青蒿琥酯皮肤擦剂在小鼠和兔体内的药代动力学研究

将青蒿琥酯溶于苯二甲酸二甲酯,加适量氨酮制成皮肤擦剂。给兔脱毛后,皮肤涂抹此擦剂25mg/kg后,血药浓度达峰时间平均为2 h,峰浓度平均为1.80μg/ml。药物在兔体内平均驻留时间为3.54 h,清除半衰期约为2.46 h。给小鼠脱毛皮肤涂抹擦剂6.7,31.3和71.4 mg/kg,血药浓度在给药后0.5～4 h达高峰,峰浓度分别为0.82,2.05和7.11μg/ml,体内药物平均驻留时间为3.39,2.79及3.54 h,清除半衰期为2.35,1.93及2.45 h。可见,给兔及小鼠皮肤擦剂后,青蒿琥酯吸收良好,血药浓度维持时间较长。     

Traumatic Injury of the Superior Mesenteric Vein: Ligate,Repair or Shunt?

Abstract We report a case of SMV injury in a critically ill patient. The patient was a 19-year-old woman involved in a motor vehicle collision. Her injuries included grade II splenic and renal lacerations, devascularized and lacerated right and transverse colon, a transected transverse mesocolon, a massive shear injury of her abdominal wall, and two partial SMV transections. At initial damage control laparotomy, the SMV was ligated, the devascularized bowel resected and a temporary abdominal closure applied. At re-operation, a mesocaval shunt using saphenous vein was employed. The shunt failed and the patient required a saphenous vein jump graft. Although visceral vascular injuries are rare, ligation of the SMV in a damage control situation is acceptable. This case study is the first to discuss appropriate treatment when interruption to a patient's collateral visceral venous drainage limits the surgeon’s ability to ligate. In these situations, bypass shunts may be successful.     

Transvenous catheter–based microwave ablation for atrial flutter

We report a case of successful transvenous, catheter-based, cavotricuspid isthmus ablation for treatment of atrial flutter using microwave energy. Microwave energy was delivered at 900–930 MHz using 21 W of power. Bidirectional cavotricuspid isthmus conduction block was achieved by microwave ablation without any patient discomfort or complication during the procedure. Our initial experience suggests that transcatheter microwave ablation is feasible for the cure of typical atrial flutter.     

Prospective randomized trial of direct endomyocardial implantation of bone marrow cells for treatment of severe coronary artery diseases (PROTECT-CAD trial).

AIMS: Experimental studies have demonstrated that bone marrow (BM) cells can induce angiogenesis in ischaemic myocardium. Recently, several non-randomized pilot studies have also suggested that direct BM cells implantation appears to be feasible and safe in patients with severe coronary artery diseases (CAD). METHODS AND RESULTS: We performed a randomized, blinded, and placebo-controlled trial in 28 CAD patients. After BM harvesting, we assigned patients to receive low dose (1 x 10(6) cells/0.1 mL, n = 9), high dose (2 x 10(6) cells/0.1 mL, n = 10) autologous BM cells or control (0.1 mL autologous plasma/injection, n = 9) catheter-based direct endomyocardial injection as guided by electromechanical mapping. Our primary endpoint was the increase in exercise treadmill time and our secondary endpoints were changes in Canadian Cardiovascular Society (CCS) and New York Heart Association (NYHA) class, and myocardial perfusion and left ventricular ejection fraction (LVEF) assessed by single-photon emission computed tomography and magnetic resonance imaging, respectively. A total 422 injections (mean 14.6 +/- 0.7 per patient) were successfully performed at 41 targeted ischaemic regions without any acute complication. Baseline exercise treadmill time was 439 +/- 182 s in controls and 393 +/- 136 s in BM-treated patients, and changed after 6 months to 383 +/- 223s and 464 +/- 196 s [BM treatment effect +0.43 log seconds (+53%), 95% CI 0.11-0.74, P = 0.014]. Compared with placebo injection, BM implantation was associated with a significant increase in LVEF (BM treatment effect +5.4%, 95% CI 0.4-10.3, P = 0.044) and a lower NYHA class (odds ratio for treatment effect 0.12, 95% CI 0.02-0.73, P = 0.021) after 6 months, but CCS reduced similarly in both groups. We observed no acute or long-term complications, including ventricular arrhythmia, myocardial damage, or development of intramyocardial tumour or calcification associated with BM implantation. CONCLUSION: Direct endomyocardial implantation of autologous BM cells significantly improved exercise time, LVEF, and NYHA functional class in patients with severe CAD who failed conventional therapy.     

Pharmacokinetics of fluvastatin after single and multiple doses in normal volunteers.

The pharmacokinetics of fluvastatin, a potent inhibitor of hydroxymethylglutaryl-CoA reductase and thus cholesterol synthesis, have been studied in 24 normal male volunteers who received [3H] fluvastatin in three different studies: a single-dose study using oral doses of 2 or 10 mg, an absolute bioavailability study using doses of 2 mg intravenously or 10 mg orally, and a multiple-dose study using 40 mg orally once daily for 6 days. Serial blood and plasma samples and complete urine and feces were collected and analyzed for total radioactivity as well as for intact fluvastatin. Fluvastatin was rapidly and almost completely (greater than 90%) absorbed from the gastrointestinal tract, although the estimated bioavailability from the 2- and 10-mg doses was only 19 to 29% because of extensive first-pass metabolism. Fluvastatin pharmacokinetics appeared to be linear over the 2- to 10-mg dose range, as indicated by dose-proportional blood levels of total radioactivity and the parent drug. Absorbed fluvastatin was completely metabolized before excretion, the biliary/fecal route being the major excretory pathway. The recovery of radioactivity after a single dose was virtually complete within 120 hours. The terminal half-lives of fluvastatin and total radioactivity averaged 0.5 to 1 hour and 55 to 71 hours, respectively, whereas the total body clearance of fluvastatin was 0.97 L/hour/kg. Repeated oral administration of 40-mg doses of [3H]fluvastatin resulted in no time-related change in pharmacokinetic characteristics, but this dose yielded greater than proportional increases in circulating levels of the parent drug, thus suggesting a saturable first-pass effect on fluvastatin.(ABSTRACT TRUNCATED AT 250 WORDS)     

ELECTRICAL REMODELLING OF CHRONIC ATRIAL FIBRILLATION

1. It is now recognized that atrial fibrillation (AF) is not a benign condition, as it is associated with a 40% increase in mortality and a doubling of the risk of stroke. 2. The development of AF leads to mechanical, electrophysiological and cellular changes in the atria that tend to sustain AF. This process is known as atrial remodelling. 3. The three electrophysiological elements in the atria that initiate and sustain AF are: (i) shortening of the refractory period and an increase in dispersion; (ii) slowing of conduction velocity; and (iii) the presence of triggerin. foci. 4. As AF is a heterogeneous disorder, therapeutic strategies include the use of devices (pacemakers and atrial defibrillators), radiofrequency ablation (focal ablation or the creation of linear lines) and drug therapy that may reverse a remodelle. atrium.     

An evaluation of numerical integration algorithms for the estimation of the area under the curve (AUC) in pharmacokinetic studies

Six numerical integration algorithms based on linear and log trapezoidal methods as well as four cubic-spline methods were proposed for estimation of area under the curve (AUC). These six different algorithms were implemented using IMSL/IDL^TM command language and evaluated using data simulated under five different dosing conditions and two different sampling conditions. Comparisons between AUC estimations using these six different algorithms and the theoretical results were made in terms of both overall AUC values and the superimposability of the concentration-time profiles. In well designed studies with ample data points, the algorithm based on IMSL/IDL^TM function CSSHAPE with concavity preservation gave the best performance. In contrast, when the frequency of blood collection was limited, the algorithm based on the log trapezoidal rule proved to be stable with reasonable accuracy, and is recommended as the practical method for numerical interpolation and integration in pharmacokinetic studies. Algorithms based on the combination of the log trapezoidal rule and cubic-spline methods using IMSL/IDL^TM function CSSHAPE can be developed to enhance overall performance.