Assay of matrix metalloproteinases types 1, 2, 3 and 9 in breast cancer.

Matrix metalloproteinases (MMPs) are zinc dependent endopeptidases implicated in cancer invasion and metastasis. Gelatin zymography was performed on 84 human breast carcinomas and seven normal breast tissues. The precursor form of MMP-2 (72 kDa) was found in 11 (12%) samples, while its two activated forms, i.e. 62 kDa and 59 kDa, were found in three (6%) and 34 (40%) samples respectively. In contrast to MMP-2, most of the samples (52%) contained MMP-9 in its precursor form. Using ELISA, MMP-1 levels were found in 12% of the samples while MMP-3 levels were found in only 2% of the samples. Levels of MMP-2, -3 and -9 correlated inversely with numbers of nodal metastases. Neither MMP-2 nor -9 levels were significantly related to patient outcome. However, patients with high levels of a 50-kDa gelatinase band after zymography had a significantly better survival than patients with low levels. This species was never observed in normal breast tissue.     

Practical attitude toward arrhythmia in the neonate and infant]

Arrhythmias in neonates and infants require a specific management due to the particular nature of the rhythm anomalies in children. Accurate diagnosis of the tachycardia is realised mainly by means of ECG recording and vagal manoeuvres. The nature of the tachycardia will determine management, therapy and prognosis. In neonates <3 months, supraventricular tachycardia due to Wolff-Parkinson-White syndrome represents 70% of all supraventricular tachycardias, which, after conversion by vagal manoeuvres, requires a preventive treatment by digoxine (10 y/kg/day tid). Neonatal flutter occurs in infants without structural heart disease. It has an excellent prognosis after conversion to sinus rhythm by transoesophageal pacing. Atrial tachycardia is less frequent but can induce a tachymyocardiopathy and often requires combined therapy including amiodarone. Long QT syndrome, clinically and genetically heterogeneous, is characterized by a prolongation of the QT interval (QTc > 440 ms) and a high risk of syncope and sudden death due to malignant ventricular arrhythmias. Beta-blockers significantly decrease cardiac events during follow-up.Congenital atrio-ventricular block is rare but potentially lethal in the first months of life in the absence of permanent pacing. The morbidity remains high during long term follow-up in unpaced children.     

Medical aspects of commercial air travel]

A high proportion of commercial plane passengers are children: two million fly every year on Air-France airlines. In this field, the physician can be called upon to authorize or prohibit travelling. He could take measures or offer his services at the request of the cabin staff. The authors review flight physiology and stress, their potential effects on healthy children or those with medical conditions, and their fitness to fly.     

Acute adrenal insufficiency in the newborn]

Neonatal acute adrenal insufficiency is a rare condition. Congenital adrenal hyperplasia with 21-hydroxylase defect appears to be the most frequent cause, but the neonatal screening has improved its potential severe outcome. The other causes and the various clinical presentations have been exposed, with a special reference to the salt-wasting syndrome. Among them, the severity of X-linked adrenal hypoplasia congenita (AHC) deserves special attention. Two other causes of adrenal hypoplasia have been recently discovered, i.e. a mutation of the SF-1 gene and the syndrome IMAGe. Adrenal insufficiency secondary to ACTH deficiency is often unrecognised despite the risk of severe seizures and hypoglycaemia with brain damage. Finally, the hormonal diagnostic testing and the main therapeutic approach by corticosteroids have been indicated. The aim of this work is to focus the attention of paediatricians who examine a newborn because the risk of delayed diagnosis and fatal outcome may be limited if the clinical symptoms are soon recognized.     

Selected ginsenosides of the protopanaxdiol series are novel positive allosteric modulators of P2X7 receptors

Background and Purpose

The P2X7 receptor is an ATP-gated ion channel predominantly expressed in immune cells and plays a key role in inflammatory processes. Ginseng is a well-known Chinese herb with both pro- and anti-inflammatory properties and many of its actions have been ascribed to constituent ginsenosides. We screened a number of ginsenoside compounds for pharmacological activity at P2X7 receptors, that might contribute to the reported immunomodulatory actions of ginseng.

Experimental Approach

We used several assays to measure responses of P2X7 receptors, ATP-mediated dye uptake, intracellular calcium measurement and whole-cell patch-clamp recordings. HEK-293 cells stably expressing human P2X7 receptors were used in addition to mouse macrophages endogenously expressing P2X7 receptors.

Key Results

Four ginsenosides of the protopanaxdiol series, Rb1, Rh2, Rd and the metabolite compound K (CK) potentiated the dye uptake responses of P2X7 receptors, whereas other ginsenosides tested were ineffective (1–10 μM). The potentiation was rapid in onset, required a threshold concentration of ATP (<50 μM) and had an EC₅₀ of 1.08 μM. CK markedly enhanced ATP-activated P2X7 currents, probably via an extracellular site of action. One of the consequences of this potentiation effect is a sustained rise in intracellular Ca²⁺ that could account for the decrease in cell viability in mouse macrophages after a combination of 500 μM ATP and 10 μM CK that are non-toxic when applied alone.

Conclusions and Implications

This study identifies selected ginsenosides as novel potent allosteric modulators of P2X7 channels that may account for some of the reported immune modulatory actions of protopanaxdiol ginsenosides in vivo.     

Placental and pituitary growth hormone secretion during pregnancy in acromegalic women

It is now well established that during the second half of normal pregnancy, the human placenta secretes its specific GH variant (placental GH) in increasing amounts up to delivery. During the same period, pituitary GH secretion is progressively suppressed. The present study was aimed at clarifying the physiology of GH secretion in pregnant acromegalic women. Two young women remained acromegalic despite transphenoidal removal of their pituitary adenoma. Increased basal levels of GH and insulin-like growth factor-I (IGF-I) as well as paradoxical GH release after TRH injection were noted. Both women became pregnant and delivered term babies without any complication. In both patients, pituitary GH remained elevated during the entire pregnancy, contrary to the situation in normal women. Paradoxical GH release after TRH treatment was also present, whereas no response was observed in five normal control subjects. GH pulsatility studies revealed a highly pulsatile secretory pattern of pituitary GH, in contrast to that in normal woman, whose placental GH is secreted tonically. Tissue placental GH concentrations were within the range of levels in normal placentas. An increase in serum IGF-I in late pregnancy was also similar to that observed in normal pregnancy. These findings confirm that increased IGF-I levels are not pituitary GH dependent in late pregnancy. They add new evidence that adenomatous somatotrophs lack an IGF-I-dependent feedback regulation present in normal somatotrophs.     

Primary percutaneous coronary intervention in acute myocardial infarction: time, time, and time!

Longer door-to-balloon times, total duration of ischaemia, and time of presentation relative to symptom onset all have an impact on outcome following primary percutaneous coronary intervention.     

Outbreaks of serogroup X meningococcal meningitis in Niger 1995-2000

In the African meningitis belt, the recurrent meningococcal meningitis epidemics are generally caused by serogroup A. In the past 20 years, other serogroups have been detected, such as X or W135, which have caused sporadic cases or clusters. We report here 134 meningitis cases caused by Neisseria meningitidis serogroup X that occurred in Niamey between 1995 and 2000. They represented 3.91% of the meningococcal isolates from all CSF samples, whereas 94.4% were of serogroup A. Meningococcal meningitis cases were detected using the framework of the routine surveillance system for reportable diseases organized by the Ministry of Public Health of Niger. The strains were isolated and determined by the reference laboratory for meningitis in Niamey (CERMES) and further typed at the WHO collaborating center of the Pharo in Marseille and at the National Reference Center for the Meningococci at the Institut Pasteur. Reference laboratories in Marseille and Paris characterized 47 isolates having the antigenic formula (serogroup:serotype:sero-subtype) X:NT:P1.5. Meningitis cases due to meningococcus serogroup X did not present any clinical or epidemiological differences to those due to serogroup A. The seasonal incidence was classical; 93.3% of the cases were recorded during the dry season. The mean age of patients was 9.2 years (+/- 6 years). The sex ratio M/F was 1.3. Case fatality rate was 11.9% without any difference related to age or sex. The increasing incidence of the serogroup X was not related to the decrease of serogroup A, but seemed cyclic, and evolved independently of the recurrence of both serogroups A and C.