Association of adiponectin genotype polymorphisms at positions 45 and 276 with obstructive sleep apnea hypopnea syndrome

Objective: To investigate the relationship between adiponectin genotype polymorphisms and obstructive sleep apnea hypopnea syndrome (OSAHS). Methods: Using the TaqMan polymerase chain reaction(PCR) method, the single nucleotide polymorphisms(SNP)at positions 45 and 276 in the adiponectin gene were determined in Chinese of the Han nationality in the Nanjing district. The OSAHS group consisted of 78 patients, and the control group contained 40 subjects. The association of adiponectin genotype polymorphisms at positions 45 and 276 with obstructive sleep apnea hypopnea syndrome was analyzed. Results: No evidence of a direct association was found between OSAHS and adiponectin genotype SNP at positions 45 and 276(P> 0.05). However, compared with those OSAHS patients having G/T+T/T genotype at position 276, the OSAHS patients with the G/G genotype showed a greater neck circumference(NC), a prolonged duration of the longest apnea event, and elevated levels of blood cholesterol and low-density lipoprotein cholesterol(P < 0.05). Conclusion: No direct association was detected between OSAHS and adiponectin genotype distribution at positions 45 and 276 in Chinese of Han nationality in the Nanjing district. However, OSAHS patients with the adiponectin GIG genotype at position 276 had a larger NC and the longest apnea event compared to those having the adiponectin SNP276 G/T +T/T genotype. This may have an indirect influence on the development of OSAHS.     

脂联素基因单核苷酸多态性与阻塞性睡眠呼吸暂停低通气综合征的关系

目的:探讨脂联素基因单核苷酸多态性(SNP)与阻塞性睡眠呼吸暂停低通气综合征(OSAHS)之间的关系。方法:采用聚合酶链反应-限制性片段长度多态性(PCR-RFLP)方法,分析了南京地区40例正常对照者、78例OSAHS患者脂联素基因的两个单核苷酸多态性(SNP 45,SNP 276)。结果:脂联素SNP 45,SNP 276的多态性分布与OSAHS的发病无直接相关性(P>0.05)。但在OSAHS患者中,携带脂联素基因SNP 276G/G基因型与(G/T T/T)基因型相比:颈围增粗,最长呼吸暂停时间延长,胆固醇升高,低密度脂蛋白增加(P<0.05)。结论:SNP 45,SNP 276的多态性分布与南京地区汉族人群OSAHS的发病无直接相关性,但在OSAHS患者中,携带脂联素SNP 276G/G基因型者与G/T T/T基因型者相比,促使OSAS发展和加重的潜在危险性可能更大。     

Relationship of plasminogen activator inhibitor 1 gene 4G/5G polymorphisms to hypertension in Korean women

Background  Hypertension (HTN) is a major determinant of various cardiovascular events. Plasma levels of plasminogen activator inhibitor 1 (PAI-1) modulate this risk. A deletion/insertion polymorphism within the PAI-1 loci (4G/4G, 4G/5G, 5G/5G) affects the expression of this gene. The present study investigated the association between PAI-1 loci polymorphisms and HTN in Korean women.

Methods  Korean women (n=1312) were enrolled in this study to evaluate the association between PAI-1 4G/5G gene polymorphisms and HTN as well as other metabolic risk factors. PAI-1 loci polymorphisms were investigated using polymerase chain reaction amplification and single-strand conformation polymorphism analysis.

Results  The three genotype groups differed with respect to systolic blood pressure (P=0.043), and diastolic blood pressure (P=0.009) but not with respect to age, body mass index, total cholesterol, low or high density lipoprotein cholesterol, triglycerides, or fasting blood glucose. Carriers of the PAI-1 4G allele had more hypertension significantly (PAI-1 4G/5G vs. PAI-1 5G/5G, P=0.032; PAI-1 4G/4G vs. PAI-1 5G/5G, P=0.034). When stratified according to PAI-1 4G/5G polymorphism, there was no significant difference in all metabolic parameters among PAI-1 genotype groups in patients with HTN as well as subjects with normal blood pressure. The estimated odds ratio of the 4G/4G genotype and 4G/5G for HTN was 1.7 (P=0.005), and 1.6 (P=0.015), respectively.

Conclusion  These findings might indicate that PAI-1 loci polymorphisms independently contribute to HTN and that gene-environmental interaction may be not associated in Korean women.

     

非糖尿病患者脂联素基因SNP+276 G/T单核苷酸多态性与冠心病的相关性研究

目的:探讨在中国南京地区汉族人群中脂联素单核苷酸多态性SNP 276 G/T与冠心病的关系.方法:采用聚合酶链反应-限制性片段长度多态性(PCR-RFLP)方法,分析了266例非糖尿病患者的冠脉造影结果和脂联素单核苷酸多态性(SNP 276 G/T)的关系,研究设立了病例组和正常对照组.结果:相对于T/T基因型,G/G基因型修正后的OR值为3.16,(P＜0.05);G/G G/T基因型的修正后OR值为2.69,(P＜0.05).结论:脂联素SNP 276 G/T各种基因型和冠心病的发病密切相关,G/G基因型很可能是冠心病的易感基因型.     

Pharyngeal aerodynamic characteristics of obstructive sleep apnea/hypopnea syndrome patients

Background  The role of nasal obstruction in the pathogenesis of obstructive sleep apnea/hypopnea syndrome (OSAHS) has been debated for decades. In this prospective study, we compared the pharyngeal aerodynamic characteristics of OSAHS patients and normal people, and investigated the contribution of total nasal airway resistance to the pathophysiology of OSAHS.

Methods  Computational fluid dynamics (CFD) was used to extract the average pressure and average airflow velocity in three transverse cross-sectional planes of the pharynx for statistical analysis, and the correlation between nasal resistance and the average pressure in the pharyngeal cavity was investigated.

Results  The negative pressure within the pharyngeal cavity was significantly higher in OSAHS patients than in normal subjects, and total nasal airway resistance correlated well with the average pressure in three consecutive transverse cross-sections of the pharyngeal cavity.

Conclusions  Greater negative pressure within the pharyngeal cavity contributed to the increased collapsibility of the pharynx in OSAHS patients, and the strong correlation between nasal resistance and pharyngeal pressure suggests that the nose plays a role in the pathogenesis of OSAHS.

     

Exome sequencing identifies compound heterozygous PKHD1 mutations as a cause of autosomal recessive polycystic kidney disease

Background  Autosomal recessive polycystic kidney disease (ARPKD) is a rare inherited disease, which is a disorder with multiple organ involvement, mainly the kidney and liver. It is caused by mutations in the PKHD1 gene. Here, we reported the clinical characteristics of a case with ARPKD and analyze the genetic features of this patient as well as of his father using targeted exome sequencing and Sanger sequencing.

Methods  Genomic DNA was extracted from peripheral blood leukocytes obtained from a patient with ARPKD. The mutations were identified using exome sequencing and confirmed by Sanger sequencing.

Results  The patient was diagnosed as ARPKD based on ultrasonography and abdominal computed tomography which showed polycystic changes, multiple calcinosis of both kidneys, and multiple dilated bile ducts of the liver. Compound heterozygous PKHD1 gene mutations A979G and G5935A, which lead to substitution of an asparagine for an aspartate at amino acid 327 (N327D) and a glycine for an arginine at amino acid 1979 (G1979R) respectively, were identified using targeted exome sequencing and confirmed by Sanger sequencing for the patient. In addition, the father of the patient was identified to be a carrier of heterozygous A979G mutation of this gene.

Conclusions  We identified that the compound heterozygous PKHD1 gene mutations are the molecular basis of the patient with ARPKD. Targeted exome sequencing is suitable for genetic diagnosis of single-gene inherited diseases like ARPKD in which the pathogenic gene is a large.     

Detection of atherosclerotic plaque progression in the abdominal aorta of rabbits with 3T magnetic resonance imaging

Background  With features of high tissue contrast, MRI can be used for the qualitative and quantitative evaluation of atherosclerosis plaques. In this study we investigated the development of atherosclerosis plaque with high resolution 3T MRI in a rabbit model and compared the findings with the histopathological results.

Method  Twenty male New Zealand white rabbits were randomly allocated into an experimental group (n=16) and a control group (n=4). Atherosclerotic lesions were induced in the abdominal aorta by balloon injury and cholesterol feeding. Multiple sequences MRI examination (ToF, T1WI, T2WI, and CE T1WI) were performed at the 2nd, 3rd, and 4th months after aortic denudation. Vessel wall thickness, total vessel area, lumen area, and vessel wall area were recorded. Plaque components were analyzed using histological results as a standard reference.

Results  Seventeen rabbits (14 in the experimental group and 3 in the control group) received all three MR examinations. Gradually, from 2 months to 4 months, vessel wall thickness and area in the experimental group increased significantly compared with the control group (P <0.01). In the lumen area progressive stenosis was not found, even a slight dilation had developed in the experimental group. Lipid, fibrotic and calcified plaques can be differentiated by MR image. According to histological results, MRI had good performance in detection of lipid plaque.

Conclusion  MRI can be used to monitor progression of atherosclerosis and differentiate plaque components.

     

Optimization of Bartonella henselae multilocus sequence typing scheme using single-nucleotide polymorphism analysis of SOLiD sequence data

Background  Multi-locus sequence typing (MLST) is widely used to explore the population structure of numerous bacterial pathogens. However, for genotypically-restricted pathogens, the sensitivity of MLST is limited by a paucity of variation within selected loci. For Bartonella henselae (B. henselae), although the MLST scheme currently used has been proven useful in defining the overall population structure of the species, its reliability for the accurate delineation of closely-related sequence types, between which allelic variation is usually limited to, at most, one or two nucleotide polymorphisms. Exploitation of high-throughput sequencing data allows a more informed selection of MLST loci and thus, potentially, a means of enhancing the sensitivity of the schemes they comprise.

Methods  We carried out SOLiD resequencing on 12 representative B. henselae isolates and explored these data using single nucleotide polymorphism (SNP) analysis. We determined the number and distribution of SNPs in the genes targeted by the established MLST scheme and modified the position of loci within these genes to capture as much genetic variation as possible.

Results  Using genome-wide SNP data, we found the distribution of SNPs within each open reading frame (ORF) of MLST loci, which were not represented by the established B. henselae MLST scheme. We then modified the position of loci in the MLST scheme to better reflect the polymorphism in the ORF as a whole. The use of amended loci in this scheme allowed previously indistinguishable ST1 strains to be differentiated. However, the diversity of B. henselae was still rare in China.

Conclusions  Our study demonstrates the use of SNP analysis to facilitate the selection of MLST loci to augment the currently-described scheme for B. henselae. And the diversity among B. henselae strains in China is markedly less than that observed in B. henselae populations elsewhere in the world.     

Correlation between dynamic contrast-enhanced MRI and histopathology in the measurement of tumor and breast volume and their ratio in breast cancer patients: a prospective study

Background  Earlier studies have examined the association between the diameter of primary tumors measured by magnetic resonance imaging (MRI) and histopathology in breast cancer patients. However, the diameter does not completely describe the dimensions of the breast tumor or its volumetric proportion relative to the whole breast. The association between breast tumor volume/breast volume ratios measured by these two techniques has not been reported.

Methods  Seventy-three patients were recruited from female patients with primary breast tumors admitted to our center between January and December 2010. They were divided into two groups. Group A (n=46) underwent modified radical mastectomy (MRM), and Group B (n=27) underwent preoperative neoadjuvant chemotherapy before MRM. They were examined by dynamic-contrast enhanced MRI (DCE-MRI) to measure breast volumes (BVs), tumor volumes (TVs), and tumor volume/breast volume ratios (TV/BV). These measurements were compared with histopathology results after MRM, and the associations between MRI and pathology were analyzed by linear regression and Bland-Altman analysis.

Results   For Group A, the correlation coefficients for BVs, TVs, and TV/BV ratios measured by the two techniques were 0.938, 0.921, and 0.897 (all P <0.001), respectively. For Group B, the correlation coefficients for BVs, TVs, and TV/BV ratios were 0.936, 0.902, and 0.869 (all P <0.01), respectively. The results suggest statistically significant correlations between these parameters measured by the two techniques for both groups.

Conclusion  For these patients, BVs, TVs, and TV/BV ratios measured by DCE-MRI significantly correlated with those determined by histopathology.

     

Seroreactivity and immunogenicity of Tp0965, a hypothetical membrane protein of Treponema pallidum

Background  Treponema pallidum (T. pallidum) subsp. pallidum is the causative agent of syphilis. Analysis of recombinant antigens of T. pallidum led to the identification of potential candidate antigens for vaccine development and syphilis serodiagnosis. Tp0965 was predicted to be a membrane fusion protein and was found to be reactive with infected human sera in previous studies, but the results were controversial. In this research, the antigenicity and immunoreactivity of recombinant protein Tp0965 were assessed.

Methods  T. pallidum subsp. pallidum (Nichols strain) was propagated and isolated and the genomic DNA was extracted. The Tp0965 gene was amplified by polymerase chain reaction (PCR). Then the recombinant protein Tp0965 was expressed in Escherichia coli and purified by nickel-nitrilotriacetic acid (Ni-NTA) purification system. The reactivities of protein Tp0965 were examined by immunoblot analysis and indirect enzyme-linked immunosorbent assay. The antisera against protein Tp0965 were obtained by immune rabbits and the immunogenicity of antisera were detected by indirect enzyme-linked immunosorbent assay.

Results  Recombinant protein Tp0965 was expressed successfully in vitro. Immunoblot assay showed that the recombinant protein Tp0965 could be recognized by human syphilitic sera of all stages. Indirect enzyme-linked immunosorbent assay showed there were only 4 of 74 human syphilitic sera that failed to show reactivity to recombinant antigen Tp0965, and lack of reactivity of Tp0965 to all 28 uninfected sera. A low titer of antiserum against Tp0965 in immune rabbits could be detected after the third time of immunization.

Conclusions  The recombinant antigen Tp0965 shows excellent sensitivity for the reactivity with sera from syphilitic individuals at all stages. The results also demonstrate a potential application for the serodiagnosis of syphilis.     

Significance of Aspergillus spp. isolation from lower respiratory tract samples for the diagnosis and prognosis of invasive pulmonary aspergillosis in chronic obstructive pulmonary disease

Background  Chronic obstructive pulmonary diseases (COPD) is an emerging population at risk for invasive infection of Aspergillus. Isolation of Aspergillus from lower respiratory tract (LRT) samples is important for the diagnosis of invasive pulmonary aspergillosis (IPA). The purpose of this study was to investigate the value of Aspergillus isolation from LRT samples for the diagnosis and prognosis of IPA in COPD population.

Methods  Clinical record with Aspergillus spp. isolation in COPD and immunocompromised patients was reviewed in a retrospective study. Patients were categorized and compared according to their severity of illness (admitted to general ward or ICU) and immunological function (COPD or immunocompromised).

Results  Multivariate statistical analysis showed that, combined with Aspergillus spp. isolation, APACHE II scores >18, high cumulative doses of corticosteroids (>350 mg prednisone or equivalent dose) and more than four kinds of broad-spectrum antibiotics received in hospital may be predictors of IPA in COPD (OR=9.076, P=0.001; OR=4.073, P=0.026; OR=4.448, P=0.021, respectively). The incidence of IPA, overall mortality, mortality of patients with IPA and mortality of patients with Aspergillus spp. colonization were higher in COPD patients in ICU than in general ward, but were similar between COPD and immunocompromised patients.

Conclusions  Aspergillus spp. isolation from LRT in COPD may be of similar importance as in immunocompromised patients, and may indicate an increased diagnosis possibility of IPA and worse prognosis when these patients received corticosteroids, antibiotics, and need to admit to ICU. Aspergillus spp. isolation from LRT samples combined with certain risk factors may be useful in differentiating colonization from IPA and evaluating the prognosis of IPA in COPD patients.

     

Proteomic analysis for detecting serum biomarkers related to smoking in humans

Background  Smoking is the leading cause of death in the world. This study focused on the difference of the serum proteomic profiling between healthy smokers and nonsmokers in order to find smoking-specific serum biomarkers.

Methods  Pattern-based proteomic profiling of 100 serum samples (from 50 Chinese male smokers and 50 matched nonsmokers) was performed through magnetic bead fractionation coupled with matrix-assisted laser desorption/ionization time-of-flight mass spectrometry analysis (MALDI-TOF-MS) and resulting data were statistically analyzed by Ciphergen ProteinChip software 3.0.2.

Results  We found 72 serum peaks were significantly different between smokers and nonsmokers (P <0.05). Marker peaks of mass-to-charge ratio (m/z) 3159.13, 7561.03 and 9407.32 were smoking-specific.

Conclusion  The preliminary data suggested that smoking-specific serum biomarkers could be detected in humans.

     

Genetic characterization of a Chinese family with familial idiopathic pulmonary fibrosis

Background  Idiopathic pulmonary fibrosis (IPF) is a chronic inflammatory interstitial lung disease with an unknown cause. Recent studies have shown that genetic factors play an important role in the pathogenesis of IPF.

Methods  To explore the genetic background of patients with IPF, a candidate gene approach was employed to screen for mutations in seven genes among members with familial IPF in mainland of China.

Results  Within six of the candidate genes, a total of 31 point mutations were identified. Among the missense mutations, the SFTPA1 exon 6 CAG>AAG (Gln238Lys) and SFTPB exon 2 CAC>CCC (His2Pro) mutations caused changes in the physical and chemical properties of amino acids. Each sequence alteration was identified in sporadic IPF patients, control specimens (pneumonia patients and healthy persons). Genotype frequencies and allele frequencies of codon 238 in exon 6 of SFTPA1 were noted significantly higher in patients with IPF than those in other two control subjects. The computational protein structure prediction by protein homology modeling confirmed differences in three-dimensional structure between mutant SFTPA1 and original SFTPA1.     

Conclusions  Although the functions of the mutant candidate genes vary, these genes may ultimately result in damage to alveolar epithelial cells, initiating the progress of pulmonary fibrosis. In particular, while pathophysiological mechanisms need to be illustrated, the Gln238Lys missense variant of exon 6 in the SFTPA1 may have potential susceptibility in the development of IPF, which was shown in patients with sporadic IPF with a statistically higher frequency.

     

Decreased hepatic glucose production in obese rats by dipeptidyl peptidase-IV inhibitor sitagliptin

Background  Dipeptidyl peptidase-IV (DPP-4) inhibitors are now used to improve postprandial glycemic control in type 2 diabetes. However, their effects on hepatic glucose production (HGP) in obesity are not clear. This study was designed to test the hypothesis that gluconeogenesis and HGP can be modulated by DPP-4 inhibitors in obesity.

Methods  Sprague Dawley male rats were divided into four groups, each on a different diet: general rat chow, n=10 (G); G+sitagliptin, n=10; high fat chow (obesity), n=10 (55% fat calories, HFO); HFO+sitagliptin, n=10. After 10 weeks, the rats were fasted overnight and glucose metabolism was determined using 3-³H-glucose and ¹⁴C-glycerol as tracers.

Results  Glycerol rate of appearance (P <0.00001), plasma glycerol (P <0.05) and free fatty acid (FFA) (P <0.05) concentrations, and HGP (P <0.05) were decreased in HFO+sitagliptin group compared with HFO group, but there was no significant difference between G and G+sitagliptin groups (P >0.05). Gluconeogenesis in HFO group was five times of that in G rats (P <0.01), but was significantly declined in HFO+sitagliptin group (P <0.0001).

Conclusions  Gluconeogenesis and HGP were inhibited by sitagliptin in high fat-induced obese rats due to decreased glycerol availability, which was a result of reduced glycerol release from adipose tissues. The finding suggests that sitagliptin is potentially useful for controlling fasting glucose in obesity, thereby delaying or preventing the development of diabetes.

     

Significance of Aspergillus spp. isolation from lower respiratory tract samples for the diagnosis and prognosis of invasive pulmonary aspergillosis in chronic obstructive pulmonary disease

Background  Chronic obstructive pulmonary diseases (COPD) is an emerging population at risk for invasive infection of Aspergillus. Isolation of Aspergillus from lower respiratory tract (LRT) samples is important for the diagnosis of invasive pulmonary aspergillosis (IPA). The purpose of this study was to investigate the value of Aspergillus isolation from LRT samples for the diagnosis and prognosis of IPA in COPD population.

Methods  Clinical record with Aspergillus spp. isolation in COPD and immunocompromised patients was reviewed in a retrospective study. Patients were categorized and compared according to their severity of illness (admitted to general ward or ICU) and immunological function (COPD or immunocompromised).

Results  Multivariate statistical analysis showed that, combined with Aspergillus spp. isolation, APACHE II scores >18, high cumulative doses of corticosteroids (>350 mg prednisone or equivalent dose) and more than four kinds of broad-spectrum antibiotics received in hospital may be predictors of IPA in COPD (OR=9.076, P=0.001; OR=4.073, P=0.026; OR=4.448, P=0.021, respectively). The incidence of IPA, overall mortality, mortality of patients with IPA and mortality of patients with Aspergillus spp. colonization were higher in COPD patients in ICU than in general ward, but were similar between COPD and immunocompromised patients.

Conclusions  Aspergillus spp. isolation from LRT in COPD may be of similar importance as in immunocompromised patients, and may indicate an increased diagnosis possibility of IPA and worse prognosis when these patients received corticosteroids, antibiotics, and need to admit to ICU. Aspergillus spp. isolation from LRT samples combined with certain risk factors may be useful in differentiating colonization from IPA and evaluating the prognosis of IPA in COPD patients.

     

Is obstructive sleep apnea syndrome a risk factor for pulmonary thromboembolism?

Background  In many studies, obstructive sleep apnea (OSA) has been shown to be an independent risk factor for cardiovascular disease. Conversely, there are few reports establishing possible relation between OSA and venous thromboembolism (VTE). In this study, the aim is to evaluate OSA via polysomnography in patients with pulmonary embolism and drawing the attention of clinicians to the presence of obstructive sleep apnea syndrome (OSAS) may be a risk factor for pulmonary embolism.

Methods  Fifty consecutive patients who were diagnosed with pulmonary embolism (PE) were evaluated prospectively for OSAS. Polysomnographic examination was conducted on 30 volunteer patients. The frequency of OSAS in PE was determined and PE cases were compared to each other after being divided into two groups based on the presence of a major risk factor.

Results  The study consisted of a total of 30 patients (14 females and 16 males). In 56.7% of the patients (17/30), OSAS was determined. The percent of cases with moderate and severe OSAS (apnea hipoapnea index >15) was 26.7% (8/30). Patients who had pulmonary thromboembolism (PTE) without any known major VTE risk (n=20), were compared to patients with VTE risk factors (n=10), and significantly higher rates of OSAS were seen (70% and 30% respectively; P=0.045). The mean age of the group with major PE risk factors was lower than the group without major PE risk factors (52 years old and 66 years old, respectively; P=0.015), however, weight was greater in the group with major PE risk factors (88 kg and 81 kg, respectively; P=0.025). By multivariate Logistic regression analysis, in the group without any visible major risk factors, the only independent risk factor for PE was OSAS (P=0.049).

Conclusions  In patients with PTE, OSA rates were much higher than in the general population. Moreover, the rate for patients with clinically significant moderate and severe OSA was quite high. PTE patients with OSA symptoms (not syndromes) and without known major risk factor should be examined for OSA. There seems to be a relationship between OSA and PTE. However, whether this relationship is a causal relationship or a relationship due to common risk factors or long-term complications of OSA is not clear. Further comprehensive studies on those special topics are needed to clarify these points.

     

脂联素基因多态性与2型糖尿病合并冠心病的关联研究

目的探讨脂联素(adiponectin,ADIPOQ)基因多态性与2型糖尿病合并冠状动脉粥样硬化性心脏病(以下简称冠心病)的关联。方法本研究分两步进行,首先预实验对ADIPOQ基因进行生物信息学分析,对20例2型糖尿病合并冠心病患者进行第2个外显子区域的测序,拼接后与参考数据库比对,筛选出候选单核苷酸多态性。大样本复制研究采用病例-对照研究设计,680例2型糖尿病患者入选,其中包括2007年2月至2009年5月首都医科大学附属北京安贞医院心内科2型糖尿病合并冠心病患者213例,以及2008年1月至2009年10月卫生部北京医院内分泌科门诊2型糖尿病患者467例。基于聚合酶链式反应-高分辨率熔解曲线(PCR-HRM)技术,观察候选单核苷酸多态性在2组间的分布差异。结果预实验结果筛选出5个单核苷酸多态性,包括:17366568G/A、9882205G/A、2241767A/G、1501299G/T、2241766T/G。其中2个单核苷酸多态性与2型糖尿病合并冠心病关联,包括rs2241766T/G(+45T/G)多态性[OR(95%CI)=2.78(1.20～8.65),P=0.015]和rs9882205G/A多态性[OR(95%CI)=3.9(1.78～13.61),P=0.000]。对rs2241766进行大样本复制研究后,未发现与2型糖尿病合并冠心病的关联或相关的趋势。结论 ADIPOQ基因rs2241766多态性可能不是与2型糖尿病合并冠心病关联的因素。     

Effect of anterior nucleus of thalamus stimulation on glucose metabolism in hippocampus of epileptic rats

Background  Electrical stimulation of the anterior nucleus of the thalamus (ANT) appears to be effective against seizures. In this study, we investigated changes in glucose metabolism during high-frequency stimulation of ANT in epileptic rats.

Methods  Three groups of rats were used: (1) a stimulation group (n=12), (2) a sham stimulation group (n=12) with seizures induced by stereotactic administration of kainic acid (KA), and (3) a control group (n=12) with sham surgery. Concentric bipolar electrodes were stereotaxically implanted unilaterally in the ANT. High-frequency stimulation was performed in each group except the sham stimulation group. Microdialysis probes were lowered into the CA3 region of the hippocampus unilaterally but bilaterally in the stimulation group. The concentrations of glucose, lactate, and pyruvate in dialysate samples were determined by an ISCUS microdialysis analyzer.

Results  The extracellular concentrations of lactate and lactate/pyruvate ratio (LPR) of epileptic rats were significantly higher than in control rats (P=0.020, P=0.001; respectively). However, no significant difference in the concentration of glucose and pyruvate was found between these groups (P >0.05). Electrical stimulation of ANT induced decreases in lactate and LPR in the ipsilateral hippocampus (KA injected) of the stimulation group (P <0.05), but it did not influence the glucose metabolism in the contralateral hippocampus (P >0.05).

Conclusions  This study demonstrated that the glycolysis was inhibited in the ipsilateral hippocampus of epileptic rats during electrical ANT stimulation. These findings may provide useful information for better understanding the mechanism of ANT-deep brain stimulation.

     

Efficacy of the long-acting octreotide formulation in patients with thyroid-stimulating hormone-secreting pituitary adenomas after incomplete surgery and octreotide treatment failure

Background  Little information about the current management of patients with thyroid-stimulating hormone (TSH)-secreting pituitary adenomas or about the usefulness of the somatostatin analogue octreotide was contained in the literature. This study aimed to report the efficacy and safety of the long-acting octreotide formulation in patients with TSH-secreting pituitary adenomas after incomplete surgery and octreotide treatment failure. 

Methods  Fifteen patients with TSH-secreting pituitary adenomas (8 men and 7 women), who previously underwent incomplete surgical resection and/or adjuvant radiotherapy (n=12) and failure of octreotide treatment (n=15), followed between 2007 and 2010 in Beijing Tiantan Hospital were included in this study. All patients received 1- to 2-months of the long-acting octreotide formulation treatment after the above combination of treatment. Paired samples t-test was used to analysis the variables.

Results  After two-month duration of the long-acting octreotide formulation treatment, the mean serum free or unbound thyroxine (FT4) ((16.02±1.72) pmol/L) and free triiodothyronine (FT3) ((2.87±0.43) pmol/L) levels of 15 patients significantly decreased compared with those after octreotide-treatment (FT4, (35.36±7.42) pmol/L, P <0.001; FT3, (17.85±7.22) pmol/L, P <0.001). Mean TSH levels stayed in the normal range after the long-acting octreotide formulation treatment ((0.72±0.21) mU/L) and were significantly lower than the pretreatment value ((5.27±1.04) mU/L, P <0.001), post-surgery value ((3.37±0.31) mU/L, P <0.001) and post-octreotide-treatment value ((4.52±0.41) mU/L, P <0.001). In these patients with TSH-secreting pituitary adenomas there was no evidence of tachyphylaxis.

Conclusion  The long-acting octreotide formulation may be a useful and safe therapeutic tool to facilitate the medical treatment of TSH-secreting pituitary adenomas in patients who underwent incomplete surgery or need long-term somatostatin analog therapy.