Biodistribution and targeting potential assessment of mucoadhesive chitosan nanoparticles designed for ulcerative colitis via scintigraphy

In the present investigation we have prepared and characterized curcumin (CN)-containing chitosan nanoparticles (CS-NPs) coated with Eudragit FS 30D for colon-specific drug delivery for treatment of ulcerative colitis. Methods: CS-NPs were prepared by ionic gelation using tripolyphosphate. To specify pH sensitive delivery, CS–CN-NPs were coated with Eudragit FS 30D by using a solvent evaporation method. Different process parameters were evaluated, and the optimized formulation was characterized by particle size, size distribution, zeta potential and encapsulation efficiency before lyophilization. The lyophilized product was further subjected to Fourier-transform infrared spectroscopy, and particle morphology and in vitro drug release in different media were studied. Results: the kinetics of in vitro drug release from the CS–CN-NPs revealed sustained release behaviour of the developed carriers. In vivo biodistribution study by gamma-scintigraphy showed good accumulation of the developed nanocarriers in the colonic region. Conclusion: sustained and pH stimulated delivery of CN to the colon was successfully attained via coating of CS-NPs with Eudragit FS 30D to circumvent poor absorption and availability of CN.

In the present investigation we have prepared and characterized curcumin (CN)-containing chitosan nanoparticles (CS-NPs) coated with Eudragit FS 30D for colon-specific drug delivery for treatment of ulcerative colitis.     

Forecasting mortality: dynamic assessment of risk in ST-segment elevation acute myocardial infarction.

AIMS: To demonstrate the feasibility and clinical utility of developing dynamic risk assessment models for ST-segment elevation myocardial infarction (STEMI) patients. METHODS AND RESULTS: In 6066 STEMI patients enrolled in the Assessment of the Safety and Efficacy of a New Thrombolytic-3 (ASSENT-3) trial with complete electrocardiographic data, we assessed the probability of 30-day mortality over the following forecasting periods beginning at day 0 (baseline), 3 h, day 2, and day 5 using multiple-logistic regression. These models were validated and simplified in independent samples of 1622 similar fibrinolytic-treated patients from the ASSENT-3 PLUS trial and in 814 STEMI patients undergoing primary percutaneous coronary intervention in the COMplement inhibition in Myocardial infarction treated with Angioplasty (COMMA) trial. The discriminatory power of these predictive models, from baseline to day 5, was excellent (c-statistics 0.80 to 0.87); and their predictive ability was supported by strong gradients in mortality outcomes as the risk score increased. Dynamic modelling also provided information on the change in prognosis over time which may be used to advise more appropriate therapeutic decisions, e.g. the identification of high-risk patients for possible co-interventions. CONCLUSION: Dynamic modelling for STEMI patients enhances the risk assessment and stratification and should provide valuable ongoing guidance for their management.     

Rapid reversal of endothelial dysfunction in hypercholesterolemic apolipoprotein E-null mice by recombinant apolipoprotein A-I(Milano)-phospholipid complex

OBJECTIVES: In this study, we examined whether a reconstituted high-density lipoprotein (HDL) utilizing recombinant apolipoprotein A-I(Milano) (apo A-I(M))/phospholipid complex (PC) could restore normal endothelial function in hypercholesterolemic apolipoprotein (apo) E-null mice. BACKGROUND: We have previously shown antiatherosclerotic and vasculoprotective effects of recombinant apo A-I(M). METHODS: A perfused vessel preparation was used to examine vascular responses in control wild-type, untreated, and treated apo E-null mice. Aortic tissue cholesterol content and platelet aggregation were also measured. RESULTS: Endothelium-dependent vasodilator responses to acetycholine were significantly inhibited in untreated apo E-null mice compared with control wild-type mice (p < 0.001). Treatment of the mice for five weeks with once every-other-day intravenous bolus injections of apo A-I(M)/PC restored endothelium-dependent dilation in a dose-dependent manner (p < 0.01 at 80 mg/kg dose). The improvement in endothelial function was associated with a reduction in aortic cholesterol content and reduced platelet aggregability and occurred despite severe and persistent hypercholesterolemia. Neither treatment with free protein nor phospholipid carrier alone produced any significant effects. We performed additional experiments in vitro in isolated rabbit carotid arteries to compare the effects on lysophosphatidylcholine (LPC)-induced endothelial dysfunction. Treatment with apo A-I(M)/PC prevented impairment of endothelium-dependent vasodilator responses to acetylcholine to a greater degree than either wild-type apo A-I or plasma-derived HDL. CONCLUSIONS: Our results indicate a rapid improvement in endothelial dysfunction with recombinant apo A-I(M)/PC that is associated with mobilization of tissue cholesterol. Taken together with previously established antiatherosclerotic and antithrombotic effects, these findings suggest significant vasculoprotective effects with apo A-I(M)/PC therapy.     

Effect of the degree of effort on the sensitivity of the exercise thallium-201 stress test in symptomatic coronary artery disease

The sensitivity of ST-segment depression on the electrocardiogram during exercise is influenced by the level of effort. Whether such is the case with thallium-201 imaging (initial defect or redistribution) has not been established. Accordingly, the prevalence of these parameters was evaluated in 288 patients (age 59 +/- 10 years, 88% men) with coronary artery disease who underwent both exercise thallium-201 imaging and coronary angiography within 3 months of each other: 159 had a prior myocardial infarction, 72 had 1-vessel, and 216 had multivessel disease. The degree of effort was evaluated by 3 criteria: (1) percentage of maximal predicted heart rate (less than or equal to 65, greater than 65 to 85, greater than 85%); (2) workload during exercise (less than or equal to 4, greater than 4 to 8, greater than 8 METs); and (3) duration of exercise (less than or equal to 3, greater than 3 to 6, greater than 6 minutes). The prevalence of defects on initial images was higher than both redistribution on delayed images and ST-segment depression on the electrocardiogram (p less than 0.01). The overall prevalence of initial defects remained the same for all levels of effort and was not influenced by the presence or absence of a prior infarction. However, it decreased in patients with 1-vessel disease who exercised to higher workloads. The prevalence of redistribution on delayed thallium-201 images was higher than that of ST-segment depression on the electrocardiogram (p less than 0.01), except at higher levels of effort where they were similar.(ABSTRACT TRUNCATED AT 250 WORDS)     

Intracoronary stent placement in thrombus containing vein graft lesions

Intracoronary stents are traditionally considered to be contraindicated in presence of thrombus. However recent advances in stent deployment technique have reduced the risk of stent thrombosis. We report the placement of a stent in a thrombus laden saphenous vein graft to the posterior descending artery. Three months later the stent site was patent with severe stenosis with thrombus in another graft which was also stented. Intracoronary stents should be considered in patients with complex lesion even in presence of intraluminal thrombus.     

Lipid abnormalities in coronary heart disease: a population-based case-control study

BACKGROUND: We performed a case-control study to estimate lipid-cholesterol fractions in patients with coronary heart disease and compared them with population-based controls. METHODS AND RESULTS: A total of 635 newly diagnosed patients with coronary heart disease (518 males and 117 females) and 632 subjects (346 males and 286 females) obtained from an ongoing urban coronary heart disease risk factor epidemiological study were evaluated. Age-specific lipid values (total cholesterol, low-density lipoprotein, high-density lipoprotein, triglycerides, and total:high-density lipoprotein cholesterol ratio) were compared using the t-test. Age-adjusted prevalence of dyslipidemia as defined by the US National Cholesterol Education Program was compared using the Chi-square test. In all the age groups, and in both males and females, levels of total and low-density lipoprotein cholesterol were not significantly different. In males, the high-density lipoprotein cholesterol (mg/dl) was significantly lower in patients with coronary heart disease as compared to controls in the age groups 30-39 years (35.1+/-11 v. 43.7+/-9), 40-49 years (39.0+/-10 v. 47.1+/-8), 50-59 years (38.9+/-11 v. 43.8+/-9) and 60-69 years (38.6+/-11, v. 42.8+/-7) (p<0.05). In females, high-density lipoprotein cholesterol was less in the age groups 30-39 years (30.2+/-9 v. 40.7+/-9), 50-59 years (39.7+/-12 v. 44.7+/-8) and 60-69 years (35.6+/-11 v. 42.2+/-9). The level of triglycerides was significantly higher in male patients in the age groups 40-49 years (195.3+/-96 v. 152.8+/-78), 50-59 years (176.7+/-76 v. 162.9+/-97), 60-69 years (175.5+/-93 v. 148.1+/-65) and >70 years (159.8+/-62 v. 100.0+/-22); and in female patients in the age group 30-39 years (170.8+/-20 v. 149.9+/-9) (p<0.05). The total:high-density lipoprotein cholesterol ratio was significantly higher in all age groups in male as well as female patients with coronary heart disease (p<0.05). CONCLUSIONS: An age-adjusted case-control comparison showed that the prevalence of hypertension, diabetes, high total cholesterol (> or =200 mg/dl) (males 48.8% v. 20.2%; females 59.8% v. 33.4%) and high low-density lipoprotein cholesterol (> or =130 mg/dl) (males 42.1% v. 15.0%; females 52.1% v. 31.0%) was significantly more in cases than in controls. The prevalence of low high-density lipoprotein cholesterol (<35 mg/dl) (males 39.6% v. 6.2%; females 39.3% iv 9.5%), high total:high-density lipoprotein ratio (> or = 5.0) and high triglycerides (> or =200 mg/ dl: males 39.6%, v. 10.2%; females 17.1% v. 11.9%) was also significantly higher in cases (p<0.05).     

Aortoarteritis presenting with hypoparathyroidism

Clinical manifestations of aortoarteritis (Takayasu's arteritis) are varied, depending on the involved segment of the aorta and its branches. A case of a young Indian woman with aortoarteritis presenting primarily with hypoparathyroidism is reported. Aortogram showed total occlusion of the arch arteries. To the best of our knowledge, the occurrence of hypoparathyroidism in aortoarteritis has not been reported. Possible mechanisms of such an involvement are discussed.     

Coronary stent thrombosis: time course and clinical outcome

The current clinical practice of stent implantation has changed over the last few years. We analysed the incidence and time course of stent thrombosis in patients undergoing successful coronary angioplasty and stenting over the last three years. All the patients were treated with aspirin and ticlopidine. A total of 13 patients experienced stent thrombosis. The mean age was 52+/-12 years; 12 were smokers and 10 had a recent history of myocardial infarction. None of these patients had received abciximab. The median time from stent implantation to stent thrombosis was 10 hours, with all the stent occlusions occurring within 18 hours of stent implantation procedure. All the patients underwent a repeat intervention at a median time of 30 minutes after the clinical suspicion of stent occlusion. On follow-up of 1 to 24 months, three patients developed reocclusion. In the present era of coronary angioplasty and stenting, when interventional procedures are not pre-planned and patients are treated with aspirin and ticlopidine or clopidogrel at the time of stent implantation, the incidence of stent thrombosis is low; it is seen mainly in patients with recent myocardial infarction, majority of them being smokers, and occurs within 18 hours in all the patients.