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Bacterial growth in saline implants: in vitro and in vivo studies.

The survival of bacteria was evaluated in custom-made saline breast implants with integral injection ports in vitro and in 10 New Zealand White rabbits for Staphylococcus aureus, Staphylococcus epidermidis, Pseudomonas aeruginosa, and Serratia marcescens. Pseudomonas and Serratia survived in vitro in saline-filled implants and multiplied 24-fold and 22-fold, respectively, from the initial inocula of 300 colony-forming units per cubic centimeter in 21 days. Serratia alone survived in saline implants placed on the dorsum of rabbits, proliferated 80-fold in 7 days, and tapered to 10-fold at the end of 3 weeks. Chemical analysis revealed the presence of glucose in fluid from the implants in the animal study (mean, 1.2 mg per deciliter; standard error of mean [SEM], 0.6) after 21 days and from human subjects (mean, 3.8 mg per deciliter; SEM, 1.0) after 8 months to 10 years. Serratia incubated in human breast implant fluid samples proliferated 7-fold to 30-fold greater than in the saline control in a nonaerated environment. We conclude that some bacteria are able to proliferate in saline in breast implants. Furthermore, their survival may be facilitated by a substance (i.e., glucose) that diffuses across the implant outer shell.

Animals↗

Effect of age on the gastrointestinal absorption of acyclovir in rats.

Drug elimination from the body after intravenous administration of acyclovir (20 mg kg-1) was delayed in 1-week-old rats but the pharmacokinetic data for 2.5-week-old rats were the same as those for 8-week-old rats. The areas under the plasma concentration-time curves at 0-infinity h (AUC) after oral administration of acyclovir (20 mg kg-1) decreased with increasing age. The absolute bioavailabilities for 1-, 2.5-, 3- and 8-week-old rats were 77.59, 51.52, 14.61 and 7.30%, respectively. The gastrointestinal absorption of poorly absorbed acyclovir was good for rats younger than 2.5 weeks but dropped abruptly between 2.5 and 3 weeks of age. The intestinal membrane permeability of acyclovir was studied using the everted sac method. The rate of transfer of an initial concentration of 10 microM acyclovir from the mucosal to the serosal side was constant until 60 min in rats of different ages while the rate in 2.5-week-old rats was significantly greater than that in 3-, 4- and 8-week-old rats. Abrupt in-vivo and in-vitro changes were observed in the experimental results between 2.5- and 3-week-old rats; this period coincided with the weaning period of the rat. The membrane transport mechanism of acyclovir in 2.5- and 8-week-old rats was also studied. Cumulative transferred amounts of acyclovir were linear (r = 0.99) over the range 5 microM-1 mM and dose-independent. The influence of metabolic inhibitors (sodium azide, 2,4-dinitrophenol, ouabain), purine and pyrimidine analogues (2-deoxyguanosine, guanine, adenine, uridine) and temperature on the permeation of acyclovir was studied. The permeation of acyclovir was inhibited only by 2-deoxyguanosine and guanine in 2.5-week-old rats. These results suggest that throughout the maturation period, the gastrointestinal absorption mechanism of acyclovir is predominantly via passive diffusion with little or no active or facilitated transport.(ABSTRACT TRUNCATED AT 250 WORDS)

Acyclovir↗

Functional significance of metabolic responses to thermal acclimation in fish muscle.

Compensatory increases of the aerobic capacity of fish swimming muscle are frequently observed in response to cold acclimation. Such thermal compensation occurs both in fish that remain active in the cold and in fish that become dormant at cold temperatures. For cold-active fish, positive thermal compensation is best explained by conservation of the capacity for aerobic metabolic flux at low temperatures. The compensatory responses of cold-active species can be used to suggest the temperature range over which the activities of glycolytic and tricarboxylic acid cycle enzymes in a muscle, i.e., the muscle's "metabolic profile," can suffice. Analysis of the available data suggests that a 16 degrees C range of temperatures cannot be covered by one metabolic profile, even when the preferred temperatures are centered between the acclimation temperatures. For cold-inactive species that remain normoxic during winter dormancy, the compensatory metabolic modifications may facilitate lipid catabolism. Alternately, an increased aerobic capacity may be adaptive during the relatively cold periods that precede and follow winter dormancy. For goldfish and carp that encounter hypoxia and anoxia during winter dormancy, increased mitochondrial abundance could facilitate ethanol production during anoxia and the diffusion of oxygen to mitochondria during hypoxia. Finally, metabolic modifications during natural acclimatization indicate both thermal compensation and direct thermal effects and suggest that thermal compensation may be masked by reproductive and feeding activities.

Acclimatization↗

Gas mixing within the acinus of the lung.

The subject is reviewed with an emphasis on recent developments in model analyses. Application of computer technology has facilitated the study of simultaneous convection and diffusion within a complex geometry approximating the airways and air spaces of the lung. During an inspiration of fresh gas the diffusion front separating inspired from "alveolar" gas is stationed within a portion of the acinus where the magnitudes of gas transport by convection and diffusion are similar. This constitutes the peripheral boundary of the Fowler dead space. Asymmetry of intra-acinar branching results in an inequality of gas concentrations within alveolar gas, despite homogeneous volume expansion. This is due to an interaction between diffusion and convection at branch points subtending units of unequal lengths. During a respiratory cycle a "diffusive Pendelluft" between these units results in a "first in-first out" pattern and a sloping alveolar plateau on the expired tracing, despite synchronous and homogeneous volume changes. Experimental results suggest that incomplete alveolar gas mixing constitutes a measurable limitation to gas exchange in the normal lung.

Animals↗

Effect of 2-(methacryloxy)ethyl phenyl hydrogen phosphate on adhesion to dentin.

A variety of methacrylate-based materials has been developed with the capacity of adhering to dentin. This study investigated the effectiveness of 2-(methacryloxy)ethyl phenyl hydrogenphosphate (phenyl-P) for bonding 5% phenyl-P in methyl methacrylate (MMA) to dentinal surfaces. Polymerization of the phenyl-P/MMA monomer was initiated by partially oxidized tri-n-butyl borane catalyst (TBB). The mean tensile bond strength of 5% phenyl-P in MMA to dentin that was pre-treated with an aqueous solution of 10% citric acid/3% ferric chloride, abbreviated as 10-3, was found to be 10.5 MPa. Scanning electron microscope examination demonstrated the formation of a transitional or "hybrid" layer of resin-reinforced dentin, created by the intermingling and entanglement of polymerized resin with collagen bundles exposed by dentin pre-treatment with 10-3, an effective remover of the dentinal smear layer. This "hybrid" layer or zone was essential for high tensile bond strength to be attained. Phenyl-P was found to be effective in promoting monomer diffusion and impregnating monomer into demineralized dentinal surfaces. The formation of the "hybrid" layer of resin-reinforced dentin followed in situ resin polymerization initiated by partially oxidized tri-n-butyl borane (TBB). Ferric (Fe3+) ions deposited on dentinal surfaces from the 10-3 solution also acted to improve monomer diffusion and entanglement with demineralized dentin, and facilitated the formation of the "hybrid" layer/zone.

Acid Etching, Dental↗

Quality circles: the nurse executive as mentor.

Changes within and around the health care environment are forcing health care executives to reexamine their managerial and leadership styles to confront the resulting turbulence. The nurse executive is charged with the profound responsibility of directing the delivery of nursing care throughout the organization. Care delivered today must be of high quality. Declining financial resources as well as personnel shortages cause the executive to be an effective innovator in meeting the increasing demands. Quality circles offer the nurse executive an avenue of recourse. Circles have been effectively implemented in the health care setting, as has been consistently documented over time. By way of a participative management approach, quality circles may lead to increased employee morale and productivity, cost savings, and decreased employee turnover rates, as well as realization of socialization and self-actualization needs. A most effective approach to their introduction would be implementation at the first-line manager level. This promotes an acceptance of the concept at the management level as well as a training course for managers to implement the process at the unit level. The nurse executive facilitates the process at the first-line manager level. This facilitation will cause a positive outcome to diffuse throughout the entire organization. Quality circles offer the nurse executive the opportunity to challenge the existing environmental turmoil and effect a positive and lasting change.

Group Processes↗

[Searching for evidence. A compilation of useful resources for health technology assessment].

The spectacular growth in the produced volume of published scientific and technical information during the last years makes it difficult to discriminate and localize the information of greater quality. The parallel development of technologies for the fast handling of great volumes of single information has partially solved the problem of the access and use of the most advisable information. Health technology assessment tries to facilitate the decision making on the introduction, diffusion or use of health technologies, being based on the best evidences available. In order to improve the process of searching for evidences, needed in the process of health technology assessment, the Agency of Health Technology Assessment of the Institute of Salud Carlos III (AETS) made a compilation of information resources that can be useful for searching biomedical information in general. This article presents the above mentioned compilation along with the description of the process of elaboration and the criteria of selection applied.

Databases as Topic↗

D-glucose uptake in intestinal brush-border membrane vesicles of rachitic rats.

We have previously reported the metabolic consequences of feeding rats Steenbock and Black's rickets-inducing diet, deficient in vitamin D and with an altered Ca/P ratio. Using isolated brush-border membrane vesicles prepared from the jejunum, ileum and duodenum of control and rachitic rats, we have demonstrated a marked decrease of Na+-dependent D-glucose uptake at jejunum-ileum level of rachitic rats. At duodenum level Na+-dependent D-glucose transport was not influenced by rickets. A lack of any significant difference between the two animal groups was observed studying the facilitated transport of D-glucose, the diffusion of L-glucose and the Na+-dependent uptake of phenylalanine and aspartate.

Animals↗

Intrinsic B lymphocyte and macrophage defects in C3H/HeJ mice.

C3H/HeJ mice are genetically defective in their responsiveness to lipopolysaccharide (LPS). Their B cells also have a characteristically low cloning efficiency in semisolid agar cultures, where LPS does not seem to be required. Adherent macrophages facilitate clonal proliferation in such cultures via diffusible substances. C3H/HeJ macrophages functioned poorly in this respect, and addition of normal C3HeB/FeJ macrophages to cultures of C3H/HeJ B cells did not lead to normal colony numbers. Although immune interferon can stimulate normal resident peritoneal macrophages to function well in semisolid agar cultures, it did not improve the cloning efficiency of C3H/HeJ cells. Similarly, addition of indomethacin or interleukin 1 to the cultures did not reveal that abnormally elevated production of prostaglandins or a deficiency in interleukin 1 are responsible for poor C3H/HeJ colony formation. These results indicate that C3H/HeJ mice have defects intrinsic to both B cells and macrophages that are not overcome by interferon. Purified B cells from these mice cloned poorly and did not respond to stimulation in liquid cultures with anti-mu-coated beads plus factors. There was a tendency for the poor cloning of C3H/HeJ B cells to improve with age.

Animals↗

Unexpected accumulation of acyclovir in breast milk with estimation of infant exposure.

Although acyclovir is prescribed to women of reproductive age, no information currently exists regarding the advisability of its use in lactating women. This report documents the first known case of acyclovir transfer to an infant through breast milk. Maternal plasma, milk, and infant urine were collected following a 200-mg oral dose of acyclovir. The drug concentration in breast milk exceeded the corresponding plasma concentration except at the time of peak plasma concentration. This would not be expected on the basis of simple diffusion, and might be caused by a facilitated or active transport mechanism. Such a mechanism has not been described for any drug in human breast milk. Subtherapeutic amounts of acyclovir were documented in the infant, and we discuss the potential effects on neonatal immune function. The use of acyclovir in lactating women remains controversial until further study can clarify pertinent questions.

Acyclovir↗

[The repetitive stimulation test in the diagnosis of neuromuscular fatigue syndromes. Critical review of the results in 62 cases].

The usefulness of the method of the repetitive stimulation of the peripheral nerves has been widely accepted since the original observations of Desmedt on patients with Myasthenia Gravis, and this test is now routinely performed in many EMG laboratories. On the other hand the technical difficulties and the variability of the results in the various syndromes of neuromuscular fatigability have put some criticism on the value of the test as a routine examination. The AA. make a critical review of the clinical history and of the EMG pattern of 62 patients, who underwent one or more tests of repetitive stimulation during a period of four years, under the suspicion of Myasthenia Gravis or myasthenic syndrome. The AA. give full details of the employed technique and analyze the results either of the 27 cases with Myasthenia Gravis, either of the 15 cases of Myasthenia Gravis with ocular involvement, either of the 16 cases with myasthenic syndrome and of the 4 cases of psychogenic fatigability. The only typical changes of the motor response are its post-tetanic decrease in the not-treated cases of diffuse form of Myasthenia Gravis and its facilitation in the myasthenic syndromes associated with bronchial carcinoma.

Electromyography↗

Interaction of phorbol esters with lipid bilayers : thermotropic changes in fluorescence polarization, phase transition and calcium ionophoresis.

The influence of phorbol esters upon the thermotropic behaviour of multilamellar liposomes formed of dipalmitoylphosphatidylcholine (DPPC) or dimyristoylphosphatidylcholine (DMPC) was investigated, as a model for possible interferences of the phorbol esters with the phospholipid domain of biological membranes. Both biologically active (TPA, 12-O-tetradecanoylphorbol-13-acetate, PDD, phorbol-12,13-didecanoate) and inactive (4 alpha-PDD, 4 alpha-phorbol-12,13-didecanoate) phorbol esters lowered the temperature required to cause a fall in fluorescence polarization of a fluorescent probe inserted in the lipid matrix of the DMPC or DPPC liposomes and facilitated the process of calcium exchange-diffusion in DPPC liposomes containing the ionophore A23187. Both of these effects could be due to a decrease in viscosity of the liposomal matrix. However, differential scanning calorimetry revealed that the thermotropic changes evoked by each of these phorbol esters were not identical. In most cases, the phorbol esters decreased both the main phase transition temperature and enthalpy of melting. However, when TPA was incorporated in DMPC liposomes, i.e. when a myristoyl chain was present in both the phorbol ester and phospholipid, no change in the enthalpy of melting could be detected, whereas the main phase transition temperature decreased in proportion to the TPA content of the liposomes. These findings emphasize the view that phorbol esters indeed interact with phospholipids and that the characteristics of such an interaction may tightly depend on the precise chemical structure of both the phorbol ester and phospholipid under consideration.

Calcimycin↗

Facilitated nuclear transport of histone H1 and other small nucleophilic proteins.

Upon microinjection into the cytoplasm, three small nonnuclear (extracellular or mitochondrial) proteins diffused into nuclei of chilled or energy-depleted cells. In contrast, the facilitated transport of two large nuclear localization signal (NLS)-containing proteins was reversibly arrested by chilling or energy depletion. Surprisingly, the transport of two small nucleophilic proteins, histone H1 and P(Lys)-cytochrome c (cytochrome c cross-linked with synthetic peptide NLSs), was also arrested by either chilling or energy depletion. In situ titration studies indicate that the transport arrest of H1 in chilled cells is mediated by a cytoplasmic receptor. Therefore, even though they are potentially able to diffuse into nuclei, histones and other small NLS-containing proteins are localized by a receptor-mediated process that precludes their diffusion through the nuclear pores.

Amino Acid Sequence↗

Working underground: respiratory adaptations in the blind mole rat.

Mole rats (Spalax ehrenbergi superspecies) perform the heavy work of digging their subterranean burrows in Israel under highly hypoxic/hypercapnic conditions. Unlike most other mammals, they can achieve high levels of metabolic rate under these conditions, while their metabolic rate at low work rates is depressed. We explored, by comparing mole rats with white rats, whether and how this is related to adaptations in the design of the respiratory system, which determines the transfer of O2 from the lung to muscle mitochondria. At the same body mass, mole rats were found to have a significantly smaller total skeletal muscle mass than ordinary white rats (-22%). In contrast, the fractional volume of muscle mitochondria was larger by 46%. As a consequence, both species had the same total amount of mitochondria and achieved, under normoxia, the same V(O2max). Whereas the O2 transport capacity of the blood was not different, we found a larger capillary density (+31%) in the mole rat muscle, resulting in a reduced diffusion distance to mitochondria. The structural pulmonary diffusing capacity for O2 was greater in the mole rat (+44%), thus facilitating O2 uptake in hypoxia. We conclude that structural adaptations in lung and muscle tissue improve O2 diffusion conditions and serve to maintain high metabolic rates in hypoxia but have no consequences for achieving V(O2max) under normoxic conditions.

Adaptation, Physiological↗

The peroxisomal proliferator clofibrate enhances the hepatic cytoplasmic movement of fatty acids in rats.

The role of cytosolic fatty acid binding protein (FABP) in cellular fatty acid metabolism remains poorly defined. The intracellular movement of fatty acids is thought to be facilitated through codiffusion with FABP. Peroxisomal proliferators like clofibrate induce FABP and may stimulate fatty acid use by increasing cytoplasmic diffusion rates. Our aim was to determine if induction of FABP by clofibrate increases the cytoplasmic transport of a fluorescent fatty acid NBD-stearate. Male rats were fed clofibrate for 9 days to increase the hepatic concentration of FABP. Hepatocytes were isolated using collagenase perfusion. Cytosolic FABP was measured by enzyme-linked immunosorbent assay (ELISA) using a specific antibody to hepatic FABP. Two-dimensional laser photobleaching (FRAP) was used to measure the cytoplasmic movement of NBD-stearate in hepatocytes. Cytoplasmic transport of NBD-stearate occurred by isotropic diffusion with no evidence for convective or directed transport. Treatment with clofibrate increased FABP levels, the fraction of NBD-stearate found in cytosol, and the observed cytoplasmic diffusion rate. The increase in cytoplasmic movement exceeded that predicted from FABP binding changes suggesting that clofibrate also enhances fatty acid diffusion within intracellular membranes. Nonspecific effects of clofibrate on cytoplasmic viscosity or pore size were not observed. These data suggest that clofibrate treatment induces cytosolic FABP and stimulates the intracellular movement of fatty acids by 2 distinct mechanisms. Soluble proteins like FABP promote the cytoplasmic transport of fatty acids by increasing diffusion. These data further support a role for intracellular binding proteins in facilitating the intracellular movements of fatty acids.

4-Chloro-7-nitrobenzofurazan↗

Transport of cyanide into guinea pig cardiac mitochondria.

The transport of cyanide (CN) into cells has been presumed to be by passive diffusion. Recently, there have been reports that CN, in the form of an anion, may enter the cell by active or facilitated transport. To characterize the mechanism(s) and kinetics of CN movement across the cell membrane, we measured the rate of 14CN (Na salt) uptake into guinea-pig mitochondria. Initial velocities of CN movement into mitochondria were determined at time points ranging from 10-100 msec and at CN concentrations ranging from 1 microM-10 mM using a rapid filtration device. A Hofstee plot of the data suggests that an active or facilitated transport predominates at lower CN concentrations (less than 10 microM), whereas passive diffusion of CN predominates at higher CN concentrations. The kinetic constants for the active phase transport were Jmax = 0.9 pmol/ms and Kt = 14 microM. These results suggest that a large portion of CN movement across the cell membrane is due to an active or facilitated transport phenomenon.

Animals↗

Binding of substrate CO2 to the active site of human carbonic anhydrase II: a molecular dynamics study.

Molecular dynamics has been used to study binding of substrate CO2 to the active site of human carbonic anhydrase II. Three potential CO2 binding sites have been located. The first is at the active-site hydrophobic pocket (the catalytically productive site), where CO2 is approximately 3.5 A from the zinc ion and interacts with His-94, His-119, Val-121, Val-143, Leu-198, Thr-199, the zinc ion, and the zinc-bound hydroxide ion. The second CO2 binding site is approximately 6 A from the zinc ion, where CO2 interacts with His-64, His-94, Leu-198, Thr-200, Pro-201, Pro-202, and some active-site water molecules. The third CO2 binding site is approximately 10 A from the zinc ion, is largely solvated by water molecules, and interacts with His-64, Asn-67, and Gln-92. At these three CO2 binding sites, the CO2 molecule is highly localized (the average Zn-CO2 distance fluctuation is approximately 1 A) and favors the linear binding orientation toward the zinc ion. This linear binding orientation of CO2 and its electrostatic interaction with the zinc ion direct diffusion of CO2 toward the zinc ion and facilitate the nucleophilic attack from O of the zinc-bound OH- to C of CO2 in the productive hydrophobic binding site. Finally, the two CO2 binding sites outside the hydrophobic binding pocket, which may represent two intermediate states along the CO2 binding pathway, could play important roles as a CO2 relay.

Amino Acid Sequence↗

Voice over IP: how computing technology is being used in mobile communications.

This article explains how computing technology was used to address the need for mobile communications among nursing staff. In 2004, nursing staff at Fauquier Hospital relocated from one nursing floor in an older building to two floors in a new structure. This resulted in complaints and supervision issues as nursing managers, who had previously been relatively sedentary, now became quite mobile as they attempted to control nursing operations on two separate floors. Complaints arose from several sources. Nursing staff and managers both complained about the increased difficulty in communicating with each other Physicians expressed frustration to hospital administration at playing "telephone tag" with managers. The solution involved Internet Protocol technology that is in widespread use on most computer networks. The article details how this technology was selected over several other communications technologies and used to implement wireless telephony over the hospital's existing computer network. It reviews key standards and technologies and issues surrounding their use. Finally, the article demonstrates how this computing technology improved patient care by facilitating mobile communications.

Diffusion of Innovation↗