Meta-analysis of a partially hydrolysed 100%-whey infant formula vs. extensively hydrolysed infant formulas in the prevention of atopic dermatitis

Abstract

Objectives:

This study presents previously unpublished point and cumulative incidence rates and relative risks (RRs) for comparing a partially hydrolysed 100% whey-based infant formula, NAN-HA^* (PHF-W) to extensively hydrolysed whey- (EHF-Whey) or casein-based (EHF-Casein) infant formulas in the prevention of atopic dermatitis (AD) in infants who cannot be breastfed exclusively. It also outlines methods to convert the above-mentioned data as well as data comparing PHF-W to cows’ milk formula (SF) into inputs to be applied to a pharmacoeconomic model.     

Safety evaluation of polydextrose in infant formula using a suckling piglet model

Oligosaccharides, the third largest component in human milk, are virtually absent from cow’s milk and most infant formula. Prebiotic carbohydrates like polydextrose (PDX) have been proposed as surrogates for human milk oligosaccharides. Safety assessments of novel infant formula ingredients include dose-response experiments in appropriate neonatal animal models such as the suckling pig. To further substantiate the safety of the ingredient, one-day old pigs were fed a cow’s milk-based formula supplemented with PDX (1.7, 4.3, 8.5 or 17 g/L) for 18 days (n = 13/dose) and compared to appropriate control (unsupplemented formula; n = 13) and reference groups (day 0 pigs, and sow-reared pigs; n = 13). Growth rate, formula intake, stool consistency, behavior score, blood chemistry and hematology, relative organ weights (% of body weight), tissue morphology (i.e. liver, kidney and pancreas) and pancreas biochemistry did not differ among formula-fed pigs (P > 0.1). Polydextrose mimicked other prebiotic carbohydrates and had no adverse effect at the highest tested level 17.0 g PDX/L, equivalent to a dose of 8.35 g/kg of body weight per day.     

山茱萸饮片与市售配方颗粒的含量对比

目的:以传统汤剂为基准,比较山茱萸中药饮片与市售配方颗粒中指标性成分的含量差异。方法:收集8批合格的山茱萸饮片和A、B、C 3个厂家的配方颗粒各5批,采用高效液相色谱(HPLC)法测定山茱萸传统汤剂和配方颗粒中莫诺苷、马钱苷的含量,并计算总含量转移率、出膏率。结果:8批山茱萸传统汤剂的指标性成分总含量均值、转移率均值、出膏率均值分别为2.09%,80.3%,68.7%;3个厂家的配方颗粒指标性成分总含量在0.24%～0.57%之间,理论转移率在20.2%～47.3%之间,出膏率在16.7%～30.0%之间。结论:山茱萸配方颗粒的含量、转移率、出膏率测定结果远低于传统汤剂,二者不具有质量一致性。     

元胡白芷配方对大鼠外周血中致痛和镇痛物质的影响

目的:研究元胡白芷配方对疼痛大鼠血清中的前列腺素、β-内啡肽和单胺类递质的影响。方法:建立大鼠痛经和福尔马林疼痛模型,采用行为学评价元胡白芷配方的镇痛效果,测定大鼠外周血中的前列腺素类物质、β-内啡肽和单胺类递质的含量。结果:元胡白芷配方药液对两种疼痛模型镇痛效果明显;给药后能降低痛经大鼠血中的前列腺素F2α的含量,降低PGF2α/PGE2(P<0.05);福尔马林模型中,元胡白芷配方可降低外周血中β-内啡肽和5-羟色胺的含量(P<0.05),对多巴胺及去甲肾上腺素无明显影响。结论:元胡白芷配方镇痛效果显著,对外周血中前列腺素、单胺类及β-内啡肽有显著影响,其作用具有多靶点的特点。     

The effect of levofloxacin, an optically-active isomer of ofloxacin, on fecal microflora in human volunteers.

Following oral administration of levofloxacin (LVFX, (S)-(-)-Ofloxacin; formerly designated as DR-3355) at 200 mg per dose 3 times a day for 7 days to 6 healthy male volunteers, degrees of disturbance of the fecal microflora and fecal drug concentrations were examined. The total viable count remained unchanged during the study period due to the minimal change in the number of members of the family Bacteroidaceae, the most predominant organisms. Most of the aerobes including facultative anaerobes were suppressed by LVFX with only a slight increase in yeasts. In particular, the members of the family Enterobacteriaceae were reduced to below the detection limit on and after day 3 through the time of discontinuation of the drug in all subjects but one. Among the obligate anaerobes, peptostreptococci and bifidobacteria decreased or disappeared in some volunteers, but no significant changes were observed in other anaerobes. Neither Clostridium difficile nor its toxin D-1 was detected in any of the volunteers. No side effects attributable to the drug were observed. During administration, LVFX was detected in the feces at high concentrations which correlated well with the decrease of susceptible members of flora as well as to their detection rate.     

六味地黄健脑方对AD小鼠学习记忆及脑组织SOD、MDA含量的影响

目的：观察六味地黄健脑方对阿尔茨海默病（AD）小鼠学习记忆能力及其脑组织超氧化物歧化酶（SOD）、微量丙二醛（MDA）含量的影响。方法：采用D-半乳糖联合氯化铝构建AD小鼠模型。疗程结束时,跳台实验观察各组对AD小鼠记忆能力的影响,测定脑组织中SOD活性和MDA的含量。结果：治疗组均可显著提高小鼠学习记忆能力及脑组织匀浆中SOD活性,降低潜伏时间及MDA含量,但以中药组作用较明显。结论：六味地黄健脑方可增强AD小鼠学习记忆的能力。     

The impact of age on the hypnotic effects of eszopiclone and zolpidem in the guinea pig

Rational  Eszopiclone and zolpidem are hypnotics that differentially affect sleep and waking states in adult animals. Therefore, it was of interest to compare their effects on the states of sleep and wakefulness in aged animals. Objectives  Our objective was to determine the responses to eszopiclone and zolpidem vis-à-vis sleep and waking states in aged guinea pigs and to compare them with the effects of these hypnotics in adult animals. Methods  Aged guinea pigs were prepared to monitor sleep and waking states and to perform a frequency analysis of the EEG. Eszopiclone and zolpidem were administered intraperitoneally (1, 3, and 10 mg/kg). Results  Eszopiclone produced a more rapid and greater increase in NREM sleep as well as longer duration episodes of NREM sleep compared with zolpidem. There was also a significant increase in the latency to REM sleep with eszopiclone, but not with zolpidem. EEG power during NREM sleep increased in the delta band and decreased in the theta band following eszopiclone administration, whereas zolpidem had no effect on any of the frequency bands analyzed. Conclusions  In aged as well as adult guinea pigs, eszopiclone is a more effective hypnotic insofar as it produces a shorter latency to NREM sleep, a greater amount of NREM sleep and EEG delta waves. Differences in the effects produced by eszopiclone and zolpidem as a function of the aging process likely reflect the fact that they bind to different subunits of the GABA_A receptors, which are differentially reactive to the aging process. This work was supported by Sepracor, Inc., Marlborough, MA, USA.     

The impact of synthetic amorphous silica (E 551) on differentiated Caco-2 cells,a model for the human intestinal epithelium

For several decades, food-grade synthetic amorphous silica (SAS) have been used as a technological additive to reduce caking of food powders. Human exposure is thus inevitable and safety concerns are taken seriously. The toxicity of silica in general and SAS in particular has been studied extensively. Overall, there is little evidence that food-grade SAS pose any health risks to humans. However, from the available data it was often not clear which type of silica was used. Accordingly, the latest report of the European food safety authority requested additional toxicity data for well-characterised “real food-grade SAS”.To close this gap, we screened a panel of ten well-defined, food-grade SAS for potential adverse effects on differentiated Caco-2 cells. Precipitated and fumed SAS with low, intermediate and high specific surface area were included to determine structure-activity relationships.In a physiological dose-range up to 50 μg/ml and 48 h of incubation, none of the materials induced adverse effects on differentiated Caco-2 cells. This held true for endpoints of acute cytotoxicity as well as epithelial specific measures of barrier integrity. These results showed that despite considerable differences in production routes and material characteristics, food-relevant SAS did not elicit acute toxicity responses in intestinal epithelial cells.     

Effects of gestrinone on uterine leiomyoma and expression of c-Src in a guinea pig model

AIM: To investigate the effect of gestrinone on uterine leiomyomas and the expression of c-Src, estradiol receptors (ER), and progesterone receptors (PR) in a guinea pig model. METHODS: After being oophorectomized, the guinea pigs were allocated into random groups. The model group was treated with estradiol benzoate (E2) for 16 weeks. In the gestrinone-treated groups, the animals were treated with E2 for 6 weeks in advance, and then in combination with gestrinone for 10 weeks. Histological examination was performed to evaluate whether there were leiomyoma features in the animals. The protein levels of c-Src, phospho-( 416)Src, ER, and PR were assayed by Western blotting and an immunohistochemical method. RESULTS: Morphological changes were observed in the myometrium of the guinea pig model, including an increase of uterine weights, proliferation of uterine smooth muscles, and the formation of nodules. High protein levels of c-Src, phospho- 416Src, ER, and PR were observed in the myometrium of the guinea pig model. In the gestrinone-treated group, there were no nodules observed. The histological features of the myometrium were similar to that of the control group. Low protein levels of c-Src, phospho-(416 )Src, ER, and PR were observed in the gestrinonetreated group. CONCLUSION: The upregulation of c-Src and phospho-(416 )Src indicated that the activity of c-Src is augmented in the uterine leiomyoma model. c-Src was associated with the formation of uterine leiomyomas in the model, and gestrinone markedly suppressed the growth of uterine leiomyomas in the model. Gestrinone inhibited not only the protein expression of ER and PR, but also c-Src and the autophosphorylation of c-Src in the guinea pig leiomyoma model.     

The effect of a commercial 2,4-D formulation on chemical- and viral-induced tumor production in mice.

Male CD-1 mice were exposed to a commercial formulation of 2,4-dichlorophenoxyacetic acid (2,4-D), the amine derivative, in the drinking water at concentrations ranging from 0 to 0.163% of the formulated product, equivalent to approximately 0-50 mg kg-1 day-1 2,4-D content. The effect of 2,4-D on urethan-induced pulmonary adenoma formation was evaluated following a 105-day exposure. Urethan-induced sleeping times observed following an i.p. injection of urethan (1.5 mg g-1) after 3 weeks of 2,4-D exposure were not altered by 2,4-D, indicating that 2,4-D did not influence urethan elimination. Pulmonary adenoma production, which was evaluated 84 days after urethan injection, was enhanced by 2,4-D exposure but had no effect on tumor size. The effect of 2,4-D on the incidence of spontaneous murine lymphocytic leukemia was evaluated during the 365-day treatment period. Mortality associated with the leukemia virus was not altered by 2,4-D treatment. Exposure to this commercial 2,4-D product at moderately high levels of exposure may modify the development or expression of certain tumors in CD-1 mice. The mechanism of the co-carcinogenic or tumor-promoting activity associated with 2,4-D exposure remains to be determined.     

The impact of compliance with a compulsory model of drug diversion on treatment engagement and reoffending

Aim: Over a 10-year period from 2003, around 1.7 million arrests in England and Wales resulted in the suspect being exposed to mandatory drug testing and assessment processes. These provisions formed part of a wider drug interventions programme costing £1.3 billion. This study sought to assess the impact of compliance with these measures on treatment uptake and reoffending. Recidivism risk factors were also investigated. Methods: The use of linked administrative data relating to matched samples of recent heroin and/or cocaine (H/C) users identified in one English police force area over a 12-month period (N?=?1630). Findings: There was no association between compliance with a compulsory model of drug diversion and subsequent engagement with structured treatment services, rates of treatment retention and successful discharge. Compliance was also not found to be associated with reductions in the rate and volume of reoffending after 12 months. The factor with the largest effect on risk of recidivism was poly use of H/C. Main offence, engagement with structured treatment, number of prior convictions and (younger) age were also identified as recidivism risk factors. Conclusions: These results are discussed in the context of subsequent legislation and policy which further expands the reach of mandatory testing and assessment measures as a form of constraints-based drug diversion.     

The impact of azole antifungal drugs on imatinib metabolism in human liver microsomes

1. Imatinib is widely used for the treatment of hematologic malignancies. It is common that imatinib is clinically co-prescribed with azole antifungal agents since these patients are more prone to invasive antifungal infection. The present study was to investigate the effects of azole antifungal drugs, including ketoconazole, fluconazole, voriconazole, itraconazole and posaconazole on imatinib metabolism.

2. The main metabolites, 1-OH midazolam and N-desmethyl imatinib, were determined in the absence and in the presence of various levels of ketoconazole, fluconazole, voriconazole, itraconazole and posaconazole. The relevant assay was also performed to screen mechanism-based inhibitors (MBI).

3. The inhibition ability of 1-OH midazolam formation from midazolam based on IC₅₀ values was ketoconazole (0.09?µM)>itraconazole (0.31?µM)>?posaconazole (0.68?µM)>voriconazole (2.10?µM)?>?fluconazole (8.90?µM). Similarly, the rank order of inhibitory effects on formation of N-desmethyl imatinib from imatinib was ketoconazole (4.58?µM)>itraconazole (17.45?µM)>?posaconazole (31.02?µM)>?voriconazole (367.9?µM)?>fluconazole (1.11?mM). Posaconazole and itraconazole displayed evidence of MBI. Additionally, imatinib was also shown as a MBI of CYP3A with IC₅₀ value of 5.40?µM against the midazolam.

4. The significant difference in IC₅₀ values of midazolam and imatinib inhibited by azole antifungal agents was observed. The role of CYP2C8 in imatinib metabolism and imatinib autoinhibits CYP3A activity may explain this difference. Our findings suggest that the azole antifungal agents might have limited impacts on imatinib exposure by CYP3A activity.     

电泳迁移率法检测中药复方对白血病CD34~+CD38~-细胞核因子-κB的影响

目的 观察中药复方对急性髓系白血病(AML)CD34+CD38-干细胞群核因子(NF)-κB的影响。方法 将符合纳入标准的30例AML患者骨髓提取单个核细胞,并进行免疫磁珠分选分离人白血病CD34+CD38-干细胞群,每一例标本分为中药原方组、扶正组、祛邪组、对照组。采用电泳迁移率法(EMSA)检测中药复方对NF-κB活化的影响。结果 NF-κB活化比较分析:中药原方组抑制NF-κB活化最明显,中药原方组与扶正组、祛邪组比较差异有统计学意义(P<0.05),扶正组与祛邪组比较差异无统计学意义(P>0.05),对照组NF-κB活化最明显。结论 中药复方可以抑制NF-κB活化,在促进细胞凋亡的层次上,此实验为中医药靶向治疗AML提供了平台。     

The impact of Sambucus nigra L. extract on inflammation,oxidative stress and tissue remodeling in a rat model of lipopolysaccharide-induced subacute rhinosinusitis

Inflammopharmacology - Rhinosinusitis is a common disorder related to inflammation of paranasal sinuses and nasal cavity mucosa. Herbal medicines&nbsp;could be an option in the treatment of...     

Cytotoxicity of human phagocytes studied in vitro in a novel model based on neutral red absorbtion.

The aim of these investigations was to establish a model for the study of neutrophil (NEU) and monocyte (MO) mediated cytotoxicity (TOX), and to study the protective actions of model protease inhibitor, peroxide scavengers and glucocorticoids in this model. Confluent human fibroblasts were used as target cells (T) and NEU and MO were used as effector cells (E), ratio E/T was 5-10:1. After triggering E with PMA (16-48 nM) for about 24 hours, remaining viable T were detected by incorporation of Neutral Red (NR). Oxidant-induced TOX was performed with H2O2 and t-BuOOH. In contrast to MO TOX, NEU TOX was inhibited by antiprotease and scavengers. On the other hand, MO TOX was inhibited by glucocorticosteroids. This indicates different TOX mechanisms by NEU and MO.     

The effects of some antirheumatic drugs on an in vitro model of human polymorphonuclear leucocyte chemokinesis.

1 Pretreatment of dogs for 20 to 24 h before the start of experiments with reserpine (0.5 mg/kg) depleted noradrenaline from cerebral and mesenteric arteries, the diminution being greater in the latter arteries. 2 Contractile responses of helically-cut strips of cerebral and mesenteric arteries to noradrenaline were unaffected by pretreatment with reserpine. Tyramine-induced contractions of mesenteric arteries were markedly attenuated by reserpine-pretreatment, whereas the contraction of cerebral arteries was not influenced. The contractile response of mesenteric arteries to transmural nerve stimulation or nicotine was abolished by reserpine-pretreatment, but the relaxation induced by nicotine of cerebral arteries contracted with prostaglandin F2 alpha was not affected. Pretreatment with reserpine attenuated the contractions of mesenteric arteries induced by angiotensin II, but did not alter the response of cerebral arteries to 5-hydroxytryptamine. 3 In prostaglandin-contracted cerebral and mesenteric arterial strips, relaxant effects of acetylcholine, isoprenaline and K+ were not significantly influenced by reserpine-pretreatment. 4 It appears that tyramine and nicotine do not release noradrenaline from dog cerebral arteries in amounts sufficient to cause significant contractions. Attenuation of the response to angiotensin II by pretreatment with reserpine is not the result of depletion of noradrenaline from the mesenteric arterial wall but may be due to interference with the mechanism specific to actions of angiotensin II.     

The impact of the opioids fentanyl and morphine on nociception and bone destruction in a murine model of bone cancer pain

Chronic pain resulting from metastasis into skeleton of certain neoplastic diseases remains poorly understood and relatively resistant to analgesic treatment. Opioids are the principal axis in drug therapy for this type of pain, especially at the end stage of cancer. Our aim was to examine whether, fentanyl as well as morphine, two potent analgesic opioids commonly used to treat cancer pain, would inhibit pain and bone lesion-related responses in a murine model of bone cancer pain. Repeated administration of equianalgesic doses of fentanyl (0.16 mg/kg s.c. once a day) and morphine (20 mg/kg s.c. once a day) initiated at day 1 (prophylactic treatment) or at day 7 (curative treatment) after tumor cell inoculation in the femoral cavity consistently decreased bone pain symptoms and tumor growth-induced bone destruction (micro-CT bone structure parameters). Both fentanyl and morphine treatments resulted in clear antinociceptive properties as well as reductions in cancer cell-induced bone lesions. The present results demonstrate that fentanyl, and to some lesser degree morphine, has potential benefits in the treatment and development of bone cancer pain. As such, chronic administration of high doses of certain opioids like fentanyl may have clinical utility in the management of bone cancer pain.     

2,3,7,8-Tetrachlorodibenzo-p -dioxin (TCDD) and congeners in infants. A toxicokinetic model of human lifetime body burden by TCDD with special emphasis on its uptake by nutrition

Contents of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) and of 16 further congeners – polychlorinated dibenzodioxins and dibenzofuranes (PCDD/PCDF) – were determined in lipids of adipose tissue and of livers of 3 stillborns and of 17 infants (0.43–44 weeks old) who died from sudden infant death syndrome. International toxic equivalents (I-TEq) calculated for the sum of TCDD together with all of the 16 congeners (1.55–29.63 ng/kg lipids of adipose tissue, n = 20; 2.05–57.73 ng/kg liver lipids, n = 19) were within the range of or lower than the values published for adults. TCDD concentrations in lipids of breast-fed infants were higher (0.38–4.1 ng/kg lipids of adipose tissue, n = 9; 0.49–3.9 ng/kg liver lipids, n = 8) compared to non breast-fed subjects (0.16–0.76 ng/kg lipids of adipose tissue, n = 8; 0.29–0.71 ng/kg liver lipids, n = 7). Neither I-TEq values nor TCDD concentrations exceeded values published for adults. Since even in stillborns PCDD/PCDF were found (I-TEq, 9.70–10.83 ng/kg lipids of adipose tissue, 6.17–8.83 ng/kg liver lipids; TCDD, 1.3–2.1 ng/kg lipids of adipose tissue, 0.76–1.5 ng/kg liver lipids; n = 3), transplacental exposure has to be deduced. All of the findings concerning TCDD concentrations in the organism become intelligible on the basis of a physiological toxicokinetic model which was developed to describe the body burden of TCDD for the entire human lifetime in dependence of TCDD uptake from contaminated nutrition. The model reflects sex and age dependent changes in the following parameters: body weight, volumes of liver, adipose and muscle tissue, food consumption, and excretion of faeces. TCDD is supposed to be taken up orally, to be distributed freely in lipids of the organism and to be eliminated unchanged by excretion in lipids of faeces as well as by metabolism in the liver. The model was used to predict the half-life of elimination of TCDD (4 months in newborns increasing to ∼5 years in adults) and concentrations of this compound in lipids of adipose tissue, blood, liver and faeces at different ages. Furthermore, the influence of breast-feeding on the TCDD burden of a mother, her milk and her child was simulated. The model was validated by means of own data gained in adipose tissue and livers of infants and also using a series of values measured by other authors in mother's milk and in tissues and faeces of infants and adults. Predictions as well as experimental findings demonstrate a distinct increase in the TCDD body burden of breast-fed infants. Generally, it can be concluded for the excretion of unchanged, non volatile, non protein bound highly lipophilic compounds that their half-life is short in infants (∼5 months) and increases to ∼10 years reached between 40 and 60 years of age. Received: 30 July 1996 / Accepted: 30 October 1996