The Effect of Monomers and of Micellar and Vesicular Forms of Non-ionic Surfactants (Solulan C24 and Solulan 16) on Caco-2 Cell Monolayers

Measurements of transepithelial electrical resistance (TEER), the MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide) test and monitoring of poly(ethylene glycol) (PEG) transport have been used to study the effects of the non-ionic surfactants Solulan C24 and Solulan 16, either free in solution or as an integral part of niosome bi-layers, on intestinal epithelial cells from man (Caco-2 cell monolayers). The effects on epithelial integrity and on the transport of the hydrophilic drug metformin depend on the concentration of the surfactants. At concentrations above 1% the effect on TEER of the surfactant in niosomal form and free in solution were equivalent whereas cell viability was preserved to a higher concentration of Solulans when the Solulans were present in the niosomal form. It was concluded that the toxic effect of niosomes arises from free surfactant present in the niosome suspension.     

The Effects of {alpha},{beta}-Unsaturated Aldehydes on Hepatic Thiols and Thiol-Containing Enzymes

The effects of series of ,ß-unsaturated aldehydeson hepatic giutathione, cytochrome P450, and NADPH-cytochromec reductase activity were compared with time. Male F-344 ratswere dosed with muconaldehyde (36 µmol/kg), acrolein (89µmol/ kg), crotonaldehyde (450 µmol/kg), or thesaturated aldehyde propionaldehyde (89 µmol/kg) and terminated0.5, 4, or 24 hr later. Acroiein or muconaldehyde reduced glutathioneto 51 and 75% of controls, respectively, at 4 hr; glutathionereturned control values at 24 hr. Only at 24 hr, acrolein, muconaldehyde,or crotonaldehyde decreased cytochrome P450 to 61, 71, and 67%of control values, respectively; ethylmorphine N-demethylationwas decreased to a greater extent, i.e., to 35, 60, and 23%of controls. The reductase activity was unchanged at any timefollowing the treatment with reactive aldehydes which were nothepatotoxic (as shown by glucose 6-phosphatase activity, histologicalchanges, or serum enzymes). Propionaidehyde changed none ofthese activities. Acroiein (44.5 mol/kg) given 4 hr prior tophenobarbital (50 mg/kg) for two consecutive days decreasedthe phenobarbital induction of cytochrome P450 45% of phenobarbitalalone. This treatment also decreased the 2, 2ß, 6ß,l6, and 16ß hydroxylation of testosterone as wellas androstenedione formation showing effects on individual cytochromeP450 isozymes. NADPH-cytochrome c reductase induction was notdecreased by this treatment, thus indicating that in vivo thesechanges are due to a mechanism other than generalized inhibitionof protein synthesis.     

MUSHROOM BODY INFLUENCE ON LOCOMOTOR ACTIVITY AND CIRCADIAN RHYTHMS IN DROSOPHILA MELANOGASTER

Whether or not mechanisms underlying circadian locomotor rhythms and learning are related anatomically through the mushroom bodies (MBs) was investigated by monitoring behavioral rhythmicity in flies with MB lesions induced by chemical ablation and by mutations in five different genes. All flies tested were later examined histologically to assess (1) MB neuroanatomy, and (2) the condition of the putative pacemaker cells -- the ventral Lateral Neurons (LN v s) and their terminals that project to the vicinity of the MB calyces. All groups of flies had normal rhythms except for mushroom body miniature ( mbm ; only in a wild-type Berlin genetic background) and mushroom body defect ( mud ). MB ablation had no effect on the gender-specific differences in the rhythmic activity profile that are typical of wild-type flies. However, ablated males had a slightly longer period than untreated males and were more active under constant dark conditions. LN v s and their arborization patterns appeared normal in MB-ablated and in most mutant flies. Activity defects of mbm flies were attributed to genetic background rather than to the mutation alone. Misrouted LN v projections and ～14% arrhythmia of mud flies were uncorrelated and attributed to pleiotropy rather than to specific effects of MB lesions. Our results imply that MBs are not involved in circadian activity rhythms but that they do have an inhibitory effect on activity levels of male flies.     

Prevalence of dental fluorosis in children taking part in an oral health programme including fluoride tablet supplements from the age of 2 years

International Journal of Paediatric Dentistry 2010; 20: 347–352 Aim. To investigate the prevalence of dental fluorosis in children who had participated in an oral health programme between the ages 2–5 years, including fluoride tablets from the age of 2 years. Design. The study group consisted of 135 10‐ to 11‐year‐old children who had participated in the programme, including parent education, tooth‐brushing instruction and prescribed fluoride tablets (0.25 mg NaF) (2–3 years: 1 tablet/day; 3–5 years: 2 tablets/day). The prevalence of dental fluorosis in the study group was compared with that in a nonintervention reference group consisting of 129 children of the same ages. The analysis was based on photos of the permanent maxillary front teeth using the Thylstrup & Fejerskov (TF) Index. Results. No statistically significant difference in prevalence of dental fluorosis was seen between the two groups. Forty‐three percent of the children in the study group and 38% in the reference group had fluorosis, the majority of a mild nature (TF‐score 1). None had a TF score above 2. The pattern was the same after correction for parent reported intake of tablets at 3 and 5 years of age. Conclusion. Introduction of fluoride tablets at the age of 2 years did not result in increased prevalence of dental fluorosis.     

Prognostic significance of urokinase plasminogen activator receptor and its cleaved forms in blood from patients with non‐small cell lung cancer

Urokinase plasminogen activator (uPA) cleaves its three‐domain cell surface receptor, uPAR, liberating domain I [uPAR(I)] and leaving the cleaved uPAR(II‐III) on the cell surface. Both intact and cleaved uPAR can be shed from the cell surface. uPAR(I) was previously shown to be a prognostic factor in lung tumour extracts. Here we analyse uPAR forms in blood from patients with non‐small cell lung cancer (NSCLC). Preoperatively sampled plasma/serum from 32 patients with NSCLC was analysed. Three time‐resolved fluoroimmunoassays (TR‐FIAs) measuring intact uPAR(I‐III) (TR‐FIA 1), uPAR(I‐III) + uPAR(II‐III) (TR‐FIA 2) and uPAR(I) (TR‐FIA 3) were applied. The Spearman rank correlations between plasma and serum levels of uPAR(I‐III), uPAR(I‐III) + uPAR(II‐III), and uPAR(I) were 0.89, 0.94 and 0.68 respectively. Survival analysis demonstrated that high levels of all uPAR forms were associated with shorter survival. Adjusted for histological subtype high plasma uPAR(I‐III) and uPAR(I) levels as well as serum uPAR(I) levels were significantly associated with shorter OS (hazards ratios = 4.3, 2.8 and 3.8 respectively). High blood levels of intact uPAR and its cleaved forms are associated with poor prognosis in NSCLC.     

Studies on Perceived Breast Milk Insufficiency: III. Consequences for Breast Milk Consumption and Growth

ABSTRACT. Fifty-one mother–infant pairs were followed prospectively during the period 3 days to 18 months after delivery. In total 54.9% of the mothers experienced transient lactation crises, emanating mostly from a perception of breast milk insufficiency. Within the crisis group no significant difference in the infants' intake of breast milk during the crises compared with control measurements 1 week later was found. Nor had the crises any immediate impact on growth of the infants. A comparison between the crisis and the non-crisis group, revealed that the breast milk consumption in the crisis group was throughout lower with significant differences at 3 and 5 months. The infants in the crisis group also had a significantly lower weight at 2, 3, 4 and 9 months and were significantly thinner for their height at 1–6 months and at 9 months, although both groups were above the NCHS mean. We conclude that even if the infants in the crisis group had a lower consumption and a slower growth development, the differences were comparatively small. Furthermore, evidence was provided that the breast milk insufficiency occasionally perceived as acute by the mothers was in most cases not real.     

CYSTIC FIBROSIS OF THE PANCREAS IN ADOLESCENCE AND ADULTHOOD

Since an increasing number of patients with cystic fibrosis now reach adolescence and adulthood, more will be treated by general physicians. Since 1953 approximately 200 patients have been cared for in this unit, and in January, 1967, 31 were over 14 years of age; five of these have since died, and their modes of death (chest infection and respiratory failure, three; moderate chest disease, massive hæmoptysis, one; mild chest disease and progressive liver disease, one) are considered. The clinical state of the survivors varies greatly and allows discussion of the natural history of the disorder. The well-being of patients depends both on the intrinsic severity of the manifestations of the disease and the efficacy of treatment. With careful attention to chest disease most of these older patients manage to lead relatively active lives and are in most instances gainfully employed.