Exogenous central angiotensin fails to stimulate a sodium appetite in diabetes insipidus Brattleboro rats.

We investigated the effect of central administration of angiotensin II (AngII) on a specific salt appetite (SSA) in homozygous diabetes insipidus Brattleboro (DI) rats because this stimulus induces such a response in all other rat strains. DI rats have a deficiency in the synthesis of arginine vasopressin (AVP) and a reduced content of pituitary oxytocin (OT). They are characterized also by polyuria, polydipsia, and they seldom ingest high concentrations of NaCl solutions. We also tested if the appetite can be influenced by neurohypophyseal hormones especially oxytocin (OT) because it inhibits SSA in other animals. DI rats and Long Evans (LE) controls were fed ad libitum and given a choice between water, and either 0.9% or 1.8% NaCl. The data showed a significant increase of daily spontaneous water intake in DI compared with LE rats. Both DI and LE ingested similar small spontaneous volumes of the isotonic NaCl solution, but DI rats drank significantly less hypertonic NaCl than the LE controls. I.c.v infusion of AngII induced significant sodium intake in LE rats, but only raised water intake in DI rats. When combined with i.c.v. Ang II, OVT enhanced salt intake in LE animals while AVP attenuated water intake in both groups of rats and blocked NaCl intake completely in LE rats. In conclusion, DI rats did not demonstrate a SSA in response to central administration of AngII, although the drinking of water was enhanced. In combination with i.c.v. AngII, AVP inhibits water drinking in both DI and LE rats. In the LE controls OT attenuates AngII-induced SSA but has no effect in DI rats.

Fluid deprivation increases isotonic NaCl intake, but not hypertonic salt intake, under normal and heated conditions in obese Zucker rats.

In the course of exposure to fluid deprivation and heated environment, mammals regulate their hydromineral balance and body temperature by a number of mechanisms including sweating, water and salt intakes. Here we challenged obese Zucker rats, known to have a predisposition to hypertension, with 0.9%NaCl alone or with 2%NaCl solution + water to drink under fluid deprivation and heated conditions. Food and fluid intakes, body weight, diuresis and natriuresis were measured daily throughout. Serum aldosterone levels and Na(+) concentration were also analyzed. Data showed that obese and lean rats presented similar baseline measurements of food, 0.9%NaCl and fluid intakes, diuresis and fluid balance; whereas hypertonic 2%NaCl consumption was almost absent. Before and during fluid deprivation animals increased isotonic but not hypertonic NaCl intake; the obese showed significant increases in diuresis and Na(+) excretion, whereas, total fluid intake was similar between groups. Heat increased isotonic NaCl intake and doubled natriuresis in obese which were wet on their fur and displayed a paradoxical increase of fluid gain. Fluid deprivation plus heat produced similar negative fluid balance in all groups. Body weight losses, food intake and diuresis reductions were amplified under the combined conditions. Animals exposed to 2%NaCl showed higher circulating levels of aldosterone and obese were lower than leans. In animals which drank 0.9%NaCl, obese showed higher serum levels of Na(+) than leans. We conclude that in spite of their higher sensitivity to high salt and heat obese Zucker rats can control hydromineral balance in response to fluid deprivation and heat by adjusting isotonic NaCl preference with sodium balance and circulating levels of aldosterone. This suggests a key hormonal role in the mechanisms underlying thermoregulation, body fluid homeostasis and sodium intake.

[Fetal distress: Information provided by lactate levels and antioxidant status, compared with the Apgar score]. / Souffrance foetale: pouvoir informant des lactates et du statut antioxydant versus le score d'Apgar.

The multitude of criteria used to assess fetal distress and the subjective character of the Apgar score led us to compare the information it provides with that from measurements of lactate and two principal antioxidant enzymes superoxide dismutase (SOD) and glutathione peroxidase (GPx). We measured plasma lactates, SOD, and GPX from the umbilical cord blood of live-born children whose mothers had had at least three prenatal consultations. The correlation of these measurements with the 5-minute Apgar score was tested with the Spearman correlation coefficient. Lactate levels were correlated with the baby's blood glucose (r=0.212; p=0.0084), and GPx activity (r=0.179; p=0.0061), the Apgar score (r=0.258; p=0.001) and the mother's blood glucose (r=0.167; p=0.035). GPx was correlated not only with the lactate level but also with birth weight (r=0.205; p=0.000) and height (r=0.316; p=0.0056), while SOD was correlated only with the mother's blood glucose (r=0.161; p=0.046). In multivariate analysis, followed by stepwise analysis, lactate was the main variable associated with the Apgar score. It thus seems better able to replace the Apgar score than the antioxidant enzyme levels. GPx was higher in children of high birth weight and may make them better able to combat the free radicals due to anoxia or hypoxia.

[Vitamin D status in Gabonese children]. / Statut et besoins en vitamine D chez le nourrisson au Gabon.

OBJECTIVE: To analyse the status of vitamin D and the influence of a supplement of vitamin D in neonates and infants during the first 6 months of life in the african equatorial environnement of Gabon. DESIGN: Clinical (weight, height, head circumference, and diseases) and biological (calcemia, phosphatemia, serum alkaline phosphatase activity and plasma 25-hydroxyvitamin D levels) parameters were compared between 2 groups of children: group 1: 41 infants receving a daily supplement of 1000 IU of vitamin D, and group 2: 38 infants without vitamin D supplement. RESULTS: No significant differences were observed between the 2 groups concerning clinical and biological parameters. In particular plasma levels of 25-hydroxyvitamin D were normal and similar in both groups. CONCLUSION: A vitamin D supplement appears to be useless in 0 to 6 months infants living in Gabon.

Mannose-6-phosphate/insulin-like growth factor-II receptor expression levels during the progression from normal human mammary tissue to invasive breast carcinomas.

The putative role of mannose-6-phosphate/insulin-like growth factor-II receptor (M6P/IGFII-R) as a tumour suppressor and its value as a prognostic marker of breast cancer was studied in 42 benign breast diseases (BBD), 61 in situ carcinomas (CIS) and 133 invasive carcinomas. The receptor was quantified by immunohistochemistry with a computerised image analyser, using specific polyclonal IGY antibodies. The M6P/IGFII-R level varied markedly according to the different patient samples, but median values and distributions were similar in lesions and normal adjacent glands. However, the receptor level was significantly increased in high-grade ductal carcinomas in situ (DCIS) and decreased in invasive carcinomas relative to adjacent normal tissue. The M6P/IGFII-R protein concentration in invasive breast carcinomas was mostly independent of prognostic parameters: tumour size, histological grade, lymph node (N) invasiveness and oestrogen receptor alpha (ERalpha) status. The only positive correlation was with cathepsin D, the progesterone receptor (PgR) and with patients aged >60 years. These results do not support the hypothesis of a frequent and early inactivation of the M6P/IGFII-R gene in breast cancer. Clinical follow-up of patients might reveal a prognostic value for one of the cathepsin receptors.

High-affinity antibodies from hen's-egg yolks against human mannose-6-phosphate/insulin-like growth-factor-II receptor (M6P/IGFII-R): characterization and potential use in clinical cancer studies.

The mannose-6-phosphate/insulin-like growth-factor-II receptor (M6P/IGFII-R) involved in trafficking of newly synthesized lysosomal enzymes, degradation of IGFII and activation of TGFbetaI, was suggested as being coded by a tumor-suppressor gene. No specific antibodies are currently available for clinical studies. Since M6P/IGFII-R is a highly conserved protein in mammals, we immunized chicken with human M6P/IGFII-R. Up to 200 mg of specific IgY from weekly pooled egg yolk was extracted by the polyethylene glycol procedure. Chicken IgY antibodies specifically recognized the human and bovine 270-kDa M6P/IGFII-R but not the 46-kDa M6P-R, as documented by immunoprecipitation and immunobloting. Using biosensor analysis, IgY antibodies were shown to bind M6P/IGFII-R with high affinity (K(D) = 7.5 x 10(-9) M). A solid-phase competitive ELISA using bovine M6P/IGFII-R coated on 96-well microplates, allowed us to titrate the M6P/IGFII-R in human sera at a sensitivity of 300 ng/ml. The M6P/IGFII-R was stained by immunoperoxidase in breast- and ovarian-cancer cell lines (T47D, MDA-MB231, MCF7 and BG1) and in frozen breast-cancer tissues, showing predominant localization in the trans-Golgi network. Staining specificity was shown with irrelevant IgY and by extinction with antigen excess. Quantitative immunohistochemical analysis of frozen sections from 40 invasive breast carcinomas indicated varying levels (from 5 to 400 units) of the M6P/IGFII-R protein which were not correlated with tumor size, histological grade and estrogen receptor or progesterone receptor. There was a trend (p = 0.08) between lymph-node invasiveness and low receptor level. Moreover, the M6P/IGFII-R level was significantly lower in cancer cells than in normal cells in 10 out of the 21 tumors in which the peritumoral normal glands could be quantified in parallel. These 2 last results agree with the hypothesis of a tumor-suppressor gene for this receptor and suggest more basic and clinical studies to prove it.