J G Gobert

Observatoire de Paris, Lutetia Parisorum, Île-de-France, France

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Publications (65)116.19 Total impact

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    ABSTRACT: Cryptosporidium parvum is a parasitic protozoa increasingly appreciated as a cause of intestinal malabsorptive syndrome leading to malnutrition and/or growth failure. Because a major mechanism for apical peptide absorption by small intestine is via the proton-coupled transporter PepT1, we investigated the expression and functionality of this transporter in our model of acute cryptosporidiosis. Four-day-old Sprague-Dawley rats were inoculated by gavage with 5 x 10(5) oocysts of C. parvum and killed at Day 12 (peak of the infection) or Day 21 (spontaneous clearance of the parasite). PepT1 expression and functionality were quantified in the distal small intestine, preferential site of C. parvum implantation, and in the proximal small intestine, free of parasite, using Western blot and Ussing chambers, respectively. No difference in total PepT1 protein expression or in glycyl-sarcosine fluxes was observed in C. parvum-infected rats compared with controls either on Day 12 or on Day 21, both in the proximal and in the distal small intestine. However, a significant decrease of apical membrane protein expression of PepT1 was observed in C. parvum-infected enterocytes compared with controls. This maintained dipeptide transport observed despite villous atrophy and decreased expression of the protein at the brush-border membrane strongly suggest a transient upregulation of PepT1 activity, probably related to gamma-interferon regulation.
    Experimental Biology and Medicine 04/2007; 232(3):454-60. · 2.80 Impact Factor
  • J G Gobert, L Barbot, N Kapel
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    ABSTRACT: Fecal analysis includes qualitative and quantitative studies which allows quantification and labelling of numerous pathophysiologic phenomenona. Malabsorption and over-absorption of water and electrolytes give rise to six types of watery diarrheas, and two types of constipations; malabsorption of nutriments and maldigestion of food, give rise to two types of fatty and nitrogenous diarrheas with metabolic consequences. Fecal analysis often discriminates organic from non-organic diseases and brings informations on increase or decrease of caloric losses, to the nutritionist. Microscopic observations which requires a high degree of competence and experience, allows the recognition of malabsorption/maldigestion phenomenona, of fortuitous presence of parasites and a good interpretation of a fecal file.
    Annales Pharmaceutiques Françaises 12/2004; 62(6):367-70.
  • J. G. Gobert, L. Barbot, N. Kapel
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    ABSTRACT: Fecal analysis includes qualitative and quantitative studies which allows quantification and labelling of numerous pathophysiologic phenomenona. Malabsorption and over-absorption of water and electrolytes give rise to six types of watery diarrheas, and two types of constipations; malabsorption of nutriments and maldigestion of food, give rise to two types of fatty and nitrogenous diarrheas with metabolic consequences. Fecal analysis often discriminates organic from non-organic diseases and brings informations on increase or decrease of caloric losses, to the nutritionist. Microscopic observations which requieres a high degree of competence and experience, allows the recognition of malabsorption/maldigestion phenomenona, of fortuitous presence of parasites and a good interpretation of a fecal file.
    Annales Pharmaceutiques Françaises. 11/2004; 62(6).
  • N. Kapel, L. Barbot, J.-G. Gobert
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    ABSTRACT: Fecal occult blood testing is the most widely prescribed screening test for colorectal cancer. Recent development of immunological tests has increased specificity. Fecal DNA analysis opens up a new field for early detection of this widespread neoplasia. Inflammatory bowel disease is another important area where the development of fecal markers provides an interesting alternative to the gold standard but costly and invasive endoscopic investigations with histological analysis of biopsy specimens. Fecal TNFα and calprotectin can now be proposed to distinguish organic from non-organic intestinal disease, so select candidates for further investigations, and to assess disease activity. Measurement of fecal elastase provides real progress in screening for exocrine pancreatic insufficiency in patients with malabsorption syndrome. The development of non-invasive fecal markers is thus of increasing interest, providing data about the entire gastrointestinal tract useful for screening and individual patient management.
    Annales Pharmaceutiques Françaises. 11/2004; 62(6).
  • L. Barbot, N. Kapel, J.-G. Gobert
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    ABSTRACT: Quality control in medical laboratories was defined in guidelines for good execution of laboratory analyses issued by the French health authorities in 1994. Application of these guidelines is difficult in coprology because the sample is a complex heterogeneous matrix which varies with disease, surgery, food intake, and treatment. In addition, commercial quality control kits are not available for stool biochemical analyses and a national quality control program has not been established. We thus developed our own fecal quality control technique using pooling lyophylized stool samples. Manual or partially automated methods are used in coprology, leading to a long pre-analysis phase which is not always taken into account in quality control. This implies the need for complementary tools to insure the quality of coprology analyses. For example, semi-quantitative microscopic lipid analysis can be used as an internal standard for a given specimen. Quality assurance also involves a post-analytical phase where results obtained for a given specimen are compared with other available data and interpreted in light of the patient‘s clinical and therapeutic status. This quality assurance strategy enables accurate reliable results useful for long-term patient management.
    Annales Pharmaceutiques Françaises 11/2004; 62(6):376-381.
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    ABSTRACT: In order to assess the impact of Cryptosporidium parvum on host intestinal physiology, we investigated absorption of the two principal amino acids in dam's milk (leucine, glutamate), using Ussing chambers and RT-PCR analyses. Experiments were performed in both heavily (ileum) and mildly (duodenum) infected segments of the small intestine at the peak of infection [day 8 post-infection (PI)] and after spontaneous clearance of the parasite (day 17 PI). At day 8 PI, amino acid fluxes across the mucosa were decreased throughout the small intestine (P<0.01) and EAAT3 mRNA expression was reduced ( from -49% to -28%). At day 17 PI, leucine and glutamate fluxes were normalized but the decrease in EAAT3 mRNA levels persisted (from -31% to -46%). Our results demonstrate that cryptosporidiosis induces major amino acid malabsorption involving the entire small intestine which is not counterbalanced by any up-regulation, even after spontaneous clearance of the parasite.
    Parasitology Research 10/2003; 91(3):197-203. · 2.85 Impact Factor
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    ABSTRACT: Cryptosporidium parvuminfection induces amino acid malnutrition leading to growth retardation in children. Owing to the nutritional efficiency of peptides compared to free amino acids and the resistance of the di-tripeptide transporter PepT1 to mucosal injury, we analyzed the intestinal expression of PepT1 during experimental acute cryptosporidiosis in suckling rats from day 4 to day 50. PepT1 mRNA levels were increased at the peak of infection (day 10) all along the small intestine and normalized after spontaneous clearance of the parasite (day 21). Immunolocalization of PepT1 showed that its expression was maintained in the brush border membrane of enterocytes in infected rats from day 4 to day 50 all along the small intestine. Our results suggest a transcriptional up-regulation during acute cryptosporidiosis in response to both C. parvum-induced malnutrition and parasite implantation. As no treatment is available, a semi-elemental diet should be considered part of the treatment of cryptosporidiosis.
    Parasitology Research 04/2003; 89(5):364-70. · 2.85 Impact Factor
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    ABSTRACT: The amount of faecal pancreatic enzyme elastase 1 was significantly lower in 42 preterm newborns than in 12 full term babies at day 2 (89 (3-539) v 354 (52-600) microg/g, p<0.0007) and day 5 (164 (3-600) v 600 (158-600) microg/g, p<0.05) and correlated positively with total nutrient intake during the first week of life in preterm infants. This should probably be taken into account during early feeding.
    Archives of Disease in Childhood - Fetal and Neonatal Edition 05/2002; 86(3):F198-9. · 3.45 Impact Factor
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    ABSTRACT: In the present study. we explored the nutritional consequences of cryptosporidiosis. In order to ascertain the direct responsibility of C. parvum for impairment of staturoponderal development observed during the infection in neonatal animals, we investigated the absorption of two major components of the total amino acids in dam's milk (leucine and glutamate) across the ileal mucosa. The infection resulted in significant (47% and 34%, respectively) reductions in leucine and glutamate fluxes (P<0.01). Moreover, the leucine aminopeptidase and alkaline phosphatase activities were reduced in the infected ileal mucosa. Interestingly, the reduction in weight gain, which began at day 6 post-infection (PI), persisted until day 20 PI, although no cryptosporidia were detected in the ileal mucosa after day 12 PI. We thus provide evidence that the malabsorption of amino acids during cryptosporidiosis contributes to impairing the development of neonatal animals, with consequences that persist beyond eradication of the parasite.
    Parasitology Research 11/2001; 87(11):891-6. · 2.85 Impact Factor
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    ABSTRACT: Cryptosporidiosis is an important cause of diarrhea associated with growth retardation in children and severe malnutrition in immunocompromised patients. The pathophysiology is poorly understood. In the suckling rat model, we show that C. parvum infection impairs net electrogenic transport across the ileal mucosa without involvement of prostaglandins, as well as trans- and paracellular permeability and leucine and glutamate absorption. These results provide evidence for the development of an intestinal malabsorptive syndrome during cryptosporidiosis. Unspecific process such as villous atrophy and inflammatory cytokines secretion should be regarded as possible mediators of this syndrome. However, specific mechanisms have to be considered since C. parvum induces a rearrangement of the host enterocyte cytoskeleton which might impaired intracellular trafficking thus reducing the membrane expression of nutrient transporters. Infection and malnutrition are known to be tightly associated, making each other worse. As no specific efficient therapy exists, cryptosporidiosis-induced malnutrition must be taken into account when establishing therapeutic scheme.
    Annales Pharmaceutiques Françaises 10/2001; 59(5):305-11.
  • Archives de Pédiatrie 05/2001; 8(4):445-6. · 0.36 Impact Factor
  • Archives De Pediatrie - ARCHIVES PEDIATRIE. 01/2001; 8(4):445-446.
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    ABSTRACT: Na(+)-glucose transport and transepithelial permeability were investigated during symptomatic acute cryptosporidiosis in newborn rats. The infection resulted in a significant (P < 0.01) decrease in the ileal short-circuit current and a nonsignificant fall in the transepithelial potential difference and conductance. In glucose-stimulated conditions, the rise in ileal short-circuit current and transepithelial permeability were significantly lower in Cryptosporidium parvum-infected rats than in controls (delta Isc = 3.24 +/- 1.21 microA.cm-2 vs delta Isc = 5.09 +/- 2.23 microA.cm-2 in infected and control animals, respectively; P < 0.001; delta PD = -0.35 +/- 0.13 mV vs delta PD = -0.44 +/- 0.14 mV for infected and control animals, respectively; P < 0.01). Electrical parameters were not affected by addition of the cyclooxygenase inhibitor indomethacin in either Cryptosporidium-infected newborn rats or controls. Horseradish peroxidase and mannitol flux studies demonstrated a significant decrease (P < 0.05) in transepithelial molecular permeability in infected enterocyte rats, HRP flux = 380, range 68-5570 ng.cm-2, and mannitol flux = 1.06, range, 0.34-1.44%.cm-2.min-1, compared with controls rats, HRP flux = 4446 range, 1121-124,363 ng.cm-2, and mannitol flux = 1.99, range, 0.57-5.09%.cm-2.min-1; P < 0.05. These effects could originate from C. parvum-induced alteration of intracellular trafficking of pinocytosis vesicles and therefore account for the decrease in permeability to solute and macromolecules, together with impaired transcellular nutrient transport, in suckling rats.
    Experimental Parasitology 02/1999; 91(2):119-25. · 2.15 Impact Factor
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    ABSTRACT: Infants with atopic eczema exhibit a specific fecal protein pattern after oral challenge with cow's milk, characterized by an increase in both eosinophil cationic protein (ECP) and tumor necrosis factor (TNF)alpha. The aim of our study was to determine the pattern of these proteins in allergic infants with intestinal manifestations. TNFalpha, ECP and immunoglobulin E (IgE) were measured in stools from 13 infants with intestinal symptoms and 10 healthy infants. The allergic infants underwent two stool collections, one before a cow's milk challenge and the other after the challenge, either at the onset of clinical manifestations (n=6) or 15 days after the challenge if no clinical manifestations occurred (n=7). Baseline TNFalpha, ECP and IgE levels were low in all infants. The concentration of TNFalpha increased after the challenge in infants positive to challenge (p<0.05) but not in those negative to challenge. ECP and IgE levels remained low after the challenge in all the allergic infants. These data confirm that fecal TNFalpha and ECP levels indicate various reaction types of food allergy and that different immunologic disturbances lead to atopic eczema or intestinal symptoms during food allergy. Fecal protein pattern can thus be a useful tool in diagnosing food allergy in infants with intestinal manifestations.
    Clinical Chemistry and Laboratory Medicine 02/1999; 37(1):29-32. · 3.01 Impact Factor
  • Archives de Pédiatrie 01/1998; 5(2):220-220. · 0.36 Impact Factor
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    ABSTRACT: Electrolyte transport was investigated during chronic cryptosporidiosis in adult anti-interferon-gamma-treated SCID mice by means of Ussing chamber techniques. In basal conditions, infection of immunocompromised mice with Cryptosporidium parvum resulted in a 30% reduction (P < .05) in the ileal short-circuit (Isc) current related to a 28% reduction (P < .05) in tissue conductance compared with controls. The rises in Isc and transepithelial potential difference induced by glucose (10 mM) were significantly reduced by Cryptosporidium infection (P < .01) compared with controls. In contrast, responses to mucosal glutamine were marginally affected. Electrical parameters of the ileum were not affected by the addition of indomethacin or furosemide, in either control or Cryptosporidium-infected mice. Thus, long-term cryptosporidiosis in immunocompromised animals leads to a reduction in net ion exchanges, decreased paracellular shunting, and impaired Na+-glucose cotransport in the ileum, without prostanoid- or enterotoxin-mediated electrogenic Cl- secretion.
    The Journal of Infectious Diseases 09/1997; 176(3):834-7. · 5.85 Impact Factor
  • G J Frayha, J D Smyth, J G Gobert, J Savel
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    ABSTRACT: The mechanisms of action of antiprotozoal and anthelmintic drugs are reviewed according to: (1) drugs interfering with metabolic processes; (2) drugs interfering with reproduction and larval physiology; and (3) drugs interfering with neuromuscular physiology of parasites.
    General Pharmacology 03/1997; 28(2):273-99.
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    ABSTRACT: Mutations of TP53, a tumor suppressor gene, are found in 60% to 70% of colorectal cancers. These mutations usually induce an overexpression caused by modification of the p53 protein conformation. The aim of this study was to investigate whether stool specimens of patients with colorectal cancer contain increased amounts of p53 protein. p53 protein was measured using a sandwich enzyme immunoassay in the stool specimens of 52 patients: 25 with colorectal cancer, 4 with colorectal adenomas and 23 apparently free of gastrointestinal disease. Results were expressed as pg/mg of total protein. The presence of fecal occult-blood was searched using Hemoccult II and Hemolex (an immunochemical assay for human hemoglobin). Median concentrations of stool p53 protein were 16.6 pg/mg (range: 0-591 pg/mg) in patients with colorectal cancers, 39.1 pg/mg (range: 5-72 pg/mg) in patients with adenomas and 5.9 pg/mg (range: 0-65 pg/mg) in control subjects. Resection of colorectal cancers caused a marked decrease of stool p53 protein concentrations. When the cut-off value for stool p53 protein was set at 60 pg/mg of fecal protein (concentrations over the 95th percentile), the positivity of the assay was independent of tumor size and Astler-Coller stage, but weakly associated with rectal location of cancer. The sensitivity of stool p53 protein for colorectal cancer was 44%, and the specificity was 96%. In contrast, the sensitivity of Hemoccult II and Hemolex tests was 48% and 44%, whereas their specificity was 91% and 96%, respectively. The detection of p53 protein is achievable in stool, but this assay is not more efficient than fecal occult blood tests for detection of colorectal cancer.
    Gastroentérologie Clinique et Biologique 02/1997; 21(10):754-9. · 1.14 Impact Factor
  • Journal of Pediatric Gastroenterology and Nutrition - J PEDIAT GASTROENTEROL NUTR. 01/1997; 24(4).
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    ABSTRACT: The intestinal absorption of the immunosuppressant cyclosporin-A (CsA) has been studied in vitro using the Grass chamber technique applied to the proximal small bowel of rat. CsA concentration in the donor-phase was 100 mg/1 for either 2-weeks or 6-weeks-old rat intestine. CsA was dissolved in different vehicles, including the oily solution Sandimmun® (CsA-S) and the new microemulsion Sandimmun Neoral® (CsA-SN) together with bile salts and pancreatic lipase. The limit of tissue viability was set at 90 min by monitoring the transepithelial electric resistance. Mucosal histology was studied by both optical and transmission electron microscopy. CsA was determined in the receptor-phase. CsA was partially metabolised by the 6-weeks-old rat intestine. In these experiments no difference was observed between CsA-S and CsA-SN absorption. On the contrary, the 2-weeks-old rat intestine did not allow CsA absorption from CsA-SN. This was related to intestinal immaturity and brush border erosion, as shown by electron microscopy. Hence, CsA absorption from microemulsion may require a mature and viable intestine. Microvilli of absorptive cells may play a role in CsA capture from the microemulsion-modified-micelles, in which CsA concentration is lower than in oily droplets. CsA absorption was not impaired by oily vehicles. Complete lipolysis of olive oil (CsA-S) induced an important decrease in CsA absorption, related to free oleic acid production.
    International Journal of Pharmaceutics 09/1996; 142(1):1-8. · 3.99 Impact Factor

Publication Stats

292 Citations
116.19 Total Impact Points


  • 2004
    • Observatoire de Paris
      Lutetia Parisorum, Île-de-France, France
  • 1995–2003
    • Hôpital La Pitié Salpêtrière (Groupe Hospitalier "La Pitié Salpêtrière - Charles Foix")
      • Service d’Hépato - Gastro - Entérologie
      Lutetia Parisorum, Île-de-France, France
  • 1987–2003
    • Université René Descartes - Paris 5
      • Faculté des Sciences Pharmaceutiques et Biologiques de Paris
      Paris, Ile-de-France, France
  • 1997
    • Unité Inserm U1077
      Caen, Lower Normandy, France
  • 1991–1996
    • Hôpital Bichat - Claude-Bernard (Hôpitaux Universitaires Paris Nord Val de Seine)
      Lutetia Parisorum, Île-de-France, France