The effect of recombinant follicle stimulating hormone (Gonal-F) on endogenous luteinizing hormone secretion in women

Parenteral administration of follicle stimulating hormone (FSH) has been shown to lower luteinizing hormone (LH) concentrations in women undergoing ovulation induction. This study was designed to explore the physiological mechanism of this effect. Seven healthy women were recruited into a double-blind placebo-controlled study. LH secretion, after the administration of variable i.v. boluses (37.5, 75 and 150 IU) of recombinant FSH (Gonal-F), was evaluated. LH was measured at 10 min intervals for 2 h before and 4 h after the FSH/placebo infusion. LH pulse frequency and amplitude were evaluated and there was no significant difference between control and trial cycles for each subject. A linear regression analysis revealed that in the group receiving 150 IU FSH, the mean plasma LH concentration decreased significantly due to a reduction tonic LH secretion. This could be a result of the suppression of secretion or an alteration of clearance. This decrease was not seen in the other dosage groups, revealing that above a dosage threshold, FSH reduced non-pulsatile LH secretion. Therefore the effect of FSH in this study exposed the likely presence of two components of LH concentration: an FSH-sensitive, non-pulsatile tonic secretion and a gonadotrophin-releasing hormone-stimulated, pulsatile release that is unaffected by FSH. Although an indirect effect involving ovarian regulation is not excluded, the rapidity of the effect suggests that FSH acts directly on the pituitary gland.      

The athlete’s heart: Is this an entity in paediatrics?

A case report of a boy who demonstrates features of an athlete's heart, associated with dilatation of the coronary artery, is presented. The importance of distinguishing this benign condition from pathologic causes such as cardiomyopathy, and risk of sudden death in these athletes is discussed.     

Effect of growth hormone on height, weight, and body composition in Prader-Willi syndrome

AIMS: To evaluate the effect of the administration of growth hormone on stature, body weight, and body composition in children aged between 4 and 10 years with Prader-Willi syndrome. METHODS: Height, weight, and skinfold thickness were recorded in 25 children using standard anthropometric techniques at recruitment, and six months later, shortly before the start of daily subcutaneous injections of growth hormone. Body composition was assessed via a measurement of total body water using stable isotopes. Measurements were repeated at the end of the six months of growth hormone administration. Measurements of height, weight, and skinfold thickness were expressed as standard deviation scores (SDSs). RESULTS: There was a significant reduction in the percentage of body fat after growth hormone treatment; height velocity doubled during treatment; body weight did not change significantly when expressed as an SDS. Skinfold thickness at both the triceps and subscapular site decreased in absolute terms and when expressed as an SDS. CONCLUSIONS: These results indicate sufficient potential benefit to justify a more prolonged trial of growth hormone treatment and an exploration of different dosage regimens in children with Prader-Willi syndrome.     

Safety of magnetic resonance imaging in preterm infants

Aim: As we progress in our knowledge of preterm brain injury, cohort studies are focusing in neuroimaging preterm infants in the first days of life. Magnetic resonance (MR) is the most powerful neuroimaging modality and valuable in understanding perinatal brain injury. The main purpose of the study is to evaluate the safety of MR imaging in very low birth weight (VLBW) infants at our hospital settings where the scanner is located at some distance from the neonatal intensive care unit (NICU). Subjects and methods: This is a prospective study of 33 VLBW infants who underwent early MR imaging (MRI), within 10 days after birth and term corrected age MRI. The study period included June to December 2008. Results: A total of 46 MRI were performed on 33 preterm infants. The mean total time the infants stayed in the bore of the magnet was 13.04 min. No incidences occurred during transfer or during the scans, and no significant changes were found in heart rate, oxygen saturation and temperature. Conclusions: At our hospital settings, the process of transport and MR imaging have been proven to be safe and not to disturb any of the variables measured. MRI should not be restricted to centres with neonatal MR system or MR‐compatible incubator, as long as the process is coordinated and supervised by a multidisciplinary team.     

Nonrandom association of free iron with membranes of sickle and beta- thalassemic erythrocytes

To further define the nature of abnormal iron deposits on the membranes of pathologic red blood cells, we have used sickle cell anemia (HbSS), HbSC, and beta-thalassemic erythrocytes (RBCs) to prepare inside-out membranes (IOM) and insoluble membrane aggregates (AGGs) containing coclustered hemichrome and band 3. Study of IOM from HbSC and thalassemic patients showed that amounts of heme iron and, especially, free iron were much higher in patients who had undergone surgical splenectomy. The membrane AGGs from HbSS and beta-thalassemic RBCs contained much more globin than heme, with this discrepancy being variable from patient to patient. Although these AGGs were enriched (compared with the ghosts from which they were derived) for heme, as expected, less than 10% of total ghost heme was recovered in them. Remarkably, these AGGs also were enriched for nonheme iron, markedly so in some patients. Iron binding studies showed that the association of free iron with these hemichrome/band 3 AGGs is explained by the fact that free iron binds to denatured hemoglobin. These results document that free iron is nonrandomly associated with the membranes of sickle and beta-thalassemic RBCs. Whether this plays a causative role in the premature removal of such cells from the circulation remains to be seen.     

Viral aetiology of lower respiratory tract infection in young Malaysian children

OBJECTIVE: To study the viral aetiology of lower respiratory tract infection (LRTI) in young Malaysian children. METHODOLOGY: A retrospective review was performed of LRTI patients aged less than 24 months who were admitted to the University Malaya Medical Centre between 1982 and 1997. Respiratory viruses in their nasopharyngeal secretion were identified by indirect immunofluorescence, viral culture, or both. RESULTS: A total of 5691 children were included in the study. The mean age was 8.6 +/- 6.6 months and the M:F ratio was 1.6:1. The most common diagnosis was pneumonia (52%) followed by bronchiolitis (45%) and croup (2%). Positive viral isolation rate was 22.0%. Respiratory syncytial virus (RSV) was the commonest virus isolated (84%), followed by parainfluenza virus (8%), influenza virus (6%) and adenovirus (2%). Patients with positive virus isolation were younger (7.8 +/- 6.2 vs 8.7 +/- 6.7 months, P = 0.0001) and were more likely to have bronchiolitis. CONCLUSION: Young Malaysian children admitted with LRTI had a 22% viral isolation rate and RSV was the commonest virus isolated.     

Anemoside A3 Enhances Cognition through the Regulation of Synaptic Function and Neuroprotection

Compounds that have the ability to both strengthen synaptic function and facilitate neuroprotection are valuable cognitive enhancers that may improve health and quality of life, as well as retard age-related cognitive deterioration. Medicinal plants are an abundant source of potential cognitive enhancers. Here we report that anemoside A3 (AA3) isolated from Pulsatilla chinensis modulates synaptic connectivity in circuits central to memory enhancement. AA3 specifically modulates the function of AMPA-type glutamate receptors (AMPARs) by increasing serine phosphorylation within the GluA1 subunit, which is a modification required for the trafficking of GluA1-containing AMPARs to synapses. Furthermore, AA3 administration activates several synaptic signaling molecules and increases protein expressions of the neurotrophin brain-derived neurotrophic factor and monoamine neurotransmitters in the mouse hippocampus. In addition to acting through AMPARs, AA3 also acts as a non-competitive NMDA receptor (NMDAR) modulator with a neuroprotective capacity against ischemic brain injury and overexcitation in rats. These findings collectively suggest that AA3 possesses a unique ability to modulate the functions of both AMPARs and NMDARs. Concordantly, behavioral studies indicate that AA3 not only facilitates hippocampal long-term potentiation but also enhances spatial reference memory formation in mice. These multifaceted roles suggest that AA3 is an attractive candidate for further development as a cognitive enhancer capable of alleviating memory dysfunctions associated with aging and neurodegenerative diseases.     

The macrocyclic lactone protein kinase C activator, bryostatin 1, either alone, or in conjunction with recombinant murine granulocyte- macrophage colony-stimulating factor, protects Balb/c and C3H/HeN mice from the lethal in vivo effects of ionizing radiation

We have examined the in vivo radioprotective effects of the macrocyclic lactone protein kinase C (PK-C) activator, bryostatin 1, administered either alone or in conjunction with recombinant murine granulocyte- macrophage colony-stimulating factor (rmGM-CSF), in Balb/c and C3H/HeN mice subjected to lethal total body irradiation (TBI). When administered alone on a divided dose schedule (24 hours and 30 minutes before TBI), rmGM-CSF (20 micrograms/kg) was ineffective in increasing survival in either strain. However, in Balb/c mice, bryostatin 1 alone (1 microgram) permitted the long-term survival (60 days) of 70% of the animals following TBI, and 80% when administered in conjunction with rmGM-CSF. Bryostatin 1 administered alone according to this schedule exerted minimal radioprotective effects in C3H/HeN mice, but, when combined with a subeffective dose of rmGM-CSF, allowed 50% of the animals to survive. Treatment of Balb/c mice with bryostatin 1 administered as a single dose 4 hours before TBI resulted in a 20% survival rate, and 45% when administered with rmGM-CSF; corresponding values for the C3H/HeN strain were 60% and 40%, respectively. Lastly, the survival rates of Balb/c mice treated with bryostatin 1 administered as a single dose 4 hours following TBI was 20%, and 25% with rmGM-CSF; corresponding values were 50% and 25% for C3H/HeN mice. These findings indicate that the PK-C activator bryostatin 1 exhibits intrinsic in vivo radioprotective effects in lethally irradiated Balb/c and C3H/HeN mice, and may, under some circumstances, augment the radioprotective capacity of rmGM-CSF. They also underscore the critical role that strain differences and scheduling considerations play in determining the in vivo radioprotective capacity of bryostatin 1, as well as its interactions with rmGM-CSF.