FORMULATION AND CHARACTERIZATION OF NANO LIPID CARRIER DRY POWDER INHALER CONTAINING CIPROFLOXACIN HYDROCHLORIDE AND N-ACETYL CYSTEINE

ABSTRACT Nanolipid carriers (NLC) are developed as an alternative to solid lipid nanocarriers in order to increase the payload and to prevent drug expulsion. In this study, NLCs loaded with ciprofloxacin hydrochloride (CIP) and N-Acetyl cysteine (NAC) were prepared and evaluated for its delivery to the lung for treatment of the symptoms of cystic fibrosis and chronic obstructive pulmonary disorder. NLCs prepared by emulsification and sonication technique using cetyl palmitate (the solid lipid, 2%) and oleic acid (as the liquid lipid, 2%) and Tween80 (surfactant, 0.25%) showed smaller particle sizes (of199.1 ±1.859 nm) and relatively high encapsulation efficiencies (72.143±1.8 %.) and optimum zeta potential (-38.27 ± 0.384 mV).A novel DPI formulations loaded with the NLC containing CIP(CIP-DPI), NAC (NAC-DPI) and CIP/NAC combination (CIP-NAC-DPI) were prepared by freeze drying method using Lactose (8%w/v) as a cryoprotectant. The DPI prepared showed good flow properties, prolonged drug release and improved stability. In-vitro drug release profile of CIP HCl in case of CIP-NLC showed 55 % release in 15 hours while it was 60% in case of CIP-NLC-DPI formulation. Similar is the case with NAC formulations. Following intratracheal administration in rat model, the percentage of CIP extracted from lungs was 70.2% in case on CIP-NAC-DPI against 49.8% for CIP-DPI and 42.1% for plain CIP. This amount is about 1.6 times increase in CIP in lungs by co-administration with NAC. However, no appreciable change in the residence time of CIP in lungs after intratracheal administration of CIP-DPI and combined DPI (CIP-NAC-DPI) was noted. Keywords: Ciprofloxacin Hydrochloride, N-Acetyl Cysteine, Nano lipid Carriers, Dry powder inhaler, cystic fibrosis.

Incidental finding of a double orifice mitral valve in an elderly patient: value of 3D imaging.

A rare isolated double orifice mitral valve (DOMV) was diagnosed in a 77-year-old male patient, being assessed for surgical repair of the ascending aorta. This is a rare congenital abnormality, usually discovered as an incidental finding during investigation of other congenital heart defects. This case shows that a detailed assessment of all cardiac structures is necessary, not only in young patients, but also in the elderly population, to minimise the under-diagnosis of such rare anomalies. The use of 3D transthoracic echocardiography (TTE) has an increasingly significant role in establishing the diagnosis and extending the morphological and functional understanding of the anomaly. LEARNING POINTS: Thoroughly assessing all cardiac structures, in accordance with the minimum dataset guidelines for transthoracic echocardiography, ensures not only a comprehensive assessment of the primary indication for the scan, but also improves the detection of concomitant and otherwise unknown lesions. Despite falling under the category of congenital heart defects, several rare anomalies such as DOMV can be present in elderly patients, and the adult echocardiographer should have appropriate knowledge and awareness for detecting these conditions. 3D TTE provides a comprehensive assessment of the morphology of DOMV, over and above the information obtained by 2D imaging

FORMULATION AND CHARACTERIZATION OF NANO LIPID CARRIER DRY POWDER INHALER CONTAINING CIPROFLOXACIN HYDROCHLORIDE AND N-ACETYL CYSTEINE

ABSTRACT Nanolipid carriers (NLC) are developed as an alternative to solid lipid nanocarriers in order to increase the payload and to prevent drug expulsion. In this study, NLCs loaded with ciprofloxacin hydrochloride (CIP) and N-Acetyl cysteine (NAC) were prepared and evaluated for its delivery to the lung for treatment of the symptoms of cystic fibrosis and chronic obstructive pulmonary disorder. NLCs prepared by emulsification and sonication technique using cetyl palmitate (the solid lipid, 2%) and oleic acid (as the liquid lipid, 2%) and Tween80 (surfactant, 0.25%) showed smaller particle sizes (of199.1 ±1.859 nm) and relatively high encapsulation efficiencies (72.143±1.8 %.) and optimum zeta potential (-38.27 ± 0.384 mV).A novel DPI formulations loaded with the NLC containing CIP(CIP-DPI), NAC (NAC-DPI) and CIP/NAC combination (CIP-NAC-DPI) were prepared by freeze drying method using Lactose (8%w/v) as a cryoprotectant. The DPI prepared showed good flow properties, prolonged drug release and improved stability. In-vitro drug release profile of CIP HCl in case of CIP-NLC showed 55 % release in 15 hours while it was 60% in case of CIP-NLC-DPI formulation. Similar is the case with NAC formulations. Following intratracheal administration in rat model, the percentage of CIP extracted from lungs was 70.2% in case on CIP-NAC-DPI against 49.8% for CIP-DPI and 42.1% for plain CIP. This amount is about 1.6 times increase in CIP in lungs by co-administration with NAC. However, no appreciable change in the residence time of CIP in lungs after intratracheal administration of CIP-DPI and combined DPI (CIP-NAC-DPI) was noted. Keywords: Ciprofloxacin Hydrochloride, N-Acetyl Cysteine, Nano lipid Carriers, Dry powder inhaler, cystic fibrosis.

Widening access to cardiovascular healthcare: community screening among ethnic minorities in inner-city Britain – the Healthy Hearts Project

<p>Abstract</p> <p>Background</p> <p>The burden of cardiovascular disease (CVD) in Britain is concentrated in inner-city areas such as Sandwell, which is home to a diverse multi-ethnic population. Current guidance for CVD risk screening is not established, nor are there specific details for ethnic minorities. Given the disparity in equitable healthcare for these groups, we developed a 'tailored' and systematic approach to CVD risk screening within communities of the Sandwell locality. The key anticipated outcomes were the numbers of participants from various ethnic backgrounds attending the health screening events and the prevalence of known and undiagnosed CVD risk within ethnic groups.</p> <p>Methods</p> <p>Data was collected during 10 health screening events (September 2005 and July 2006), which included an assessment of raised blood pressure, overweight, hyperlipidaemia, impaired fasting glucose, smoking habit and the 10 year CVD risk score. Specific features of our approach included (i) community involvement, (ii) a clinician who could deliver immediate attention to adverse findings, and (iii) the use of an interpreter.</p> <p>Results</p> <p>A total of 824 people from the Sandwell were included in this study (47% men, mean age 47.7 years) from community groups such as the Gujarati Indian, Punjabi Indian, European Caucasian, Yemeni, Pakistani and Bangladeshi. A total of 470 (57%) individuals were referred to their General Practitioner with a report of an increased CVD score – undetected high blood pressure in 120 (15%), undetected abnormal blood glucose in 70 (8%), undetected raised total cholesterol in 149 (18%), and CVD risk management review in 131 (16%).</p> <p>Conclusion</p> <p>Using this systematic and targeted approach, there was a clear demand for this service from people of various ethnic backgrounds, of whom, one in two needed review from primary or secondary healthcare. Further work is required to assess the accuracy and clinical benefits of this community health screening approach.</p

Catheter ablation vs. thoracoscopic surgical ablation in long-standing persistent atrial fibrillation: CASA-AF randomized controlled trial.

AIMS: Long-standing persistent atrial fibrillation (LSPAF) is challenging to treat with suboptimal catheter ablation (CA) outcomes. Thoracoscopic surgical ablation (SA) has shown promising efficacy in atrial fibrillation (AF). This multicentre randomized controlled trial tested whether SA was superior to CA as the first interventional strategy in de novo LSPAF. METHODS AND RESULTS: We randomized 120 LSPAF patients to SA or CA. All patients underwent predetermined lesion sets and implantable loop recorder insertion. Primary outcome was single procedure freedom from AF/atrial tachycardia (AT) ≥30 s without anti-arrhythmic drugs at 12 months. Secondary outcomes included clinical success (≥75% reduction in AF/AT burden); procedure-related serious adverse events; changes in patients' symptoms and quality-of-life scores; and cost-effectiveness. At 12 months, freedom from AF/AT was recorded in 26% (14/54) of patients in SA vs. 28% (17/60) in the CA group [OR 1.128, 95% CI (0.46-2.83), P = 0.83]. Reduction in AF/AT burden ≥75% was recorded in 67% (36/54) vs. 77% (46/60) [OR 1.13, 95% CI (0.67-4.08), P = 0.3] in SA and CA groups, respectively. Procedure-related serious adverse events within 30 days of intervention were reported in 15% (8/55) of patients in SA vs. 10% (6/60) in CA, P = 0.46. One death was reported after SA. Improvements in AF symptoms were greater following CA. Over 12 months, SA was more expensive and provided fewer quality-adjusted life-years (QALYs) compared with CA (0.78 vs. 0.85, P = 0.02). CONCLUSION: Single procedure thoracoscopic SA is not superior to CA in treating LSPAF. Catheter ablation provided greater improvements in symptoms and accrued significantly more QALYs during follow-up than SA. CLINICAL TRIAL REGISTRATION: ISRCTN18250790 and ClinicalTrials.gov: NCT02755688

The prevalence of hypertension, obesity and dyslipidemia in individuals of over 30 years of age belonging to minorities from the pasture area of Xinjiang

<p>Abstract</p> <p>Background</p> <p>The prevalence of population-wide hypertension, obesity and dyslipidemia has not been well studied in the pasture area of Xinjiang. The present epidemiological study was performed to determine the prevalence of hypertension, obesity and dyslipidemia in minority populations from the pasture area of Xinjiang and to discuss the potential risk factors for hypertension.</p> <p>Methods</p> <p>A population-based, cross-sectional study in the Xinjiang pasture area was performed which included 2251 participants aged over 30 years (90.33% participation rate) of whom 71.26% were Kazaks. Several risk factors were considered: hypertension (defined as systolic or diastolic blood pressure or both of at least 140/90 mmHg measured on one occasion or treatment for hypertension) overweight/obesity (body mass index ≥ 25 kg/m²) alcohol intake, smoking/tobacco use and dyslipidemia. Outcomes were prevalence of hypertension, obesity and dyslipidemia and the associated risk factors of hypertension detected by multivariate logistic regression analysis taking into account various metabolic and lifestyle characteristics.</p> <p>Results</p> <p>The prevalence of hypertension, overweight/obesity and dyslipidemia in all participants from the pasture area of Xinjiang was 51.9%, 47.9% and 49.2% respectively. Independently, the prevalence and awareness of hypertension was 52.6% and 15.3% among Kazaks (n = 1604), 54.6% and 14.1% among Uygurs (n = 418), 39.5% and 16.1% among Mongolians (n = 81) and 43.9% and 18.2% among non-Xinjiang-born Han immigrants (n = 148). The prevalence of overweight/obesity in Kazaks, Uygurs, Mongolians and Han immigrants was 46.7%, 48.9%, 62.5% and 50.3%, respectively. The prevalence of dyslipidemia in the four ethnic groups mentioned was 53.5%, 34.8%, 49.3% and 47.3%, respectively. The mean blood pressure in all participants was 136/86 mmHg (pre-hypertensive), the mean BMI was 24.7 kg/m². Based on multiple logistic regression analysis, the significant risk factors for hypertension were age [1.07(1.06-1.09), P < 0.0001], overweight/obesity [overweight: 1.61(1.22-2.13), p = 0.0007; obesity: 1.95 (1.33-2.87), p = 0.0007], hypercholesterolemia [1.30(1.15-1.47), p < 0.0001] and an alcohol intake of over 30 g/day [2.22(1.43-3.45), p = 0.0004].</p> <p>Conclusions</p> <p>The considerably high prevalence of hypertension, overweight/obesity and dyslipidemia among the minority population aged over 30 from the pasture area of Xinjiang calls for effective preventive measures. Age, increased body mass index, hypercholesterolemia and ≥30 g/d alcohol intake can be counted as risk factors for hypertension, but further genetic or environmental clarification would be desirable to explain the unusually high prevalence of the conditions mentioned above.</p

Physical activity, sedentary time and physical capability in early old age: British birth cohort study.

PURPOSE: To investigate the associations of time spent sedentary, in moderate-to-vigorous-intensity physical activity (MVPA) and physical activity energy expenditure (PAEE) with physical capability measures at age 60-64 years. METHODS: Time spent sedentary and in MVPA and, PAEE were assessed using individually calibrated combined heart rate and movement sensing among 1727 participants from the MRC National Survey of Health and Development in England, Scotland and Wales as part of a detailed clinical assessment undertaken in 2006-2010. Multivariable linear regression models were used to examine the cross-sectional associations between standardised measures of each of these behavioural variables with grip strength, chair rise and timed up-&-go (TUG) speed and standing balance time. RESULTS: Greater time spent in MVPA was associated with higher levels of physical capability; adjusted mean differences in each capability measure per 1 standard deviation increase in MVPA time were: grip strength (0.477 kg, 95% confidence interval (CI): 0.015 to 0.939), chair rise speed (0.429 stands/min, 95% CI: 0.093 to 0.764), standing balance time (0.028 s, 95% CI: 0.003 to 0.053) and TUG speed (0.019 m/s, 95% CI: 0.011 to 0.026). In contrast, time spent sedentary was associated with lower grip strength (-0.540 kg, 95% CI: -1.013 to -0.066) and TUG speed (-0.011 m/s, 95% CI: -0.019 to -0.004). Associations for PAEE were similar to those for MVPA. CONCLUSION: Higher levels of MVPA and overall physical activity (PAEE) are associated with greater levels of physical capability whereas time spent sedentary is associated with lower levels of capability. Future intervention studies in older adults should focus on both the promotion of physical activity and reduction in time spent sedentary.This work was supported by the UK Medical Research Council (U120063239, U123092720, MC_UU_12019/1, MC_UU_12019/4, MC_UU_12015/3, and MC_UU_12015/4).This is the final published version. It first appeared at http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0126465

Blimp1 Activation by AP-1 in Human Lung Cancer Cells Promotes a Migratory Phenotype and Is Inhibited by the Lysyl Oxidase Propeptide

B lymphocyte-induced maturation protein 1 (Blimp1) is a master regulator of B cell differentiation, and controls migration of primordial germ cells. Recently we observed aberrant Blimp1 expression in breast cancer cells resulting from an NF-κB RelB to Ras signaling pathway. In order to address the question of whether the unexpected expression of Blimp1 is seen in other epithelial-derived tumors, we selected lung cancers as they are frequently driven by Ras signaling. Blimp1 was detected in all five lung cancer cell lines examined and shown to promote lung cancer cell migration and invasion. Interrogation of microarray datasets demonstrated elevated BLIMP1 RNA expression in lung adenocarcinoma, pancreatic ductal carcinomas, head and neck tumors as well as in glioblastomas. Involvement of Ras and its downstream kinase c-Raf was confirmed using mutant and siRNA strategies. We next addressed the issue of mechanism of Blimp1 activation in lung cancer. Using knockdown and ectopic expression, the role of the Activator Protein (AP)-1 family of transcription factors was demonstrated. Further, chromatin immunoprecipitation assays confirmed binding to identified AP-1 elements in the BLIMP1 promoter of ectopically expressed c-Jun and of endogenous AP-1 subunits following serum stimulation. The propeptide domain of lysyl oxidase (LOX-PP) was identified as a tumor suppressor, with ability to reduce Ras signaling in lung cancer cells. LOX-PP reduced expression of Blimp1 by binding to c-Raf and inhibiting activation of AP-1, thereby attenuating the migratory phenotype of lung cancer cells. Thus, Blimp1 is a mediator of Ras/Raf/AP-1 signaling that promotes cell migration, and is repressed by LOX-PP in lung cancer