The transition from fetus to neonate – an endocrine perspective

Gluckman PD, Sizonenko SV, Bassett NS. The transition from fetus to neonate - an endocrine perspective. Acta Pædiatr 1999; Suppl 428: 7–11. Stockholm. ISSN 0803–5326
The transition from fetus to neonate involves three phases: late gestation, parturition and the processes needed to establish independent homoeostatic regulation after separation from the placenta. These phases are regulated by a series of fetal and placental endocrine events. Glucocorticoids have an important role in the preparation for birth, including involvement in lung and cardiac development, and the maturation of enzymes in a variety of pathways. Fetal Cortisol production is, in turn, also under hormonal control. Parturition is a complex process, which is still poorly understood in humans. The final steps are largely dependent on the effect of prostaglandin F_2α on the myometrium associated with increased oxytocin activity. The transition to birth is accompanied by changes in respiration, circulation, glucose homoeostasis, and the onset of independent oral feeding and thermoregulation. Several examples of endocrine components of the transition from fetal to neonatal life are reviewed here: the role of prostanoids, the onset of thermogenesis, and changes in the thyroid hormone and growth hormone axes. The effects of hormone levels on prematurity and growth retardation are also discussed. □ Birth transition, fetus, gestation, hormonal control, neonate, parturition     

Three-Dimensional Anorectal Manometry Enhances Diagnostic Gain by Detecting Sphincter Defects and Puborectalis Pressure

Digestive Diseases and Sciences - Constipation and fecal incontinence (FI) are common and are often evaluated with anorectal manometry. Three-dimensional high-resolution anorectal manometry (HRAM)...     

Brassiere wearing and breast cancer risk: A systematic review and meta-analysis

AIM: To evaluate existing evidence for the association between different type of brassiere exposures and the risk of breast cancer. METHODS: Ovid Medline, CINAHL, Cochrane Data Base of Systematic Reviews, Pubmed, Scopus, Proquest, Sciencedirect, Wiley Online Library, WanFang Data, Hong Kong Index to Chinese Periodicals, China Journal Net, Chinese Medical Current Contents, Chinese Biomedical Literature Database, China Academic Journals Full-Text database, Taiwan Electronic Periodical Services and HyRead; reference lists of published studies; original research studies published in English or Chinese examining the association between type and duration of brassiere-wearing and breast cancer risk. Data were abstracted by a first reviewer and verified by a second. Study quality was rated according to predefined criteria. “Fair” or “good” quality studies were included. Results were summarised by meta-analysis whenever adequate material was available. RESULTS: Twelve case-control studies were included in the review. Meta-analysis showed brassiere wearing during sleep was associated with a two times of increased odds. CONCLUSION: The present review demonstrates insufficient evidence to establish a positive association between the duration and type of brassiere wearing and breast cancer. Further research is essential; specifically, a large-scale epidemiological study of a better design is needed to examine the association between various forms of brassiere exposure in detail and breast cancer risk, with adequate control of confounding variables.     

The selective sphingosine 1-phosphate receptor modulator BAF312 redirects lymphocyte distribution and has species-specific effects on heart rate

BACKGROUND AND PURPOSE

BAF312 is a next-generation sphingosine 1-phosphate (S1P) receptor modulator, selective for S1P₁ and S1P₅ receptors. S1P₁ receptors are essential for lymphocyte egress from lymph nodes and a drug target in immune-mediated diseases. Here, we have characterized the immunomodulatory potential of BAF312 and the S1P receptor-mediated effects on heart rate using preclinical and human data.

EXPERIMENTAL APPROACH

BAF312 was tested in a rat experimental autoimmune encephalomyelitis (EAE) model. Electrophysiological recordings of G-protein-coupled inwardly rectifying potassium (GIRK) channels were carried out in human atrial myocytes. A Phase I multiple-dose trial studied the pharmacokinetics, pharmacodynamics and safety of BAF312 in 48 healthy subjects.

KEY RESULTS

BAF312 effectively suppressed EAE in rats by internalizing S1P₁ receptors, rendering them insensitive to the egress signal from lymph nodes. In healthy volunteers, BAF312 caused preferential decreases in CD4⁺ T cells, T_naïve, T_{central memory} and B cells within 4–6 h. Cell counts returned to normal ranges within a week after stopping treatment, in line with the elimination half-life of BAF312. Despite sparing S1P₃ receptors (associated with bradycardia in mice), BAF312 induced rapid, transient (day 1 only) bradycardia in humans. BAF312-mediated activation of GIRK channels in human atrial myocytes can fully explain the bradycardia.

CONCLUSION AND IMPLICATIONS

This study illustrates species-specific differences in S1P receptor specificity for first-dose cardiac effects. Based on its profound but rapidly reversible inhibition of lymphocyte trafficking, BAF312 may have potential as a treatment for immune-mediated diseases.     

Complementary and alternative medicine use in British Columbia--a survey of HIV positive people on antiretroviral therapy

In 2002, the British Columbia (BC) Centre for Excellence in HIV/AIDS collected final detailed data on complementary and alternative medicine (CAM) use in their HIV treatment program. This cross-sectional study of 682 participants examines types and determinants of CAM use in this program, and examines adverse effects associated with CAM use and antiretroviral therapy (ART). Among the 47% ever CAM users in the included population, vitamins/minerals (81%), meditation/yoga (36%), massage (31%), marijuana (30%), dietary supplements (24%), and herbal medicines (19%), were most commonly used. Multivariate analysis indicated CAM users were less likely to have low education (AOR=0.51), more likely to be unemployed (AOR=1.52), more likely to have been on ART longer (AOR=1.19), and more likely to experience objective, action-requiring (OA) side effects (AOR=1.45). CAM use is common. Both patients and health professionals should be aware of potential toxicities and drug interactions related to the use of CAM and HIV/AIDS treatment.     

Ultrasound and Doppler findings in a rare case of Castleman's disease of the parotid

Castleman''s disease of the parotid gland is an extremely rare entity, with fewer than 20 cases reported in world literature so far and only 1 previous case report describing the ultrasound findings. The Doppler findings of parotid Castleman''s disease have never been described before to the best of the authors'' knowledge. This report describes the ultrasonographic and Doppler findings in a histopathologically proven case of Castleman''s disease of the left parotid gland in a young man.     

Platelet-activating factor receptor (PAF-R)-dependent pathways control tumour growth and tumour response to chemotherapy

Background  

Phagocytosis of apoptotic cells by macrophages induces a suppressor phenotype. Previous data from our group suggested that this occurs via Platelet-activating factor receptor (PAF-R)-mediated pathways. In the present study, we investigated the impact of apoptotic cell inoculation or induction by a chemotherapeutic agent (dacarbazine, DTIC) on tumour growth, microenvironmental parameters and survival, and the effect of treatment with a PAF-R antagonist (WEB2170). These studies were performed in murine tumours: Ehrlich Ascitis Tumour (EAT) and B16F10 melanoma.