Esophageal varices during pregnancy in the course of cirrhosis.

Esophageal variceal bleeding is one of the most severe complications that may occur during pregnancy in patients with liver cirrhosis. It may result in death of the mother and the fetus. Therefore, screening endoscopy should be performed both before the conception and in the second trimester. Endoscopic band ligation is a method of choice in case of variceal bleeding. Close cooperation of hepatologist, obstetrician-gynecologist and endoscopist is recommended in order to provide maximum care and increase the chances of successful delivery. We present a case of 28-years-old primigravida, at 27 weeks pregnant with esophageal varices and liver cirrhosis.

[Risk assessment of developing aggressive behavior]. / Estimation du risque d'apparition des comportements agressifs.

The article concerns the problem of patients with aggressive behaviour and the most common methods for estimating the potential risk of appearance of such behaviour. The problem mentioned above is related in particular to psychiatric facilities, but it is also present in medical facilities of general type. The importance of this problem is underlined by epidemiological data. The article includes a description of two widely used instruments, namely the HCR 20 (The Historical Clinical and Risk Management Scale 20) and the PCL-R (The Hare Psychopathy Checklist-Revised) but also the actuarial instruments the VRAG (The Violence Risk Assessment Guide) and the SORAG (The Sex Offender Risk Assessment Guide). The article also presents an instrument for the dynamic assessment, the START (The Short-Term Assessment of Risk and Treatability). The usefulness and limitations of these instruments are developed. Some personality disorders may predispose an individual to commit acts of aggression or violence. This topic is also developed in the text. The article focuses on the rationale for the usefulness of regular training of risk assessment for staff, which increases security and helps to plan the care correctly.

Synthesis and structure-activity studies of peptide-acridine/acridone conjugates.

This paper consists in information about structure, synthesis and biological activity of peptide-acridine/acridone conjugates which are potential anticancer, antiviral and antiprion drugs.

Role of endogenous zinc in bones of newborn rats.

Concentration of abundant elements e.g. calcium as well as of elements present in trace amount e.g. zinc in mandibles of 7, 14 an 28 day old newborn rats were determined by X-ray fluorescence analysis. The measurements were carried out by using a measurement system containing X-ray tube ECLIPSE-III and X-ray and gamma ray detector XR-100T-CdTe (Amptek Inc.). Concentration of calcium and zinc depended on the region of interest on the rat's mandible due to mineralization degree conditioned by its function. Increasing age produced a remarkable increase in Ca content in contrast to Zn content in the bone tissue obtained from 7, 14 and 28 day old newborn rats. The calculated Zn/Ca concentration ratio was the biggest for 7 day old newborns and successively decreased with age indicating the important role of zinc at the beginning of bone ontogenesis.

Effects of withdrawal of inhaled steroids in men with severe irreversible airflow obstruction.

Inhaled corticosteroid therapy has proven efficacy for asthmatics, but the benefit for patients with chronic obstructive pulmonary disease (COPD) is less well supported. We hypothesized that withdrawal of inhaled steroids in elderly patients with severe irreversible airway obstruction would not lead to a deterioration in respiratory function. We designed a prospective, double-blind, randomized, placebo-controlled, crossover study to follow spirometry, quality of life questionnaire, six-minute (6-min) walk test, and sputum markers of inflammation during a 6-wk placebo treatment period and a 6-wk treatment period with beclomethasone dipropionate (BDP), 336 microg/d. There were 24 men receiving BDP who entered the study; 15 completed the study. Their mean age was 66.9 +/- 1.9 yr, and mean FEV(1) was 1.61 +/- 0.1 L (47% of predicted). There was a significant decrease in the mean FEV(1 )while using the placebo inhaler (1.70 L versus 1.60 L, baseline versus placebo: 95% CI, 0.002 to 0.195; p < 0.05). There was a decrease in the mean percentage change in FEV(1) for the study subjects during the placebo treatment period as compared with the BDP treatment period (-6.28 versus 5.03%, placebo versus BDP: 95% CI, -23.38 to 0.76; p = 0.06). Six-minute walk test results and sputum analysis for cell count and differential were not significantly different during placebo and BDP treatment periods. Borg scale assessment of dyspnea after exercise was increased while using the placebo inhaler as compared with baseline, and decreased during the BDP treatment period. Chronic Respiratory Disease Questionnaire (CRQ) scores revealed no significant difference between placebo and BDP. This study has demonstrated that in elderly patients with severe irreversible airway obstruction, withdrawal of inhaled corticosteroid therapy leads to a deterioration in ventilatory function and increased exercise-induced dyspnea.

Hydrogen peroxide production from reactive liposomes encapsulating enzymes.

Reactive cationic and anionic liposomes have been prepared from mixtures of dimyristoylphosphatidylcholine (DMPC) and cholesterol incorporating dimethyldioctadecylammonium bromide and DMPC incorporating phosphatidylinositol, respectively. The liposomes were prepared by the vesicle extrusion technique and had the enzymes glucose oxidase (GO) encapsulated in combination with horseradish peroxidase (HRP) or lactoperoxidase (LPO). The generation of hydrogen peroxide from the liposomes in response to externally added D-glucose substrate was monitored using a Rank electrode system polarised to +650 mV, relative to a standard silver-silver chloride electrode. The effects of encapsulated enzyme concentration, enzyme combinations (GO+HRP, GO+LPO), substrate concentration, electron donor and temperature on the production of hydrogen peroxide have been investigated. The electrode signal (peroxide production) was found to increase linearly with GO incorporation, was reduced on addition of HRP and an electron donor (o-dianisidine) and showed a maximum at the lipid chain-melting temperature from the anionic liposomes containing no cholesterol. To aid interpretation of the results, the permeability of the non-reactive substrate (methyl glucoside) across the bilayer membranes was measured. It was found that the encapsulation of the enzymes effected the permeability coefficients of methyl glucoside, increasing them in the case of anionic liposomes and decreasing them in the case of cationic liposomes. These observations are discussed in terms of enzyme bilayer interactions.

The use of lectins for liposome targeting in drug delivery.

Most mammalian cell surfaces are covered with a layer of oligosaccharides covalently linked to glycoproteins and glycolipids that form part of the surface structure, or "glycocalyx," of the plasma membrane. In bacteria, the cells' outer walls contain sugar-amino heteropolymers (peptidoglycans) in the case of Gram-positive strains or lipopolysaccharides in the case of Gram-negative strains. These cell surface sugar (monosaccharide) units are potential binding sites or receptors for many lectins and offer a means of targeting materials, such as drugs to the cell.

Reactive liposomes encapsulating a glucose oxidase-peroxidase system with antibacterial activity.

Liposomes were prepared from phospholipid mixtures of dipalmitoylphosphatidylcholine (DPPC) and phosphatidylinositol (PI), encapsulating the enzymes glucose oxidase (GO) and GO in combination with horse radish peroxidase (HRP) by both extrusion (VET) and reverse-phase evaporation (REV). The optimum level of PI in DPPC/PI liposomes for targeting to biofilms of the oral bacterium Streptococcus gordonii has been established. The liposomes were characterised in terms of the content and activity of the encapsulated enzymes. The antibacterial activity of these 'reactive' liposomes arising from hydrogen peroxide and oxyacids in the presence of the substrates glucose and iodide ions, after targeting to the biofilms, were measured both as a function of liposome-biofilm incubation time and incubation time with the substrates. Bacterial inhibition increases with both liposome-biofilm and substrate-biofilm incubation time and with the extent of enzyme encapsulation. The reactive liposomes also display antibacterial activity in the presence of saliva. The reactive liposomes have potential value in the context of oral hygiene.

The interaction of phospholipid liposomes with bacteria and their use in the delivery of bactericides.

Liposomes have been prepared from dipalmitoylphosphatidylcholine (DPPC) incorporating the cationic lipids stearylamine (SA), dimethyldioctadecylammonium bromide (DDAB) and dimethylaminoethane carbamoyl cholesterol (DCchol) and the anionic lipids dipalmitoylphosphatidylglycerol (DPPG) and phosphatidylinositol (PI). Their adsorption to biofilms of skin-associated bacteria (Staphylococcus epidermidis and Proteus vulgaris) and oral bacteria (Streptococcus mutans and sanguis) has been investigated as a function of mole % cationic and anionic lipid. Targeting (adsorption) was most effective for the systems DPPC-chol-SA, DPPC-DPPG and DPPC-PI liposomes to S. epidermidis. The effect of extracellular mucopolysaccharide on targeting was investigated for S. epidermidis biofilms. It was found that targeting increased with the level of extracellular mucopolysaccharide for all liposome compositions studied. The delivery of the oil-soluble bactericide Triclosan and the water soluble bactericide chlorhexidine was studied for a number of liposomal compositions. Superior delivery of both bactericides relative to the free bactericide occurred for DPPC-chol-SA liposomes and for Triclosan delivery by DPPC-DPPG and DPPC-PI liposomes targeted to S. epidermidis at low bactericide concentrations. DPPC-chol-SA liposomes were also effective for delivery of Triclosan to S. sanguis biofilms. Double labelling experiments using [14C]-chlorhexidine and [3H]-DPPC suggested that there was exchange between adsorbed liposomes which had delivered bactericide to the biofilm and those in the bulk solution implying a diffusion mechanism for bactericide delivery.

The targeting of phospholipid liposomes to bacteria.

Phospholipid liposomes have been prepared from phospholipid mixtures including dipalmitoylphosphatidylcholine/phosphatidylinositol (DPPC/PI) and DPPC/dipalmitoylphosphatidylglycerol (DPPC/DPPG) mixtures and targeted to adsorbed biofilms of the skin-associated bacteria Staphylococcus epidermidis and Proteus vulgaris and the oral bacterium Streptococcus sanguis. The effects of time, liposome concentration and density of bacteria in the biofilm have been studied in detail for Staphylococcus epidermidis. The targeting (as assessed by the apparent monolayer coverage of the biofilms by liposomes) to the biofilms was found to be sensitive to the mol% of PI and DPPG in the liposomes and optimum levels of PI were found for targeting to each bacterium. The use of PI and DPPG-containing liposomes for the delivery of the bactericide, Triclosan, to biofilms of Staphylococcus epidermidis was studied as a function of the amount of Triclosan carried by the liposomes. All the liposome systems tested inhibited the growth of bacteria from the biofilms after brief (2 min) exposure to Triclosan-carrying liposomes. At low Triclosan levels bacterial growth inhibition by Triclosan-carrying liposomes exceeded that by an equivalent level of free Triclosan. After short periods (min) of exposure of biofilms to Triclosan-carrying liposomes the bactericide was shown to preferentially concentrate in the biofilms relative to its liposomal lipid carrier. The results suggest that phospholipid liposomes with appropriately chosen lipid composition have potential for the targeting and delivery of bactericide to bacteria.

Polyhydroxy-mediated interactions between liposomes and bacterial biofilms.

A theoretical model has been developed for the interaction of the surface polymers of the bacterial glycocalyx with liposomes incorporating lipids with polyhydroxy headgroups such as phosphatidylinositol (PI). The theory is based on a lattice model and equations are derived for the potential energy of interaction between the surfaces of a bacterium and a liposome as a function of their separation. It is shown that a relatively small energy of interaction, less than that of a single hydrogen bond, between the polyhydroxyl headgroup of the liposomal lipid and bacterium surface polymer residues could give rise to a potential energy of interaction in excess of the classical double layer repulsive force and attractive dispersion force interactions. The most important prediction of the theory is that the potential energy of interaction goes through a minimum as a function of the polyhydroxy lipid (PI) concentration in the liposomal surface, thus predicting an optimal liposomal composition for adsorption of liposome to bacterium. This result is in concordance with the adsorption of dipalmitoylphosphatidylcholine-PI liposomes to a range of biofilms of oral and skin-associated bacteria on solid supports, where optimum levels of PI for adsorption have been found. The theory demonstrates that subtle changes in the composition of liposomal and bacterial surfaces involving relatively small interaction energies can markedly influence the nature of their interactions.

The use of phospholipid liposomes for targeting to oral and skin-associated bacteria.

Phospholipid (dipalmitoylphosphatidylcholine (DPPC) plus phosphatidylinositol (PI)) proteoliposomes with surface bound lectins (succinylated concanavalin A (s con A) and wheat germ agglutinin (WGA)) have been prepared covering a range of size and surface density of lectin. Negatively charged phospholipid liposomes from DPPC-PI mixtures covering a range of PI mole % and positively charged liposomes from DPPC-cholesterol-stearylamine (SA) mixtures covering a range of SA mole % have been prepared. The targeting of the liposomes and proteoliposomes to a range of oral and skin-associated been prepared. The targeting of the liposomes and proteoliposomes to a range of oral and skin-associated bacterial biofilms has been investigated. The oral bacteria Streptococcus mutans and gordonii and the skin-associated bacterium Coryneform hofmanni can be targeted with s con A bearing proteoliposomes while the skin associated bacterium Staphylococcus epidermidis can be targeted with WGA bearing proteoliposomes. Both oral and skin-associated bacteria can be targeted with positively charged liposomes although the extents of adsorption to the biofilm are low except for Staphylococcus epidermidis. In the case of negatively charged liposomes targeting is critically dependent on the PI content of the liposomes and for all the bacteria studied optimum levels PI for targeting have been found. The adsorption of the oral bacterium Streptococcus gordonii to immobilised monolayers having the optimum PI level for adsorption has been studied by total internal reflection microscopy (TIRM). Both the phospholipid and proteoliposomes have been used to deliver the bactericide Triclosan to biofilms. All the systems studied inhibited bacterial growth to varying degrees.(ABSTRACT TRUNCATED AT 250 WORDS)

Protection against membrane damage: a 1H-NMR investigation of the effect of Zn2+ and Ca2+ on the permeability of phospholipid vesicles.

1H-NMR spectroscopy of small, unilamellar dipalmitoyl phosphatidylcholine (DPPC) vesicles in conjunction with the lanthanide shift reagent Pr3+ was used to study the effect of Zn2+ and Ca2+ ions on the permeability induced at the lipid phase transition temperature (Tc) of the vesicles and by the bee venom polypeptide melittin. In addition, the effects of Zn2+ and Ca2+ were studied on Triton X-100 stabilized channels at Tc and in the presence of n-alcohols. The results show that the presence of 10 mM Zn2+ and Ca2+ inhibited most of the forms of vesicular permeability investigated. The results are discussed in terms of the nature of the binding of the metal ions to the vesicles and support the proposal that one biological function of Zn2+ and Ca2+ is protection against membrane damage.

31P- and 1H-NMR investigations of the effect of n-alcohols on the hydrolysis by phospholipase A2 of phospholipid vesicular membranes.

31P- and 1H-NMR spectroscopy of small, unilamellar egg yolk phosphatidylcholine (PC) vesicles in the presence of the lanthanide ion Dy3+ have been used to study the effect of various n-alcohols on the permeability induced by the action of the enzyme phospholipase A2 (PLA2). The method allows the monitoring of the number of PC and lysoPC molecules in the outer and inner monolayers. The results indicate that the initial rate of hydrolysis of PC by PLA2 is increased by all the n-alcohols but in a chain-length dependent manner and that the maximum rate occurs at n = 8 (octan-1-ol). The subsequent rate is dependent upon the rate of transbilayer lipid exchange (flip-flop) of PC molecules from the inner to the outer monolayer. The vesicles only become permeable to the Dy3+ ions when lysoPC is mobilised in the flip-flop process of exchange of lipid molecules between the two monolayers. The n-alcohols affect both the time taken to initiate flip-flop of inner monolayer PC and the subsequent rate of permeability to Dy3+. The n-alcohols are seen to affect all the above rates in an identical chain-length dependent manner, indicating a common cause for all observations which we identify as the degree of clustering of the n-alcohol molecules in the bilayer. The results are discussed in terms of the chain-length dependent mechanism of n-alcohol interactions with the membrane and the mechanism by which the vesicles become permeable to Dy3+ ions.

The effect of n-alcohols on vesicular permeability induced at the lipid phase transition temperature: a 1H-NMR study.

The effect of a series of n-alcohols on the permeability of small, unilamellar dipalmitoyl phosphatidylcholine (DPPC), dimyristoyl phosphatidylcholine (DMPC) and distearoyl phosphatidylcholine (DSPC) vesicles at the gel-to-liquid crystal phase transition temperature was investigated. It was found that the permeability took the form of the transient lysis of a fraction of the population of vesicles. The effect on this lysis of the n-alcohols was seen to be very chain-length dependent, with a minimum at n = 8 (octan-1-ol) for DPPC vesicles. A similar minimum was observed in the presence of 0.1 mM Triton X-100, but the detergent could then interact with certain of the alcohols to produce permanent channels. The results are discussed in terms of the semi-empirical model of Brasseur et al. (1985) Biochim. Biophys. Acta 814, 227-236, for the interaction of the n-alcohols with a DPPC membrane. The effect of various n-alcohols on the outer and inner monolayers of DPPC vesicles was also studied and the results related to their fluidising effect, allowing channels to open at the phase transition temperature.

Do the intracellular beta adrenoreceptors exist in the rabbit auricle.

Propranolol introduced by a cut-end method into atrial trabeculae evoked negative inotropic response without any significant changes in basic electrical parameters. This effect was resistant to noradrenaline but not to dibutyryl cAMP. These results suggest that existence of intracellular beta adrenoreceptors involved in the control of the contraction.