High extracellular potassium ion concentration attenuates the blockade action of ketanserin on Kvl.3 channels expressed in xenopus oocytes

Background Ketanserin (KT), a selective serotonin (5-HT) 2-receptor antagonist, reduces peripheral blood pressure by blocking the activation of peripheral 5-HT receptors. In this study electrophysiological method was used to investigate the effect of KT and potassium ion on Kv1.3 potassium channels and explore the role of blocker KT in the alteration of channel kinetics contributing to the potassium ion imbalances. Methods Kvl.3 channels were expressed in xenopus oocytes, and currents were measured using the two-microelectrode voltage-clamp technique. Results KCI made a left shift of activation and an inactivation curve of Kv1.3 current and accelerated the activation and inactivation time constant. High extracellular [K+] attenuated the blockade effect of KT on Kv1.3 channels. In the presence of KT and KCI the activation and inactivation time constants were not influenced significantly no matter what was administered first. KT did not significantly inhibit Kv1.3 current induced by tetraethylammonium (TEA). Conclusions KT is a weak blocker of Kv1.3 channels at different concentrations of extracellular potassium and binds to the intracellular side of the channel pore. The inhibitor KT of ion channels is not fully effective in clinical use because of high [K+]o and other electrolyte disorders.     

体外培养视网膜神经元电压门控钾离子通道特性的研究

目的探讨体外培养不同时期新生小牛视网膜神经元电压门控钾离子通道的特性。方法分别取培养2、4、6周的视网膜神经元,进行全细胞膜片钳记录,并进行统计学分析。结果去极化刺激可诱导3组细胞产生IK电流,各组检出率差异无统计学意义(P>0.05);随培养时间延长,IK电流平均峰值增高(P<0.05)。超极化刺激可诱导培养6周的部分细胞产生内向整流钾电流。结论体外培养新生小牛视网膜神经元表达不同电压门控钾电流。某些神经元的电生理学特性在不同培养阶段发生变化。     

HEK293细胞内源性电压门控钾离子通道电生理学特性研究

目的探讨人胚胎肾细胞(HEK293细胞)内源性电压门控钾通道的电生理特性,避免HEK293细胞上内源性离子通道对外源性离子通道表达时的干扰。方法利用全细胞膜片钳技术分析了HEK293细胞内源性电压门控钾通道的电生理特性。结果在HEK293细胞上去极化电压从-80 mV开始可触发1个外向电流。在+100 mV时电流为(422.78±68.87)pA,电流密度为(21.91±3.20)pA/pF。钾通道阻断剂四乙胺(tetraethylammonium,TEA)、4-氨基吡啶(4-aminopyri-dine,4-AP),在将细胞外液钾浓度由4 mmol/L提高到40 mmol/L时,对外向电流有影响。结论正常培养的HEK293细胞本身有内源性的钾通道。该外向电流可能包括了IK、IK1、IKur和Ito。     

Experimental studies on imaging of infected site with 99mTc-labeled ciprofloxacin in mice

Background Bacterial infection can pose a substantial diagnostic dilemma. 99m^Tc-labeled ciprofloxacin （CPF） was developed as a biologically active radiopharmaceutical to diagnose infection. In the present research, we studied the biodistribution and imaging properties of infection tracer 99m^Tc-CPF in a mouse model of infection. Methods CPF was labeled with 99m^Tc and the radiochemical purity and labeling rate were measured. A mouse model of infection was established. We then determined the biodistribution of 99m^Tc-CPF and conducted the whole body scintigraphy of the animal model. Results 99m^Tc-Ciprotech was stable for at least 6 hours at room temperature. The labeling rate of CPF by 99m^Tc was over 90%. Clearance of radioactivity mainly occurred in the liver and kidney, and the clearance from blood was rapid. Both biodistribution and imaging results showed higher uptake of 99m^Tc-CPF at sites of infection. The infectious tissue/normal tissue ratio peak was 4.30 at 4 hours after injection. Conclusions 99m^Tc-CPF is a sensitive radiopharmaceutical for scintigraphy of infectious lesions and it is easy to prepare.     

Multiple serotonergic brainstem abnormalities in sudden infant death syndrome

Context  The serotonergic (5-hydroxytryptamine [5-HT]) neurons in the medulla oblongata project extensively to autonomic and respiratory nuclei in the brainstem and spinal cord and help regulate homeostatic function. Previously, abnormalities in 5-HT receptor binding in the medullae of infants dying from sudden infant death syndrome (SIDS) were identified, suggesting that medullary 5-HT dysfunction may be responsible for a subset of SIDS cases. Objective  To investigate cellular defects associated with altered 5-HT receptor binding in the 5-HT pathways of the medulla in SIDS cases. Design, Setting, and Participants  Frozen medullae from infants dying from SIDS (cases) or from causes other than SIDS (controls) were obtained from the San Diego Medical Examiner's office between 1997 and 2005. Markers of 5-HT function were compared between SIDS cases and controls, adjusted for postconceptional age and postmortem interval. The number of samples available for each analysis ranged from 16 to 31 for SIDS cases and 6 to 10 for controls. An exploratory analysis of the correlation between markers and 6 recognized risk factors for SIDS was performed. Main Outcome Measures  5-HT neuron count and density, 5-HT_1A receptor binding density, and 5-HT transporter (5-HTT) binding density in the medullary 5-HT system; correlation between these markers and 6 recognized risk factors for SIDS. Results  Compared with controls, SIDS cases had a significantly higher 5-HT neuron count (mean [SD], 148.04 [51.96] vs 72.56 [52.36] cells, respectively; P<.001) and 5-HT neuron density (P<.001), as well as a significantly lower density of 5-HT_1A receptor binding sites (P.01 for all 9 nuclei) in regions of the medulla involved in homeostatic function. The ratio of 5-HTT binding density to 5-HT neuron count in the medulla was significantly lower in SIDS cases compared with controls (mean [SD], 0.70 [0.33] vs 1.93 [1.25] fmol/mg, respectively; P = .001). Male SIDS cases had significantly lower 5-HT_1A binding density in the raphé obscurus compared with female cases (mean [SD], 16.2 [2.0] vs 29.6 [16.5] fmol/mg, respectively; P = .04) or with male and female controls combined (mean [SD], 53.9 [19.8] fmol/mg; P = .005). No association was found between 5-HT neuron count or density, 5-HT_1A receptor binding density, or 5-HTT receptor binding density and other risk factors. Conclusions  Medullary 5-HT pathology in SIDS is more extensive than previously delineated, potentially including abnormal 5-HT neuron firing, synthesis, release, and clearance. This study also provides preliminary neurochemical evidence that may help explain the increased vulnerability of boys to SIDS.      

大鼠消化道平滑肌细胞K_(ATP)通道的牵张敏感性

目的探讨大鼠结肠平滑肌细胞上是否存在ATP敏感K+通道(ATP-sensitive potassium channel,KATP)及其牵张敏感性。方法用RT-PCR方法检测SD大鼠结肠平滑肌组织KATPmRNA的表达;联合应用单通道膜片钳技术和压力钳技术,采用inside-out模式记录大鼠结肠平滑肌细胞上KATP通道的电活动。结果在大鼠结肠平滑肌组织中可检测出较高水平的KATPmRNA的表达;用inside-out模式在大鼠结肠平滑肌上可记录到KATP通道的电活动,该通道在膜电位钳制电压为+60 mV时电导值为(44.5±1.5)pS。KATP通道特异性阻断剂——glibenclamide能抑制该通道的活动。且该KATP通道在负压刺激下开放概率增加。结论大鼠结肠平滑肌细胞上分布有KATP通道,该KATP通道对牵张刺激敏感。     

多巴胺引起大鼠结肠黏膜离子转运的节段异质性

目的探究多巴胺(DA)引起的大鼠远端结肠黏膜离子转运在不同节段的异质性及其可能的原因。方法用短路电流技术(ISC)探测DA引起的大鼠远端结肠黏膜离子转运在不同节段的差异及其介导受体;用realtime-PCR方法检测介导DA反应的受体在大鼠结肠黏膜不同节段的表达是否具有差异性。结果DA在结肠近肛门端(结直肠交界处,DC1)引起的短路电流(ΔISC)为(-14.32±3.14)μA/cm2,明显高于远端结肠的其他部位(-3.19±1.44)μA/cm2(P<0.01)。多巴胺D1样、D2样受体拮抗剂及α受体拮抗剂phentolamine均不能抑制该反应。但β1和β2肾上腺素能受体拮抗剂atenolol和ICI118、551却明显抑制多巴胺产生的反应,抑制程度分别为63.79%(P<0.05),87.27%(P<0.01)。realtime-PCR结果显示,在远端结肠黏膜上,介导该反应的β1和β2受体的mRNA在远离肛门处的远端结肠(DC4)的表达为DC1表达量的48.6%(P<0.001)和56.5%(P<0.05)。结论DA在大鼠远端结肠引起的黏膜离子转运具有异质性,即在DC1的反应明显高于远端结肠的其他部位,这可能与为介导该反应的β1和β2肾上腺素能受体在DC1的高表达有关。     

Role of vitamin K2 in the development of hepatocellular carcinoma in women with viral cirrhosis of the liver

Context  Previous findings indicate that vitamin K₂ (menaquinone) may play a role in controlling cell growth. Objective  To determine whether vitamin K₂has preventive effects on the development of hepatocellular carcinoma in women with viral cirrhosis of the liver. Design, Setting, and Participants  Forty women diagnosed as having viral liver cirrhosis were admitted to a university hospital between 1996 and 1998 and were randomly assigned to the treatment or control group. The original goal of the trial was to assess the long-term effects of vitamin K₂ on bone loss in women with viral liver cirrhosis. However, study participants also satisfied criteria required for examination of the effects of such treatment on the development of hepatocellular carcinoma. Interventions  The treatment group received 45 mg/d of vitamin K₂ (n = 21). Participants in the treatment and control groups received symptomatic therapy to treat ascites, if necessary, and dietary advice. Main Outcome Measure  Cumulative proportion of patients with hepatocellular carcinoma. Results  Hepatocellular carcinoma was detected in 2 of the 21 women given vitamin K₂ and 9 of the 19 women in the control group. The cumulative proportion of patients with hepatocellular carcinoma was smaller in the treatment group (log-rank test, P = .02). On univariate analysis, the risk ratio for the development of hepatocellular carcinoma in the treatment group compared with the control group was 0.20 (95% confidence interval [CI], 0.04-0.91; P = .04). On multivariate analysis with adjustment for age, alanine aminotransferase activity, serum albumin, total bilirubin, platelet count, -fetoprotein, and history of treatment with interferon alfa, the risk ratio for the development of hepatocellular carcinoma in patients given vitamin K₂ was 0.13 (95% CI, 0.02-0.99; P = .05). Conclusion  There is a possible role for vitamin K₂ in the prevention of hepatocellular carcinoma in women with viral cirrhosis.      

齐墩果酸和去氧胆酸衍生物合成及抗血管生成活性研究

目的合成齐墩果酸、去氧胆酸-丙酮基衍生物并评价2者对新生血管生成的影响。方法以丙酮/K2CO3作为反应体系,利用溴代川芎嗪分别与齐墩果酸和去氧胆酸发生亲核取代反应,得到齐墩果酸和去氧胆酸衍生物。采用鸡胚绒毛尿囊膜模型(chorioallantoic membrane,CAM)对其进行在体新生血管活性评价。结果产物结构经1H-NMR、13C-NMR及IR确证为齐墩果酸乙酰甲酯和和去氧胆酸乙酰甲酯;二者作用于CAM模型后,新生血管的数目均比空白组减少。结论在丙酮/K2CO3/溴代川芎嗪反应体系中,得到齐墩果酸和去氧胆酸-丙酮基衍生物;经CAM模型测试发现去氧胆酸-丙酮基衍生物对新生血管具有较好抑制活性。     

Effects of arotinoid acid on induction of apoptosis and differentiation and telomerase activity and cell cycle in the HL-60 cell line

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Coarse particulate matter air pollution and hospital admissions for cardiovascular and respiratory diseases among Medicare patients

Roger D. Peng, PhD; Howard H. Chang, BS; Michelle L. Bell, PhD; Aidan McDermott, PhD; Scott L. Zeger, PhD; Jonathan M. Samet, MD; Francesca Dominici, PhD

JAMA. 2008;299(18):2172-2179.

Context  Health risks of fine particulate matter of 2.5 µm or less in aerodynamic diameter (PM_2.5) have been studied extensively over the last decade. Evidence concerning the health risks of the coarse fraction of greater than 2.5 µm and 10 µm or less in aerodynamic diameter (PM_10-2.5) is limited.

Objective  To estimate risk of hospital admissions for cardiovascular and respiratory diseases associated with PM_10-2.5 exposure, controlling for PM_2.5.

Design, Setting, and Participants  Using a database assembled for 108 US counties with daily cardiovascular and respiratory disease admission rates, temperature and dew-point temperature, and PM_10-2.5 and PM_2.5 concentrations were calculated with monitoring data as an exposure surrogate from January 1, 1999, through December 31, 2005. Admission rates were constructed from the Medicare National Claims History Files, for a study population of approximately 12 million Medicare enrollees living on average 9 miles (14.4 km) from collocated pairs of PM₁₀ and PM_2.5 monitors.

Main Outcome Measures  Daily counts of county-wide emergency hospital admissions for primary diagnoses of cardiovascular or respiratory disease.

Results  There were 3.7 million cardiovascular disease and 1.4 million respiratory disease admissions. A 10-µg/m³ increase in PM_10-2.5 was associated with a 0.36% (95% posterior interval [PI], 0.05% to 0.68%) increase in cardiovascular disease admissions on the same day. However, when adjusted for PM_2.5, the association was no longer statistically significant (0.25%; 95% PI, –0.11% to 0.60%). A 10-µg/m³ increase in PM_10-2.5 was associated with a nonstatistically significant unadjusted 0.33% (95% PI, –0.21% to 0.86%) increase in respiratory disease admissions and with a 0.26% (95% PI, –0.32% to 0.84%) increase in respiratory disease admissions when adjusted for PM_2.5. The unadjusted associations of PM_2.5 with cardiovascular and respiratory disease admissions were 0.71% (95% PI, 0.45%-0.96%) for same-day exposure and 0.44% (95% PI, 0.06% to 0.82%) for exposure 2 days before hospital admission.

Conclusion  After adjustment for PM_2.5, there were no statistically significant associations between coarse particulates and hospital admissions for cardiovascular and respiratory diseases.

     

Novel side branch ostial stent （BIGUARD^TM）： first-in-man study

Background Stenting a bifurcation lesion is technically challenging. No study has reported the clinical outcome of a dedicated bifurcation stent in China. We aimed to analyze the safety and clinical outcome of a novel side branch ostial stent （BIGUARDTM） stent in treating coronary bifurcation lesions. Methods Forty-seven patients were enrolled in this first-in-man study, with 61.7% true bifurcation lesions （0,1,1 and 1,1,1） and 26.7% diabetes. A two-stent technique was used in 27.6% of the patients, and 64.7% of patients crossed from the one-stent technique to the two-stent arm. Clinical and angiographic follow-up data at 12 months were available in all the 47 patients and in 43 patients （91.9%）, respectively. The study endpoint was the occurrence of major adverse cardiac events （MACE） at 12 months. Results Only one patient had a non-ST segment elevation myocardial infarction, which led to 2% of the in-hospital composite MACE. Notably, the target lesion revascularization at 12 months was 8.6%, with a 10.6% composite MACE at 12 months. Neither cardiac death nor stent thrombosis was seen during the follow-up. By quantitative coronary analysis, the restenosis rate at the main vessel and ostium of the side branch was 9.4% and 2.1%, respectively. Four of 12 patients （33.3%） treated with one-stent and kissing balloon inflation had restenosis in the main vessel. Conclusion BIGUARDTM stent was safe and feasible in treatment of bifurcation lesions.     

Effect of calcium carbonate on the absorption of levothyroxine

Context  The effect of calcium carbonate on the absorption of levothyroxine has not been studied systematically. Such a potential drug interaction merits investigation because concurrent treatment with both drugs is common, particularly in postmenopausal women. Objective  To investigate the potential interference of calcium carbonate in the absorption of levothyroxine. Design  Prospective cohort study conducted from November 1998 to June 1999, supplemented with an in vitro study of thyroxine (T₄) binding to calcium carbonate. Setting  Veterans Affairs Medical Center in West Los Angeles, Calif. Patients  Twenty patients (age range, 27-78 years; n=11 men) with hypothyroidism who were taking a stable long-term regimen of levothyroxine were included in the study. All patients had serum free T₄ and thyrotropin values in the normal range before beginning the study. Intervention  Subjects were instructed to take 1200 mg/d of elemental calcium as calcium carbonate, ingested with their levothyroxine, for 3 months. Main Outcome Measures  Levels of free T₄, total T₄, total triiodothyronine (T₃), and thyrotropin, measured in all subjects at baseline (while taking levothyroxine alone), at 2 and 3 months (while taking calcium carbonate and levothyroxine), and 2 months after calcium carbonate discontinuation (while continuing to take levothyroxine). Results  Mean free T₄ and total T₄ levels were significantly reduced during the calcium period and increased after calcium discontinuation. Mean free T₄ levels were 17 pmol/L (1.3 ng/dL) at baseline, 15 pmol/L (1.2 ng/dL) during the calcium period, and 18 pmol/L (1.4 ng/dL) after calcium discontinuation (overall P<.001); mean total T₄ levels were 118 nmol/L (9.2 µg/dL) at baseline, 111 nmol/L (8.6 µg/dL) during the calcium period, and 120 nmol/L (9.3 µg/dL) after calcium discontinuation (overall P=.03). Mean thyrotropin levels increased significantly, from 1.6 mIU/L at baseline to 2.7 mIU/L during the calcium period, and decreased to 1.4 mIU/L after calcium discontinuation (P=.008). Twenty percent of patients had serum thyrotropin levels higher than the normal range during the calcium period; the highest observed level was 7.8 mIU/L. Mean T₃ levels did not change during the calcium period. The in vitro study of T₄ binding to calcium showed that adsorption of T₄ to calcium carbonate occurs at acidic pH levels. Conclusions  This study of 20 patients receiving long-term levothyroxine replacement therapy indicates that calcium carbonate reduces T₄ absorption and increases serum thyrotropin levels. Levothyroxine adsorbs to calcium carbonate in an acidic environment, which may reduce its bioavailability.      

西地那非抑制低氧对人肺动脉平滑肌细胞电压依赖性钾通道的下调作用

目的探讨西地那非对低氧下调人肺动脉平滑肌细胞(pulmonary artery smooth muscle cells,PASMCs)电压依赖性钾通道(voltage-dependent potassium channels,Kv)的干预作用。方法应用膜片钳技术记录PASMCs K+电流;观察低氧刺激前后钾离子(K+)电流的变化以及西地那非(sildenafil)的干预作用;通过特异性Kv1.5抗体透析,分析西地那非作用于人PASMCs Kv分子靶点即通道亚单位;运用Real-time PCR及Western blotting技术检测低氧刺激前后及西地那非对人PASMCs上的Kv1.5通道基因转录水平和蛋白表达水平的影响。结果低氧明显抑制了人PASMCs细胞膜上的全细胞K+电流;而西地那非则可以对抗低氧对全细胞K+电流的抑制作用;而且西地那非对低氧下人PASMCs Kv的调控作用靶点主要是Kv1.5;同时西地那非部分恢复了低氧抑制的细胞上的Kv1.5 mRNA和蛋白表达。结论西地那非能够抑制低氧对人肺动脉平滑肌细胞电压依赖性钾通道功能与表达的下调作用。     

Hypercalcemia Due to Endogenous Overproduction of Active Vitamin D in Identical Twins With Cat-Scratch Disease

Context.— The extrarenal synthesis of active vitamin D sterols has a central causative role in the hypercalcemia associated with various granulomatous diseases. Objective.— To study the calcium metabolism in patients with cat-scratch disease who have hypercalcemia. Design.— Case report. Setting.— University hospital in Barcelona, Spain. Patients.— Two identical twins who developed asymptomatic hypercalcemia during the acute phase of cat-scratch disease. Main Outcome Measures.— Serial measures of calcium homeostasis and metabolism over a 2-month period. Results.— On admission and 6 and 7 days later, both patients were found to have increased levels of serum and urinary calcium, serum phosphate, and serum 1,25-dihydroxyvitamin D [1,25(OH)₂D], whereas they had normal values of serum 25-hydroxyvitamin D and urinary cyclic adenosine monophosphate and decreased serum concentrations of intact parathyroid hormone. Sixteen and 20 days after admission, these abnormalities had resolved without treatment. A direct correlation was observed between the serum 1,25(OH)₂D levels and both the serum and 24-hour urinary calcium concentrations. Also, the concentrations of calcium and 1,25(OH)₂D paralleled the clinical activity of the infectious disease over the period these parameters were measured. Conclusions.— Our cases provide evidence that cat-scratch disease can produce hypercalcemia through the unregulated production of the metabolite 1,25(OH)₂D. Cat-scratch disease should be added to the list of granuloma-forming diseases that are responsible for 1,25(OH)₂D-mediated hypercalcemia.      

Voltage-gated potassium channel Kvl.3 in rabbit ciliary epithelium regulates the membrane potential via coupling intracellular calcium

Background The cell layer of the ciliary epithelium is responsible for aqueous humor secretion and maintenance.Ion channels play an important role in these processes.The main aim of this study was to determine whether the well-characterized members of the Kvl family (Kv1.3) contribute to the Kv currents in ciliary epithelium.Methods New Zealand White rabbits were maintained in a 12 hours light/dark cycle.Ciliary epithelium samples were isolated from the rabbits.We used Western blotting and immunocytochemistry to identify the expression and location of a voltage-gated potassium channel Kvl.3 in ciliary body epithelium.Membrane potential change after adding of Kv1.3 inhibitor margatoxin (MgTX) was observed with a fluorescence method.Results Western blotting and immunocytochemical studies showed that the Kv1.3 protein expressed in pigment ciliary epithelium and nonpigment ciliary epithelium,however it seemed to express more in the apical membrane of the nonpigmented epithelial cells.One nmol/L margatoxin,a specific inhibitor of Kv1.3 channels caused depolarization of the cultured nonpigmented epithelium (NPE) membrane potential.The cytosotic calcium increased after NPE cell depolarization,this increase of cytosolic calcium was partially blocked by 12.5 μmol/L dantrolene and 10 μmol/L nifedipine.These observations suggest that Kv1.3 channels modulate ciliary epithelium potential and effect calcium dependent mechanisms.Conclusion Kv1.3 channels contribute to K+ efflux at the membrane of rabbit ciliary epithelium.     

Voltage-gated potassium channel Kv1.3 in rabbit ciliary epithelium regulates the membrane potential via coupling intracellular calcium

Background The cell layer of the ciliary epithelium is responsible for aqueous humor secretion and maintenance. Ion channels play an important role in these processes. The main aim of this study was to determine whether the well-characterized members of the Kvl family （Kv1.3） contribute to the Kv currents in ciliary epithelium. Methods New Zealand White rabbits were maintained in a 12 hours light/dark cycle. Ciliary epithelium samples were isolated from the rabbits. We used Western blotting and immunocytochemistry to identify the expression and location of a voltage-gated potassium channel Kvl.3 in ciliary body epithelium. Membrane potential change after adding of Kvl.3 inhibitor margatoxin （MgTX） was observed with a fluorescence method. Results Western blotting and immunocytochemical studies showed that the Kv1.3 protein expressed in pigment ciliary epithelium and nonpigment ciliary epithelium, however it seemed to express more in the apical membrane of the nonpigmented epithelial cells. One nmol/L margatoxin, a specific inhibitor of Kv1.3 channels caused depolarization of the cultured nonpigmented epithelium （NPE） membrane potential. The cytosolic calcium increased after NPE cell depolarization, this increase of cytosolic calcium was partially blocked by 12.5 μmol/L dantrolene and 10 μmol/L nifedipine. These observations suggest that Kv1.3 channels modulate ciliary epithelium potential and effect calcium dependent mechanisms. Conclusion Kv1.3 channels contribute to K＋ efflux at the membrane of rabbit ciliary epithelium.     

Platelet activation in obese women: role of inflammation and oxidant stress

Context  Obesity, in particular abdominal adiposity, is associated with increased cardiovascular morbidity and mortality through mechanisms possibly linking the metabolic disorder to platelet and vascular abnormalities. Objective  To investigate the clinical and biochemical determinants of lipid peroxidation and platelet activation in obese women. Design, Setting, and Participants  Cross-sectional comparison, conducted between September 1999 and September 2001, of urinary 8-iso prostaglandin F₂ (8-iso PGF₂) and 11-dehydrothromboxane B₂ (11-dehyhdro-TxB₂) excretion levels in 93 women: 44 with a body mass index (BMI) higher than 28 and a waist-to-hip ratio (WHR) of 0.86 or higher, android obesity; 25 with a BMI higher than 28 and a WHR lower than 0.86, gynoid obesity; and 24 nonobese women with a BMI lower than 25. An additional study was conducted to determine the short-term effects of weight loss in 20 of the 44 women with android obesity. Intervention  During a 12-week period, 20 women with android obesity followed a weight loss program to reduce caloric intake to about 1200 kcal/d. Main Outcome Measures  Plasma C-reactive protein, insulin and leptin levels, and urinary 8-iso PGF₂ (marker of in vivo lipid peroxidation) and 11-dehyhdro-TxB₂ (marker of in vivo platelet activation) excretion. Weight loss was defined as successful when the initial body weight decreased by at least 5 kg after a 12-week period of caloric restriction. Results  Women with android obesity had higher levels of 8-iso PGF₂ (median [interquartile range {IQR}] 523 [393-685] vs 187 [140-225] pg/mg creatinine) and 11-dehyhdro-TxB₂ (median [IQR], 948 [729-1296] vs 215 [184-253] pg/mg creatinine) than nonobese women (P<.001). Both 8-iso PGF₂and 11-dehyhdro-TxB₂ were higher in women with android obesity than women with gynoid obesity (P<.001). Based on multiple regression analysis, C-reactive protein levels and WHRs of 0.86 or higher predicted the rate of 8-iso PGF₂ excretion independently of insulin and leptin levels. Of 20 women with android obesity, 11 achieved successful weight loss, which was associated with statistically significant reductions in C-reactive protein (median change, 23%; P<.05), 8-iso PGF₂ (median change, 32%; P = .04) and 11-dehydro-TxB₂ (median change, 54%; P = .005). Conclusions  Android obesity is associated with enhanced lipid peroxidation and persistent platelet activation. These abnormalities are driven by inflammatory triggers related to the degree of abdominal adiposity and are, at least in part, reversible with a successful weight-loss program.