<Emphasis Type="Italic">In vitro</Emphasis> Enhancement of Lactate Esters on the Percutaneous Penetration of Drugs with Different Lipophilicity

Lactate esters are widely used as food additives, perfume materials, medicine additives, and personal care products. The objective of this work was to investigate the effect of a series of lactate esters as penetration enhancers on the in vitro skin permeation of four drugs with different physicochemical properties, including ibuprofen, salicylic acid, dexamethasone and 5-fluorouracil. The saturated donor solutions of the evaluated drugs in propylene glycol were used in order to keep a constant driving force with maximum thermodynamic activity. The permeability coefficient (K _p), skin concentration of drugs (SC), and lag time (T), as well as the enhancement ratios for K _p and SC were recorded. All results indicated that lactate esters can exert a significant influence on the transdermal delivery of the model drugs and there is a structure-activity relationship between the tested lactate esters and their enhancement effects. The results also suggested that the lactate esters with the chain length of fatty alcohol moieties of 10–12 are more effective enhancers. Furthermore, the enhancement effect of lactate esters increases with a decrease of the drug lipophilicity, which suggests that they may be more efficient at enhancing the penetration of hydrophilic drugs than lipophilic drugs. The influence of the concentration of lactate esters was evaluated and the optimal concentration is in the range of 5∼10 wt.%. In sum, lactate esters as a penetration enhancer for some drugs are of interest for transdermal administration when the safety of penetration enhancers is a prime consideration.     

A yeast's eye view of mammalian reproduction: cross-species gene co-expression in meiotic prophase

Background  

Meiotic prophase is a critical stage in sexual reproduction. Aberrant chromosome recombination during this stage is a leading cause of human miscarriages and birth defects. However, due to the experimental intractability of mammalian gonads, only a very limited number of meiotic genes have been characterized. Here we aim to identify novel meiotic genes important in human reproduction through computational mining of cross-species and cross-sex time-series expression data from budding yeast, mouse postnatal testis, mouse embryonic ovary, and human fetal ovary.     

Chemiluminescence associated with phagocytosis of foreign particles in rabbit alveolar macrophages

Rabbit alveolar macrophages exhibit a chemiluminescent response which is associated with phagocytosis of zymosan and polystyrene-butadiene particles. The chemiluminescence reaches a peak in 15 to 25 minutes and then gradually diminishes over the next 1 to 3 hours. During the time of maximal light emission there appears to be no actual uptake of particles, but the response is dependent upon the particle concentration. The metabolic inhibitor, DNP (2,4-dinitrophenol), causes a rapid inhibition of the chemiluminescent response. The addition of ATP to the medium prior to exposure of the cells to particles causes the chemiluminescent response to be greatly diminished, i.e., 0.3mM ATP virtually abolishes the response. These experiments suggest that some metabolic response of the cell to phagocytosis is responsible for the chemiluminescence.     

Genetic linkage of Beckwith-Wiedemann syndrome to 11p15.

Beckwith-Wiedemann syndrome (BWS), characterized by multiorgan developmental abnormalities and predisposition to cancer, usually occurs sporadically, but small apparently dominant pedigrees have been described. Since rare patients show varying karyotypic abnormalities on the short arm of chromosome 11, it has been suggested that BWS may be related to the Wilms tumor gene on 11p13 or, alternatively, to growth factor genes on 11p15. We performed genetic linkage analysis on two BWS kindreds, using RFLPs for loci on 11p. BWS was linked to the insulin gene (11p15.5), with an overall maximum lod score of 3.60 (recombination fraction = .00). Linkage to D11S16 (11p13) could be excluded for recombination fractions less than or equal to .03. These results suggest that BWS defines a tumor-predisposition gene on 11p15.     

The lipopolysaccharide of the phototrophic bacterium Ectothiorhodospira vacuolata

The lipopolysaccharide of Ectothiorhodospira vacuolata was obtained by the phenol-water procedure. It contained a 3-O-methyl-hexose, glucose, galacturonic and glucuronic acids. The finding of d-glycero-d-mannoheptose and 2-keto-3-deoxyoctonate (tentatively identified) suggested a core-structure. The lipid fraction of the lipopolysaccharide contained phosphate and both, 2,3-diamino-2,3-dideoxy-d-glucose and d-glucosamine. The major fatty acids were amine-bound 3-OH-10:0 and 3-OH-12:0 and esterbound 14:0 and 16:0 Sodium deoxycholate gel-electrophoresis, showing a single band only, indicated R-type character of the lipopolysaccharide of Ectothiorhodospira vacuolata.Abbreviations DOC sodium deoxycholate - GC/MS combined gasliquid chromatography - PAGE polyacrylamide gel-electrophoresis     

电损毁海马CA3区及连合前穹窿对大鼠血浆胰岛素水平...

Bilateral electrical lesioning of the hippocampal CA3 region (HCA3-EL) or anterior commissura hippocampi (ACHF-EL) caused marked elevations in plasma basal levels of insulin. 2 weeks later, fasting blood glucose levels were also augmented with decreased glucose tolerance. In contrast, the secretory response of pancreatic B cells to glucose stimulation was markedly enhanced. Following intravenous glucose tolerance test (IVGTT), the relative amounts of glucagon-like and insulin-like immunoreactants were reduced in the pancreatic islets of both HCA3-EL and ACHF-EL rats in comparison with the controls. In the HCA3-EL group, the relative amounts of somatostatin-like immunoreactants and gross numbers of such immunostained cells in islets were also decreased as compared with the control. No difference was seen in pancreatic-polypeptide-like immunoreactivities as assessed by immunohistochemistry plus microphotometry method. The above results suggest strongly that HCA3 and ACHF exert a tonic inhibitory action on the insulin secretion in the rat.     

Surface properties of Streptococcus salivarius HB and nonfibrillar mutants: measurement of zeta potential and elemental composition with X-ray photoelectron spectroscopy.

To characterize the functional cell surface, the zeta potentials and elemental surface composition of Streptococcus salivarius HB and a range of mutants with known molecular surface structures were determined. Zeta potentials of fully hydrated cells were measured as a function of pH in dilute potassium phosphate solutions, yielding isoelectric points of the strains. Elemental composition (O, C, N, and P) of the outer 2 to 5 nm of the freeze-dried cell surfaces were measured by X-ray photoelectron spectroscopy. An increasing loss of proteinaceous fibrillar surface antigens of the mutants was found to be accompanied by a progressive decrease in the N/C ratio from 0.104 in the parent strain HB to 0.053 in mutant HBC12. Simultaneously, the value of the isoelectric point shifted from 3.0 to 1.3. In a previous study (A.H. Weerkamp, H.C. van der Mei, and J. W. Slot, Infect. Immun. 55:438-455, 1987) on the cell surfaces of the same strains, it was shown that removal of fibrils led to increased exposure of (lipo)teichoic acid at the surface, which explains the low isoelectric point caused by the low pKa of the phosphate groups.