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E Florio

Publications and source records attributed to E Florio.

12 recordsLinked to original sources
PubMed2004

Progress in understanding and using over-the-counter pharmaceuticals for syndromic surveillance.

INTRODUCTION: Public health researchers are increasingly interested in the potential use of monitoring data on over-the-counter (OTC) pharmaceutical sales as a source of timely information about community health. However, fundamental uncertainties persist, including how timely such information is and how best to aggregate information about hundreds of products. OBJECTIVES: This analysis provides new information about OTC timeliness and illustrates a method of OTC product aggregation for surveillance purposes. METHODS: Timeliness measurements were made by correlating pharmaceutical sales counts with counts of physician encounters, after adjustment to remove seasonal effects from both counts. OTC product aggregations were formed by a two-stage process. In the first stage, individual products were placed into small groups based on qualitative observations. In the second stage, a clustering algorithm was used to form supergroups (i.e., product group clusters) sharing similar sales histories. RESULTS: Even after seasonal correction, OTC counts correlated with clinical measures of community illness. However, the lead time of nonseasonal fluctuations was substantially shorter than that for uncorrected data. The clustering approach produced 16 meaningful supergroups containing products that behaved approximately alike. CONCLUSIONS: Measurements of OTC lead time sensitive to the timing of annual cyclic trends in the behavior of persons seeking health care do not reliably indicate the lead time observed for short-term (e. g. weekly or monthly) fluctuations in community health-care utilization.

Algorithms↗
PubMed1995

Liposomal cefoxitin in a porcine model of intra-abdominal sepsis: bactericidal efficacy.

The bactericidal effect of free versus liposomal cefoxitin was evaluated in the major reticuloendothelial organs in a porcine model of intra-abdominal sepsis. Yorkshire Landrace pigs were inoculated with 3.2 x 10(10) (n = 5) or 1.4 x 10(11) (n = 7) cfu of Escherichia coli mixed in sterile feces/animal. Two treatment groups inoculated with 1.4 x 10(11) cfu were established: free cefoxitin (n = 9) and liposomal cefoxitin (n = 9). All animals were maintained under anesthesia and euthanized after 24 h. The number of E. coli recovered in the liver, lungs, and spleen was significantly affected by inoculum size (p < .05). The liver had significantly higher numbers of bacteria (p < .05) compared with the other organs, regardless of the inoculum size. The liver and the lung of the liposomal cefoxitin-treated group showed significantly lower numbers of E. coli (5.0 x 10(4) and 6.3 x 10(2), respectively) compared with the untreated (liver, 6.3 x 10(7); lung, 2.0 x 10(6)) and free cefoxitin (liver, 5.0 x 10(6); lung, 7.9 x 10(4))-treated groups (p < .05). At 2 h following the injection of free and liposomal cefoxitin, the decrease of E. coli in peritoneal fluid compared with the nontreated septic group was significant (p < .05). No growth was observed from blood cultures taken 24 h after sepsis induction. All control experiments yielded negative cultures. The results of these experiments demonstrated that liposomal cefoxitin exerts an enhanced bactericidal effect in liver and lungs during Gram-negative sepsis.

Analysis of Variance↗
PubMed1992

Effects of fatty acid alpha-hydroxylation on glycosphingolipid properties in phosphatidylcholine bilayers.

The role of glycosphingolipid fatty acid alpha-hydroxylation as a modulator of glycolipid organization and dynamics was considered by 2H-NMR in bilayer membranes. For these experiments, galactosylceramides were prepared in which the natural fatty acid mixture was replaced with perdeuterated 18-carbon hydroxylated or non-hydroxylated stearic acid. The L-stereoisomer of N-(alpha-OH-stearoyl-d34)galactosylceramide and its naturally-occurring D-alpha-OH analogue, were isolated for independent study. Bilayers were formed using 10 mol% galactosylceramide in a shorter chain phospholipid, dimyristoylphosphatidylcholine, in an attempt to reproduce several features of glycolipid-phospholipid interactions typical of cell membranes. Spectra of deuterated galactosylceramide in gel phase phospholipid membranes indicated that alpha-hydroxylation led to greater motional freedom and/or conformational disorder, with no measurable difference between D- and L-alpha-OH fatty acid derivatives. In fluid phosphatidylcholine bilayers the effects were modest. Glycolipid fatty acid hydroxylation led to broadening of the range of order parameters associated with methylene groups near the membrane surface (frequently referred to as the 'plateau region') - this effect being more marked for the naturally-occurring (D) stereoisomer. The degree of overall molecular order sensed by the glycolipid fatty acid chain in a fluid host matrix was minimally affected by alpha-hydroxylation; although the plateau region of the D isomer was slightly more ordered than that of the L isomer and the non-hydroxylated species. These results suggest that a significant aspect of the alpha-hydroxy group effect on glycosphingolipid behaviour in bilayer membranes with low glycolipid content was interference with glycolipid packing amongst host phospholipids in the upper portion of the acyl chains. For the D stereoisomer, there was some evidence that the hydroxy group led to strengthening of interlipid interaction near the membrane surface.

Fatty Acids↗
PubMed1991

Glycosphingolipids: 2H NMR study of the influence of carbohydrate headgroup structure on ceramide acyl chain behavior in glycolipid-phospholipid bilayers.

Galactosyl- and glucosylceramide, globoside, and dihydrolactosylceramide, bearing [2,2-2H2]stearic acid, have been studied at a concentration of 10 mol% in bilayers of dimyristoylphosphatidylcholine by 2H NMR. The quadrupolar splitting delta vQ of the C2 deuterons were measured at several temperatures in the range of 30-60 degrees C. Spin-lattice relaxation times T1 of C2 deuterons were determined in the same temperature range for all lipids but globoside. T1 values at 30 and 50 degrees C were unexpectedly short (6-8 ms), indicating reduced mobility of the ceramide acyl chains compared to that of the host phospholipid. At all temperatures, both delta vQ and T1 were essentially identical for the monoglycosylated species, GalCer and GlcCer, indicating that the order and dynamics of the upper portion of the fatty acyl chain are insensitive to this small change in the headgroup structure. In the case of globoside, where the glycolipid headgroup is equivalent to that of GlcCer extended by three sugar residues, values for the quadrupolar splittings associated with the acyl chain C2-position were very close to those obtained for Gal- and GlcCer. In contrast, the delta vQ values obtained for the diglycosyl species, LacCer, were significantly different at all temperatures. This different behavior of LacCer relative to that of the other glycolipids most likely originates from an orientational change of the acyl chain at the C2-position due to the absence of a 4,5 double bond in dihydrosphingosine. T1 values for the GlcCer and GalCer systems increased with temperature, indicating that the motions responsible for relaxation were in the short correlation time regime.(ABSTRACT TRUNCATED AT 250 WORDS)

Ceramides↗
PubMed1991

Comparative evaluation of two membrane-based liposomal MRI contrast agents.

Two phospholipids--one bearing a nitroxide free radical covalently attached to its polar headgroup, and the other bearing a similarly attached chelating agent with bound gadolinium--were compared in vivo as liposomal contrast agents for MR imaging. In each case the phospholipid contrast agent was incorporated into the membranes of sonicated unilamellar vesicles. The agent with bound gadolinium proved to be considerably more potent at highlighting regions of liposome biodistribution than did its spin-labelled analogue. Injected intramuscularly into rats, the spin-label liposomes produced local tissue contrast that persisted for 1 h; while under similar conditions, the liposomal gadolinium persisted for over 24 h. By comparison, water-soluble, nonliposomal DTPA-Gd3+ (dimeglumine), was rapidly cleared from the same intramuscular sites--appearing in kidney bladder within 15 min of injection. When delivered intravenously, maximum effect from both liposomal agents was observed in liver and spleen within 1-2 h, although the spin-label agent produced only marginal contrast. The concomitant use of fat suppression proved a valuable adjunct to liposomal contrast for imaging organs of the reticuloendothelial system.

Animals↗
PubMed1990

Glycosphingolipid interdigitation in phospholipid bilayers examined by deuterium NMR and EPR.

Glycosphingolipid fatty acids commonly have up to eight methylene carbons more than do their surrounding phospholipid-attached counterparts. The resultant 'extra' segment may very well modulate glycosphingolipid function as receptor and structural element. As part of an investigation of this phenomenon, galactosylceramide was prepared with a deuterated 18-carbon fatty acid chain. Deuterium-labelled galactosylceramide was assembled at 10 mol% into unsonicated phosphatidylcholine bilayers having all 14-carbon or all 18-carbon saturated fatty acid chains (DMPC and DSPC, respectively). The systems were studied by 2H-NMR spectroscopy above and below the phase transition temperatures, Tm, of the host matrices. At comparable reduced temperatures in fluid membranes the degree of motional order exhibited by the glycolipid fatty acid was significantly higher in the phospholipid host matrix that was four carbons shorter. The fatty acid chain segment least affected by the change from long to short chain host matrix was the terminal (deutero)methyl group (an increase of 8% in quadrupolar splitting for the terminal methyl vs. 16% for deuterons at C17 and 23-28% for the remainder of the chain). Order parameter profiles for galactosylceramide were qualitatively very similar in the two host membranes, arguing against any major conformational difference between the arrangement of the 18-carbon glycolipid fatty acid in the 18-carbon vs. 14-carbon host matrices. Similarly a nitroxide spin probe covalently attached to carbon-12 of the galactosylceramide fatty acid gave clear indication of greater order in the fluid 14-carbon fatty acid phospholipid bilayer. These results are consistent with 'tethering' of the extra length of fatty acid via interdigitation into the opposing monolayer. There was no spectroscopic evidence of any intrinsic difference in glycolipid behaviour in the two fluid host matrices. 2H-NMR spectra of galactosylceramide at comparable reduced temperatures below Tm of the phospholipid bilayer were very different for 14-carbon vs. 18-carbon host matrices. The glycolipid fatty acid showed evidence of relatively reduced mobility in the shorter chain matrix.

Electron Spin Resonance Spectroscopy↗
PubMed1989

A liposomal MRI contrast agent: phosphatidylethanolamine-DTPA.

The chelating agent, diethylenetriaminepentaacetic acid (DTPA), was attached via one -COOH group to the amino headgroup of phosphatidylethanolamine to produce a phospholipid which is also a powerful chelating agent. It readily assembles into the walls of lipid bilayer structures as a liposome-associated carrier of cations for MR contrast or radioisotope studies. Freeze-etch electron microscopy showed that phosphatidylethanolamine-DTPA formed satisfactory sonicated vesicles when mixed with natural phospholipids at up to 50 wt%. The resultant structures with bound gadolinium effectively shortened T1 and T2 of surrounding water protons. When sonicated liposomes bearing chelating agent with bound 111In3+ were injected intravenously into rats, uptake was primarily by liver and spleen. By 24 h postinjection there was biliary excretion of this material. Phosphatidylethanolamine-DTPA may have some general utility as an amphiphilic liposomal chelating agent for polyvalent cations.

Animals↗
PubMed1988

Evidence that trans-bilayer interdigitation of glycosphingolipid long chain fatty acids may be a general phenomenon.

'Interdigitation' is a term coined to describe the phenomenon whereby pure phosphatidylcholines with intramolecular fatty acid chain length heterogeneity when hydrated to form bilayers may insert the methyl ends of long fatty acids from one side across more than half of the membrane thickness to protrude amongst the acyl chains of the opposite side of the bilayer (Keough, K.M.W. and Davis, P.J. (1979) Biochemistry 18, 1453-1459; Huang, C. and Mason, J.T. (1986) Biochim. Biophys. Acta 864, 423-470). In this article we address the fate of long fatty acid chains of glycosphingolipids present as minor components in membranes of non-interdigitating phosphatidylcholines. In this pursuit, derivatives of galactosyl ceramide, lactosyl ceramide, globoside and GM1 were synthesized having either 18-carbon or 24-carbon fatty acid with a spin label covalently attached at C-16. Labelled glycolipids were incorporated at 1-2 mol% into bilayers of synthetic phosphatidylcholines, their mixtures with cholesterol, or natural egg phosphatidylcholine. In each case the C-16 carbon of the glycolipid long chain fatty acid showed considerably greater 'order' and immobility than did C-16 of the fatty acid which was similar in length to the host matrix phospholipids. We interpret this as strong evidence that the long chain fatty acid interdigitates across the mid point of the bilayer in the systems studied. Clearly this phenomenon did not require that the phospholipid host matrix have mixed chain lengths. Furthermore it was totally independent of glycolipid family: for a given host matrix and (glycolipid) fatty acid chain length the order parameter values found were the same amongst all four glycolipid families tested.

Fatty Acids↗
PubMed1987

A long chain spin label for glycosphingolipid studies: transbilayer fatty acid interdigitation of lactosyl ceramide.

16-Carbon and 18-carbon fatty acids with covalently attached nitroxide free radicals have seen wide usage in membrane studies of phospholipid dynamics, orientation, and associations. However, they are inadequate for dealing with some very important questions that relate to glycosphingolipids. We report here the synthesis of a long chain (24-carbon) spin-labelled fatty acid designed for such problems. We have used both the new 24-carbon and the more conventional 18-carbon spin-labelled fatty acids to replace the natural fatty acid of lactosyl ceramide so that we may begin to compare short and long chain derivatives to analyse the molecular basis of their functional differences. Spectra seen are consistent with the view that in a bilayer host matrix the methyl end of the long fatty acid crosses the hydrophobic membrane center and interdigitates with fatty acids of phospholipids of the opposing monolayer.

Antigens, CD↗
PubMed1987

A phospholipid spin label used as a liposome-associated MRI contrast agent.

Given current clinical use of phospholipid bilayer structures (liposomes/vesicles) as nontoxic drug delivery vehicles, we have addressed the possibility of employing the phospholipids themselves as MRI contrast agents. To this end we have synthesized phosphatidylcholine with a nitroxide spin label replacing one methyl residue of the choline headgroup. This material was mixed with natural phosphatidylcholine in mole ratios from 1:50 to 1:1 and used to prepare sonicated unilamellar vesicles in saline. Expected structural features of these vesicles were verified by freeze-fracture electron microscopy. Proton T1 values of saline were readily decreased to less than 0.3 s by such preparations, yielding a net relaxivity of 0.6 M-1 s-1. The approach seems to be a realistic way of firmly associating a contrast agent of minimal toxicity with ordinary liposomes/vesicles in a manner that is not subject to leakage.

Contrast Media↗
PubMedDate not supplied

[A micromethod for assaying HIV reverse transcriptase].

A micromethod for assaying HIV reverse transcriptase was developed. Accuracy, and sensitivity of the micromethod were comparable to those of the traditional macromethod. The micromethod is easy to perform and can be used in non specialised laboratories.

AIDS Serodiagnosis↗