Analysis of ERCC2/XPD functional polymorphisms in systemic lupus erythematosus

Sunlight/ultraviolet (UV) irradiation has been recognized as an important risk factor for developing systemic lupus erythematosus (SLE). However, the interpretation of genetic variations involved in UV‐light sensitivity is largely unknown. Recent studies indicated that two genetic variations of ERCC2/XPD gene (rs1799793 in exon 10 and rs13181 in exon 23) have been found to exert negative influences on nucleotide excision repair system. To analyse the possible contribution of the ERCC2/XPD functional single nucleotide polymorphisms in genetic susceptibility to SLE, the rs13181 and rs1799793 SNPs in ERCC2/XPD were genotyped by polymerase chain reaction followed by restriction fragment length polymorphism analysis. Association was studied by case–control analyses using samples from 172 SLE patients and 160 healthy controls. Haplotype analysis was performed to detect the association with genetic predisposition to SLE and the clinical features. Although these two functional genetic variations are linked to several immune dysfunction‐induced diseases, no statistically significant differences in allele or genotype frequencies were observed between SLE patients and controls. Haplotype analysis showed that none of ERCC2/XPD haplotypes was associated with the incidence of SLE disease, nor the preference of clinical features. In conclusion, the ERCC2/XPD functional polymorphisms analysed in this study showed no association in genetic susceptibility to SLE.     

Protocadherin PCDH10, involved in tumor progression,is a frequent and early target of promoter hypermethylation in cervical cancer

Cervical cancer (CC) is the second most common cancer in women. Currently, no tractable molecular‐based therapeutic targets exist for patients with invasive CC and no predictive markers of risk assessment for progression of precancerous lesions are identified. New molecular insights into CC pathogenesis are urgently needed. Towards this goal, we first determined the copy number alterations of chromosome 4 and then examined the role of PCDH10 mapped to 4q28 as a candidate tumor suppressor gene. We identified monosomy 4 in 47% of 81 invasive CC studied by SNP array and found that 91% of 130 invasive CC harboring methylation in the promoter region of the PCDH10 gene. We then showed that aberrant promoter hypermethylation of PCDH10 is associated with downregulation of gene expression and cell lines exposed to demethylating agent resulted in profound reactivated gene expression. We also showed that the promoter methylation in the PCDH10 gene occurs at an earliest identifiable stage of low‐grade squamous intraepithelial lesion. Our studies demonstrate that inactivation of PCDH10 may be a critical event in CC progression and form a potentially useful therapeutic target for CC. © 2009 Wiley‐Liss, Inc.     

Synergistic effects of dehydroepiandrosterone and fluoxetine on proliferation of progenitor cells in the dentate gyrus of the adult male rat

The 5-HT re-uptake inhibitor (SSRI) fluoxetine and the adrenal hormone dehydroepiandrosterone (DHEA) both increase the proliferation of progenitor cells in the adult hippocampus and also have antidepressant activity. This paper explores the combined ability of fluoxetine and DHEA to affect this process in the dentate gyrus of adult rats. We show that DHEA can render an otherwise ineffective dose of fluoxetine (2.5 mg/kg) able to increase progenitor cell proliferation to the same extent as doses four times higher (10 mg/kg). This synergistic action does not appear to be mediated by alterations in brain-derived neurotrophic factor (BDNF) gene expression; or by TrkB, mineralocorticoid, glucocorticoid, or 5-HT (5HT1A) receptor expression in the dentate gyrus; or by altered levels of plasma corticosterone. In a second experiment, the synergism between DHEA and fluoxetine was replicated. Furthermore, flattening the diurnal rhythm of plasma corticosterone by implanting additional corticosterone pellets s.c. prevented the effect of fluoxetine on progenitor cell division. This was not overcome by simultaneous treatment with DHEA, despite the latter's reported anti-glucocorticoid actions. The cellular mechanism for the potentiating action of DHEA on the pro- proliferative effects of fluoxetine in the adult hippocampus remains to be revealed. Since altered neurogenesis has been linked to the onset or recovery from depression, one consequence of these results is to suggest DHEA as a useful adjunct therapy for depression.     

Patent applications for using DNA technologies to authenticate medicinal herbal material

Herbal medicines are used in many countries for maintaining health and treating diseases. Their efficacy depends on the use of the correct materials, and life-threatening poisoning may occur if toxic adulterants or substitutes are administered instead. Identification of a medicinal material at the DNA level provides an objective and powerful tool for quality control. Extraction of high-quality DNA is the first crucial step in DNA authentication, followed by a battery of DNA techniques including whole genome fingerprinting, DNA sequencing and DNA microarray to establish the identity of the material. New or improved technologies have been developed and valuable data have been collected and compiled for DNA authentication. Some of these technologies and data are patentable. This article provides an overview of some recent patents that cover the extraction of DNA from medicinal materials, the amplification of DNA using improved reaction conditions, the generation of DNA sequences and fingerprints, and the development of high-throughput authentication methods. It also briefly explains why these patents have been granted.     

Impact of Baby‐Friendly Hospital Practices on Breastfeeding in Hong Kong

Abstract: Background: The World Health Organization (WHO) developed the Baby‐Friendly Hospital Initiative to improve hospital maternity care practices that support breastfeeding. In Hong Kong, although no hospitals have yet received the Baby‐Friendly status, efforts have been made to improve breastfeeding support. The aim of this study was to examine the impact of Baby‐Friendly hospital practices on breastfeeding duration. Methods: A sample of 1,242 breastfeeding mother‐infant pairs was recruited from four public hospitals in Hong Kong and followed up prospectively for up to 12 months. The primary outcome variable was defined as breastfeeding for 8 weeks or less. Predictor variables included six Baby‐Friendly practices: breastfeeding initiation within 1 hour of birth, exclusive breastfeeding while in hospital, rooming‐in, breastfeeding on demand, no pacifiers or artificial nipples, and information on breastfeeding support groups provided on discharge. Results: Only 46.6 percent of women breastfed for more than 8 weeks, and only 4.8 percent of mothers experienced all six Baby‐Friendly practices. After controlling for all other Baby‐Friendly practices and possible confounding variables, exclusive breastfeeding while in hospital was protective against early breastfeeding cessation (OR: 0.61; 95% CI: 0.42–0.88). Compared with mothers who experienced all six Baby‐Friendly practices, those who experienced one or fewer Baby‐Friendly practices were almost three times more likely to discontinue breastfeeding (OR: 3.13; 95% CI: 1.41–6.95). Conclusions: Greater exposure to Baby‐Friendly practices would substantially increase new mothers’ chances of breastfeeding beyond 8 weeks postpartum. To further improve maternity care practices in hospitals, institutional and administrative support are required to ensure all mothers receive adequate breastfeeding support in accordance with WHO guidelines. (BIRTH 38:3 September 2011)     

The Dangers of Hymenotomy for Imperforate Hymen: A Case of Iatrogenic Pelvic Inflammatory Disease with Pyosalpinx

BackgroundComplications associated with imperforate hymen include cyclical abdominal pain, acute urinary retention, endometriosis, and even iatrogenic infections.CaseA 14-year-old young woman was diagnosed with an imperforate hymen, hematocolpos, and right hematosalpinx. A hymenotomy was performed, followed by a hymenectomy 3 days later. On postoperative day 7, she was admitted for pelvic inflammatory disease with a right pyosalpinx. The infection was refractory to intravenous gentamicin, ampicillin, and clindamycin so the patient underwent computed tomography-guided drainage of the pyosalpinx. Two days later, she was discharged home in good condition.Summary and ConclusionSmall incisions and punctures into imperforate hymens without immediate definitive management should be avoided because inoculation of the newly introduced bacteria can ascend the gynecologic tract and lead to serious infections.     

Effects of high dose of simvastatin on levels of dopamine and its reuptake in prefrontal cortex and striatum among SD rats

Statins are increasingly being used for the treatment of a variety of conditions beyond their original indication for cholesterol lowering. We previously reported that simvastatin increased dopamine receptors in the rat prefrontal cortex [Q. Wang, W.L. Ting, H. Yang, P.T. Wong, High doses of simvastatin upregulate dopamine D₁ and D₂ receptor expression in the rat prefrontal cortex: possible involvement of endothelial nitric oxide synthase, Br. J. Pharmacol. 144 (2005) 933–939] and restored its downregulation in a model of Parkinson's disease (PD) [Q. Wang, P.H. Wang, C. McLachlan, P.T. Wong, Simvastatin reverses the downregulation of dopamine D1 and D2 receptor expression in the prefrontal cortex of 6-hydroxydopamine-induced Parkinsonian rats, Brain Res. 1045 (2005) 229–233]. Here we explore the effects of simvastatin treatment on tissue dopamine content and reuptake. Sprague–Dawley rats were given simvastatin (1 and 10 mg kg⁻¹ day⁻¹, p.o.) for 4 weeks. Brain tissue from prefrontal cortex and striatum were taken out for dopamine content and its reuptake. Using high-performance liquid chromatographic-mass spectrometer (HPLC-MS), simvastatin (10 mg kg⁻¹ day⁻¹) was found to increase dopamine content by 110% in the striatum but decreased by 76% in the prefrontal cortex compared with the saline treated group. Dopamine (DA) reuptake was unchanged in both brain regions. These results suggest that chronic treatment with high dose of simvastatin may affect DA tissue level in prefrontal cortex and striatum without changing on DA reuptake. This may have important clinical implications in psychiatric and striatal dopaminergic disorders.