Air classifier technology (ACT) in dry powder inhalation. Part 2. The effect of lactose carrier surface properties on the drug-to-carrier interaction in adhesive mixtures for inhalation

The effect of carrier surface properties on drug particle detachment from carrier crystals during inhalation with a special test inhaler with basic air classifier has been studied for mixtures containing 0.4% budesonide. Carrier crystals were retained in the classifier during inhalation and subsequently examined for the amount of residual drug (carrier residue: CR). Carrier surface roughness and impurity were varied within the range of their appearance in standard grades of lactose (Pharmatose 80, 100, 110, 150 and 200 M) by making special sieve fractions. It was found that roughness and impurity, both per unit calculated surface area (CSA), tend to increase with increasing mean fraction diameter for the carrier. Drug re-distribution experiments with two different carrier sieve fractions with distinct mean diameters showed that the amount of drug per CSA (drug load) in the state of equilibrium is highest for the coarsest fraction. This seems to confirm that surface carrier irregularities are places where drug particles preferentially accumulate. However, a substantial increase in surface roughness and impurity appears to be necessary to cause only a minor increase in CR at an inspiratory flow rate of 30 l/min through a classifier. At 60 l/min, CR is practically independent of the carrier surface properties. From the difference in CR between 30 and 60 l/min, it has been concluded that particularly the highest adhesive forces (for the largest drug particles) in the mixture are increased when coarser carrier fractions (with higher rugosity) are used. Not only increased surface roughness and impurities may be responsible for an increase in the adhesive forces between drug and carrier particles when coarser carrier fractions are used, but also bulk properties may play a role. With increasing mean carrier diameter, inertial and frictional forces during mixing are increased too, resulting in higher press-on forces with which the drug particles are attached to carrier crystals and to each other.     

Levels of certain metals, organochlorine pesticides and dioxins in cord blood, maternal blood, human milk and some commonly used nutrients in the surroundings of the Aral Sea (Karakalpakstan, Republic of Uzbekistan)

Since the 1960s a massive decline in the volume of the Aral Sea has occurred as a result of the diversion of the supplying rivers to cotton irrigation schemes. The contaminated sediment of the former seabed has been disseminated over the surrounding area by strong winds. This deterioration of the ecosystem has created a hazardous situation for the health of approximately 3.5 million people. This pilot study was undertaken to assist Karakalpak health workers in investigating the degree of exposure to metals, persistent organochlorine pesticides (OCPs) and dioxins during the most vulnerable prenatal and postnatal period and to provide guidelines for future research. All subjects came from areas located within 200 km of the southern border of the Aral Sea. Blood was obtained from 18 pregnant women and 28 newborns (cord blood) to determine the levels of metals, lead, cadmium, zinc and selenium and the OCPs alpha-, beta- and gamma-hexachlorocyclohexane (HCH; lindane is the product name of gamma-hexachlorocyclohexane), hexachlorobenzene (HCB), and isomers and metabolites of dichlorodiphenyltrichloroethane (DDT), i.e. op-DDT, pp-DDT, pp-DDE and pp-TDE. Levels of metals were also determined in blood from 28 non-pregnant women. In addition, levels of 17 dioxins were determined in 41 human milk samples and 1batch of formula. Information about possible dietary sources of the fat-soluble OCPs and dioxins was obtained from a pooled sample of butter and from seven cottonseed oil samples. A mass-selective detector coupled to a gas chromatograph equipped with a large volume injector was used to analyse the selected OCPs, whereas the dioxins were determined by gas chromatography with high-resolution mass spectrometry. The levels of metals in cord and maternal blood were consistent with concentrations observed in European countries. Only three women (7%) had lead levels greater than 100 ppb. The most notable pollutants in maternal and cord blood were the OCPs, notably HCB, beta-HCH, pp-DDE and the most toxic dioxin, 2,3,7,8-TCDD, when calculated as TEQs. A similar pattern was observed in human milk: beta-HCH and pp-DDE levels of more than 1,000 ng g(-1) fat were found in 68 and 43% of the subjects, respectively. Levels of 2,3,7,8-TCDD were six times higher than those observed in Western Europe. Traces of pp-DDE were detected in the batch of formula milk. Contaminated animal fat, but not cottonseed oil, is the most likely dietary source of OCPs and dioxins. CONCLUSION: Further epidemiological research is needed to elucidate the health implications of these pollutants on perinatal and maternal health, including lactation. More importantly, an investigation should be initiated to identify the emission sources of persistent organic pollutants in Karakalpakstan and adjacent regions.     

Vitamin C is reduced in human milk after storage

In order to establish how cold storage of human milk affects levels of bioavailable vitamin C, 11 samples were stored for 24 h in the refrigerator or up to 2 mo in the freezer. Total vitamin C levels decreased on average by one-third in the refrigerator or after I mo of freezing, with wide variations between individuals (6 to 76% and 3 to 100%, respectively). After 2 mo of freezing, the average decrease was two-thirds (7-100%). CONCLUSION: We recommend a change in human milk storage practices, to under 24 h in a refrigerator or under 1 mo in a freezer. Alternatively, vitamin C supplementation may be considered.     

A phantom with tissue-like optical properties in the visible and near infrared for use in photomedicine

BACKGROUND AND OBJECTIVE: Modeling of light transport in tissue requires development of theoretical models and experimental procedures, as well as tissue-simulating phantoms. Our purpose was to develop a phantom that matches the optical characteristics of human skin in the visible and near infrared spectral range. STUDY DESIGN/MATERIALS AND METHODS: The phantom consists of a transparent silicone rubber in which Al(2)O(3) particles and a cosmetic powder are embedded. Layers with thickness as thin as 0.1 mm can be made. The optical properties of Al(2)O(3) particles and cosmetic powder, i.e., total attenuation, absorption and scattering coefficients, and phase function, have been determined in the visible and near infrared spectral range, by using direct and indirect techniques. RESULTS: By varying the concentration of scattering and absorbing particles, tissue-like layers can be produced with predictable optical properties. In particular, mixing at suitable concentration Al(2)O(3) particles and cosmetic powder with the silicone rubber, the optical properties of human skin have been simulated over a range of wavelengths from 400 to 1,000 nm. The comparison between the phantom diffuse reflectance spectrum and that of human skin, averaged over a sample of 260 patients, showed a good agreement. CONCLUSION: The proposed technique allows to produce a stable and reproducible phantom, with accurately predictable optical properties, easy to make and to handle. This phantom is a useful tool for numerous applications involving light interaction with biologic tissue.     

Dietary prevention of allergic diseases in infants and small children.

Because of scientific fraud four trials have been excluded from the original Cochrane meta-analysis on formulas containing hydrolyzed protein for prevention of allergy and food intolerance in infants. Unlike the conclusions of the revised Cochrane review the export group set up by the Section on Paediatrics, European Academy of Allergology and Clinical Immunology (SP-EAACI) do not find that the exclusion of the four trials demands a change of the previous recommendations regarding primary dietary prevention of allergic diseases. Ideally, recommendations on primary dietary prevention should be based only on the results of randomized and quasi-randomized trials (selection criteria in the Cochrane review). However, regarding breastfeeding randomization is unethical, Therefore, in the development of recommendations on dietary primary prevention, high-quality systematic reviews of high-quality cohort studies should be included in the evidence base. The study type combined with assessment of the methodological quality determines the level of evidence. In view of some methodological concerns in the Cochrane meta-analysis, particularly regarding definitions and diagnostic criteria for outcome measures and inclusion of non peer-reviewed studies/reports, a revision of the Cochrane analysis may seem warranted. Based on analysis of published peer-reviewed observational and interventional studies the results still indicate that breastfeeding is highly recommended for all infants irrespective of atopic heredity. A dietary regimen is effective in the prevention of allergic diseases in high-risk infants, particularly in early infancy regarding food allergy and eczema. The most effective dietary regimen is exclusively breastfeeding for at least 4-6 months or, in absence of breast milk, formulas with documented reduced allergenicity for at least the first 4 months, combined with avoidance of solid food and cow's milk for the first 4 months.     

黄芪、黄连复方有效成分对二亚硝基哌嗪诱导气虚状态大鼠鼻咽上皮组织癌前病变的影响

目的观察二亚硝基哌嗪在正常状态和气虚状态大鼠鼻咽上皮细胞的诱癌效率差异以及黄芪、黄连复方有效成分的防护作用。方法SD大鼠每日力竭游泳10min,连续30d以建立气虚状态模型,然后分组,每组动物10只。DNP皮下注射法诱癌,并应用黄芪、黄连复方有效成分进行干预。干预完成后200天,分别取各组动物鼻咽黏膜行常规病理组织学和超微病理观察。结果力竭游泳联合DNP诱癌组动物中,鼻咽黏膜上皮细胞出现癌前病变例数（n1=8）显著多于单纯DNP诱癌组（n2=3,P〈0.05）,而应用益气解毒中药干预后,该类动物鼻咽黏膜上皮细胞癌前病变例数显著降低（n3=3,P〈0.05）。结论气虚状态下,实验动物鼻咽黏膜上皮细胞对DNP诱癌效应更加敏感,而黄芪、黄连复方活性成分能够有效阻逆该类病理过程。     

不同分娩方式与早发型母乳性黄疸及胃肠激素水平的相关研究

目的:探讨不同分娩方式与早发型母乳性黄疸发病率的关系及和胃动素(MOT)、胃泌素(GAS)水平的相关性。方法:由专人对该院产科出生正常的新生儿218例进行监测,其中剖宫产136例,自然分娩82例,将符合早发型母乳性黄疸诊断标准的50例对象进一步采集血液标本,通过放射免疫法测定MOT和GAS水平。结果:剖宫产组早发型母乳性黄疸的发病率为27.49%,高于正常分娩组发病率14.63%(P<0.05);剖宫产组MOT、GAS的水平分别为(206.84±32.10)ng/L和(94.54±16.42)ng/L明显低于正常分娩组(256.20±28.32)ng/L和(137.06±16.15)ng/L(P<0.001)。结论:剖宫产分娩的新生儿较自然分娩的新生儿更易发生早发型母乳性黄疸,且同时有胃肠激素MOT、GAS水平的降低。对剖宫产分娩的新生儿更应严密监测黄疸的发生,及早干预。     

原子荧光光谱法同时测定发酵虫草菌粉中砷和汞

目的：建立采用原子荧光光谱法同时测定发酵虫草菌粉中砷和汞的方法。方法：标准及样品经消解,直接用AFS-9130型双道原子荧光仪分析,并对实验条件进行优化。结果：在选定的最佳条件下,测得砷和汞的相对标准偏差分别为0.75和1.86。砷和汞的回收率分别为94.5%～104.0%和89.4%～107.8%。结论：该方法具有较高的灵敏度、准确度和精密度。     

哺乳期农村乳母乳汁无机元素含量的变化

目的了解哺乳期人乳无机元素含量的变化及其与乳母膳食的关联。方法采用横断面调查方法,收集55名陕西省澄城县农村健康乳母清晨乳样,利用原子吸收分光光度法测定乳汁钙、镁、铁、锰、锌和铜的浓度。采用24小时回顾法进行连续3天膳食调查,计算膳食营养素的摄入量。结果农村乳母乳汁中镁、锌、铜浓度随哺乳期延长明显降低,铁浓度随哺乳期延长而上升。乳母膳食钙摄入量约为钙膳食参考摄入量(DRI)1/3,膳食无机元素的摄入量与人乳相应元素之间无明显相关性。多因素分析表明,乳汁中钙与镁、铁与铜、锰与锌均呈正相关,钙分别与乳脂、铁、锌呈负相关。结论随哺乳期时间延长,成熟乳中镁、锌、铜浓度降低而铁浓度增加,乳母膳食钙的摄入严重不足,乳汁各元素与膳食相应元素之间无关联。     

原发性肾病综合征患儿血清低密度脂蛋白胆固醇理论预测值与实测值的差异

目的:比较原发性肾病综合征(primary nephrotic syndrome,PNS)患儿血清低密度脂蛋白胆固醇(low densitylipoprotein-cholesterol,LDL-C)理论预测值与实测值之间的差异。方法:78例PNS患儿,血清甘油三酯(triglyeride,TG)浓度均小于4.5 mmol/L,根据血清总胆固醇(total cholesterol,TC)水平,将其分成TC<6.21mmol/L组(29例)和TC≥6.21 mmol/L组(49例);液体双试剂法直接检测血清LDL-C浓度,并与Friedewald公式及Planella公式计算结果进行比较。结果:①PNS患儿LDL-C浓度三种测算方法之间存在显著性差异(P<0.05);②TC≥6.21 mmol/L时,Friedewald公式预测值与实测值之间未见显著性差异(P>0.05);③两种公式预测值与实测值均存在显著正相关,当TC≥6.21 mmol/L时,Friedewald公式预测值与实测值相关性最明显(R=0.79,P=0.00)。结论:当TC≥6.21 mmol/L且TG<4.5 mmol/L时,Friedewald公式预测值与实测值最为接近,可以为临床评价PNS患儿血清LDL-C水平提供参考。