Implication of distinct proteins in cadmium uptake and transport by intestinal cells HT-29.

The mechanisms of intestinal absorption have not been clearly elucidated for cadmium, a toxic metal. In this work, we show the implication of distinct proteins in cadmium transport, and the transport step where these proteins are involved. We first validated the HT-29 model by evaluating nontoxic doses of cadmium (ranging from 1 to 20 micromol/L), and by quantifying metal uptake and transepithelial transport. The time-course of 1 micromol/L cadmium uptake at pH 7.5 showed three steps: a rapid one during the first 4 min, probably due to cadmium binding to the membrane; a slower one, characterized by Km of 1.65+/-0.54 micromol/L and Vmax of 3.9+/-0.3 micromol/min per mg protein; and a third, corresponding to slow accumulation that was not equilibrated even after 48 h of cadmium exposure. Intracellular metallothionein content following 1 or 5 micromol/L cadmium exposure showed a significant increase after 6 h of exposure, and was not equilibrated even after 72 h, allowing cadmium accumulation. After 24 h of exposure, metallothionein content was 5-fold, 14-fold, 26-fold, and 50-fold, respectively, for cells grown in the presence of 1, 5, 10, and 20 micromol/L cadmium, compared to control cells. The second step of uptake, characterized by carrier-mediated transport, was markedly increased at pH 5.5, compared to pH 7.5, and strongly inhibited by the metabolic inhibitor dinitrophenol. Moreover Nramp2 transporter cDNA was present in HT-29 cells. These data suggest the involvement of a proton-coupled transporter, which may be the divalent cation transporter Nramp2 (natural resistance-associated macrophage protein 2). Cadmium uptake was also inhibited by copper, zinc, and para-chloromercuribenzenesulfonate (pCMBS), but not by verapamil or ouabain. Taken together, our results indicate that cadmium could enter HT-29 cell by Nramp2 proton-coupled active transport and by diffusion, and accumulates in the cell as long as it binds to metallothionein. Cadmium toxicity could depend partly on the activity of Nramp2, and partly on metallothionein content.

Measurement of joint space width in hip osteoarthritis: influence of joint positioning and radiographic procedure.

OBJECTIVES: We assessed the influence of patient positioning and radiographic procedure, and defined a smallest detectable difference (SDD) in hip osteoarthritis (OA). METHODS: OA hip patients each had a standardized pelvic radiograph and, 5 min later, a modified pelvic radiograph with the feet internally rotated 5 degrees (part 1 of the study), the X-ray beam centred on the umbilicus (part 2), or another standardized pelvic radiograph (part 3). RESULTS: Corresponding mean differences in joint space width (JSW) measurements (limits of agreement) between views were +0.03 (-0.53 to +0.59), -0.31 (-1.15 to +0.53) and -0.02 (-0.48 to +0.44) mm. The two views differed significantly in mean JSW in part 2 of the study (P=1.6x10(-4)), but not in part 1 (P=0.375) and part 3 (P=0.580). The SDD estimate was 0.46 mm. CONCLUSIONS: Modifying the X-ray beam and foot rotation increases variability in JSW measurements. Use of urograms to evaluate radiological progression should be avoided. A change greater than 0.46 mm could define radiological hip OA progression.

Phenotypic diversity is not determined by independent genetic factors in familial spondylarthropathy.

OBJECTIVE: To analyze the segregation of manifestations belonging to the spectrum of spondylarthropathy (SpA) among patients and unaffected siblings within SpA multiplex families. METHODS: Ninety-five multiplex families have been investigated. The diagnosis of SpA was made according to European Spondylarthropathy Study Group criteria. The prevalence of SpA manifestations was determined in unaffected siblings and compared with their prevalence in patients. RESULTS: We compared 241 SpA patients with 259 unaffected siblings. The prevalence of skeletal and extraarticular features not used as diagnostic criteria, i.e., radiographic sacroiliitis, peripheral enthesitis, uveitis, psoriasis, and inflammatory bowel disease, was significantly increased in patients compared with unaffected siblings. This result was not accounted for by sex or HLA-B27 distribution differences. CONCLUSION: In familial SpA, skeletal and extraarticular manifestations tend to segregate together, implying that all subsets are predominantly determined by a shared component, and that accessory factors must be responsible for phenotype diversity.

The familial form of spondylarthropathy: a clinical study of 115 multiplex families. Groupe Français d'Etude Génétique des Spondylarthropathies.

OBJECTIVE: To investigate the interrelationships among different phenotypes, and their relationship to the HLA-Blocus, in multiplex families with spondylarthropathy (SpA). METHODS: We recruited 115 white French families, each of which had at least 2 members with SpA. Pedigrees were established. Clinical data and pelvic radiographs were collected. The HLA-B27 status of all patients was determined. Analysis was performed to determine the prevalence of SpA manifestations according to sex, disease duration, and HLA-B status, and to examine clustering of specific manifestations in subsets of families. RESULTS: We identified 329 SpA patients. Mean +/-SD age at onset was 24+/-9.4 years. The male:female ratio was 186:143, or 1.3, with few sex differences in disease expression. Axial manifestations and HLA-B27 were each present in 97% of the patients. Inflammatory bowel disease and HLA-B35 were overrepresented in the 7 families containing HLA-B27-negative patients. The frequency of radiographic sacroiliitis increased in parallel with disease duration. Peripheral enthesitis, radiographic sacroiliitis, and psoriasis were evenly distributed in the families. Clustering independent of age was only observed for peripheral arthritis, suggesting that specific factors may predispose individuals to this manifestation. CONCLUSION: Familial SpA appears to be homogeneous, based on the high frequencies of axial skeletal involvement and HLA-B27. The lack of clustering of most manifestations in families suggests that a predominant shared component, including HLA-B27, predisposes individuals to all forms of familial SpA, and that ubiquitous genetic or environmental factors contribute to phenotype diversity.

[Systemic mastocytosis]. / Les mastocytoses systémiques.

UNLABELLED: HEMATOPOIESIS DISORDER: Systemic mastocytosis is a primary proliferation of mast cells in several noncutaneous tissues. It remains an uncommon disease, difficult to diagnosis and often missed. The spectrum of clinical signs is wide and the course and prognosis are quite variable. CLINICAL ASPECTS: Sudden release of mediators by mast cell degranulation lead manifestations of paroxysmal congestion. Pigmentary urticaria is the most frequent cutaneous form. Among visceral localizations, bone involvement is encountered in 90% of the cases, digestive tract and hematological involvement are less frequent. Respiratory and cardiovascular involvement is exceptional. DIAGNOSIS: Osteomedullary biopsy is required for diagnosis. Urinary histamine metabolites may be suggestive. PROGNOSIS: Prognosis depends on the presence of an associated hematological disorder, found in 30% of the cases. TREATMENT: Symptomatic treatment is the rule, aimed at blocking histamine release by mast cell degranulation and avoid the subsequent paroxysmal manifestations.

[Autoimmune hepatitis and lupus syndrome associated with minocycline]. / Hépatite auto-immune et syndrome lupique secondaires à la prise de minocyline.

INTRODUCTION: Among several adverse effects following treatment with minocycline, certain cases of autoimmune hepatitis, associated with lupus erythematosus, have been described. The possibility of hepatic damage, although rare, is important to keep in mind because of its delicate diagnostic. EXEGESIS: We report one case of autoimmune hepatitis following treatment with minocycline for acne, in a 25-year-old woman. This autoimmune hepatitis was associated with induced lupus syndrome. Usual causes of hepatitis were eliminated. Evolution was spontaneously favorable upon minocycline treatment interruption, with the disappearance of clinical symptoms and normalization of hepatic and immunologic biological values. CONCLUSION: The possibility of hepatic damage and lupus syndrome, following treatment with minocycline, should be recalled and verified in cases of long-term prescription. This observation stresses the difficulties of anamnesis in internal medicine. For those who know how to listen cautiously and rigorously, anamnesis may prove more helpful than many complementary examinations.

Comparative study of cadmium transfer in ewe and cow milks during rennet and lactic curds preparation.

Cadmium transfer from whole milk to cream, rennet, or lactic curds was studied before and following a repeated oral cadmium administration to three lactating ewes and one cow. Before cadmium administration, the cadmium levels in milk were around 0.4 microg/L in ewes and less than 0.2 microg/L in cow. Throughout cadmium administration the mean cadmium levels in milk were 3.3+/-1.4 microg/L in ewes and 2.5+/-1 microg/L in cow. During cadmium administration, 86% of cadmium in ewe milk was dispersed in the skimmed milk and 17% in the cream, whereas only 72% was dispersed in the cow skimmed milk and 27% in the cow cream. Most of milk cadmium was associated with casein fractions. About 70% of milk cadmium was transferred to the rennet or lactic curds of ewe. The remaining cadmium present in whole milk, about 9%, was transferred to the rennet or lactic curd whey. In cow, the proportion of cadmium associated with rennet or lactic curds, rennet curd whey, and lactic curd whey was, respectively, 60%, 56%, 14% and 12% of total milk cadmium. The fraction of total cadmium transferred from milk to its milk products, whatever the species, ranged from 94% to 103%. The factor of concentration of cadmium from whole milk to milk products ranged from three to six. We suggest that the excretion of cadmium into milk is mainly achieved via the milk casein secretion. This is, to our knowledge, the first in vivo study where the cadmium transfer from milk to its milk products after repeated cadmium oral administration to ewe and cow has been studied.

[Evaluation of side effects of interferon-alpha in 72 patients treated for chronic active hepatitis C]. / Bilan des effets indésirables de l'interféron alpha chez 72 patients traités pour hépatite C chronique active.

Interferon alfa (INF alpha), which is used in chronic active viral hepatitis, presents some safety problems. Side effects observed in 72 treated patients with chronic active hepatitis C are analysed in this retrospective study. Doses used were 3 or 9 M IU, three times a week, for 12 to 24 weeks. There were no contra-indications to the treatment and all patients had the factors predictive of a satisfactory therapeutic response. Apart from general debility, there were side effects in 65 of the 72 patients as follows: flu-like syndrome (n = 39), gastrointestinal (n = 29), dermatological (n = 24), haematological (n = 23), neurological (n = 20), cardiovascular (n = 6) and thyroid (n = 6) disorders. For 30 per cent of the patients, the dose was decreased (n = 6) or the treatment was withdrawn, temporarily (n = 5) or permanently (n = 10). These results are in accordance with those published and emphasize the need for clinico-biological monitoring during and after treatment. Indeed delayed thyroid disorders appear to be relatively common.

[Chemical composition of feces from bovines, sheep and goats feeding from Sahelo-Sudanese natural or farming fields: its use for estimating the nutritive value of their diet]. / Composition chimique des fèces de bovins, d'ovins et de caprins exploitant des parcours naturels ou agro-pastoraux sahélo-soudaniens: utilisation pour estimer la valeur nutritive de leur régime.

The chemical composition of grazing cattle, sheep and goat feces is described according to animal species, type of range (natural pasture or fields after crops) and season in a sub-Sahelian environment. Nutritive value (organic matter digestibility and digestible crude protein) of forages can be estimated from some chemical fecal criteria.