Persistent reduction in sialylation of cerebral glycoproteins following postnatal inflammatory exposure

Background

The extension of sepsis encompassing the preterm newborn’s brain is often overlooked due to technical challenges in this highly vulnerable population, yet it leads to substantial long-term neurodevelopmental disabilities. In this study, we demonstrate how neonatal neuroinflammation following postnatal E. coli lipopolysaccharide (LPS) exposure in rat pups results in persistent reduction in sialylation of cerebral glycoproteins.

Methods

Male Sprague-Dawley rat pups at postnatal day 3 (P3) were injected in the corpus callosum with saline or LPS. Twenty-four hours (P4) or 21?days (P24) following injection, brains were extracted and analyzed for neuraminidase activity and expression as well as for sialylation of cerebral glycoproteins and glycolipids.

Results

At both P4 and P24, we detected a significant increase of the acidic neuraminidase activity in LPS-exposed rats. It correlated with significantly increased neuraminidase 1 (Neu1) mRNA in LPS-treated brains at P4 and with neuraminidases 1 and 4 at P24 suggesting that these enzymes were responsible for the rise of neuraminidase activity. At both P4 and P24, sialylation of N-glycans on brain glycoproteins decreased according to both mass-spectrometry analysis and lectin blotting, but the ganglioside composition remained intact. Finally, at P24, analysis of brain tissues by immunohistochemistry showed that neurons in the upper layers (II–III) of somatosensory cortex had a reduced surface content of polysialic acid.

Conclusions

Together, our data demonstrate that neonatal LPS exposure results in specific and sustained induction of Neu1 and Neu4, causing long-lasting negative changes in sialylation of glycoproteins on brain cells. Considering the important roles played by sialoglycoproteins in CNS function, we speculate that observed re-programming of the brain sialome constitutes an important part of pathophysiological consequences in perinatal infectious exposure.

     

Mobilizing the community to address the prenatal health needs of Immigrant Punjabi women

In Canada, although prenatal education is available to all women, there are groups who do not access these services. One such group is Immigrant Punjabi women residing in the Lower Mainland of British Columbia. It was apparent that structured prenatal education, even when translation was available, would not meet the needs of this group. Efforts were required to help bring this issue into the community so that the community would endorse women's participation in prenatal preparation. The purpose of the project described in this article was to explore how community mobilization strategies could be used to improve the health of pregnant women in the Punjabi community. A collaborative approach was used with representatives from a variety of service agencies and the community. The mobilization strategy involved creating a platform to communicate with the community about prenatal health and health care, creating "buy-in" from the physicians serving the women of the community, and providing prenatal sessions that built on the existing knowledge of the women. We describe the mobilization process and discuss the insights gained.     

Coronary artery bypass grafting and concomitant excision of chest wall chondrosarcoma

Coexistence of coronary artery disease and cancer with both requiring surgical treatment at the same time is rare. A 52 year male undergoing elective coronary artery bypass grafting was incidentally discovered to have a large soft tissue mass of variable consistency with cartilaginous elements arising from the right costal margin and adjoining ribs by a broad attachment and protruding into right pleural cavity. Frozen section suggested it to be either a chondrosarcoma or a teratoma. A wide excision of the mass with the adjoining muscle and periosteum along with quadruple coronary artery bypass grafting was done. This report is unusual on account of a) being the first reported case in world literature of concomitant excision of chondrosarcoma and coronary artery bypass grafting and b) the conservative management of the incidentally discovered chondrosarcoma by wide excision rather than chest wall resection with no local recurrence to date. Pathology of chondrosarcoma, in particular, and various management strategies when coronary artery disease and cancer coexist, in general, is discussed.     

Catalase and superoxide dismutase double staining zymogram technique for Deinococcus and Kocuria species exposed to multiple stresses

Superoxide dismutase (SOD) and catalase expression is associated with oxidative stress. Existing techniques for the individual staining of SOD and catalase have been described in the past. The objective of this study was to achieve a simple and rapid technique for the double staining of bacterial SOD and catalase on the same polyacrylamide gel. SOD detection was carried out using nitro‐blue tetrazolium (NBT) dye reduction followed by ferricyanide precipitation for negative staining of the catalase enzyme on the same gel. The staining procedure resulted in pale blue SOD bands while catalase appeared as yellow bands against a greenish blue background on the same gel. This technique was used to detect changes in the polymorphic forms of these enzymes in Deinococcus radiodurans R1 and Kocuria sp. C2 subjected to stresses like UV and gamma radiation and desiccation. (© 2009 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)     

Is it trichotillomania? Hair pulling in childhood: a developmental perspective

A cohort of children with hair pulling as the presenting symptom was followed up to enhance clinical understanding of the nature of hair-pulling behaviour in childhood. Thirty-eight children were clinically assessed for a diagnosis of trichotillomania, co-morbidity, co-existing habits and other relevant factors. Intervention consisted of a combination of behavioural strategies, self-esteem work, supportive family approaches, attachment-focused parenting models and medication. In this group of children it was difficult to define their symptoms as a clinical diagnosis of trichotillomania, using ICD-1O/DSM-IV. This article concludes that hair pulling, as a symptom in children, is a heterogeneous condition. It is useful to approach this issue from a developmental perspective. Our data warrant reappraisal of the diagnosis of trichotillomania in childhood. We explore the framework of a developmental continuum to understand and manage the problem of hair pulling in childhood.     

Characterization of GABAergic neurons in rapid-eye-movement sleep controlling regions of the brainstem reticular formation in GAD67-green fluorescent protein knock-in mice

Recent experiments suggest that brainstem GABAergic neurons may control rapid-eye-movement (REM) sleep. However, understanding their pharmacology/physiology has been hindered by difficulty in identification. Here we report that mice expressing green fluorescent protein (GFP) under the control of the GAD67 promoter (GAD67-GFP knock-in mice) exhibit numerous GFP-positive neurons in the central gray and reticular formation, allowing on-line identification in vitro . Small (10–15 µm) or medium-sized (15–25 µm) GFP-positive perikarya surrounded larger serotonergic, noradrenergic, cholinergic and reticular neurons, and > 96% of neurons were double-labeled for GFP and GABA, confirming that GFP-positive neurons are GABAergic. Whole-cell recordings in brainstem regions important for promoting REM sleep [subcoeruleus (SubC) or pontine nucleus oralis (PnO) regions] revealed that GFP-positive neurons were spontaneously active at 3–12 Hz, fired tonically, and possessed a medium-sized depolarizing sag during hyperpolarizing steps. Many neurons also exhibited a small, low-threshold calcium spike. GFP-positive neurons were tested with pharmacological agents known to promote (carbachol) or inhibit (orexin A) REM sleep. SubC GFP-positive neurons were excited by the cholinergic agonist carbachol, whereas those in the PnO were either inhibited or excited. GFP-positive neurons in both areas were excited by orexins/hypocretins. These data are congruent with the hypothesis that carbachol-inhibited GABAergic PnO neurons project to, and inhibit, REM-on SubC reticular neurons during waking, whereas carbachol-excited SubC and PnO GABAergic neurons are involved in silencing locus coeruleus and dorsal raphe aminergic neurons during REM sleep. Orexinergic suppression of REM during waking is probably mediated in part via excitation of acetylcholine-inhibited GABAergic neurons.     

What is the proper workup of a patient with hypertension?

Because hypertension is common and many tests are available, an uncritical approach to laboratory and radiologic evaluation leads to unnecessary expenses. However, in most patients, accurate blood pressure measurement, a focused history and physical examination, and a handful of basic tests are enough. In this review we address the key questions in the evaluation of the patient with an elevated pressure reading, ie, does the patient have sustained high blood pressure? And if so, is the hypertension primary or secondary, are other cardiovascular risk factors present, and is there evidence of target organ damage?