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Biomedical subjects

M Baudrimont

Publications and source records attributed to M Baudrimont.

At least 19 recordsLinked to original sources

Evidence of an altered protective effect of metallothioneins after cadmium exposure in the digenean parasite-infected cockle (Cerastoderma edule).

The aim of the present study was to analyse the relation between parasitism and subsequent metallothioneins (MT) in the case of metal contamination. Experimental exposure of parasitized and unparasitized cockles (Cerastoderma edule) to cadmium (Cd) was performed, with the cockle as first or second intermediate host of 2 digenean species. After 7 days of Cd exposure in microcosms, cockles infected as first intermediate host by Labratrema minimus exhibited metal concentrations in tissues double that in uninfected cockles. Jointly, MT concentrations of parasitized cockles were not modified in comparison with uninfected individuals in which concentrations were increased 4.3-fold compared with controls. In cockles experimentally infected as the second intermediate host by Himasthla elongata, cadmium concentrations significantly increased again in parasitized cockles compared with uninfected individuals in contaminated conditions. Simultaneously, MT concentrations in healthy cockles increased, whereas they significantly decreased in parasitized individuals. Therefore, the presence of digenean parasites in Cd-exposed cockles leads to a maintenance or a decrease in MT concentrations compared with healthy individuals, whereas Cd accumulation in tissues is significantly increased. These experiments indicate a significant alteration of the protective effect of metallothioneins towards metals which could consequently enhance cockle vulnerability. Moreover, these results highlight the limit of the use of MT as a biomarker of metal pollution in field monitoring if parasitism is not taken into account.

Animals↗

Challenging the model for induction of metallothionein gene expression.

Metallothioneins (MTs) are low-molecular-weight, cysteine-rich metal-binding proteins found in a wide variety of organisms including bacteria, fungi and all eukaryotic plant and animal species. MTs bind essential and non-essential heavy metals. In mammalian cells MT genes are highly inducible by many heavy metals including Zn, Cd, Hg, and Cu. Aquatic systems are contaminated by different pollutants, including metals, as a result of man's activities. Bivalve molluscs are known to accumulate high concentrations of heavy metals in their tissue and are widely used as bioindicators for pollution in marine and freshwater environments, with MTs frequently used as a valuable marker of metal contamination. We here describe the MT isoform gene expression patterns of marine and freshwater molluscs and fish species after Cd or Zn contamination. Contamination was carried out at a river site polluted by a zinc ore extraction plant or in the laboratory at low, environmentally relevant metal concentrations. A comparison for each species based on the accumulated MT protein levels often shows discrepancies between gene expression and protein level. In addition, several differences observed in the pattern of MT gene expression between mollusc and mammalian species enable us to discuss and challenge a model for the induction of MT gene expression.

Animals↗

Genotoxic and stress inductive potential of cadmium in Xenopus laevis larvae.

The present investigation evaluates the toxic potential of Cd in larvae of the frog Xenopus laevis after 12 days of exposure to environmentally relevant contamination levels, close to those measured in the river Lot (France). Several genotoxic and detoxification mechanisms were analyzed in the larvae: clastogenic and/or aneugenic effects in the circulating blood by micronucleus (MN) induction, metallothionein (MT) production in whole larvae, gene analyses and Cd content in the liver and also in the whole larvae. The results show: (i) micronucleus induction at environmental levels of Cd contamination (2, 10, 30 microgL(-1)); (ii) an increased and concentration-dependent quantity of MT in the whole organism after contamination with 10 and 30 microgCdL(-1) (a three- and six-fold increase, respectively) although no significant difference was observed after contamination with 2 microgCdL(-1); (iii) Cd uptake by the whole organism and by the liver as a response to Cd exposure conditions; (4) up-regulation of the genes involved in detoxification processes and response to oxidative stress, while genes involved in DNA repair and apoptosis were repressed. The results confirm the relevance of the amphibian model and highlight the complementarity between a marker of genotoxicity, MT production, bioaccumulation and genetic analysis in the evaluation of the ecotoxicological impact.

Animals↗

Temporal artery biopsy for diagnosing giant cell arteritis: the longer, the better?

OBJECTIVE: To investigate the relation between temporal artery biopsy (TAB) length and diagnostic sensitivity for giant cell arteritis. METHODS: Histological TAB reports generated from four hospital pathology departments were reviewed for demographics, histological findings, and formalin fixed TAB lengths. A biopsy was considered positive for giant cell arteritis if there was a mononuclear cell infiltrate predominating at the media-intima junction or in the media. RESULTS: Among 1821 TAB reports reviewed, 287 (15.8%) were excluded because of missing data, sampling errors, or age < 50 years. Mean TAB length of the 1520 datasets finally analysed (67.2% women; mean (SD) age, 73.1 (10.0) years) was 1.33 (0.73) cm. Histological evidence of giant cell arteritis was found in 223 specimens (14.7%), among which 164 (73.5%) contained giant cells. Statistical analyses, including piecewise logistic regression, identified 0.5 cm as the TAB length change point for diagnostic sensitivity. Compared with TAB length of < 0.5 cm, the respective odds ratios for positive TAB without and with multinucleated giant cells in samples > or = 0.5 cm long were 5.7 (95% confidence interval, 1.4 to 23.6) and 4.0 (0.97 to 16.5). CONCLUSIONS: A fixed TAB length of at least 0.5 cm could be sufficient to make a histological diagnosis of giant cell arteritis.

Aged↗

Geochemical survey and metal bioaccumulation of three bivalve species (Crassostrea gigas, Cerastoderma edule and Ruditapes philippinarum) in the Nord Medoc salt marshes (Gironde estuary, France).

A 15-month experiment combining a geochemical survey of Cd, Cu, Zn and Hg with a bioaccumulation study for three filter-feeding bivalve species (oysters, Crassostrea gigas; cockles, Cerastoderma edule; and clams, Ruditapes philippinarum) was conducted in a breeding basin of the Nord Medoc salt marshes connected to the Gironde estuary, which is affected by historic polymetallic pollution. Regular manual surface measurements of temperature, salinity, pH and dissolved O(2) concentration and hourly multiprobe in situ measurements throughout several periods for 6-8 weeks were performed. The geochemical behavior of metals in water, suspended particulate matter and sediment and their ecotoxicological impact on the three bivalve species were evaluated by in situ exposure of juvenile oysters (water column) and adult cockles and clams (sediment surface). The physico-chemical parameters reflected seasonal variations and basin management. A distinct daily periodicity (except salinity) indicated intense photosynthesis and respiration. In summer, low dissolved O(2) saturations ( approximately 40-50%) occurred in the early morning at 30 cm above the sediment, whereas in depressions, the water column near the sediment surface was suboxic. Cadmium, Zn and Cu concentrations in suspended particulate matter exceeded typical estuarine values and were much higher than the homogeneously distributed concentrations in different depth ranges of the basin sediment. Particles collected in sediment traps showed intermediate metal concentrations close to sediment values. These results suggest trace metal recycling due to reductive dissolution under suboxic conditions at the sediment surface resulting in trace metal release to the water column and adsorption onto suspended particles. Dissolved Cd, Zn and Hg concentrations (e.g. 13-136 ng l(-1); 0.3-25.1 microg l(-1) and 0.5-2.0 ng l(-1), respectively) in the basin corresponded to the concentration range typically observed in the Gironde estuary, except for some maximum values attributed to metal recycling. In contrast, dissolved Cu concentrations (1.08-6.08 microg l(-1)) were mostly higher than typical estuarine values, probably due to recycled Cu complexation by dissolved organic matter. Growth, bioaccumulation rates and kinetics in the whole soft body of the bivalves were analyzed every 40 days. Although Cd bioaccumulation of oysters was lower in the basin than in the estuary during the same period (27,000 ng g(-1), dry weight and 40,000 ng g(-1), respectively) these values are largely above the new human consumption safety level (5000 ng g(-1), dw; European Community, 2002). For cockles and clams, Cd bioaccumulation was lower, reaching 1400 ng g(-1) and 950 ng g(-1), respectively. Similar results were obtained for Zn and Cu suggesting physiological differences between the species and/or differences in the exposure of the organisms due to physico-chemical conditions and metal distribution between dissolved and particulate phases. In contrast, Hg bioaccumulation was highest for cockles reaching bioconcentration factors of approximately 200,000, which even exceeded that of Cd in oysters (50,000) for the same exposition period. Nevertheless, Hg concentrations remained relatively low in the three bivalve species.

Animals↗

Induction of a multixenobiotic resistance protein (MXR) in the Asiatic clam Corbicula fluminea after heavy metals exposure.

Multixenobiotic resistance mechanisms (MXR) related to the mammalian P-glycoprotein multidrug transporter protein (P-gp) are known to occur in several marine invertebrates. In the present work, we report on the induction of an MXR protein by various heavy metals in the gills of the freshwater clam Corbicula fluminea. The evaluation of the MXR protein level was assessed by Western blot using a specific monoclonal antibody raised against the human P-gp (C219). A field transplantation experiment, where clams were caged in a gradient relative to an industrial site, demonstrated a positive relationship between MXR levels and (a) metal pollution (Cd and Zn) in the environment and (b) metal bioaccumulation in the gills. To establish this correlative relationship, clams were exposed to different levels of cadmium (15-60 microg l(-1)) for up to 15 days in a controlled laboratory experiment. MXR protein levels increased in time for all treatments (including the control). However, the highest levels of MXR protein titer were expressed in clams that had been exposed to the lowest dose of cadmium. The causes for this observed inverse relationship between the exposure dose and the MXR induction is discussed. MXR protein titer was also shown to be induced by other heavy metals (zinc, inorganic mercury, and copper).

ATP Binding Cassette Transporter, Subfamily B↗

[Febrile pseudotumor lesion of the arm. Atypical presentation of Shulman syndrome]].

INTRODUCTION: The diagnostic approach when confronted with a pseudo-tumoral lesion and fever is difficult since it evokes an infectious, rheumatismal inflammatory or even systemic disease. OBSERVATION: A 39 year-old Vietnamese man was hospitalised for polyarthralgia if the arm and fever (39 degrees C). He was treated with non-steroidal anti-inflammatories, which were only partially effective. Biological examinations revealed a severe inflammatory syndrome and cytolysis three-fold higher than normal. Since the infectious, rheumatismal and immunological explorations were negative and in view of the appearance of a pseudo-tumoral inflammatory lesion of the left arm concomitant to infiltration of the underlying muscle revealed on MRI, a muscle biopsy was performed showing eosinophilic fasciitis. Diagnosis of Shulman's syndrome was made and the affection rapidly improved with corticosteroids. COMMENTS: The presentation of our patient was atypical for several reasons: his Vietnamese origin, the initial fever peak at 39 degrees C, the unilateral involvement, the severe inflammatory syndrome, the initial absence of hypereosinophilia, the visceral involvement and notably myositis are all uncommon in Shulman's syndrome. Hence, it is important to rule out its differential diagnosis from local edematous scleroderma, which does not share the same prognosis.

Adult↗

Survival and differentiation of porcine hepatocytes encapsulated by semiautomatic device and allotransplanted in large number without immunosuppression.

BACKGROUND/AIMS: The aim of this study was to evaluate the survival and functions of porcine hepatocytes transplanted in large quantities in the peritoneal cavity of allogeneic animals following semiautomatic encapsulation. METHODS: Isolated porcine hepatocytes and a polymer solution composed of AN69 were coextruded through a double lumen spinneret. Minitubes containing hepatocytes were transplanted in the peritoneal cavity of 12 pigs (4 x 10(9) cells/animal) in the absence of immunosuppressive therapy. Seven, 15, and 21 days after transplantation, minitubes was collected and processed for analyses. The morphology was examined under light and electron microscopy. Albumin synthesis was assessed by semi-quantitative reverse transcription-polymerase chain reaction. Cytochrome P450 3A (CYP3A) gene expression was analyzed by Western blot and by testosterone 6-beta-hydroxylation assay. RESULTS: The device allowed to encapsulate 55 x 10(6) hepatocytes/min. Hepatocytes exhibited normal structural and ultrastructural features up to day 21. Albumin gene expression decreased progressively between days 0 and 21. The amount of CYP3A protein and 6-beta-hydroxylase activity were approximately 2-fold lower at days 7 and 15 than in freshly encapsulated hepatocytes, and further decreased thereafter. CONCLUSIONS: The preservation of hepatocyte functions during 1-2 weeks is encouraging for potential short-term use of such bioartificial liver in future clinical application.

Albumins↗

Neutrophilic myositis as an extracutaneous manifestation of neutrophilic dermatosis.

Neutrophilic dermatoses are characterized histologically by a sterile infiltration of neutrophils throughout the dermis. The condition may affect various internal organs, notably the lungs, the digestive tract, and the joints, whereas muscle impairment is considered to be extremely rare. We describe the case of a patient with pyoderma gangrenosum in whom severe sterile neutrophilic myositis developed as the first manifestation of an acute myelogenous leukemia.

Aged↗

Survival and functions of encapsulated porcine hepatocytes after allotransplantation or xenotransplantation without immunosuppression.

BACKGROUND: This study evaluated the survival and functions of encapsulated porcine hepatocytes after intraperitoneal allotransplantation and xenotransplantation without immunosuppression. METHODS: Isolated porcine hepatocytes were encapsulated in AN 69 polymer capsules (45.10(6)/capsule) and transplanted intraperitoneally in 12 rats and 12 pigs. Fifteen, 30, and 60 days after transplantation, capsules were removed and the viability and morphology of explanted hepatocytes were examined under light and electronic microscopy. The potential to produce albumin was assessed by evaluating the level of albumin messenger RNA, using semiquantitative reverse transcription-polymerase chain reaction. 6beta-Hydroxylase activity was measured by high-performance liquid chromatography. In addition, cytochrome P450 3A proteins were detected by Western blot only in allogeneic hepatocytes. RESULTS: Similar results were observed after allotransplantation and xenotransplantation. Histologic studies showed that hepatocytes were well-preserved and arranged in cords for up to 30 days. The expression of porcine albumin gene was maintained up to 15 days. 6beta-Hydroxylase activity was 2.5-fold lower at day 15 than in freshly encapsulated hepatocytes, which were not transplanted. In allogeneic hepatocytes, the expression of CYP 3A protein was detected up to 60 days after transplantation. CONCLUSIONS: Encapsulated porcine hepatocytes remain viable and functional for at least 15 days after allotransplantation and xenotransplantation without immunosuppression. The demonstration of maintained hepatic functions in transplanted porcine hepatocytes up to 15 days is a first step toward application in the treatment of acute liver failure.

Albumins↗

[Atypical CADASIL phenotypes and pathological findings in two new French families].

Atypical phenotypes of CADASIL and corresponding anatomical data in two cases are described in 6 members of 2 new French families. In the first family, 4 cases in the same kindred were probably affected, two of them with a predominant psychiatric presentation, two others with dementia and a pseudo-bulbar syndrome of progressive evolution. No history of migraine or ischemic event were documented in any. In the propositus, the diagnosis was documented by skin biopsy, Notch 3 gene mutation and autopsy after the patient had died when 67 years old, 8 years after onset. Brain examination showed a widespread leukoencephalopathy with subcortical infarcts. Characteristic granular lesions of the small arteries of the brain and other organs were observed. In the second family, two cases are reported. One patient died when 63 years old after a subacute evolution mimicking intracranial hypertension. The anatomical diagnosis was retrospectively proven typical of CADASIL with Notch 3 immunostaining of arterial smooth muscle cells. The other case had a progressive evolution over 20 years of limb paresthesia with a mild spasticity diagnosed as a progressive form of multiple sclerosis. It was followed by a pseudo-bulbar syndrome and a mild subcortical dementia without acute ischemic attack. The diagnosis was confirmed by skin biopsy and mutation of the Notch 3 gene. This report illustrates

Aged↗

Semiautomatic macroencapsulation of fresh or cryopreserved porcine hepatocytes maintain their ability for treatment of acute liver failure.

We have previously demonstrated that fresh or cryopreserved xenogeneic hepatocytes manually macroencapsulated in AN69 polymer and transplanted intraperitoneally in rats were able to improve the survival rate after 95% hepatectomy without immunosuppression. In addition, we developed a semiautomatic device where porcine hepatocytes were coextruded with AN69 hydrogel in order to macroencapsulate large amounts of cells. The purpose of the present study was to 1) test whether transplanted porcine hepatocytes macroencapsulated in this device remained functional as evaluated by their ability to prevent death from acute liver failure, and 2) compare the efficiency of cryopreserved or freshly isolated hepatocytes. Fresh or cryopreserved porcine hepatocytes were macroencapsulated in the semiautomatic device by coextrusion in AN69 polymer in 2-m minitubes containing 6 x 10(7) cells. Acute liver failure was induced in rats by two-step 95% hepatectomy. At the time of completion of liver resection, rats were either not transplanted with minitubes (control group I, n = 13), or were implanted with two minitubes containing culture medium (control group II, n = 11), hepatocytes killed by heat treatment (control group III, n = 10), coextruded fresh hepatocytes (group IV, n = 11), or coextruded cryopreserved hepatocytes (group V, n = 11), without immunosuppression. The survival rate at day 7 was between 0% and 31% in the three control groups. By contrast, coextruded fresh hepatocytes significantly improved the survival rate (group IV, 82%) as did cryopreserved cells (group V, 91% survival). In surviving rats, minitubes were explanted after 20 days; either fresh or cryopreserved hepatocytes appeared morphologically viable and their ultrastructure was preserved. Their detoxification capacities evaluated by the activity of the cyt P450 CYP3A4 were partly maintained. In conclusion, porcine hepatocytes macroencapsulated by coextrusion using a semiautomatic device and transplanted without immunosuppression were able to prevent death from acute liver failure in rats. Cryopreserved cells were as efficient as fresh hepatocytes.

Animals↗

Transplanted cryopreserved encapsulated porcine hepatocytes are as effective as fresh hepatocytes in preventing death from acute liver failure in rats.

BACKGROUND: An implantable bioartificial liver (BAL) using xenogeneic isolated hepatocytes may be an alternative method to orthotopic liver transplantation for treatment of acute liver failure. The purpose of this study was to demonstrate that not only fresh but also cryopreserved porcine hepatocytes could be used in a BAL to prevent death after the onset of acute liver failure in rats. METHODS: Acute liver failure was induced by two-stage 95% hepatectomy. At the time of completion of liver resection, 100 rats were assigned to undergo or not undergo transplantation into the peritoneum of 4 meters of hollow fibers filled with 60 million either fresh or cryopreserved porcine hepatocytes, or syngeneic hepatocytes, or culture medium, or of 60 million nonencapsulated cryopreserved porcine hepatocytes without immunosuppressive therapy. Survival rates at 7 days were compared between the different groups. RESULTS: In the control groups of hepatectomized animals not receiving encapsulated hepatocytes, 69-79% of the rats died from acute liver failure. The mortality rate was reduced to 15% (2 of 13) in rats receiving fresh porcine hepatocytes (P<0.01), 25% (4 of 16) in rats transplanted with either cryopreserved or syngeneic hepatocytes (P<0.05). Survival rates were maintained when hollow fibers were explanted > or =4 days after hepatectomy. In surviving rats, the weight of the remnant native liver increased with time and returned to the initial weight after 1 month. CONCLUSIONS: The implantable BAL using xenogeneic porcine hepatocytes was able in preventing death from acute liver failure without immunosuppressive therapy. Encapsulated cryopreserved hepatocytes were as effective as fresh hepatocytes.

Animals↗

A reversible model of acute hepatic failure by temporary hepatic ischemia in the pig.

BACKGROUND: To evaluate new therapies for human fulminant hepatic failure, a suitable large animal model is needed. The purpose of this study was to develop a reversible surgical model of acute hepatic liver failure by transient ischemia in pigs. MATERIALS AND METHODS: Under general anesthesia, an end-to-side portacaval shunt was performed in 17 pigs and tape was laid around the hepatoduodenal ligament. Two days after construction of the functional portacaval shunt, 13 ambulant pigs underwent transient total liver ischemia by tightening of the tape around the hepatoduodenal ligament for 5.5 h. During ischemia, 10% glucose was continuously infused intravenously to prevent hypoglycemia. RESULTS: Ten animals (77%) died with hepatic coma after a mean duration of 22.5 +/- 1.9 h. The 3 remaining animals survived more than 5 days and were sacrificed. In dying animals, encephalopathy was observed 14 +/- 1.7 h after the onset of ischemia. During ischemia, similar progressive decrease of fibrinogen, platelets, prothrombin time, and factors V and VII activities was observed in dying and surviving animals. Just before death, mean prothrombin and factors V and VII activities were respectively 22 +/- 2, 21 +/- 4.4, and 24 +/- 5%. At 22 h, plasma ammonia and lactate levels were respectively 705 +/- 93 micromol/L and 10.5 +/- 0.4 mmol/L in dying animals and 249 +/- 75 micromol/L and 2.9 +/- 0.1 mmol/L in surviving animals (P < 0.01). Estimation of the percentage liver cells necrosed was 74 +/- 4.7% in the survivors and 86 +/- 5.5% in animals who died of hepatic coma (NS). CONCLUSIONS: This model is reproducible and reversible and should allow the quantitative evaluation of new technologies, such as bioartificial liver, for the support of hepatic failure in humans.

Acute Disease↗

Semiautomatic macroencapsulation of large numbers of porcine hepatocytes by coextrusion with a solution of AN69 polymer.

We have previously demonstrated that allogenic and xenogenic hepatocytes macroencapsulated manually in AN-69 polymer and transplanted intra-peritoneally in rats remained viable for several weeks. However, this manual technique is inadequate to encapsulate several billions of hepatocytes which would be required to correct hepatic failure in big animals or humans. In the present study, we developed an original semiautomatic device in which isolated pig hepatocytes and the polymer solution containing 6% poly(acrylonitrile-sodium methallylsulfonate), 91% dimethylsulfoxide and 3% 0.9% NaCl solution were coextruded through a double-lumen spinneret. The extruded minitube (inner diameter: 1.8 mm, wall thickness: 0.07-0.1 mm) containing the encapsulated hepatocytes fell and coiled up in a 0.9% NaCl solution at 4 degrees C and was cut down in 4 m units containing about 120 million hepatocytes. This process allowed to encapsulate 50 million hepatocytes by minute with a preserved immediate cell viability (92 +/- 5%). To test prolonged cell viability after coextrusion, the minitubes were implanted intraperitoneally in rats. Three and seven days after implantation, they were explanted and analyzed. Cells were viable and well-preserved. Therefore, the semiautomatic device appears able to efficiently macroencapsulate in a limited time several billions of porcine hepatocytes which remain viable after transplantation in xenogenic conditions.

Acrylic Resins↗

[Viability and differentiation of human hepatocytes immunoprotected by macroencapsulation and transplanted in rats].

OBJECTIVES: To determine the viability and differentiation of human hepatocytes immunoprotected by encapsulation and transplanted in rats without immunosuppression. METHODS: Freshly isolated human hepatocytes were encapsulated in hollow fibers and transplanted in the peritoneal cavity of immunocompetent rats. The fibers were explanted for analysis at D3, D7 and D14 following transplantation. Morphological features under light and electron microscopy and gene expression were compared to those of non-transplanted encapsulated hepatocytes (D0). Human cytochrome P450 3A and albumin mRNAs were quantified by Northern blot. Cytochrome P450 3A proteins were detected by Western blot and cytochrome P450 3A enzyme activity was assessed by measuring the formation of 6beta-hydroxytestosterone by high performance liquid chromatography. RESULTS: Transplanted hepatocytes were more than 60 % viable and exhibited morphological criteria of hepatocytic differentiation up to D7. Albumin and cytochrome P450 3A transcripts were also detected up to D14. At D3 and D7, albumin mRNA levels were of 30 %, compared to control D0 hepatocytes, while cytochrome P450 3A5 and cytochrome P450 3A4 mRNA levels were 65 % and 0 %, respectively. Cytochrome P450 3A immunoreactivity was detected by Western blot up to D14 and 6beta-hydroxylase activity was 17 % at D3 compared to D0, supporting with disappearance of cytochrome P450 3A4 mRNA. CONCLUSIONS: Human hepatocytes remain viable for a short period, following encapsulation and intraperitoneal transplantation in rat. Other experimental conditions need to be tested to prevent or delay a decrease in hepatocyte specific gene expression.

Animals↗