Aim To investigate the expression of or-ganic anion transporting polypeptide 4C1(Oatp4c1)-P-glycoprotein(P-gp)in the kidneys of obese mice in-duced by high-fat diet(HFD),and its impact on the pharmacokinetic changes of digoxin.Methods C57BL/6 mice were randomly divided into the Chow group and the HFD group.Body weight and blood glu-cose were recorded weekly.After successful model es-tablishment,digoxin was intraperitoneally injected,and blood was collected at different time points.Part of the blood samples was used for LC-MS/MS detection,and the other part was used for the detection of other bio-chemical indicators.After 16 weeks,the organs were removed and weighed.HE and immunohistochemical staining was used to observe the renal pathology and the expression of Villin,a marker of proximal tubules.Western blot and qPCR were combined to detect the expression of Villin,Oatp4c1 and P-gp.Results In the HFD group,body weight and blood glucose in-creased significantly.The blood concentration of digox-in rose,the area under the curve increased,and the half-life was prolonged.The proximal tubular epithelial cells shed,and the protein expression of Villin,Oatp4c1 and P-gp decreased significantly.Conclu-sions The down-regulation of Oatp4c1-P-gp expres-sion in the kidneys of HFD mice leads to an increase in the blood concentration of digoxin and a decrease in re-nal clearance.

Aim To investigate the expression of or-ganic anion transporting polypeptide 4C1(Oatp4c1)-P-glycoprotein(P-gp)in the kidneys of obese mice in-duced by high-fat diet(HFD),and its impact on the pharmacokinetic changes of digoxin.Methods C57BL/6 mice were randomly divided into the Chow group and the HFD group.Body weight and blood glu-cose were recorded weekly.After successful model es-tablishment,digoxin was intraperitoneally injected,and blood was collected at different time points.Part of the blood samples was used for LC-MS/MS detection,and the other part was used for the detection of other bio-chemical indicators.After 16 weeks,the organs were removed and weighed.HE and immunohistochemical staining was used to observe the renal pathology and the expression of Villin,a marker of proximal tubules.Western blot and qPCR were combined to detect the expression of Villin,Oatp4c1 and P-gp.Results In the HFD group,body weight and blood glucose in-creased significantly.The blood concentration of digox-in rose,the area under the curve increased,and the half-life was prolonged.The proximal tubular epithelial cells shed,and the protein expression of Villin,Oatp4c1 and P-gp decreased significantly.Conclu-sions The down-regulation of Oatp4c1-P-gp expres-sion in the kidneys of HFD mice leads to an increase in the blood concentration of digoxin and a decrease in re-nal clearance.

BACKGROUND: Ciprofloxacin is usually used in the treatment of lower respiratory tract infections (LRTIs). Recent studies abroad have shown ciprofloxacin is inadequately dosed and might lead to worse outcomes. The aim of this study was to perform pharmacokinetic and pharmacodynamic analyses of ciprofloxacin in elderly Chinese patients with severe LRTIs caused by Gram-negative bacteria. METHODS: From September 2012 to June 2014, as many as 33 patients were empirically administered beta-lactam and ciprofloxacin combination therapy. Patients were infused with 200 or 400 mg of ciprofloxacin every 12 h, which was determined empirically by the attending physician based on the severity of the LRTI and the patient's renal condition. Ciprofloxacin serum concentrations were determined by high-performance liquid chromatography. Bacterial culture was performed from sputum samples and/or endotracheal aspirates, and the minimum inhibitory concentrations (MICs) of ciprofloxacin were determined. The ratios of the area under the serum concentration-time curve to the MIC (AUC/MIC) and of the maximum serum concentration of the drug to the MIC (Cmax/MIC) were calculated. The baseline data and pharmacokinetic parameters were compared between clinical success group and clinical failure group, bacteriologic success group and bacteriologic failure group. RESULTS: Among the 33 patients enrolled in the study, 17 were infected with Pseudomonas aeruginosa, 14 were infected with Acinetobacter baumannii, and two were infected with Klebsiella pneumoniae. The mean age of the patients was 76.9 ± 6.7 years. Thirty-one patients (93.4%) did not reach the target AUC/MIC value of >125, and 29 patients (87.9%) did not reach the target Cmax/MIC value of >8. The AUC/MIC and Cmax/MIC ratios in the clinical success group were significantly higher than those in the clinical failure group (61.1 [31.7-214.9] vs. 10.4 [3.8-66.1], Z = -4.157; 9.6 [4.2-17.8] vs. 1.3 [0.4-4.7], Z = -4.018; both P < 0.001). The AUC/MIC and Cmax/MIC ratios in the patients for whom the pathogens were eradicated were significantly higher than those in the patients without the pathogens eradicated (75.3 [31.7-214.9] vs. 10.5 [3.8-66.1], Z = -3.938; 11.4 [4.2-17.8] vs. 1.4 [0.4-5.4], Z = -3.793; P < 0.001 for both). Receiver operating characteristic curve analysis showed that the AUC/MIC and Cmax/MIC values were closely associated with clinical and bacteriologic efficacies (P < 0.001 in both). CONCLUSIONS Ciprofloxacin is inadequately dosed against Gram-negative bacteria, especially for those with relatively high MIC values. Consequently, the target values, AUC/MIC > 125 and Cmax/MIC > 8, cannot be reached.
Acinetobacter baumannii ; drug effects ; pathogenicity ; Aged ; Aged, 80 and over ; Chromatography, High Pressure Liquid ; Ciprofloxacin ; pharmacokinetics ; pharmacology ; Female ; Gram-Negative Bacteria ; drug effects ; pathogenicity ; Humans ; Male ; Microbial Sensitivity Tests ; Pseudomonas aeruginosa ; drug effects ; pathogenicity ; Respiratory Tract Infections ; drug therapy ; metabolism ; microbiology

BACKGROUNDThe prognostic values of the coronary computed tomography angiography (CCTA) score for predicting future cardiovascular events have been previously demonstrated in numerous studies. However, few studies have used the rich information available from CCTA to detect functionally significant coronary lesions. We sought to compare the prognostic values of Gai's plaque score and the coronary artery calcium score (CACS) of CCTA for predicting functionally significant coronary lesions, using fractional flow reserve (FFR) as the gold standard.

METHODSWe retrospectively analyzed 107 visually assessed significant coronary lesions in 88 patients (mean age, 59.6 ± 10.2 years; 76.14% of males) who underwent CCTA, invasive coronary angiography, and invasive FFR measurement. An FFR <0.80 indicated hemodynamically significant coronary stenosis. Lesions were divided into two groups using an FFR cutoff value of 0.80. We compared Gai's plaque scores and CACS between the two groups and evaluated the correlations of these scores with FFR. The statistical methods included unpaired t-test, Mann-Whitney U-test, and Spearman's correlation coefficients.

RESULTSCoronary lesions with FFR <0.80 had higher Gai's scores than those with FFR ≥0.80. Gai's score had the strongest correlation with FFR (r = -0.48, P < 0.01) and had a greater area under the curve = 0.72 (95% confidence interval: 0.61-0.82; P < 0.01) than the CACS of whole arteries and a single artery.

CONCLUSIONSBoth CACS in a single artery and Gai's plaque score demonstrated a good capacity to assess functionally significant coronary artery stenosis when compared to the gold standard FFR. However, Gai's plaque score was more predictive of FFR <0.80. Gai's score can be easily calculated in daily clinical practice and could be used when considering revascularization.

Aged ; Computed Tomography Angiography ; Coronary Angiography ; Coronary Stenosis ; pathology ; Coronary Vessels ; pathology ; Female ; Fractional Flow Reserve, Myocardial ; physiology ; Humans ; Male ; Middle Aged ; Prognosis ; Retrospective Studies ; Vascular Calcification ; pathology

BACKGROUNDAccurately, characterizing plaques is critical for selecting the optimal intervention strategy for the left main coronary artery (LMCA) bifurcation. Coronary angiography cannot precisely assess the location or nature of plaques in bifurcation lesions. Few intravascular ultrasound (IVUS) classification scheme has been reported for angiographic imaging of true bifurcation lesions of the unprotected LMCA thus far. In addition, the plaque composition at the bifurcation has not been elucidated. This study aimed to detect plaque composition at LMCA bifurcation lesions by IVUS.

METHODSFifty-eight patients were recruited. The location, concentricity or eccentricity, site of maximum thickness, and composition of plaques of the distal LMCA, ostial left anterior descending (LAD) coronary artery and, left circumflex (LCX) coronary artery were assessed using IVUS and described using illustrative diagrams.

RESULTSTrue bifurcation lesions of the unprotected LMCA were classified into four types: Type A, with continuous involvement from the distal LMCA to the ostial LAD and the ostial LCX with eccentric plaques; Type B, with concentric plaques at the distal LMCA, eccentric plaques at the ostial LAD, and no plaques at the LCX; Type C, with continuous involvement from the distal LMCA to the ostial LCX, with eccentric plaques, and to the ostial LAD, with eccentric plaques; and Type D, with continuous involvement from the distal LMCA to the ostial LAD, with eccentric plaques, and to the ostial LCX, with concentric plaques. The carina was involved in only 3.5% of the plaques. A total of 51.7% of the plaques at the ostium of the LAD were soft, while 44.8% and 44.6% were fibrous in the distal LMCA and in the ostial LCX, respectively.

CONCLUSIONSWe classified LMCA true bifurcation lesions into four types. The carina was always free from disease. Plaques at the ostial LAD tended to be soft, whereas those at the ostial LCX and the distal LMCA tended to be fibrous.

Aged ; Aged, 80 and over ; Coronary Angiography ; Coronary Artery Disease ; pathology ; Coronary Stenosis ; pathology ; Coronary Vessels ; pathology ; Female ; Humans ; Male ; Middle Aged ; Percutaneous Coronary Intervention ; Plaque, Atherosclerotic ; diagnosis ; Ultrasonography, Interventional ; methods

BACKGROUNDOxygen inhalation therapy is essential for the treatment of patients with chronic mountain sickness (CMS), but the efficacy of oxygen inhalation for populations at high risk of CMS remains unknown. This research investigated whether oxygen inhalation therapy benefits populations at high risk of CMS.

METHODSA total of 296 local residents living at an altitude of 3658 m were included; of which these were 25 diagnosed cases of CMS, 8 cases dropped out of the study, and 263 cases were included in the analysis. The subjects were divided into high-risk (180 ≤ hemoglobin (Hb) <210 g/L, n = 161) and low-risk (Hb <180 g/L, n = 102) groups, and the cases in each group were divided into severe symptom (CMS score ≥6) and mild symptom (CMS score 0-5) subgroups. Severe symptomatic population of either high- or low-risk CMS was randomly assigned to no oxygen intake group (A group) or oxygen intake 7 times/week group (D group); mild symptomatic population of either high- or low-risk CMS was randomly assigned to no oxygen intake group (A group), oxygen intake 2 times/week group (B group), and 4 times/week group (C group). The courses for oxygen intake were all 30 days. The CMS symptoms, sleep quality, physiological biomarkers, biochemical markers, etc., were recorded on the day before oxygen intake, on the 15th and 30th days of oxygen intake, and on the 15th day after terminating oxygen intake therapy.

RESULTSA total of 263 residents were finally included in the analysis. Among these high-altitude residents, CMS symptom scores decreased for oxygen inhalation methods B, C, and D at 15 and 30 days after oxygen intake and 15 days after termination, including dyspnea, palpitation, and headache index, compared to those before oxygen intake (B group: Z = 5.604, 5.092, 5.741; C group: Z = 4.155, 4.068, 4.809; D group: Z = 6.021, 6.196, 5.331, at the 3 time points respectively; all P < 0.05/3 vs. before intake). However, dyspnea/palpitation (A group: Z = 5.003, 5.428, 5.493, both P < 0.05/3 vs. before intake) and headache (A group: Z = 4.263, 3.890, 4.040, both P < 0.05/3 vs. before intake) index decreased significantly also for oxygen inhalation method A at all the 3 time points. Cyanosis index decreased significantly 30 days after oxygen intake only in the group of participants administered the D method (Z = 2.701, P = 0.007). Tinnitus index decreased significantly in group A and D at 15 days (A group: Z = 3.377, P = 0.001, D group: Z = 3.150, P = 0.002), 30 days after oxygen intake (A group: Z = 2.836, P = 0.005, D group: Z = 5.963, P < 0.0001) and 15 days after termination (A group: Z = 2.734, P = 0.006, D group: Z = 4.049, P = 0.0001), and decreased significantly in the group B and C at 15 days after termination (B group: Z = 2.611, P = 0.009; C group: Z = 3.302, P = 0.001). In the population at high risk of CMS with severe symptoms, oxygen intake 7 times/week significantly improved total symptom scores of severe symptoms at 15 days (4 [2, 5] vs. 5.5 [4, 7], Z = 2.890, P = 0.005) and 30 days (3 [1, 5] vs. 5.5 [2, 7], Z = 3.270, P = 0.001) after oxygen intake compared to no oxygen intake. In the population at high risk of CMS with mild symptoms, compared to no oxygen intake, oxygen intake 2 or 4 times/week did not improve the total symptom scores at 15 days (2 [1, 3], 3 [1, 4] vs. 3 [1.5, 5]; χ2 = 2.490, P = 0.288), and at 30 days (2 [0, 4], 2 [1, 4.5] vs. 3 [2, 5]; χ2 = 3.730, P = 0.155) after oxygen intake. In the population at low risk of CMS, oxygen intake did not significantly change the white cell count and red cell count compared to no oxygen intake, neither in the severe symptomatic population nor in the mild symptomatic population.

CONCLUSIONSIntermittent oxygen inhalation with proper frequency might alleviate symptoms in residents at high altitude by improving their overall health conditions. Administration of oxygen inhalation therapy 2-4 times/week might not benefit populations at high risk of CMS with mild CMS symptoms while administration of therapy 7 times/week might benefit those with severe symptoms. Oxygen inhalation therapy is not recommended for low-risk CMS populations.

Adolescent ; Adult ; Aged ; Altitude Sickness ; drug therapy ; Chronic Disease ; drug therapy ; Female ; Humans ; Hypoxia ; drug therapy ; Male ; Middle Aged ; Oxygen ; administration & dosage ; therapeutic use ; Oxygen Inhalation Therapy ; methods ; Young Adult

BACKGROUNDMyocardial perfusion grade (MPG) is an accepted method of evaluating myocardial perfusion. However, it does not take into the account, the extent of the perfusion. We hypothesized that myocardial blush area times MPG (total blush) would be more accurate than simple MPG, and yield better prognostic information.

METHODSAbout 34 patients were recruited after they had consented to both coronary angiography (CAG) and single photon emission computed tomography (SPECT), and divided into two groups. A special dedicated computer was employed to calculate the total blush. The CAG was performed as a conventional way. Scintigraphic technetium 99m methoxyisobutyl-isonitrile rest and stress images were evaluated quantitatively. The comparison was made between stenosis versus chronic total occlusion (CTO), MPG 1, 2 versus MPG 3, percutaneous intervention (PCI) successful versus failure. A correlation was made between ejection fraction (EF) and myocardial perfusion by MPG, total blush, SPECT, and syntax score.

RESULTSThe perfusion indices of total blush, summed difference score (SDS) and syntax score were insignificant between the two groups (P > 0.05). However, the left ventricular end diastolic volume was significantly larger in CTO (P < 0.05). The patients with stenosis had better MPG than with CTO (P < 0.05). The increased MPG was associated with increased total blush, higher syntax score, and EF (P < 0.05). Successful PCI resulted in better perfusion indicated by increased total blush, and MPG (P < 0.05) but successful PCI did not change syntax score, EF and SDS significantly. Multivariate linear analysis with EF as the dependent factor and syntax score, SDS, total blush, blush area, and MPG as the independent factors showed a significantly higher degree of correlation (R = 0.87, P < 0.05).

CONCLUSIONAfter PCI the total blush and EF improved significantly indicating its potential application in the future.

Aged ; Coronary Angiography ; methods ; Coronary Artery Disease ; diagnosis ; diagnostic imaging ; Female ; Humans ; Male ; Middle Aged ; Tomography, Emission-Computed, Single-Photon

OBJECTIVETo compare the long-term outcomes of patients receiving percutaneous coronary intervention (PCI), coronary artery bypass grafting (CABG), or medical therapy for treatment of chronic total coronary occlusion (CTO).

METHODSThe patients with CTO were selected from a consecutive cohort of patients who underwent coronary angiography (CAG) between 2008 and 2009. The patients with multiple CAG were excluded. The patients received treatments with PCI, CABG, or conservative medication therapy and were followed for major adverse cardiovascular events (MACE) within 5 years.

RESULTSA total of 253 patients were enrolled in this study, including 192 receiving PCI, 48 receiving CABG, and 13 treated conservatively with medications. The baseline clinical characteristics were similar among the 3 groups except for increased low-density lipoprotein (LDL) and total cholesterol (TC) in the medication group, and increased Syndax score in CABG group. During the follow-up, the incidences of MACE, AMI, death, stroke or heart failure did not differ significantly among the 3 groups (P>0.05). However, CABG group showed a higher incidence of the stroke than the other two groups although this difference did not reach a statistically significantly level (P=0.06).

CONCLUSIONOur study did not demonstrate that recanalization offers greater long-term benefits than medications for treatment of CTO, and the patients receiving CABG appeared to have a higher incidence of stroke.

Chronic Disease ; Cohort Studies ; Coronary Angiography ; Coronary Artery Bypass ; Coronary Occlusion ; surgery ; therapy ; Humans ; Incidence ; Percutaneous Coronary Intervention ; Stroke ; epidemiology ; Treatment Outcome

Coronary Artery Bypass ; adverse effects ; Humans ; Male ; Middle Aged ; Radiodermatitis ; etiology

BACKGROUNDPercutaneous coronary intervention (PCI) is indicated for angina with coronary stenosis. However, PCI for asymptomatic coronary stenosis remains controversial. We prospectively followed a group of patients for four years who underwent coronary computed tomography angiography (CCTA) for major adverse cardiac events (MACE). We hypothesized that the results of this trial would reliably reflect the natural outcome of the coronary disease.

METHODSConsecutive patients who underwent CCTA from June 2008 to May 2009 were selected. Those who could not be reached by telephone, had significant angina, had CT images that were not interpretable, or poor kidney and left ventricular (LV) function were excluded. The patients were divided into five groups: group A normal CCTA without stenosis, group B mild stenosis (1% - 49%), group C moderate stenosis (50% - 74%), group D severe stenosis (= 75%) and they were treated with optimal medical therapy (OMT) or PCI. The group E had PCI before the CCTA examination. The patients were then followed for MACE after different treatments. MACE included acute myocardial infarction (MI), heart failure (HF) and death.

RESULTSThe patient population consisted of 419 patients. The follow-up time was (51 ± 5) months. The age was (60 ± 31) years. Male made up 67.78% of the population (n = 284). A total of 51 cases of MACE occurred including 25 MI, eight HF and 18 all-cause deaths. There was no MACE in group A. Although MACE occurred in two patients in group B, they were not attributed to cardiac death. We further compared the MACE in groups C-E and no significant difference was found (P > 0.05). However, a difference was detected among patients with unstable angina pectoris (UAP), stable angina pectoris (SAP), re-hospitalization, and cerebrovascular events from groups A-E (P < 0.05). The plaque scores were used to predict MACE. The scores progressively increased significantly with lesion severity (P < 0.05). Receiver operating curve (ROC) was performed to determine the sensitivity and specificity in predicting MACE. Our scores predicted MI with area of 0.76, predicted HF with area of 0.77, and predicted death with area of 0.70.

CONCLUSIONSNormal and mild lesions had very few events. With increased stenosis the MACE rate increased progressively. PCI did not significantly reduce the MACE in comparison with OMT in asymptomatic patients. Furthermore, UAP, re-hospitalization, and re-PCI were significantly increased in patients who were treated with PCI.

Adult ; Aged ; Aged, 80 and over ; Coronary Angiography ; Coronary Stenosis ; diagnostic imaging ; therapy ; Female ; Heart Failure ; diagnostic imaging ; Humans ; Male ; Middle Aged ; Myocardial Infarction ; diagnostic imaging ; Percutaneous Coronary Intervention ; Prospective Studies ; Tomography, X-Ray Computed ; Treatment Outcome