Different response to epidermal growth factor of hepatocytes in cultures isolated from male or female rat liver. Inhibitor effect of estrogen on binding and mitogenic effect of epidermal growth factor

Deoxyribonucleic acid (DNA) synthesis in hepatocytes isolated from the livers of male and female rats has been compared in monolayer culture. Plating efficiency, DNA and protein content, viability, and morphologic appearance were the same in cultures prepared with hepatocytes isolated from male or female rats. Epidermal growth factor (EGF)-induced DNA synthesis was significantly higher in hepatocytes from male rats than in hepatocytes from female rats. This was the case whether hepatocytes were isolated from normal or partially hepatectomized male or female rats. Hepatocytes isolated from regenerating liver synthesize more DNA than those isolated from normal liver in response to EGF. This increased response to EGF in hepatocytes derived from regenerating liver was relatively the same for male- and female-derived hepatocytes, but the magnitude of the response was considerably higher in male-derived hepatocytes. In contrast, in vivo DNA synthesis in the liver remnant after partial hepatectomy was similar in male and female rats if measured 24 h after the operation. A comparison of EGF binding to male- and female-derived hepatocytes maintained in primary culture indicated a lower number of high-affinity receptors for EGF in the female hepatocytes. The addition of estrogen to primary cultures of hepatocytes isolated from male rats inhibited EGF binding as well as EGF-induced DNA synthesis. Our studies show significant differences in DNA synthesis in response to EGF when male and female hepatocytes are compared in primary culture. The regenerative response after partial hepatectomy, on the other hand, was the same in male and female rats. Thus, our studies indicate that the sex of the donor rat is important when hepatocytes in culture are used for a variety of studies, such as hepatocyte metabolism, induction and control of DNA synthesis, and hepatocarcinogenesis. In addition, our results indicate that caution is advised when inferences are made from in vitro findings for in vivo conditions. © 1987

Clay-biosurfactant materials as functional drug delivery systems: Slowing down effect in the in vitro release of cinnamic acid

The main objectives of the present paper were the preparation and characterization of new surfactant-modified clays and the evaluation of their potential applicability as drug delivery systems for the oral administration of the cinnamic acid (CA) drug. The organoclays (OC) were prepared by loading different amounts of the biocompatible nonionic polyoxyethylene sorbitan monolaurate surfactant (Tween20) onto K10 montmorillonite (Mt) clay and characterized through the construction of the adsorption isotherms by means of the spectrophotometric method. The performance of the prepared material was verified by gathering the adsorption isotherms of the cinnamic acid onto the Mt/Tween20 organoclay and by monitoring the release profiles in both simulated gastric (SGF) and intestinal fluids (SIF). The quantitative analysis of the adsorption isotherms revealed that the uptake of the aromatic component onto both the blank and Tween20-loaded Mt was governed by positive cooperative processes and that the presence of the bio-surfactant enhanced the loading efficiency of the clay. By relating the raw montmorillonite uptake capability with that of the OC it was assessed that the presence of the bio-surfactant enhanced about 2 times the loading efficiency of the clay. From the XRD characterization of the obtained complexes, the successful intercalation of the drug into the prepared organoclay was demonstrated. Very useful information was obtained by the in vitro release studies, which showed that the release of the drug from both the clay and organoclay was prolonged in comparison with the pharmacokinetics of the free drug. Besides, the intercalation of the surfactant into the nano-carrier ensured the complete release of the CA after oral drug administration and the kinetics of the release process was strongly dependent on the type of drug formulation used, which means that the CA release can be modulated by properly functionalizing the clay surface

Exhaled breath condensate nitrates, but not nitrites or FENO, relate to asthma control.

SummaryBackgroundAsthma is a chronic respiratory disease, characterised by airways inflammation, obstruction and hyperresponsiveness. Asthma control is the goal of asthma treatment, but many patients have sub-optimal control. Exhaled NO and exhaled breath condensate (EBC) NO metabolites (nitrites and nitrates) measurements are non-invasive tools to assess airways inflammation. Our aim was to investigate the relationships between asthma control and the above-named biomarkers of airways inflammation.MethodsThirty-nine non-smoking asthmatic patients (19 women) aged 50 (21–80) years performed measurements of exhaled NO (FENO), EBC nitrates, nitrites and pH, and answered Asthma Control Questionnaire (ACQ) and Asthma Control Test (ACT)-questionnaire.ResultsThe ACT and ACQ score were strongly interrelated (ρ=−0.84, p<0.001). No relationships between ACT or ACQ score and FENO were found (p>0.05). EBC nitrates were negatively related to ACT score (ρ=−0.34, p=0.03) and positively related to ACQ score (ρ=0.41, p=0.001) while no relation of EBC nitrites to either ACQ or ACT score was found (p>0.05).ConclusionEBC nitrates were the only biomarker that was significantly related to asthma control. This suggests that nitrates, but not nitrites or FENO, reflect an aspect of airways inflammation that is closer related to asthma symptoms. Therefore there is a potential role for EBC nitrates in objective assessment of asthma control

Superallowed 0+ to 0+ nuclear beta decays: A new survey with precision tests of the conserved vector current hypothesis and the standard model

A new critical survey is presented of all half-life, decay-energy and branching-ratio measurements related to 20 0+ to 0+ beta decays. Compared with our last review, there are numerous improvements: First, we have added 27 recently published measurements and eliminated 9 references; of particular importance, the new data include a number of high-precision Penning-trap measurements of decay energies. Second, we have used the recently improved isospin symmetry-breaking corrections. Third, our calculation of the statistical rate function now accounts for possible excitation in the daughter atom. Finally, we have re-examined the systematic uncertainty associated with the isospin symmetry-breaking corrections by evaluating the radial-overlap correction using Hartree-Fock radial wave functions and comparing the results with our earlier calculations, which used Saxon-Woods wave functions; the provision for systematic uncertainty has been changed as a consequence. The new corrected Ft values are impressively constant and their average, when combined with the muon liftime, yields the up-down quark-mixing element of the Cabibbo-Kobayashi-Maskawa (CKM) matrix, V_{ud} = 0.97425(22). The unitarity test on the top row of the matrix becomes |V_{ud}|^2 + |V_{us}|^2 + |V_{ub}|^2 = 0.99995(61). Both V_{ud} and the unitarity sum have significantly reduced uncertainties compared with our previous survey, although the new value of V_{ud} is statistically consistent with the old one. From these data we also set limits on the possible existence of scalar interactions, right-hand currents and extra Z bosons. Finally, we discuss the priorities for future theoretical and experimental work with the goal of making the CKM unitarity test even more definitive.Comment: 36 pages, 11 tables, 9 figure

Modified montmorillonite as drug delivery agent for enhancing antibiotic therapy

The appealing properties of surfactant‐intercalated Montmorillonites (Organo-montmorillonite, OMt) were successfully investigated to propose an effective drug delivery system for metronidazole (MNE) antibiotic therapy. This represents a serious pharmaceutical concern due to the adverse drug reactions and the low targeting ability of MNE. The non‐ionic surfactant Tween 20 was used to functionalize montmorillonite, thus accomplishing the two‐fold objective of enhancing the stability of clay dispersion and better controlling drug uptake and release. The adsorption process was performed under different experimental conditions and investigated by constructing the adsorption isotherms through high‐performance liquid chromatography (HPLC) measurements. Powder X‐ray diffraction (XRD) measurements were performed to characterize the MNE/OMt compounds. The gathered results revealed that the uptake of the drug occurs preferentially in the clay interlayer, and it is governed by positive cooperative processes. The presence of surfactant drives the adsorption into clay interlayer and hampers the adsorption onto external lamella faces. The good performances of the prepared OMt in the controlled release of the MNE were proved by investigating the release profiles under physiological conditions, simulating oral drug administration. Cytotoxicity measurements demonstrated the biocompatibility of the complexes and evidenced that, under specific experimental conditions, nanodevices are more biocompatible than a free drug