Differential expression of vasopressin receptor binding in the hypothalamus during lactation in golden hamsters

Vasopressin (AVP) receptor binding within hypothalamic sites was compared between cycling and lactating female golden hamsters. The density of AVP receptor binding was analyzed by quantitative autoradiography within the ventrolateral hypothalamus and dorsomedial hypothalamic nucleus. Lactation was correlated with a disappearance of AVP receptor binding within the ventrolateral hypothalamus. In contrast, lactation was associated with a two- to three-fold increase in the density of AVP receptor binding within the dorsomedial hypothalamic nucleus. These results suggest that AVP receptor binding within the ventrolateral hypothalamus is responsive to gonadal hormones in female golden hamsters. However, the increase in binding observed within the dorsomedial hypothalamus may be related to other neurobiological changes associated with lactation.     

Early treatment of juvenile xanthogranuloma of the iris with subconjunctival steroids.

Five infants with biopsy proved juvenile xanthogranuloma of the iris were reviewed. Early treatment with subconjunctival injection of steroids and topical steroid drops resulted in regression of the lesion in four patients. One patient, reviewed at the age of 8 months after glaucoma which had developed secondary to the iris xanthogranuloma, had been treated by surgery alone: the visual outcome was very poor.     

Development of a new radioimmunoassay for human osteocalcin: evidence for a midmolecule epitope

Osteocalcin is a vitamin K-dependent bone-specific protein that can be found circulating in the serum. The circulating levels of osteocalcin have been shown to be an index of bone turnover. Existing radioimmunoassays for osteocalcin have been shown to be specific for C-terminal epitopes, a region that is identical in the human and bovine osteocalcin. There are, however, five amino acids different in the N-terminal region of the molecule. We describe here an immunoassay for a midmolecule epitope of osteocalcin using osteocalcin purified from human femoral head bone powder. Antibody specificity was determined using tryptic digests and a synthetic fragment of human osteocalcin. This assay has only a partial crossreactivity with bovine osteocalcin. This is the first report of an assay against a midmolecular epitope of osteocalcin involving a region in which the human and bovine osteocalcins differ. Osteocalcin levels determined by this assay have a significant correlation with both the total serum alkaline phosphatase and the serum skeletal alkaline phosphatase levels in normal adult human serum and, to a greater degree, in sera of patients with conditions associated with increased bone turnover (Paget's disease, hyperparathyroidism, and newborn sera). These correlations are greater than those previously reported for C-terminal assays, suggesting the possibility that different regions of the molecule may elicit different information concerning bone turnover.     

Increased procollagenase activating angiogenic factor in the vitreous humour of oxygen treated kittens.

Previous studies have demonstrated an increase in a low molecular weight angiogenic factor (ESAF) present in the retinae of kittens with oxygen induced retinopathy. The present paper describes differences in the quantity of ESAF extracted from the vitreous humour of control and oxygen treated animals and proposes a mechanism for the induction of intravitreal neovascularisation.     

Hybridization of Aedes (protomacleaya) zoosophus with Ae. (Pro.) triseriatus group species: hybrid morphology

Morphology of hybrids between Aedes (Protomacleaya) zoosophus and Ae. (Pro.) triseriatus group species is described. Adult females of hybrids key to Ae. zoosophus. Hybrids are differentiated from Ae. zoosophus by the dark longitudinal medial or submedial lines on the thorax and by the reduced width of the light tarsal and abdominal bands. The transverse band of light scales on the anterior scutum is complete in Ae. hendersoni/Ae. zoosophus hybrids and incomplete in Ae. triseriatus/Ae. zoosophus hybrids. Aedes brelandi/Ae. zoosophus hybrids are similar to Ae. hendersoni/Ae. zoosophus hybrids. However, due to the allopatric distributions of Ae. brelandi and Ae. zoosophus, such hybrids are not expected.     

The cardiac effects of terfenadine after inhibition of its metabolism by grapefruit juice

Objective: To determine whether the pharmacokinetics and electrocardiographic pharmacodynamics of terfenadine are affected by the concomitant administration of grapefruit juice. Methods: Six healthy volunteers were recruited for a balanced cross-over study. Each volunteer received 120 mg terfenadine 30 min after drinking 300 ml of either water or freshly squeezed grapefruit juice. The alternative treatment was administered on the second study day 2 weeks later. Measurements of the area under the terfenadine plasma concentration-time curve (AUC), maximum terfenadine concentration (C_max) and the time to maximum concentration (t_max) were made, and the corrected QT (QTc) interval was measured from the surface electrocardiogram. Results: Terfenadine was quantifiable in plasma in all 6 subjects on both study days for up to 24 h post-dosing. The AUC of terfenadine was significantly increased by concomitant grapefruit administration (median values 40.6 vs 16.3 ng · ml⁻¹ · h), as was the C_max (median values 7.2 vs 2.1 ng · ml⁻¹). The t_max was not significantly increased and there was no significant change in the median QTc interval despite the increased terfenadine levels. The 95% confidence interval for the difference in the change in QTc interval at C_max was −13 to +38 ms. Conclusion: Administration of grapefruit juice concomitantly with terfenadine may lead to an increase in terfenadine bioavailability, but the increase observed in this study did not lead to significant cardiotoxicity in normal subjects. However, this does not exclude the risk of cardiotoxicity in high-risk subjects given greater doses of grapefruit juice over longer periods of time. Received: 14 October 1996 / Accepted in revised form: 10 December 1996     

How are nations trying to prevent suicide? An analysis of national suicide prevention strategies

Recent increases in suicide rates internationally have focused attention on suicide as an important area of public health concern. In this review, strategies developed by various countries to halt this trend are compared. Nine out of 15 countries respond to enquiry about the state of development of suicide prevention strategies and programmes. Comprehensive strategies have been or are being developed by Finland, Norway, Australia, New Zealand and Sweden. The organization of these strategies differs between countries. The interventions have similar targets and are presented in detail. There are some similarities in strategy content but evident differences in organization. Further developments should not only be based on research, but also consider the diverse experiences of other countries, and they should incorporate appropriate structures for monitoring and evaluation.     

Pituitary Adenylate Cyclase-Activating Polypeptide (PACAP) Actions on αT3-1 Gonadotrophs Show Desensitization

PACAP is a hypothalamic hypophysiotropic factor that acts upon a number of pituitary cells, including gonadotrophs. In the gonadotroph-derived αT3-1 cell line, PACAP acts via PVR1 receptors to stimulate adenylyl cyclase and phosphoinositidase C. PACAP-stimulated cAMP accumulation is inhibited by protein kinase C-activating phorbol esters in these cells and the current work was undertaken primarily to establish whether it is also subject to homologous regulation. In acute experiments, PACAP27-stimulated cAMP accumulation (intracellular plus extracellular) was measured (in the presence of phosphodiesterase inhibitor) both in intact cells and in cell membranes. The peptide increased cAMP accumulation, but initial rates of PACAP27-stimulated cAMP accumulation were reduced to between 10 and 50% within 10 min of stimulation in both cells and membranes. The initial rate of forskolin-stimulated cAMP accumulation was maintained in membranes but not in intact cells (although the deviation from linearity was less pronounced than with PACAP27). Thus, rapid homologous desensitization to PACAP27 occurs in intact αT3-1 cells, but is not entirely receptor specific. Rapid homologous desensitization of PACAP27-stimulated cAMP accumulation also occurred in the presence of a protein kinase C activating phorbol ester, which inhibited cAMP accumulation without altering the kinetics of the PACAP27 effect. Brief pre-treatment (3 min) with PACAP27 also reduced the ability of PACAP27, but not gonadotrophin-releasing hormone, to cause a spike-type elevation of cytosolic Ca²⁺ concentration (a consequence of phosphoinositidase C activation). In chronic desensitization studies, pre-treatment for 6 h with PACAP27 caused a dose-dependent (IC₅₀ approximately 10 nM) reduction of PACAP-stimulated cAMP accumulation and down regulated cell surface PVR1 receptors (to approximately 50%). Thus, it appears that PACAP27-stimulated (PVR-1 receptor mediated) adenylyl cyclase undergoes rapid homologous desensitization in αT3-1 cells, which is paralleled by homologous desensitization of PACAP27-stimulated phosphoinositidase C activity and involves mechanisms distinct from those underlying heterologous desensitization by phorbol esters. Chronic desensitization of PACAP-stimulated cAMP accumulation and down-regulation of cell surface PVR-1 receptors also occurs in these cells although the receptor loss may not entirely explain the observed desensitization.     

Radiotherapy in the treatment of low-grade astrocytomas

Between 1954 and 1986 inclusive, 160 children in the North West Region of England were registered with histologically proven lowgrade astrocytomas (grade 1 or 2). Ten died before receiving any treatment, and a further seven died within 28 days of surgery, leaving 143 children whose survival in relation to treatment modality is the subject of this paper. Low-grade astrocytomas are responsive to radiation therapy. This treatment has no clear benefit to offer children with superficial tumours that can be resected completely or nearly so, but significantly improves survival rates when tumours are deep-seated and not amenable to excision.     

The taking of adequate cervical smears

In order for cytological examination of a cervical smear to be an adequate method of screening for pre-invasive lesions, the smear must contain both squamous and endocervical cells. Figures obtained for 1988 indicated that in South Africa 45% of smears do not contain endocervical cells. The study reported, in which the same patients were compared in successive years but using different techniques, showed that with the use of biomedically designed tools 98.3% of smears can be classified as adequate.