Additive effect of three noradrenergic genes (ADRA2A, ADRA2C, DBH) on attention-deficit hyperactivity disorder and learning disabilities in Tourette syndrome subjects

Halperin et al. (Halperin JM. Newcorn JH, Koda VH, Pick L, McKay KE, Knott P. Noradrenergic mechanisms in ADHD children with and without reading disabilities: a replication and extension. J Am Acad Child Adolesc Psychiatry 1997: 36: 1688 1696) reported a significant increase in plasma norepinephrine (NE) in attention-deficit hyperactivity disorder (ADHD) children with reading and other cognitive disabilities compared to ADHD children without learning disabilities (LD). We examined the hypothesis that ADHD + LD was associated with NE dysfunction at a molecular genetic level by testing for associations and additive effects between polymorphisms at three noradrenergic genes the adrenergic alpha2A receptor (ADRA2A), adrenergic alpha2C receptor (ADRA2C), and dopamine beta-hydroxylase (DBH) genes. A total of 336 subjects consisting of 274 individuals with Tourette syndrome (TS) and 62 normal controls were genotyped. Regression analysis showed a significant correlation between scores for ADHD, a history of LD, and poor grade-school academic performance that was greatest for the additive effect of all three genes. Combined, these three genes accounted for 3.5% of the variance of the ADHD score (p = 0.0005). There was a significant increase in the number of variant NE genes progressing from subjects without ADHD (A-) or learning disorders (LD-) to A + LD - to A - LD + to A + LD + (p = 0.0017), but no comparable effect for dopamine genes. These data support an association between NE genes and ADHD, especially in ADHD + LD subjects.     

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.     

Prevalence of Vitamin D Deficiency in Uninsured Women

Background Vitamin D deficiency, an important risk factor for osteoporosis and other chronic medical conditions, is epidemic in the United States. Uninsured women may be at an even higher risk for vitamin D deficiency than others owing to low intake of dietary and supplemental vitamin D and limited sun exposure. Objective Our goal was to determine the prevalence of vitamin D deficiency in this vulnerable population. Setting and Participants We enrolled 145 uninsured women at a County Free Medical Clinic in urban Michigan. Questionnaires were used to obtain information about demographics, medical history, vitamin supplementation, sunlight exposure, and dietary vitamin D intake. Results The 96 women who were tested for vitamin D status ranged in age from 21 to 65 years (mean 48 ± 11), and 67% were vitamin D deficient as indicated by a 25-hydroxyvitamin D [25(OH)D)] level <50 nmol/L (20 ng/mL). Non-Caucasians were 3 times more likely than Caucasians to be vitamin D deficient (P = .049). Mean dietary vitamin D intake was low (125 ± 109 IU/d) and only 24% of the participants used any supplemental vitamin D. Participants with total vitamin D intake <400 IU/day from diet and supplements were 10 times more likely to be vitamin D deficient than others (P < .001). Conclusions These results demonstrate a high prevalence of vitamin D deficiency in an uninsured, medically underserved female population. Uninsured women should be strongly encouraged to increase their vitamin D intake.     

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)