Adult attachment and gene polymorphisms of the dopamine D4 receptor and serotonin transporter (5-HTT)

Recently, the Dopamine D4 Receptor Gene (DRD4) and the Serotonin Transporter Gene (5-HTT) have been found to be candidate genes for infant attachment disorganization. The present study aimed to explore the relationship of these genes to adult attachment representations. The Adult Attachment Interview was used to assess attachment representations in 167 German adults. DNA from buccal cells was genotyped for the DRD4 VNTR Exon III and 5-HTT LPR polymorphisms with respect to the presence of the 7repeat allele and the short allele, respectively. DRD4 7repeat allele carriers were significantly more likely to be securely attached than those without 7repeat but only for subjects with unloving caregiver recollections. No association between the 5-HTT LPR polymorphism and adult attachment was found. These findings encourage further investigations to explore endophenotypical and mediating psychological processes between the DRD4 Gene and secure attachment patterns.     

中国儿童与老年健康证据转化平台的构建与应用

目的介绍并推广中国儿童与老年健康证据转化平台(Chinese Clearinghouse for Evidence Translation in Child & Aging Health,CCET)。方法分别成立儿童、老年健康顾问委员会,利用科学的评价量表评价筛选国内外相关的儿童、老年健康促进项目并由研究团队翻译转化。与兰州博阳软件工程有限公司合作,根据网站需呈现的内容与目标功能,共同规划设计网站框架与界面,初步建立站点。将转化的健康证据及其他信息资源（疾病基本情况、项目评价量表、研究报告标准等）上传使之在网站相应栏目中呈现,建立CCET网站,并通过微信和微博媒介定期传播儿童及老年健康最新进展、循证研究最新方法。结果CCET主要由儿童健康、老年健康、评价量表、报告标准、推广应用和老年抑郁症循证防治数据库6个版块组成。CCET儿童与老年健康促进项目由国内外专家采用科学的评价量表筛选和评价,转化的证据科学性强,目前已有相关研究机构和社区有意向参与CCET研究和应用转化项目。结论CCET致力于循证方法培训,建立国内健康干预项目的科学性和适用性评价系统,对国外证据转换后的后续干预项目培训,提升服务机构能力,以及综合干预课程研发。CCET信息全面、界面简单、用户友好,为促进我国儿童与老年健康提供证据支持。     

FGF23 Is Endogenously Phosphorylated in Bone Cells

Levels of serum phosphate are controlled by the peptide hormone FGF23, secreted from bone osteocytes. Elevated levels of circulating FGF23 are a key factor in several hypophosphatemic disorders and play a role in chronic kidney disease. Posttranslational processing of FGF23 includes multi‐site O‐glycosylation, which reduces intracellular cleavage by proprotein convertases. The FGF23 protein also contains four serine phosphorylation consensus sequences (S‐X‐D/E); in this work, we asked whether FGF23 is a substrate for secretory phosphorylation. Both HEK cells as well as IDG‐SW3 cells, an osteocyte model, incorporated radiolabeled orthophosphate into intact FGF23, as well as into the 14‐kDa carboxy‐terminal—but not the 17‐kDa N‐terminal—fragment. Sequential serine‐to‐alanine site‐directed mutagenesis of four kinase consensus sites showed that labeling occurred on three serines within the carboxy‐terminal fragment, Ser180 (adjacent to the cleavage site), Ser207, and Ser212. Liquid chromatography‐coupled mass spectroscopy indicated the presence of phosphate at Ser212 in recombinant R&D mouse FGF23^R179Q, confirming labeling results. A phosphopeptide‐specific antibody was raised against phospho‐Ser212 and exhibited immunoreactivity in osteocytes present in mouse long bone, providing further evidence that FGF23 is naturally phosphorylated in bone. Bone SIBLING proteins are serine‐phosphorylated by the ubiquitous Golgi secretory kinase FAM20C. Cotransfection of HEK and MC3T3 cells with FGF23 and active, but not inactive, FAM20C kinase increased the storage and release of FGF23 in radiolabeling experiments, indicating potential effects of phosphorylation on FGF23 stability. Collectively, these data point to an important role for phosphorylation of FGF23 in bone. © 2014 American Society for Bone and Mineral Research.     

Tamoxifen and Src kinase inhibitors as neuroprotective/neuroregenerative drugs after spinal cord injury

Spinal cord injury(SCI) is a devastating condition that produces significant changes in the lifestyle of patients. Many molecular and cellular events are triggered after the initial physical impact to the cord. Two major phases have been described in the field of SCI: an acute phase and late phase. Most of the therapeutic strategies are focused on the late phase because this provides an opportunity to target cellular events like apoptosis, demyelination, scar formation and axonal outgrowth. In this mini-review, we will focus on two agents(tamoxifen and a Src kinase family inhibitor known as PP2) that have been shown in our laboratory to produce neuroprotective(increase cell survival) and/or regenerative(axonal outgrowth) actions. The animal model used in our laboratory is adult female rat(~250 g) with a moderate contusion(12.5 mm) to the spinal cord at the T10 level, using the MASCIS impactor device. Tamoxifen or PP2 was administered by implantation of a 15 mg pellet(Innovative Research of America, Sarasota, FL, USA) or by intraperitoneal injections(1.5 mg/kg, every 3 days), respectively, to produce a long-term effect(28 days). Tamoxifen and the Src kinase inhibitor, PP2, are drugs that in rats with a moderate spinal cord injury promote functional locomotor recovery, increase spared white matter tissue, and stimulate axonal outgrowth. Moreover, tamoxifen reduces the formation of reactive oxygen species. Therefore, these drugs are possible therapeutic agents that have a neuroprotective/regenerative activity in vertebrates with SCI.     

Role of nNOS in regulation of renal function in angiotensin II-induced hypertension

Previous studies have indicated that in normotensive rats, NO produced by neuronal NO synthase (nNOS) plays an important role in modulating tubuloglomerular feedback (TGF)-mediated afferent arteriolar constriction. It has also been shown that in angiotensin (Ang) II-infused hypertensive rats, there is a reduced ability of nNOS-derived NO to counteract this vasoconstriction. The present study was performed to (1) assess in vivo renal functional responses to intrarenal nNOS inhibition in control and Ang II-infused rats and (2) determine whether changes in renal function following nNOS inhibition are mediated by unopposed stimulation of Ang II receptor subtype 1 (AT(1)). Wistar rats were infused with either saline (SAL) or Ang II (80 ng/min) by osmotic minipumps implanted subcutaneously. Mean arterial blood pressure of SAL- and Ang II-infused rats on day 13 after implantation averaged 121+/-4 (n=28) and 151+/-5 (n=30), respectively (P<0.05). There were no differences in glomerular filtration rate (GFR) (0.68+/-0.09 versus 0.59+/-0.09 mL. min(-1). g(-1)), renal plasma flow (RPF) (2.66+/-0.31 versus 2.34+/-0.39 mL. min(-1). g(-1)), and absolute sodium excretion (0.37+/-0.07 versus 0.42+/-0.09 micromol. min(-1). g(-1)). Intrarenal infusion of SAL did not change GFR, RPF, and sodium excretion in either SAL-infused (n=7) or Ang II-infused rats (n=8). Acute intrarenal administration of the nNOS inhibitor S-methyl-L-thiocitrulline (L-SMTC; 0.3 mg/h) decreased GFR, RPF, and sodium excretion in SAL-infused rats (n=9) by 29+/-4%, 38+/-4%, and 70+/-4% compared with control values (P<0.05). The pretreatment by the AT(1) receptor antagonist candesartan (750 ng IR) in SAL-infused rats (n=7) effectively prevented the decrease in RPF (-3+/-3%) elicited by nNOS inhibition and resulted in an increase in GFR (+25+/-12, P<0.05) and a concomitant greater increase in sodium excretion (84+/-12%, P<0.05) compared with control values. In contrast, in Ang II-infused rats (n=10) intrarenal inhibition of nNOS by L-SMTC did not cause significant decreases in GFR, RPF and sodium excretion (-2+/-2%, -15+/-10%, and -14+/-10%, respectively). These results suggest that in normotensive rats nNOS-derived NO counteracts Ang II-mediated vasoconstriction in the pre- and postglomerular microcirculation. Furthermore, Ang II-infused rats exhibit an impaired ability to release NO by nNOS. Decreased nNOS activity is likely to account at least partially for the enhanced TGF responsiveness in Ang II-infused rats and thus may contribute to the maintenance of hypertension in this model.     

Obstructive sleep apnea and ischemic heart disease in southwestern US veterans: implications for clinical practice

This study describes associations between obstructive sleep apnea (OSA), intake of food rich in antioxidant nutrients, and ischemic heart disease (IHD) in military veterans. Subjects were male veterans (n=211), 54 to 85 years of age, and enrolled in primary care clinics at the Southern Arizona Veterans Affairs Health Care System (SAVAHCS), Tucson, AZ. Measures included the SAVAHCS Minority Vascular Center Questionnaire, the Sleep Heart Health Study Sleep Habits Questionnaire, the Arizona Food Frequency Questionnaire, height, weight, and blood pressure. Veterans with OSA were significantly more likely to be obese, to have elevated systolic blood pressure and physician-diagnosed IHD, more likely to undergo coronary angiography, and less likely to consume foods rich in cardioprotective antioxidants compared to veterans without OSA. After adjusting for confounding variables, the association between OSA and IHD remains significant [adjusted OR=2.99, confidence interval (CI)=1.07–8.42]. These data reinforce the importance of recognizing OSA within the veterans affairs health care system and suggest that early detection of OSA may improve veterans' health and well-being and reduce associated medical costs. This study was presented as a poster at the 17th Annual American Professional Sleep Society Meeting, Chicago, IL, USA June 3–8 2003     

Carbohydrate-Deficient Transferrin in Healthy Women: Relation to Estrogens and Iron Status

The determination of carbohydrate-deficient transferrin (CDT) in serum has been found useful as a marker of increased alcohol consumption of >60 g/day. It is not clear why the reference range is different for women (0 to 26 units/liter) and men (0 to 20 units/liter). We evaluated serum COT in 286 healthy subjects (209 women, 77 men) using a commercially available radioimmunoassay. Premenopausal women had higher CDT levels than postmenopausal women, whereas no age-related difference of CDT levels was found in men. In postmenopausal women, higher CDT levels were associated with estrogen replacement therapy. In premenopausal women, however, neither the phase of the menstrual cycle nor contraceptive steroid use showed a significant association with the increase in CDT levels. No significant correlations were found between CDT and either serum estradiol or serum iron. In conclusion, both premenopausal state and postmenopausal estrogen replacement therapy seem to increase serum levels of CDT. Therefore, menopausal status and exogenous estrogens should be considered when interpreting CDT values in women.     

Association between memory impairment and insomnia among older adults

Chronic insomnia and memory impairment are both common complaints among older adults. Even so, only a few studies to date have examined the effects of chronic insomnia on memory processes among older people, and the results of these studies are contradictory. Therefore, in the current study we examined whether late-life insomnia is associated with the memory status of older adults. The study population comprised two groups: 50 older adult subjects without sleep disorders, and 23 older adult insomniacs. Memory processing for each of the two groups was evaluated using the Rey Auditory Verbal Learning Test (AVLT). The results demonstrate that chronic insomnia in older adults is associated with impairment in memory. Specifically, we found that older people suffering from late-life insomnia exhibit significantly reduced performance in learning rate and in temporal order judgment as well as significantly reduced resistance to proactive interference. The present findings suggest that late-life insomnia may be one of the factors contributing to the decline in memory processing seen among older people.