Development Of Granulomas Research Articles

Visualization of Mycobacterial Biomarkers and Tuberculosis Drugs in Infected Tissue by MALDI-MS Imaging.

MALDI mass-spectrometry imaging (MALDI-MSI) is a technique capable of the label-free identification and visualization of analytes in tissue sections. We have previously applied MALDI-MSI to the study of the spatial distribution of tuberculosis (TB) drugs in necrotic lung granulomas characteristic of pulmonary TB disease, revealing heterogeneous and often suboptimal drug distributions. To investigate the impact of differential drug distributions at sites of infection, we sought to image mycobacterial biomarkers to coregister drugs and bacteria in lesion sections. The traditional method of visualizing Mycobacterium tuberculosis inside lesions is acid-fast staining and microscopy. Directly analyzing and visualizing mycobacteria-specific lipid markers by MALDI-MSI provides detailed molecular information on bacterial distributions within granulomas, complementary to high-spatial-resolution staining and microscopy approaches. Moreover, spatial monitoring of molecular changes occurring in bacteria during granuloma development can potentially contribute to a greater understanding of pulmonary-TB pathogenesis. In this study, we developed a MALDI-MSI method to detect and visualize specific glycolipids of mycobacteria within TB lesions. The biomarker signal correlated well with the bacteria visualized by IHC and acid-fast staining. This observation was seen in samples collected from multiple animal models. Although individual bacteria could not be visualized because of the limit of spatial resolution (50 μm), bacterial clusters were clearly detected and heterogeneously distributed throughout lesions. The ability to visualize drugs, metabolites, and bacterial biomarkers by MALDI-MSI enabled direct colocalization of drugs with specific bacterial target populations (identifiable by distinct metabolic markers). Future applications include assessing drug activity in lesions by visualizing drug-mediated lipid changes and other drug-induced mycobacterial metabolic responses.

Sarcoidosis of respiratory system at the beginning of the III Millennium

Sarcoidosis of respiratory system is a systemic granulomatosis disease accompanied by the development of epithelioid cell granulomas. During the treatment by glucocorticosteroid drugs or spontaneously, these granulomas disperse or get compacted. Connective tissue with annular distribution is formed around them. Sarcoidosis is etiologically, clinically and morphologically close to tuberculosis. The highest incidence of sarcoidosis has been observed among the urban population of the North of Europe (England, France, Sweden, Poland) - from 20 to 40 per 100000 population. In Russia summary data on the incidence of sarcoidosis does not exist. In the beginning of the Third Millennium according to the St. Petersburg sarcoidosis data it was 8-11 per 100000 people. The basis for justification of the tuberculous nature of sarcoidosis was the similarity of granulomas structure, its combination with tuberculosis and its transformation into tuberculosis with the release of Mycobacterium tuberculosis. The main argument among the opponents of this etiology of the sarcoidosis - is the lack of effect from taking antituberculous medicine. Inefficiency takes place because the point of application of these drugs is the microbial wall. In sarcoidosis, granular and L-forms of mycobacteria with thin cell wall and changes in its structure with which antituberculous drugs contact them are detected in patients. Growth of such microorganisms on special nutrient media causes the restoration of the structure of microbial wall with the restoration of the bacteriostatic effect of anti-tuberculosis drugs.

Variation in the Early Host-Pathogen Interaction of Bovine Macrophages with Divergent Mycobacterium bovis Strains in the United Kingdom.

ABSTRACTBovine tuberculosis has been an escalating animal health issue in the United Kingdom since the 1980s, even though control policies have been in place for over 60 years. The importance of the genetics of the etiological agent, Mycobacterium bovis, in the reemergence of the disease has been largely overlooked. We compared the interaction between bovine monocyte-derived macrophages (bMDM) and two M. bovis strains, AF2122/97 and G18, representing distinct genotypes currently circulating in the United Kingdom. These M. bovis strains exhibited differences in survival and growth in bMDM. Although uptake was similar, the number of viable intracellular AF2122/97 organisms increased rapidly, while G18 growth was constrained for the first 24 h. AF2122/97 infection induced a greater transcriptional response by bMDM than G18 infection with respect to the number of differentially expressed genes and the fold changes measured. AF2122/97 infection induced more bMDM cell death, with characteristics of necrosis and apoptosis, more inflammasome activation, and a greater type I interferon response than G18. In conclusion, the two investigated M. bovis strains interact in significantly different ways with the host macrophage. In contrast to the relatively silent infection by G18, AF2122/97 induces greater signaling to attract other immune cells and induces host cell death, which may promote secondary infections of naive macrophages. These differences may affect early events in the host-pathogen interaction, including granuloma development, which could in turn alter the progression of the disease. Therefore, the potential involvement of M. bovis genotypes in the reemergence of bovine tuberculosis in the United Kingdom warrants further investigation.

A Case of foreign body granuloma after Plastibell® circumcision

Male circumcision is one of the most commonly performed surgical procedures and the Plastibell® device is a popular method used to perform circumcisions in neonates and young children. We report a case of a 9-year-old otherwise healthy boy who developed foreign body granulomas following Plastibell® circumcision which was carried out in the community by a medically trained practitioner. His post-operative course was complicated by a retained Plastibell® ring and development of multiple non-healing wounds and granulomas. This patient underwent a semi-elective examination under general anesthesia, wound exploration and re-do modified circumcision. At 4 month follow up the wound was well healed without scarring and the patient reported a normal single straight stream urinary flow.

Impact of Flab Technique Versus Non-Flap Techniques on Endoscopic Dacryocystorhinostomy

Objective: to compare the influence of flap versus non-flap technique on endoscopic dacryocystorhinostomy (EDCR). Patients and Method: A prospective randomized trial in patients with bilateral nasolacrimal duct obstruction, comparing the two techniques to avoid inter-patient variability. We included all patients where bilateral epiphora, excluding unilateral, previously operated or recurrent cases. Results: One hundred patients, fifty females and fifty males with bilateral epiphora due to naso-lacrimal duct obstruction were operated upon by EDCR with or without flap technique. Out of 100 EDCR procedures with flap technique, only 3 had recurrent epiphora with stenosis of the ostium on endoscopic examination and failed fluorescein dye test. In contrast, 4 procedures without flap failed as evident by recurrent epiphora, endoscopic and fluorescein dye test criteria. Conclusion: There is no difference between DCR with flap preservation and flap removal in success rate but the preservation of both lacrimal and mucosal flaps aids in reducing the post-operative granuloma development.

Up-regulation of Interleukin-21 Contributes to Liver Pathology of Schistosomiasis by Driving GC Immune Responses and Activating HSCs in Mice

The pathology of schistosome egg-induced liver granuloma, fibrosis and eventually liver scarring is complicated. CD4+ helper T (Th) cells play critical roles in both host humoral immunity and cellular immunity against parasitic infection and immunopathology in schistosomiasis. Follicular helper T (Tfh) cells are another specialized subset of Th cells and involved in infectious diseases. However, the immune regulatory mechanism of Tfh cells in severe liver pathology of schistosomiasis is still poorly understood. In this study, using a S. japonicum-infected mouse model, we studied the dynamics and effects of Tfh cells in vivo and demonstrated that Tfh phenotype molecules ICOS, PD-1 and functional factor IL-21 were positively correlated with disease development by flow cytometry. Meanwhile, our results also showed that Tfh cells enriched in splenic germinal center (GC) and promoted B cells producing IgM with the progress of hepatic immunopathology by B-T co-culture experiments. More importantly, our data indicated that IL-21 contributed to the formation and development of hepatic egg granuloma and subsequent fibrosis by driving GC responses and activating HSCs by immunohistochemical detection and blocking assay in vitro. Our findings contribute to the better understanding of the immunopathogenesis of schistosomiasis and have implications for therapeutic intervention of hepatic fibrotic diseases.

Water quality and fish diseases

Certain water quality parameters are known to cause serious problems to fish, especially when they are living under intensive farming conditions. These problems range from discomfort of fish to heavy mortalities and factors, such as the fish species, the time and level of exposure and the synergic effect of other coexisting stressful conditions, play an important role. In addition, when these parameters are outside the preferable for each fish species range, they can induce stress to fish, compromising their immune system and making them vulnerable to many opportunistic pathogens. Oxygen is, probably, the main limiting factor under farming conditions and when its levels are below the preferable range for any fish species, many morphological, as well as physiological alterations develop. Increased levels of carbon dioxide in the water usually coexist with decreased levels of oxygen and can cause respiratory acidosis and nephrocalcinosis. The latter is characterized by the development of granulomas in many internal organs and urolithiasis. Ammonia usually causes problems under intensive farming conditions, especially when the wateris recirculated and the pH is high. Increased levels of ammonia in the water can cause extensive alterations in the gills and degenerative changes in the liver and kidney. Gas supersaturation of the water, depending on the level of saturation and the time of exposure, can result in the gas bubble disease. Formation of bubbles in the eyes, skin and gills and extensive necrotic areas inmany organs due to gas emboli are the main findings caused by this disease. Many contaminants in the water can, also, create serious problems to fish. Fin erosion, epidermal hyperplasia or papilloma and degenerative and necrotic alterations in many internalorgans are common findings observed in fish on many cases of water pollution. Many of the factors mentioned above, as well as others, such as nutrition and bad management, can result in abnormal development of the body offish, when exposed at their early life stages. Due to farming conditions, cultured fish tend to exhibit increased rate of body malformation compared to wild ones. Careful design of the facilities, use of specialized equipment and, probably, application of genetic selection program can minimize or even eliminate the effects these water parameters have on the cultured fish.

Interleukin-17 limits hypoxia-inducible factor 1α and development of hypoxic granulomas during tuberculosis.

Mycobacterium tuberculosis (Mtb) is a global health threat, compounded by the emergence of drug-resistant strains. A hallmark of pulmonary tuberculosis (TB) is the formation of hypoxic necrotic granulomas, which upon disintegration, release infectious Mtb. Furthermore, hypoxic necrotic granulomas are associated with increased disease severity and provide a niche for drug-resistant Mtb. However, the host immune responses that promote the development of hypoxic TB granulomas are not well described. Using a necrotic Mtb mouse model, we show that loss of Mtb virulence factors, such as phenolic glycolipids, decreases the production of the proinflammatory cytokine IL-17 (also referred to as IL-17A). IL-17 production negatively regulates the development of hypoxic TB granulomas by limiting the expression of the transcription factor hypoxia-inducible factor 1α (HIF1α). In human TB patients, HIF1α mRNA expression is increased. Through genotyping and association analyses in human samples, we identified a link between the single nucleotide polymorphism rs2275913 in the IL-17 promoter (-197G/G), which is associated with decreased IL-17 production upon stimulation with Mtb cell wall. Together, our data highlight a potentially novel role for IL-17 in limiting the development of hypoxic necrotic granulomas and reducing disease severity in TB.

PYOGENIC GRANULOMA: A CASE REPORT

Purpose: The purpose of this study is to evaluate the treatment and pursuit process of the pyogenic granuloma which has seen on 12 years old girl patient. Case Presentation: Pyogenic granuloma is a lesion which classified in vascular tumors which constitute 30-60% of all the reactive lesions of gingival tissue. Trauma, infections of capillary wall, hormonal factors, foreign materials, hypertension and poor oral hygiene are accused for development of pyogenic granuloma. It may occur at all age groups and in both sexs. In the oral cavity, pyogenic granuloma lesions are most frequently encountered on the gingiva. Definitive diagnosis can only be made by histopathologic examination of biopsied tissue. The treatment of this lesion is surgical excision. If surgical excision removal is incomplete, the lesion has got the risk of the recurrence. A twelve years old female child applied to our clinic with complaints like on anterior palatinal region gingival bleeding and swollen condition on the same region. As beginning treatment oral hygiene education was given to the patient and plaque and calculus were removed. Under local anesthesia the lesion was taken with excisional biopsy for doing distinctive diagnosis from the other pathological lesions which can be seen in oral cavity. In addition frenectomy surgery in the maxilla and ridge augmentation operation in the mandible is performed to provide more comfortable oral hygiene. Three-month follow-up results of the patients were found to occur again in the region of the palatal gingival enlargement. As a result, it was decided to re-operations performed gingivectomy. Patient after operations carried out gingivectomy was called to the appointment checked and encourage oral hygiene. Conclusion: After taking of the excisional biopsy, the diagnose was made shaping “The Pyogenic Granuloma” to the mass which was examined histopathologically under the light microscope. In the control inspection, there was not any recurrence clinically. Keywords: Pyogenic granuloma, excisional biopsy.

Participation of osteoclastogenic factors in immunopathogenesis of human chronic periapical lesions.

Chronic periapical lesions (CPLs) are common lesions of the oral cavity and are the result of caries, tooth fracture, iatrogenic causes, or factors causing contamination and pulp necrosis. Inflammatory cells participate in the expansion of CPLs by releasing factors that stimulate or inhibit osteolytic activity. The objective of this study was to investigate the participation of RANKL, TNF-α, cathepsin K, IL-33, and OPG in the development of radicular cysts (RCs) and periapical granulomas (PGs). Paraffin-embedded sections of 30 RCs and 22 PGs were submitted to immunohistochemistry. Immunoexpression of the proteins studied was observed in the epithelium and capsule of RCs, as well as in connective tissue of PGs. The expression of the osteoclastogenic factors studied differed significantly in RCs and PGs (P<.001), with lower expression of OPG in RCs. In PGs, the lowest expression was observed for cathepsin K. Comparison of the 2 lesions showed a similar participation of RANKL and IL33, while a significant difference was observed for OPG (P<.001), TNF-α (P=.002), and cathepsin K (P=.016). No association of the expression of the proteins with lesions size was observed. This study demonstrated the participation of RANKL, TNF-α, IL-33, cathepsin K, and OPG in the development of RCs and PGs, with emphasis on the highest immunoreactivity of cathepsin in RCs and TNF-α and OPG in PGs. OPG possibly determines the slower growth of PGs compared to RCs.

Imaging for Sarcoidosis.

AbstractSarcoidosis is a systemic disease characterized by widespread development of noncaseating epithelioid granulomas. Based on a joint statement by the American Thoracic Society (ATS), European Thoracic Society (ERS), and the World Association for Sarcoidosis and other Granulomatous Disorders (WASOG), the diagnosis of sarcoidosis requires a compatible clinical picture, histologic demonstration of noncaseating granulomas, and exclusion of other diseases that may give a similar histologic or clinical picture. Although to a casual reader these recommendations suggest that making a diagnosis of sarcoidosis is straightforward, a consensus on the diagnostic role of imaging in sarcoidosis remains unclear. First, despite the primacy of chest computed tomography (CT) for evaluating diffuse lung disease, a guideline-based diagnosis of sarcoidosis without biopsy requires specific appearances on chest radiography (Löfgren's syndrome) or 67Ga Scintigraphy (Heerfordt's syndrome). Second, although the literature on CT as a prognostic tool in interstitial lung disease is relatively extensive, very little of this focuses specifically on sarcoidosis. Third, staging of sarcoidosis relies on radiographic appearances at presentation using a system devised by Scadding more than 40 years ago. This is in stark contrast to idiopathic pulmonary fibrosis where significant advances have been made in imaging-based staging and computer-assisted quantification of disease in the past 10 years. In this article, in addition to describing the myriad of imaging patterns seen in sarcoidosis, the impact imaging has on diagnosis, staging, and prediction of outcome will also be discussed. Cardiac-related sarcoidosis and neurosarcoidosis will be discussed in separate articles.

Active nuclear transcriptome analysis reveals inflammasome-dependent mechanism for early neutrophil response to Mycobacterium marinum

The mechanisms governing neutrophil response to Mycobacterium tuberculosis remain poorly understood. In this study we utilise biotagging, a novel genome-wide profiling approach based on cell type-specific in vivo biotinylation in zebrafish to analyse the initial response of neutrophils to Mycobacterium marinum, a close genetic relative of M. tuberculosis used to model tuberculosis. Differential expression analysis following nuclear RNA-seq of neutrophil active transcriptomes reveals a significant upregulation in both damage-sensing and effector components of the inflammasome, including caspase b, NLRC3 ortholog (wu: fb15h11) and il1β. Crispr/Cas9-mediated knockout of caspase b, which acts by proteolytic processing of il1β, results in increased bacterial burden and less infiltration of macrophages to sites of mycobacterial infection, thus impairing granuloma development. We also show that a number of immediate early response genes (IEGs) are responsible for orchestrating the initial neutrophil response to mycobacterial infection. Further perturbation of the IEGs exposes egr3 as a key transcriptional regulator controlling il1β transcription.

Positron Emission Tomography Imaging of Macaques with Tuberculosis Identifies Temporal Changes in Granuloma Glucose Metabolism and Integrin α4β1-Expressing Immune Cells.

Positron emission tomography and computed tomography imaging (PET/CT) is an increasingly valuable tool for diagnosing tuberculosis (TB). The glucose analog [18F]fluoro-2-deoxy-2-d-glucose ([18F]-FDG) is commonly used in PET/CT that is retained by metabolically active inflammatory cells in granulomas, but lacks specificity for particular cell types. A PET probe that could identify recruitment and differentiation of different cell populations in granulomas would be a useful research tool and could improve TB diagnosis and treatment. We used the Mycobacterium-antigen murine inflammation model and macaques with TB to identify [64Cu]-labeled CB-TE1A1P-PEG4-LLP2A ([64Cu]-LLP2A), a high affinity peptidomimetic ligand for very late Ag-4 (VLA-4; also called integrin α4β1) binding cells in granulomas, and compared [64Cu]-LLP2A with [18F]-FDG over the course of infection. We found that [64Cu]-LLP2A retention was driven by macrophages and T cells, with less contribution from neutrophils and B cells. In macaques, granulomas had higher [64Cu]-LLP2A uptake than uninfected tissues, and immunohistochemical analysis of granulomas with known [64Cu]-LLP2A uptake identified significant correlations between LLP2A signal and macrophage and T cell numbers. The same cells coexpressed integrin α4 and β1, further supporting that macrophages and T cells drive [64Cu]-LLP2A avidity in granulomas. Over the course of infection, granulomas and thoracic lymph nodes experienced dynamic changes in affinity for both probes, suggesting metabolic changes and cell differentiation or recruitment occurs throughout granuloma development. These results indicate [64Cu]-LLP2A is a PET probe for VLA-4, which when used in conjunction with [18F]-FDG, may be a useful tool for understanding granuloma biology in TB.

Dynamics of Th9 cells and their potential role in immunopathogenesis of murine schistosomiasis

BackgroundTh1, Th2, Th17, Treg and Tfh cells play important roles in schistosomiasis. Th9 cells secrete IL-9 as a signature cytokine and contribute to several classes of inflammatory disease. However, the effects of Th9 cells in schistosomiasis are unknown. We aimed to explore the dynamic changes and potential roles of Th9 cells in the pathogenesis of hepatic egg granulomatous inflammation in mice infected with Schistosoma japonicum.MethodsTwenty mice with S. japonicum infection and five normal controls (NC) were used as models. The average areas of egg granulomas were estimated by hematoxylin-eosin (H & E) staining. Hepatic IL-9 and transcription factor PU.1 levels were detected by immunohistochemistry. Flow cytometry techniques were used to analyze the proportions of Th9 cells. With the help of ELISA, serum levels of IL-9 were examined.ResultsThe egg granulomas began to form from four weeks after infection and continued to develop. In parallel with the development of egg granulomas, the hepatic levels of IL-9 and PU.1 increased very slowly during the first four weeks post-infection and increased rapidly thereafter. Moreover, the proportions of splenic Th9 cells and levels of serum IL-9 had similar developmental trends with the egg granulomas.ConclusionThe proliferation of Th9 cells and levels of IL-9 were significantly higher in S. japonicum-infected mice compared to NC. In addition, dynamic changes of Th9 and IL-9 were synchronous with the developmental trend of hepatic egg granulomatous inflammation, suggesting that Th9 cells might be a new subset in the pathogenesis of schistosomiasis.

Pseudotumor bronchial lesion in sarcoidosis: A rare case

A case of recurrent sarcoidosis of intrathoracic lymth nodes and the lungs with development of tumor-like sarcoid granuloma narrowing the middle lobe bronchus and the right intermediate bronchus is reported in the article. The tumor-like sarcoid endobronchial mass was destructed using endoscopic Holmium YAG lazer. Combined treatment with endoscopic lazer ablation and systemic steroids resulted in successful reopening the bronchi.

A case of sarcoidosis with isolated hepatosplenic onset and development of inflammatory bowel disease during recovery stage

Sarcoidosis is a systemic disease characterized by an immune-mediated disorder, which leads to the development of non-caseating granulomas in the involved organs. More than 90% of patients with sarcoidosis present lungs and lymphatic system involvement at onset, while less than 10% has an isolated extrapulmonary localization. Here, we describe the case of an elderly patient with isolated hepato-splenic onset (multiple splenic lesions at imaging and cholestasis), and subsequent pulmonary involvement. The liver biopsy showed the presence of non-caseating granulomas, suggesting sarcoidosis. Despite the complete recovery was obtained with steroid therapy, after dosage reduction the patient presented watery diarrhea. Endoscopic investigations with biopsies were performed, describing the presence of an important lympho-plasmacytic infiltrate of terminal ileum mucosa with typical aspects of inflammatory bowel disease. The symptomatology completely disappeared after steroid dosage increase. This case confirms that sarcoidosis could present in a very atypical way, involving several organs in a different manner at the same time and that every symptom should not be underestimated, despite the rare presentation.

The presence of donor liver granuloma requiring further workup to rule out parasitic disease

A shortage of donor organs is a major limitation to liver transplantation. Expansion of donor pool criteria to include patients with schistosomiasis diagnosed on liver biopsy might allow the allocation of more transplant livers. Schistosomiasis is a chronic parasitic disease affecting millions in endemic areas including sub-Sahara Africa that might lead to the development of granulomas as a response to the parasite’s ova and might cause chronic liver disease and portal hypertension. Due to increased mobility globally, schistosomiasis may be encountered in non-endemic areas. Currently, the usage of donor livers with known Schistosomiasis is not universally defined.

Enhanced Wnt Signalling in Hepatocytes is Associated with Schistosoma japonicum Infection and Contributes to Liver Fibrosis

Liver fibrosis is the most serious pathology caused by Schistosoma japonicum infection, which arises when schistosome eggs are deposited in the liver. Eosinophils, macrophages and hepatic stellate cells (HSCs) have been identified as major cellular contributors to the development of granulomas and fibrosis, but little is known about the effects of hepatocytes on granuloma formation. Here, we found that the levels of Wnt signalling-related molecules, transforming growth factor β (TGF-β) and connective tissue growth factor (CTGF) in hepatocytes were markedly elevated after S. japonicum infection. Liver fibrosis was exacerbated when exogenous Wnt3a was introduced, but was alleviated when Wnt signalling was suppressed by DKK1, accompanied by the reduced expression of TGF-β and CTGF in hepatocytes. These results indicate that the hepatocytic expression of TGF-β and CTGF is mediated by Wnt signalling. Additionally, the hepatocytes isolated from infected mice promoted the activation of primary HSCs in vitro, however, this effect was not observed when hepatocytes from DKK1 treated S. japonicum-infected mice was employed in the co-culture system. Our findings identify a novel pro-fibrogenic role of hepatocytes in schistosomiasis-induced liver fibrosis that is dependent on Wnt signalling, which may serve as a potential target for ameliorating hepatic fibrosis caused by helminths.

Coeliac disease associated with sarcoidosis and antiphospholipid syndrome: A case report

BackgroundSarcoidosis is a clinically heterogenous disease of unknown etiology with a hallmark of the development and accumulation of non-caseating granulomas in any organ. The antiphospholipid syndrome (APS) is an autoimmune disorder characterized by an elevated risk for arterial and venous thrombosis and pregnancy-related morbidity. Celiac disease (CD) is a chronic, immune-mediated form of enteropathy that is now presenting later in life and often with extraintestinal manifestations. Co-existence of sarcoidosis, CD and APS is extremely rare. Case presentationWe describe a 27-year-old Tunisian woman with a history of non-explored superficial vein thrombosis and 4 successive miscarriages, who was explored for abdominal pain, vomiting, hypercalcemia, hepatic cytolyses and cholestasis and was complicated later with pancreatitis and anterior uveitis. Hepatic biopsy revealed noncaseating-granulomas, a high serum angiotensin converting enzyme activity was detected and the diagnosis of sarcoidosis was considered. A high titer of antiphopsholipid antibodies concluded the diagnosis of APS. Duodenal biopsies showed a total villous atrophy indicative of CD, confirmed by positivity of serum anti-endomisium and anti-transglutaminase antibodies. She had normocytic anemia (hemoglobin 9g/dl) and elevated transaminases. Thorough investigation established the diagnosis of extra pulmonary sarcoidosis associated with CD and APS. ConclusionCo-existence of sarcoidosis, CD and APS is extremely rare. APS should be recognized as an accompanying disorder of sarcoidosis and antiphospholipids measured especially when there is a history of thrombosis or miscarriages. CD should not be overlooked in association to sarcoidosis, given the shared immunological and genetic background, even in the absence of a typical presentation of the disease.

The contraceptive efficacy of intravas injection of Vasalgel\u2122 for adult male rhesus monkeys

BackgroundOptions for male contraception are limited. The purpose of this study was to use a nonhuman primate model to evaluate Vasalgel™, a high molecular weight polymer being developed as a contraceptive device for men.MethodsSixteen adult male rhesus monkeys received intravas injections of Vasalgel, consisting of 25% styrene maleic acid in dimethyl sulfoxide. After a one-week recovery, males were returned to outdoor group housing, which included at least 3 and up to 9 intact, breeding females with a successful reproductive history.ResultsTreated males have had no conceptions since Vasalgel injections. All males were housed with intact females for at least one breeding season and seven have been almost continually housed with females for 2 years. Complications were minor and included one incident of incorrect placement of Vasalgel into the vas deferens and the development of a sperm granuloma in one animal. Three unilateral vasectomies were performed, one was necessary for incorrect placement of Vasalgel, the other two were elective.ConclusionsIntravas injection of Vasalgel in sexually mature adult male rhesus monkeys was effective in preventing conception in a free-living, group environment. Complications were few and similar to those associated with traditional vasectomy.