavity are usually sufficient in order to fully diagnose and to qualify such a person for surgery. The most effective treatment is surgical treatment supplemented with pre- and postsurgical treatment with Albendazole.

Dynamic changes of proteasome and protective effect of bortezomib, a proteasome inhibitor, in mice with acute pancreatitis.

The proteasome is involved in the activation of NF-κB and can regulate the progression of inflammatory diseases. However, the role of proteasome in acute pancreatitis (AP) has not been demonstrated. In this study, we first observed that the protein level and activity of proteasome 20S were increased significantly in pancreatic injury tissues after caerulein-induced mild acute pancreatitis (MAP) induction, which was in consistent with the expression of the NF-κB nucleoprotein and positively correlated with the severity of AP. Then, bortezomib, a classical proteasome inhibitor, was used to intervene the progression of MAP in mice. The results showed that bortezomib administration reduced the serum amylase and lipase levels and mitigated histopathological manifestation of pancreatic injury in mice. Meanwhile, bortezomib decreased the expression of NF-κB p65 nucleoprotein as well as total proteasome 20S protein, and inhibited the activity of 20S in pancreatic tissues. In addition, we found that bortezomib could protect pancreatic acinar cell against necrosis and mitigate the severity of AP in a severe acute pancreatitis model induced by sodium taurocholate hydrate. Taken together, our study for the first time confirmed that the proteasome participated in the pathogenesis of AP and its inhibitor bortezomib could protect against AP in mice.

Hydatid cyst of the pancreas causing both acute pancreatitis and splenic vein thrombosis.

Hydatid cyst of the pancreas is a rarely seen entity even in endemic countries. Cyst may causes several symptoms due to external compression or fistulisation to pancreaticobiliary tract or small bowel. A 23-year-old female patient was referred with a complaint of abdominal pain. Preoperative imaging revealed an undefined cyst in the tail of pancreas. She underwent distal pancreatectomy and splenectomy, with a diagnosis of acute pancreatitis due to cystopancreatic duct fistula and also left-sided portal hypertension due to splenic vein thrombosis. Pathological examination reported a final diagnosis of hydatid cyst. To the best of our knowledge, coincidence of cystopancreatic duct fistula and splenic vein thrombosis due to pancreatic hydatid cyst has not previously been reported.

Primary hydatid cyst of the pancreas of the child: a case report.

Primary pancreatic hydatid lesions are very rare with an incidence of less than 1% in the adult population. We report an observation of a 5-year-old girl who consulted for isolated abdominal pain occurring for 2 weeks without vomiting, transit disorders or jaundice and evolving in a context of conservation of the general condition and apyrexia. Clinical examination and preoperative imaging have suggested the diagnosis of a choledochal cyst or duodenal duplication rather than a hydatid cyst of the pancreas due to the presence of a cystic hepatic image projecting into the liver hilum. During the procedure, a hydatid cyst was found occupying the head of the pancreas. Primary hydatidosis of the pancreas in children is extremely rare. Possible sources of infection include: blood diffusion, local spread via biliopancreatic ducts and peripancreatic lymphatic invasion. In the endemic areas, hydatid disease should be mentioned in the list of differential diagnoses of cystic lesions located around the biliopancreatic junction in children.

Cattle naturally infected by Eurytrema coelomaticum: Relation between adenosine deaminase activity and zinc levels.

The enzyme adenosine deaminase (ADA) is critical for modulating the immune system, and in the presence of zinc, its activity is catalyzed. The aim of this study was to evaluate the ADA activity in pancreas of cattle naturally infected by Eurytrema coelomaticum in relation to the results of zinc levels, pathological findings and parasite load. For this study 51 slaughtered cattle were used. The animals were divided into two groups: Group A consisting of animals naturally infected by E. coelomaticum (n=33) and Group B of uninfected animals (n=18). Blood and pancreas were collected of each animal for analysis of zinc and ADA, respectively. Infected cattle showed a reduction on seric levels of zinc, and decreased ADA activity in the pancreas (P>0.05). A positive correlation between zinc levels and ADA activity was observed. Thus, high parasite load and severity of histopathologic lesions affect the ADA activity in pancreas, as well as the zinc levels in serum of infected animals (negative correlation between these variables). Therefore, we can conclude that cattle infected by E. coelomaticum have low ADA activity in pancreas, which can be directly related to zinc reduction, responsible for ADA activation and catalyzes.

Alterations in pancreatic ß cell function and Trypanosoma cruzi infection: evidence from human and animal studies.

The parasite Trypanosoma cruzi causes a persistent infection, Chagas disease, affecting millions of persons in endemic areas of Latin America. As a result of immigration, this disease has now been diagnosed in non-endemic areas worldwide. Although, the heart and gastrointestinal tract are the most studied, the insulin-secreting ß cell of the endocrine pancreas is also a target of infection. In this review, we summarize available clinical and laboratory evidence to determine whether T. cruzi-infection-mediated changes of ß cell function is likely to contribute to the development of hyperglycemia and diabetes. Our literature survey indicates that T. cruzi infection of humans and of experimental animals relates to altered secretory behavior of ß cells. The mechanistic basis of these observations appears to be a change in stimulus-secretion pathway function rather than the loss of insulin-producing ß cells. Whether this attenuated insulin release ultimately contributes to the pathogenesis of diabetes in human Chagas disease, however, remains to be determined. Since the etiologies of diabetes are multifactorial including genetic and lifestyle factors, the use of cell- and animal-based investigations, allowing direct manipulation of these factors, are important tools in testing if reduced insulin secretion has a causal influence on diabetes in the setting of Chagas disease. Long-term clinical investigations will be required to investigate this link in humans.

NTPDase and 5'-nucleotidase as inflammatory markers in cattle naturally infected by Eurytrema coelomaticum.

The aim of this study was to evaluate seric NTPDase and 5'nucleotidase activities of cattle naturally infected by Eurytrema coelomanticum, as well as to correlate them to histopathological lesions in the pancreas and the degree of parasitism. Blood samples and pancreas of 51 bovines were collected on a slaughterhouse in Southern Brazil: 33 from cattle naturally infected by E. coelomanticum (the Group A), and 18 from uninfected animals (the Group B). Infected animals showed an average of 532 parasites per pancreas. In the pancreatic histology, ducts displayed hyperplasia, stenosis, proliferation of fibrous tissue, and interstitial inflammatory infiltration of lymphocytes. The serum from infected animals showed an increase in NTPDase activity when ATP was used as substrate (P<0.001). For the ADP substrate, there was no difference between groups regarding NTPDase activity (P=0.37), as well as 5'-nucleotidase activity (P=0.27). Correlating NTPDase activity (ATP substrate) with the degree of histopathological lesions (rho=0.66, P<0.001) and the parasitic load on the pancreas (rho=0.65, P<0.001), a positive correlation was observed. Similar results were found between the degree of histopathological lesions and NTPDase activity (ADP substrate; rho=0.29, P=0.03), and 5'nucleotidase activity (rho=0.35, P=0.01). Based on the results of NTPDase and 5'nucleotidase enzymes in cattle naturally infected by E. coleomanticum, it is possible to suggest that these enzymes are involved in the modulation of inflammation, and they can act as markers of inflammatory response.

Oxidative stress associated with pathological changes in the pancreas of cattle naturally infected by Eurytrema coelomaticum.

Although Eurytrema coelomaticum is considered a parasite with low pathogenicity, it may be associated with mortality and loss of productive performance in animals due to chronic pancreatitis. The aim of this study was to evaluate the occurrence of oxidative stress caused by E. coelomaticum in naturally infected cattle, correlating the biochemical findings with the parasite load and histopathological changes. For this study, blood and pancreas samples from 51 cattle were collected, and levels of the thiobarbituric acid reactive substances (TBARS), advanced oxidation protein products (AOPP) and ferric reducing ability of plasma (FRAP) were measured in the serum and pancreas, and superoxide dismutase (SOD) activity was measured in total blood. Parasite burden was determined opening the pancreatic ducts, and then fragments of pancreas were collected and fixed in 10% buffered formalin and routinely processed for histopathology. From the 51 collected pancreas, 33 (63.5%) were parasitized. The average parasite burden per pancreas was 532 (12-2,578). TBARS and FRAP showed higher levels in serum and pancreas of infected animals (p<0.05), with a positive correlation between the histopathological changes and the number of parasites. SOD level in blood was 42% higher in parasitized group compared with control group (p<0.05), as well as AOPP in serum. Based on these results, we concluded that in natural infection by E. coelomaticum in cattle, oxidative stress occurs, characterized by the occurrence of protein oxidation, lipid peroxidation and activation of antioxidant system.

Isolated pancreatic cysticercal cyst presenting as a diagnostic challenge: diagnosis and treatment review.

Human cysticercosis most commonly affects the subcutaneous tissues, skeletal muscles, lungs, brain, eyes, liver and, rarely, the heart, thyroid and pancreas. Owing to vague clinical presentation and unfamiliarity of clinicians with this entity, it is difficult to diagnosis when seen as an isolated cyst. We present a case of a 16-year-old boy who presented with an upper abdominal lump and jaundice. Ultrasonography (USG) and MRI of the abdomen were carried out, which revealed a cystic mass (8.5 × 7 × 7 cm) in the pancreas. No evidence of solid component or papillary projections was noted within the lesion. Tumour markers carcinoembryonic antigen (CEA) and cancer antigen (CA 19-9) were normal. Fine needle aspiration cytology was performed, which revealed the presence of cysticercus larvae, along with a foreign body giant cell reaction. The patient was treated with therapeutic aspiration and antihelminthic therapy. Since then, he has been symptom free and under regular follow-up for the last 1 year. A diagnosis of cysticercal cyst at atypical sites is very rare and depends mainly on histopathological examination, which, along with USG and MRI, can give an accurate analysis. These cysts can be very well treated non-surgically with antihelminthics and aspiration.

Incidental isolated pancreatic hydatid cyst.

Isolated pancreatic hydatid cysts are a rare parasitic disease even in endemic areas. It is difficult to discriminate primary pancreatic hydatid cysts from other cystic and solid lesions of the pancreas. This is a case report of an incidental isolated pancreatic hydatid cyst. A heterogeneous cystic lesion in the body of the pancreas was identified on magnetic resonance imaging of a patient previously diagnosed patient with cholelithiasis, and because of the malignant possibility of the lesion, splenectomy with distal pancreatectomy and cholecystectomy was performed. The histopathologic diagnosis was reported as a hydatid cyst. Pancreatic hydatid cysts should be kept in mind in the differential diagnosis of pancreatic pseudocysts and cystic malignancies.