Intestinal immunopathology is associated with decreased CD73-generated adenosine during lethal infection.

The ectonucleotidases CD39 and CD73 sequentially degrade the extracellular ATP pool and release immunosuppressive adenosine, thereby regulating inflammatory responses. This control is likely to be critical in the gastrointestinal tract where high levels of ATP are released in particular by commensal bacteria. The aim of this study was therefore to evaluate the involvement of the adenosinergic regulation in the intestine of mice in steady-state conditions and on acute infection with Toxoplasma gondii. We show that both conventional (Tconv) and regulatory (Treg) CD4(+) T lymphocytes express CD39 and CD73 in the intestine of naive mice. CD73 expression was downregulated during acute infection with T. gondii, leading to impaired capacity to produce adenosine. Interestingly, the expression of adenosine receptors was maintained and treatment with receptor agonists limited immunopathology and dysbiosis, suggesting that the activation of adenosine receptors may constitute an efficient approach to control intestinal inflammation associated with decreased ectonucleotidase expression.

Back to the reinnervation of the pancreas after transplantation? (Experimental study on dogs, cats, and rats).

BACKGROUND: Significant functional decrease and sclerosis of the pancreas graft in late delays cannot only be related to chronic rejection. Any transplantation leads to graft denervation, which may be an important cause of dysfunction. Studies concerning graft reinnervation were controversial. PURPOSE OF THE STUDY: The purpose of this study was to investigate the feasibility and pertinence of a surgically directed reinnervation (SDR) of denervated/neuro-reflex isolated (NRI) or autotransplanted (aTx) pancreas. BASIC PROCEDURES: Anatomy of the nerves penetrating into the pancreas was studied in humans, dogs, cats, and rats. Surgery and physiological investigations were performed in dogs, cats, and rats. Nervous conductivity between NRI, NRI+SDR pancreas, and brain was tested. Load tests with glucose, insulin, and adrenalin were performed; amylase and lipase were determined in fasted and not fasted animals to evaluate the influence of NRI and SDR on pancreatic function. Histology was provided. Observation delays were 6 months. MAIN FINDINGS: Anatomic feasibility of SDR in humans and animals was proved. Models of pancreatic tail NRI and surgical reconstitution of the interrupted nervous pathways (SDR) were elaborated in animals. The restoration of the pancreas-brain reflex axis after SDR was electro physiologically proved. As blood glucose curves after load test, exocrine amylase and lipase determination have shown that pancreas NRI or aTx leads to an exaggerated reaction to usual stimulations that may cause the observed graft functional exhaustion in late delays. SDR shortened the period of the graft neuro-reflex isolation, contributed to a quick normalization of its function, and prevented its late degradation. CONCLUSION: SDR was shown to be a simple surgical technique, easily performed after the graft surgical revascularization. Its functional and morphological efficiency was tested and proved. Thus, SDR may be recommended in human pancreas transplantation as pertinent.

Intriguing location of myeloperoxidase in the prostate: a preliminary immunohistochemical study.

BACKGROUND: Myeloperoxidase (MPO) is a member of the peroxidase-cyclooxygenase superfamily, which is secreted from stimulated leucocytes at inflammatory sites. It is well known that MPO catalyses oxidation reactions via the release of reactive halogenating and nitrating species and thus induces tissue damage. Several studies have already implicated MPO in the development of neoplasia. Chronic or recurrent prostatic inflammation has long been recognized as having the potential to initiate and promote the development of prostate cancer. The objective was to investigate whether MPO is present in the prostate. METHODS: Human prostate material was obtained from biopsies, transurethral resections of the prostate (TURP), prostatic adenomectomies, and retropubic radical prostatectomies. Twenty-nine slides of normal prostate tissue, benign prostatic hyperplasia (BPH), and prostate cancer were reviewed by a pathologist. Immunohistochemical analysis using MPO-specific human antibody was performed to detect MPO in the prostate tissue. RESULTS: Immunocytohistochemistry showed cellular colocalization of MPO in the secretory epithelial cells of the prostate with staining varying from light to strong intensity. Staining in the glandular apical snouts was often reinforced although staining of basal as well as of luminal glandular cells was also present. CONCLUSIONS: We identified, for the first time, the presence of MPO at the surface of prostatic epithelial cells. In view of the pro-oxidant properties of this enzyme, further research is needed to define whether MPO contributes to the development of prostatic lesions.

[Malignant solitary fibrous tumor of the abdominal wall in a man]. / Tumeur fibreuse solitaire maligne de la paroi abdominale chez un homme.

We report the first case of malignant solitary fibrous tumor of the abdominal wall in a man. Immunohistochemical staining for CD34 and bcl-2 were positive. Surprisingly, estrogen and progesterone receptors were focally positive. Expression of steroid hormone receptor in solitary fibrous tumor was rarely reported in the literature. In a few series, these receptors were identified as a risk factor of recurrences after surgical excision. Six months after complete surgical resection of the mass, our patient has been quite well without any evidence of recurrence.

Ovarian cancer associated with carcinomatous meningitis: a case report and review of the literature.

We report the case of a 62-year-old patient who developed a carcinomatous meningitis while on second-line chemotherapy for ovarian cancer. Cytologic analyses confirmed that carcinomatous cells of ovarian origin were present in cerebrospinal fluid. Carcinomatous meningitis is a very rare event in the natural history of ovarian carcinoma. We discuss the specificity of our case in the light of the literature. In addition, we present some relevant radiologic and pathologic documents illustrating this rare entity.

[Malignant peripheral nerve sheath tumor in the posterior mediastinum]. / Tumeur maligne de la gaine d'un nerf périphérique: une lésion rare du médiastin postérieur.

We report the case of a 52-year-old male patient who developed a malignant peripheral nerve sheath tumor (MPNST) localized in the posterior mediastinum. The diagnosis of this rare tumor is difficult because the clinical presentation of the benign or malignant types is often similar, i.e. elective pain and bone erosions. Similarly, radiological procedures do not always allow distinction between the two types. MNR and CT-scan are the first line procedures: they localize and characterize the lesions, and CT-scan can also be a guide for biopsies. Histological diagnosis is required, but diagnosis can be compromised by the heterogeneous nature of the tumor. Surgical treatment should be undertaken whenever possible. Survival was unusually long in our patient, more than 5 years after discovery of the MPNST. This type of sarcoma is often very aggressive with frequent development of local recurrences and metastases.

Antigens and granularity of blood monocytes in relation to inflammatory markers and lipids in postmenopausal women.

OBJECTIVES: The menopause is associated with an increase of inflammatory markers (C-reactive protein, fibrinogen), cytokines (INFgamma, TNF, etc.) and blood lipoproteins. In vitro, CRP, LDL and fibrinogen can modulate or potentiate interleukines production by monocytes. The aim of this work was to study, the relationships in vivo between hs-CRP, fibrinogen, lipoproteins and the phenotype of circulating monocytes. METHODS: The monocytes phenotype, in postmenopausal women (n=26) without history of cardiovascular disease, was determined, by flow cytometry, measuring granularity and CD14, HLA-DR and CD62-L antigens expression. Blood monocytes were divided in CD14+dim monocytes (low CD14 expression) and CD14+bright monocytes (high CD14 expression). RESULTS: HLA-DR was negatively correlated with hs-CRP and fibrinogen. The relationships between ApoB, LDL/ApoB ratio and CD14 expression was restricted to the CD14+bright monocytes. Blood lipids, i.e. total cholesterol, LDL-c and ApoB were correlated with the granularity of both subsets. CD14+dim monocytes were characterized by a low granularity and CD62-L expression. CONCLUSIONS: Our data show that fibrinogen and hs-CRP are correlated with a reduced antigen-presenting capacity. Expression of CD14 on CD14+bright monocytes is negatively associated to atherogenic LDL. Blood monocytes granularity was positively correlated with serum lipids indicating that monocytes could uptake modified LDL in circulation and not restricted to subendothelial space.

[Experimental comparative evaluation of the functional capacities of ectopically grown fetal organs].

The interest for fetal organ, tissue, and cell implantation as therapeutic means in the treatment of some diseases is presently increasing. Hence, the aim of the present investigation was the comparative evaluation of the functional potential of ectopically grown fetal organs of different (ecto-, meso- and endodermic) origins. Unified operative model was the fetal organ fragment implantation into an ear subcutaneous pouch (without restoration of vascular and nervous links of the implant with the recipient organism). The implant isolation in vitro varied from 15 to 50 min. As control, intact animals and animals with streptozotocin diabetes and hepatic lesions due to the main bile duct ligature, were used. The implanted and ectopically grown fetal organs, though of different origins, developed functional activity. The best adult-like function was obtained in intestinal, gastric and cardiac implants, i.e. in organs with a cavity and a well developed self-regulation system. Poorer results were obtained in great digestive glandular implants--pancreas and liver. In the best cases when the implant function was very closed to the adult organ, a difference nevertheless was observed. The model of ectopic implantation of fetal organs may be useful for study of the organ and tissue function ontogenesis (up to the moment of natural ageing involution), for the evaluation of different isolated factor influence on organ and tissue physiology and pathology. Although being optimistic in respect to clinical application of fetal organ and cell implantation, this study does not prevent us from being cautions.

Oxidation of low density lipoproteins by myeloperoxidase at the surface of endothelial cells: an additional mechanism to subendothelium oxidation.

The present paradigm of atherogenesis proposes that low density lipoproteins (LDL) are trapped in subendothelial space of the vascular wall where they are oxidized. Myeloperoxidase (MPO) plays a key role in oxidative damage. We propose that LDL oxidation by myeloperoxidase (Mox-LDL) could occur at the surface of the endothelial cells and not restricted to the subendothelial space. The triad constituted by endothelial cells, circulating LDL and MPO in close interaction, constitutes a synergic mechanism for the genesis of Mox-LDL.

Monoclonal antibodies against LDL progressively oxidized by myeloperoxidase react with ApoB-100 protein moiety and human atherosclerotic lesions.

Oxidized-LDL are involved in atherosclerosis pathogenesis, while the production of anti-ox-LDL monoclonal antibodies is critical for the development of diagnostic tools. This work reports the production of four monoclonal antibodies raised against human LDL, oxidized at different levels by the myeloperoxidase system. Characterization of these monoclonal antibodies showed that they do not cross-react with neither native LDL, VLDL nor hydrogen peroxide or Cu(2+)-oxidized LDL. Three of these antibodies recognize an epitope restricted to the protein moiety of mildly oxidized LDL, whereas the fourth antibody was partly dependent on the lipid presence of strongly oxidized LDL. All the antibodies were shown to react with human atherosclerotic lesions.

[Multiple cholesterol emboli syndrome: beneficial effects of early heparin therapy. A case report]. / Le syndrome d'embolies multiples de cholestérol: effet bénéfique de l'héparinothérapie précoce? A propos d'un cas.

The multiple cholesterol emboli syndrome (MCES) is a rare, multi-organ disease than can occur spontaneously or after arterial or cardiac catheterization, arteriography, angioplasty, cardiovascular surgery, oral or intravenous anticoagulation, systemic fibrinolysis and cardiorespiratory resuscitation, predominantly in male subjects with disseminated atherosclerosis over the age of 60 years. Clinical signs of MCES vary considerably depending on the organs involved, but the signs most frequently encountered are renal failure, skin lesions (livedo reticularis, purple toc, ulcers, etc) and transient eosinophilia. Optimal treatment of this syndrome is controversial and is often symptomatic. However, the most effective measure remains prevention based on identification of high-risk patients, treatment with platelet antiaggregants and careful handling of catheters. This syndrome has a serious prognosis in the majority of cases. In this article, the authors describe a case of MCES. After thoracic aortography, this 73-years-old patient presented typical clinical sign of MCES (angina, cerebrovascular accident, bilateral blindness, transient renal failure and splenic infarction). The clinical course was favourable in response to heparin therapy and splenectomy and caudal pancreatectomy. Histology confirmed the presence of cholesterol emboli in the lumen of splenic arterioles. Except in the case of severe bleeding diathesis, the authors recommend early heparin therapy for MCES caused by catheterization, angioplasty or cardiovascular surgery. However, complementary studies must be performed to more clearly define the effects of heparin on MCES.

Sciatic nerve regeneration through venous or nervous grafts in the rat.

This study analyses the interest of isologous venous grafts filled with saline or with Schwann cells versus nerve grafts as guides for regeneration of the sciatic nerve in 35 Wistar rats. Electrophysiological parameters (conduction velocities and distal latencies of motor responses) and the functional index of De Medinacelli were measured several times from 1 month to 1 year after surgery. An histological analysis was performed on 2 control rats and on 3 rats killed 6 or 12 months after surgery: the total number of fibers was counted on a montage photoprint of the whole nerve, and the diameters of axons and the thickness of the myelin sheath were measured on digitized images. With a portion of nerve as guide, the regeneration is faster than with a vein. However, regeneration after 6 months is at least as good with a venous graft filled with Schwann cells, as assessed by electrophysiological, functional, and histological analysis. The addition of Schwann cells in grafted veins allows the nerve to regenerate through longer gaps than previously described (25 vs 15 mm). In order to assess the quality of nerve regeneration, functional, electrophysiological, and histological analysis are complementary.

Effects of Schwann cell transplantation in a contusion model of rat spinal cord injury.

Cultured Schwann cells were transplanted at various delays into a spinal cord contusion injury performed at low thoracic level in adult female rats. The Schwann cells were purified from the dorsal root ganglia of adult syngeneic animals. the transplants were well tolerated, and the transplanted Schwann cells invaded the injured spinal cord. As quantified using video image analysis, the survival and growth of the transplanted cells were poor when the grafting procedure was performed 3-4 days after injury and very good when performed immediately or 10 days after injury, in which cases post-traumatic micro- and macrocavitation were strongly reduced. In animals grafted immediately after injury but not in animals grafted after 10 days, post-traumatic astrogliosis was much reduced. The Schwann cells transplanted area was invaded by numerous regenerating axons, the vast majority of which were, based on the neurotransmitter (CGRP and SP) profile, originating from dorsal root ganglion. No regeneration of the corticospinal tract as assessed after anterograde tracing or of descending aminergic fibers could be demonstrated.

Preparation of a macroporous biodegradable polylactide implant for neuronal transplantation.

This article reports the production of a surgical implant meeting several specific requirements such as biocompatibility, biodegradability, macroporosity, and flexibility. Porosity was controlled by an original method consisting of the aggregation of calibrated poly-D,L-lactide microparticles. The size of the interstices between the aggregated microspheres was in a direct relationship to the microsphere diameter. A first approach was based on coating the microspheres with poly(vinyl alcohol) followed by chemically crosslinking the coating layers that were in mutual contact. This method was disregarded because of the acute cytotoxicity of glutaraldehyde used as the crosslinking agent, the absence of macroporosity, and the complete lack of flexibility. A physical technique of aggregation was then tested, which relied on the plasticization of poly-D,L-lactide microspheres with triethylcitrate to the point where microspheres strongly adhered to each other when they were in contact. This method has proved to be straightforward and definitely superior to the chemical approach, particularly with respect to cytotoxicity, control of macroporosity, and flexibility. A polymer support was thus successfully which was biodegradable, macroporous( interconnected pores of 10-100 microns in diameter), and flexible. This potential medical device is presently being used for neuronal transplantation in the central nervous system.

Image analysis of neuritic regeneration by adult rat dorsal root ganglion neurons in culture: quantification of the neurotoxicity of anticancer agents and of its prevention by nerve growth factor or basic fibroblast growth factor but not brain-derived neurotrophic factor or neurotrophin-3.

Peripheral neuropathies are a common side effect of chemotherapeutic agents, particularly antineoplastic drugs such as taxol, cisplatin, or vinca-alkaloids (vincristine, vinblastine, vindesine). Using dissociated cultures of adult rat dorsal root ganglion (DRG) neurons and video image analysis after neurofilament immunostaining, we have designed a system that allows: (i) rapid screening of potential neurotoxic agents, with the establishment of dose-response curves and the calculation of IC50; (ii) quantification of neurotrophic effects; and (iii) demonstration of neuroprotection by trophic factors. In particular, we show that nerve growth factor (NGF) and basic fibroblast growth factor (bFGF) stimulate in vitro neuritic regeneration by adult rat DRG neurons, while brain-derived neurotrophic factor and neurotrophin-3 lack such effects. Furthermore, 24 h of pretreatment by NGF or bFGF drastically decreases the neurotoxic effect of vincristine and cisplatin.

Plasticity of developing and adult dorsal root ganglion neurons as revealed in vitro.

We review recent data on the plasticity of dorsal root ganglion (DRG) neurons as revealed during cultivation in vitro. Some experiments on cultured developing DRG neurons and on adult DRG neurons in vivo are also mentioned. Cultured developing and adult DRG neurons can be switched from an apolar to a multipolar phenotype by fetal calf serum or fibronectin. The effect is concentration dependent and occurs through an early modification of cell-substratum interaction. Adult DRG neurons synthesize and release within hours after injury TGF beta-1, which is a mitogen and a differentiation factor for Schwann cells. Finally, adult DRG neurons express in vitro neurotransmitters that are not expressed in vivo. This neurotransmitter plasticity can be modulated in vitro by some growth factors and in vivo by distal or proximal axotomy.

Syngeneic grafting of adult rat DRG-derived Schwann cells to the injured spinal cord.

A subdural inflatable micro-balloon was used to induce closed traumatic contusion to adult rat spinal cord. This spinal cord injury model was associated with reproducible and graded neurological deficits and histopathological alterations. At various delays after injury, transplantations of syngeneic adult cultured dorsal root ganglion-derived Schwann cells were performed into the spinal cord lesion. The transplants were well integrated and reduced the microcystic posttraumatic cavitation as well as the gliosis. Schwann cells transplants were invaded by numerous regenerating neurites most of which, based upon their neurotransmitter contents, seem to originate from the dorsal root ganglion.