Effect of haemodilution with diaspirin cross-linked haemoglobin on the oxygen reserve in a rodent model of surgical blood loss

The efficacy of pre-operative haemodilution is limited by the reduction in haemoglobin concentration. Acellular haemoglobin-based oxygen carriers provide an alternative to colloid as a haemodiluent, potentially extending the safe limits of this procedure. The aim of this investigation was to determine whether haemodilution with a cross-linked haemoglobin solution, diaspirin cross-linked haemoglobin solution (DCLHb), would enhance the oxygen reserve compared to pentastarch. Sprague Dawley rats were placed in a metabolic box to directly measure systemic oxygen consumption (VO2). Rats were randomized to be haemodiluted to a cellular haemoglobin of 80 g L(-1) with either DCLHb or pentastarch. Oxygen reserve was assessed during isovolemic haemorrhage by determining the critical oxygen delivery (DO2crit) and haemoglobin concentration at the point of oxygen supply dependency (OSD). Following haemodilution and for the duration of the experiment, cardiac index (CI) was significantly lower and systemic vascular resistance was significantly higher in the DCLHb than the pentastarch group. The DO2crit (3.2 +/- 0.4 mL minAg(-1) and 3.4 +/- 0.5 mL minAg(-1), DCLHb versus pentastarch) and cellular haemoglobin concentration (51 +/- 9 g L(-1) and 48 +/- 9 g L(-1)), at which rats entered OSD were similar in both groups. Total haemoglobin concentration (cellular and plasma DCLHb) and arterial oxygen content were significantly higher in the DCLHb group (total haemoglobin, 66 +/- 8 g L(-1) and arterial content, 9.2 +/- 1.4 mL dL(-1)) compared to the pentastarch group (total haemoglobin, 48 +/- 9 g L(-1) and arterial content, 7.3 +/- 1.4 mL dL(-1)). Oxygen extraction ratios increased from baseline levels to 0.53 +/- 0.07 and 0.56 +/- 0.1, for the DCLHb and pentastarch groups, respectively, and were not significantly different. The increase in arterial oxygen content from DCLHb in plasma was offset by the decrease in CI observed in this group. Plasma DCLHb did not extend the limits of haemodilution beyond the capacity of the cellular haemoglobin concentration.     

Photodynamic therapy-mediated hypericin-loaded nanostructured lipid carriers against vulvovaginal candidiasis

Introduction and Aim: The indiscriminate use and adverse effects of the main conventional antifungal agents compromise the effectiveness of treating vulvovaginal candidiasis (VVC), mainly caused by the species Candida albicans. This study evaluated the effectiveness of photodynamic therapy (PDT) and the in vitro and in vivo anti-candida potential of the hypericin (HYP)-loaded nanostructured lipid carriers (NLC). Materials and Methods: Empty NLC and NLC-HYP were characterized by the dynamic light scattering technique and transmission electron microscopy to evaluate the average particle size distribution and its morphologies. The in vitro inhibition photodynamic effect of the systems was tested to reduce the planktonic viability of C. albicans. The therapeutic assay photodynamic of the systems was performed to treat VVC in mice. Results: Empty NLC and NLC-HYP presented values of average hydrodynamic diameter, polydispersity index, and ζ-potential from 136 to 133 nm, 0.16 to 0.22, and -18 to -30 mV, respectively, on day 30. Microscopically, the systems showed spherical morphologies and nanoscale particles. Furthermore, in the in vitro inhibition assay, the treatment of PDT with NLC-HYP (NLC-HYP+) showed a significant reduction of the C. albicans planktonic viability compared to YNB negative control after 5 min of LED light irradiation. In the in vivo therapeutic assay, the antifungal group (vaginal antifungal cream) and NLC-HYP+ evaluated in the dark and by PDT, respectively, had a significant log₁₀ reduction in fungal burden compared to the infected group on day 8 of the VVC treatment. Conclusion: Due to the in vitro and in vivo anti-candida potential, PDT-mediated systems can be an effective strategy in VVC therapy.     

Sonographic features of breast carcinoma presenting as masses in BRCA gene mutation carriers.

OBJECTIVE: The purpose of this study was to review the sonographic features of breast cancer gene BRCA1- and BRCA2-associated breast carcinomas in comparison with "sporadic" breast carcinomas and benign breast masses. METHODS: Sonograms of 233 breast masses, including 33 BRCA-associated malignant masses (BRCA1, 15; BRCA2, 18), 148 sporadic malignant masses, and 52 benign masses, were reviewed by consensus by 2 radiologists according to American College of Radiology Breast Imaging Reporting and Data System (BI-RADS) terminology. RESULTS: Most of the sporadic and BRCA1-and BRCA2-associated cancers displayed an irregular shape (91.2%, 93.3%, and 83.3%, respectively). BRCA1-associated cancers showed microlobulated margins in 53.3% versus 33.8% (sporadic) and 33.3% (BRCA2). A parallel orientation was most frequently encountered in BRCA1-associated lesions (46.7%) versus sporadic (33.8%) and BRCA2 (33.3%), whereas posterior acoustic shadowing was least frequently seen in BRCA1-associated lesions (13.3%) versus BRCA2 (16.7%) and sporadic (31.1%). Most (73.3%) of the BRCA1-associated lesions were classified as BI-RADS category 4, whereas most of the sporadic and BRCA2-associated lesions were classified as BI-RADS category 5 (66.2% and 72.2%). CONCLUSIONS: Sonographic features of BRCA-associated and sporadic breast carcinomas do not differ substantially. BRCA1-associated breast carcinomas trend toward less malignant sonographic characteristics, but strict application of the BI-RADS categorizations demands that they be classified as category 4 or 5.     

乙型肝炎病毒携带者健康教育研究进展

从健康教育的需求、健康教育的内容、健康教育的方法及形式等方面综述了乙肝病毒携带者健康教育研究进展。     

Cryohydrocytosis: increased activity of cation carriers in red cells from a patient with a band 3 mutation

Background

Cryohydrocytosis is an inherited dominant hemolytic anemia characterized by mutations in a transmembrane segment of the anion exchanger (band 3 protein). Transfection experiments performed in Xenopus oocytes suggested that these mutations may convert the anion exchanger into a non-selective cation channel. The present study was performed to characterize so far unexplored ion transport pathways that may render erythrocytes of a single cryohydrocytosis patient cation-leaky.

Design and Methods

Cold-induced changes in cell volume were monitored using ektacytometry and density gradient centrifugation. Kinetics, temperature and inhibitor-dependence of the cation and water movements in the cryohydrocytosis patient’s erythrocytes were studied using radioactive tracers and flame photometry. Response of the membrane potential of the patient’s erythrocyte membrane to the presence of ionophores and blockers of anion and cation channels was assessed.

Results

In the cold, the cryohydrocytosis patient’s erythrocytes swelled in KCl-containing, but not in NaCl-containing or KNO₃-containing media indicating that volume changes were mediated by an anion-coupled cation transporter. In NaCl-containing medium the net HOE-642-sensitive Na⁺/K⁺ exchange prevailed, whereas in KCl-containing medium swelling was mediated by a chloride-dependent K⁺ uptake. Unidirectional K⁺ influx measurements showed that the patient’s cells have abnormally high activities of the cation-proton exchanger and the K⁺,Cl⁻ co-transporter, which can account for the observed net movements of cations. Finally, neither chloride nor cation conductance in the patient’s erythrocytes differed from that of healthy donors.

Conclusions

These results suggest that cross-talk between the mutated band 3 and other transporters might increase the cation permeability in cryohydrocytosis.     

奥扎格雷纳米结构脂质载体的制备及体外评价

目的:制备奥扎格雷纳米结构脂质载体(ozagrel-loaded nanostructured lipid carriers,OZ-NLC),并考察其理化性质及体外释放。方法:采用熔融-超声乳化法制备OZ-NLC,通过正交设计法优化处方与制备工艺,使用透射电镜(TEM)、激光粒度测定仪、差示扫描量热仪(DSC)及X-射线衍射仪(XRD)考察OZ-NLC的理化性质,通过溶出试验评价其体外释放效果。结果:所制备的OZ-NLC呈球形或类球形;平均粒径为(115±10)nm;Zeta电位为(-37.6±8.9)mV;平均包封率为(61.3±5.2)%;XRD与DSC表明药物以无定形形式分散于OZ-NLC中。与奥扎格雷混悬液相比,OZ-NLC的体外溶出量明显提高且具有很好的缓释效果。结论:熔融-超声乳化法制备的OZ-NLC对促进难溶性药物奥扎格雷的口服吸收具有一定的指导价值。     

Aboriginal Taiwanese hepatitis B carriers have more favorable viral factors than Han Chinese carriers

Several viral factors are associated with disease progression in hepatitis B virus (HBV) carriers. Compared with Taiwanese Han Chinese, Taiwanese aborigines have a higher prevalence of chronic HBV infection and a higher standardized mortality rate of chronic liver diseases but a lower standardized mortality rate of hepatocellular carcinoma (HCC). The aim of this study was to investigate whether aboriginal Taiwanese HBV carriers have more favorable viral factors which reduce the risk for HCC than Han Chinese carriers. Blood samples from 3,488 HBV carriers (1,527 aborigines and 1,961 Han Chinese) were assayed for aminotransferases, hepatitis B e antigen (HBeAg), HBV DNA, and HBV genotype. Aboriginal HBV carriers had a lower HBeAg‐positive rate (5.3% vs. 10.2%, P < 0.0001) and a lower viral load of HBV DNA > 2,000 IU/ml (27.4% vs. 36.7%, P < 0.0001) but a higher rate of alcohol consumption (40.0% vs. 19.3%, P < 0.0001) than Han Chinese carriers. The prevalence of HBV genotype B in aboriginal carriers (92.7%) was significantly higher than that in Han Chinese carriers (72.7%) in all age groups (P < 0.05). In addition, patients with rare genotype D infections were clustered in a township in southern Taiwan. In conclusion, aboriginal Taiwanese HBV carriers have more favorable viral factors than Han Chinese carriers, which may be partly responsible for the lower standardized mortality rate of HCC in Taiwanese aborigines. J. Med. Virol. 83:1326–1331, 2011. © 2011 Wiley‐Liss, Inc.     

Novel one-stop multidisciplinary follow-up clinic for BRCA1/2 carriers: patient satisfaction and decision making

Objective: To evaluate patient' satisfaction and cancer risk management decision making, following attendance at a novel multidisciplinary one‐stop follow‐up clinic (MDOSC) for BRCA1/2 carriers. Patients and Methods: 172 patients attended the MDOSC over a 2‐year period between 2006 and 2008. A total of 96 and 76 patients were seen in the first and second year, respectively. All patients who attended the MDOSC were sent a 17‐item Satisfaction Questionnaire (SQ) designed to examine their views about the MDOSC, using rating scales and open questions after the first year. Patients were asked to comment on the most helpful aspects of the MDOSC and on how the service might be improved. Changes were made based on this feedback. During the second year, all patients were given the SQ with three questions about cancer risk management decision making on the day of the MDOSC. Results: In total, 132 (77%) patients responded and overall satisfaction was high with a mean of 8.94 (range 1–10). BRCA1/2 carriers were pleased to see a range of health care professionals on the same day, who they viewed gave consistent information, considered every aspect of care and addressed psychosocial needs. Following improvements, based on patients' feedback, satisfaction significantly increased in year 2. Furthermore, the MDOSC also helped patients to move forward with their cancer risk management decisions. Conclusions: BRCA1/2 carriers were highly satisfied with the MDOSC, which met their needs and helped them to make informed decisions regarding their cancer risk management. Copyright © 2010 John Wiley & Sons, Ltd.     

Lipid nanocapsules: Ready-to-use nanovectors for the aerosol delivery of paclitaxel

Aerosol drug delivery permits the development of dose-intensification strategies in severe, malignant lung diseases. The aim of the study was to demonstrate that the encapsulation of paclitaxel in lipid nanocapsules (LNCs), a novel drug nanocarrier for lipophilic components, allows one to provide pulmonary drug delivery of paclitaxel by nebulisation, thereby allowing preclinical and clinical studies. LNC dispersions are made into aerosols with commercial nebulisers. The structure, drug payload and cytotoxicity of nebulised LNCs were compared to fresh LNCs. The results demonstrated that LNC dispersions could be made into aerosols by using mesh nebulisers without altering the LNC structure. Only eFlow^® rapid-produced aerosols are compatible with human use: the mean duration to nebulise 3 ml of LNC dispersion is less than 9 min, with an aerosol mass median aerodynamic diameter equal to 2.7 ± 0.1 μm and a fine-particle fraction (between 1.0 and 5.0 μm) of 81.5 ± 3.1%. No modifications of drug payload or cytotoxicity effects of paclitaxel-loaded LNC (PTX–LNC) were observed. In order to carry out preclinical studies, a scaled-up LNC formulation protocol was used. Chemical parameters, such as acidity and osmolarity, were optimised, and a storage procedure for PTX–LNC batches was set-up. Animal studies are now needed to determine the tolerance and therapeutic potential of LNC dispersion aerosols.