Coffee polyphenols improve peripheral endothelial function after glucose loading in healthy male adults

Brewed coffee is a widely consumed beverage, and many studies have examined its effects on human health. We investigated the vascular effects of coffee polyphenols (CPPs), hypothesizing that a single ingestion of CPP during glucose loading would improve endothelial function. To test this hypothesis, we conducted a randomized acute clinical intervention study with crossover design and measured reactive hyperemia index (RHI) to assess the acute effects of a 75-g glucose load with CPP in healthy, nondiabetic adult men. Blood glucose and insulin levels were elevated after glucose loading with and without CPP, with no significant differences between treatments. The RHI did not significantly decrease after glucose loading without CPP. With CPP, however, RHI significantly (P < .05) increased over baseline after glucose loading. The difference between treatments was statistically significant (P < .05). No significant changes were observed in an oxidative stress marker after glucose loading with or without CPP. These findings suggest that a single ingestion of CPP improves peripheral endothelial function after glucose loading in healthy subjects.     

The Impact of Gabapentin Administration on Brain GABA and Glutamate Concentrations: A 7T 1H-MRS Study

Gamma-aminobutyric acid (GABA) and glutamate are implicated in numerous neuropsychiatric and substance abuse conditions, but their spectral overlap with other resonances makes them a challenge to quantify in humans. Gabapentin, marketed for the treatment of seizures and neuropathic pain, has been shown to increase in vivo GABA concentration in the brain of both rodents and humans. Gabapentin effects on glutamate are not known. We conducted a gabapentin (900 mg) challenge in healthy human subjects to confirm and explore its effects on GABA and glutamate concentrations, respectively, and to test the ability of single voxel localized proton magnetic resonance spectroscopy (¹H-MRS) to reliably measure GABA and glutamate in the visual cortex at the ultra-high magnetic field of 7 Tesla. Reproducibility of GABA and glutamate measurements was determined in a comparison group without drug twice within day and 2 weeks apart. Although GABA concentration changes were small both within day (average 5.6%) and between day (average 4.8%), gabapentin administration was associated with an average increase in GABA concentration of 55.7% (6.9–91.0%). Importantly, drug-induced change in GABA levels was inversely correlated to the individual''s baseline GABA level (R²=0.72). Mean glutamate concentrations did not change significantly with or without drug administration. In conclusion, localized ¹H-MRS at 7 Tesla can be successfully applied to the measurement of GABA concentration and is sensitive to acute drug-induced changes in cortical GABA. Whether baseline GABA concentrations predict clinical efficacy of gabapentin is an area worthy of exploration.     

Uracil nucleotides: from metabolic intermediates to neuroprotection and neuroinflammation

Uracil nucleotides (i.e., UTP and UDP) have been known for years as fundamental intermediates in the de novo synthesis of the other pyrimidine nucleotides, which altogether represent key building blocks for nucleic acid synthesis. In addition, their sugar conjugates (i.e., UDP-glucose and UDP-galactose) enter in several biochemical routes, for example leading to glycogen biosynthesis, and protein and lipid glycosylation, which in turn contribute to the synthesis of essential components of the cellular plasma membrane. More recently, the existence of a "pyrimidinergic transmission" has arisen from the discovery that several purinergic G protein-coupled P2Y receptors can be activated also or exclusively by uracil nucleotides and sugar conjugates. The number of these receptors is continuously growing over years with the discovery that previously "orphan" G protein-coupled receptors are actually responding to this class of molecules. Therefore, new unforeseen effects mediated by uracil derivatives have emerged, in particular in the nervous system, and previously unexplored avenues for the pharmacological manipulation of this system are currently under investigation. In this commentary we shall try to put together our current knowledge on the biochemical and receptor-mediated effects of uracil nucleotide derivatives with a specific focus on the nervous system in order to depict a clearer view of the importance of the pyrimidinergic system in both physiological and pathological conditions.     

High-dose vitamin K supplementation reduces fracture incidence in postmenopausal women: a review of the literature

Although systematic review and meta-analysis of randomized controlled trials (RCTs) have concluded that vitamin K is effective in preventing fractures, the effect of vitamin K on the skeleton remains a matter of controversy. The objective of the present review of the literature was to evaluate the effect of vitamin K supplementation on the skeleton of postmenopausal women. PubMed was used to search the reliable literature for RCTs by using the search terms “vitamin K₁ or vitamin K₂,” “bone,” and “postmenopausal women” and the following inclusion criteria: approximately 50 or more subjects per group and study period of 2 years or longer. Seven RCTs met the inclusion criteria. The results of these RCTs showed that vitamin K₁ and vitamin K₂ supplementation reduced serum undercarboxylated osteocalcin levels regardless of dose but that it had inconsistent effects on serum total osteocalcin levels and no effect on bone resorption. Despite the lack of a significant change or the occurrence of only a modest increase in bone mineral density, high-dose vitamin K₁ and vitamin K₂ supplementation improved indices of bone strength in the femoral neck and reduced the incidence of clinical fractures. The review of the reliable literature confirmed the effect of vitamin K₁ and vitamin K₂ supplementation on the skeleton of postmenopausal women mediated by mechanisms other than bone mineral density and bone turnover.     

Synthesis and evaluation of a glutamic acid-modified hPAMAM complex as a promising versatile gene carrier

Hyperbranched poly(amidoamine) (HPAMAM), structurally analogous to polyamidoamine dendrimer (PAMAM) dendrimers, has been suggested to be an effective carrier for gene delivery. In the present study, glutamic acid-modified hPAMAM was developed as a novel non-viral gene carrier for the first time. The hPAMAM was synthesized by using a modified one-pot method. DNA was found to be bound to hPAMAM at different weight ratios (W_hPAMAM/W_DNA). The resulting HPAMAM–Glu20 was able to efficiently protect the encapsulated-DNA against degradation for over 2?h. In addition to low cytotoxicity, the transfection efficiency of hPAMAM–Glu20 represented much higher (p?<?0.05) than that of Lipofectamine 2000 in both MCF7 and MDA-MB231 cells. Cellular uptake of the hPAMAM–Glu20 in MDA-MB231 cells, 173.56?±?1.37%, was significantly higher than that of MCF7 cells, 65.00?±?1.73% (p?<?0.05). The results indicated that hPAMAM–Glu20-mediated gene delivery to breast cancer cells is a feasible and effective strategy that may provide a new therapeutic avenue as a non-viral gene delivery carrier. In addition, it was found that hPAMAM–glutamic amino acid (Glu)-based gene delivery is an economical, effective and biocompatible method.     

抗呆合剂对小鼠缺血再灌注脑内氨基酸、乙酰胆碱酯酶活力的影响

反复脑缺血再灌注后５０ｍｉｎ,小鼠脑内谷氨酸（Ｇｌｕ）、天冬氨酸（Ａｓｐ）均升高,γ－氨基丁酸（ＧＡＢＡ）,也随之升高。抗呆合剂大、小剂量均可抑制Ｇｌｕ、Ａｓｐ的升高,大剂量还使升高的ＧＡＢＡ恢复至接近正常。造模后５０ｍｉｎ以及７ｄ,模型组小鼠乙酰胆碱酯酶（ＡｃｈＥ）活力降低,抗呆合剂可升高ＡｃｈＥ活力。     

巨噬细胞移动抑制因子在妊娠期糖尿病病情变化中的诊断价值

目的:探讨妊娠期糖尿病(GDM)患者体内巨噬细胞移动抑制因子(MIF)水平变化及其与血糖(Glu)水平的关系。方法:ELISA法检测GDM、2型糖尿病(T2DM)患者血清MIF;采用高效液相法检测GHbA1C,采用生化法检测Glu。结果:GDM组及T2DM组MIF水平高于正常对照组,但MIF水平在GDM患者及T2DM组无统计学差别。T2DM组MIF与Glu水平均呈正相关(r=0.826,P<0.001),GHbA1C与Glu呈正相关(r=0.471,P<0.05)。GDM组MIF与Glu水平均呈正相关(r=0.605,P<0.01),GHbA1C与Glu水平呈正相关(r=0.528,P<0.01),正常对照组内各指标间无相关性。GDM组血清MIF水平与孕龄呈正相关(r=0.938,P<0.001)。结论:GDM及糖尿病患者血糖及GHbA1C水平可致患者MIF高表达。高水平MIF可能对妊娠过程产生影响,应引起临床重视。     

Beta(2)-adrenergic receptor mutation and abdominal obesity risk: effect modification by gender and HDL-cholesterol

Summary Objective and design A case-control study was conducted to examine the association between the 27Glu polymorphism of the β₂-adrenergic receptor gene (ADRB2) and the risk of abdominal obesity (defined by a waist/hip ratio: WHR higher than 0.85). Methods The case series encompassed 112 obese subjects with body mass index (BMI) > 30 kg/m² and WHR > 0.85 and no other major disease except for type 2 diabetes, while the controls were 127 healthy subjects, BMI < 25 kg/m² and WHR < 0.85. Results The association between the risk of abdominal obesity and the 27Glu polymorphism was estimated using multivariate logistic regression. A higher crude odds ratio (OR) of 4.08 (95 % confidence interval: 0.98–16.3) for the 27Glu allele was found among men, while no increased risk was apparent among female participants. Moreover, when the model was adjusted for age, male subjects carriers of the 27Glu allele had a significant ten-fold higher risk of abdominal obesity (OR = 10.31; 95 % CI: 1.4–76.8) and the product-term for the interaction (effect modification) between gender and the ADRB2 mutation was near to the limits of statistical significance (Likelihood ratio test p = 0.056). Interestingly, we also found an effect modification with higher OR among individuals with low HDL-cholesterol (< 1.5 mmol/l) after adjustment for age and gender (OR = 2.87 95 % CI 1.09–7.50) and the product-term for interaction between the 27Glu allele and HDL-cholesterol was statistically significant (Likelihood ratio test p = 0.003). Conclusions. Our results showed that the 27Glu allele of the ADRB2 gene appears to be a risk factor for abdominal obesity among male subjects, specially among those with lower HDL-cholesterol levels. Received: 26 November 2001, Accepted: 2 March 2002     

TM与PET/CT联合诊断肺结节的临床意义

目的：探讨分子生物学（TM）与PET/CT联合诊断肺结节的临床意义。方法经PET/CT检查可疑肺部肿瘤及结节患者98例,并行同期血清肿瘤标记物检测。所有患者均经纤维支气管镜、穿刺、手术等组织病理学检查、多种影像学检查及临床随访确诊。结果肿瘤标记物的灵敏度、特异度、准确度为70.5%、75.6%、73.5%,PET/CT为86.8%、86.5%、87.7%,二者联合检测为95.1%、81.1%、93.9%。结论TM与18F-FDG PET/CT联合检测,对肺部病灶良、恶性诊断的准确率高于单独一种检测方法,具有一定的互补性,可为临床的诊断与治疗提供更多信息。     

High prevalence of polymorphisms of angiotensin-converting enzyme (I/D) and endothelial nitric oxide synthase (Glu298Asp) in patients with systemic sclerosis

PURPOSE: Systemic sclerosis is characterized by progressive microvascular occlusion and fibrosis and by an imbalance in the fibrinolytic system. In vivo and in vitro studies suggest that the renin-angiotensin system partly regulates vascular fibrinolytic balance. Angiotensin II increases the production and secretion of plasminogen activator inhibitor-1, while angiotensin-converting enzyme (ACE) contributes to reduced production of tissue plasminogen activator and endothelial nitric oxide synthesis by bradykinin degradation. The aim of our study was to investigate the effects of ACE insertion/deletion (I/D) and endothelial nitric oxide synthase (eNOS) Glu298Asp (G894-->T) and T-786-->C polymorphisms in patients with systemic sclerosis. SUBJECTS AND METHODS: We studied 73 consecutive patients (47 with limited and 26 with diffuse cutaneous systemic sclerosis) and 112 control subjects. ACE I/D and eNOS polymorphisms were genotyped by polymerase chain reaction-restriction fragment length polymorphism analysis. RESULTS: The ACE I/D and the eNOS G894-->T polymorphisms were more common in patients than in controls (for the ACE D allele: odds ratio [OR] = 3.4; 95% confidence interval [CI]: 1.5 to 7.9; P = 0.003; for the eNOS T allele: OR = 1.9; 95% CI: 1.0 to 3.4; P = 0.04). There was no association between the eNOS T-786-->C polymorphism and systemic sclerosis. CONCLUSIONS: Our findings of an increased risk of systemic sclerosis in ACE D and eNOS 894T allele carriers suggest that these polymorphisms may contribute to the pathogenesis of the disease.