Minimally invasive coronary surgery at the beginning of the new millennium

Several formulations of poly(epsilon-caprolactone) (PCL), poly(lactic acid) (PLA), and poly(lactic-co-glycolic acid) (PLGA) nanocapsules containing phenylbutazone were prepared according to the interfacial deposition technique. These formulations differed in the type of polymer used to form the shell of the nanocapsules. Analysis of particle size distribution and encapsulation efficiency of the nanocapsules revealed that the type and molecular weight of polyester used were the main factors influencing these properties. PLA had the highest encapsulation efficiency with the best reproducibility. From in vitro release studies, a small amount of drug release was observed at pH 7.4. However, in the gastric medium, an important burst effect occurred and was highest with the PLGAs and lowest with PCL, suggesting that drug release from these systems is affected by the type of polymer and the environmental conditions. The two formulations of phenylbutazone-loaded nanocapsules should be evaluated based on PCL and PLA in vivo in order to determine to what extent they are able to reduce the local side effects of this drug.     

Screening for fetal abdominal wall defects

Polylactic acid (PLA) polymer film was degraded in abiotic and biotic environments to understand the role of microbes in the degradation process of lactic acid based polymers. The degradation studies were conducted in a well-characterized biotic system, an abiotic system, a sterile aqueous system, and a desiccated environment maintained at 40, 50, and 60 degrees C. The combination of experiments in different environments isolated the distinct effect of microbes, water, and temperature on the morphological changes in the polymer during degradation. Due to lack of availability of radiolabeled PLA, various analytical techniques were applied to observe changes in the rate and/or mechanism of degradation. CO2 evolved, weight loss, and molecular weights were measured to evaluate the extent of degradation. X-ray diffraction and differential scanning calorimetry techniques monitored the morphological changes in the polymer. FTIR was used as a semiquantitative tool to gather information about the chemistry of the degradative process. Neither of the above analytical techniques indicated any difference in the rate or mechanism of degradation attributable to the presence of microorganisms. The extent of degradation increased at higher process temperatures. FTIR data were evaluated for significant statistical difference by t-test hypothesis. The results confirmed hydrolysis of ester linkage as the primary mechanism of degradation of PLA. On the basis of these data, a probable path of PLA degradation has been suggested.     

Erosion of biodegradable block copolymers made of poly(D,L-lactic acid) and poly(ethylene glycol)

Biodegradable block copolymers made of poly(ethylene glycol) monomethylether (Me.PEG) and poly(D,L-lactic acid) (PLA) were investigated for their erosion properties. Wide angle X-ray diffraction (WAXD) and differential scanning calorimetry (DSC) investigations prior to erosion revealed that despite the low content of crystallizable Me.PEG of 10%, Me.PEG5-PLA45 is a partially crystalline polymer. The erosion of the polymer was investigated using cylindrical polymer matrix discs with a diameter of 8 mm and a height of 1.5 mm. WAXD and DSC spectra obtained from eroded polymer matrix discs suggest that both polymer blocks separate completely during erosion. The crystallinity of Me.PEG5-PLA45 was found to increase during erosion, which is probably due to the improved mobility of Me.PEG inside the polymer with a progressive degree of degradation. The erosion kinetics were found to be similar to that of PLA or poly(lactic-co-glycolic acid). During erosion the polymer matrix weight of dried samples remains constant for 11 weeks after which erosion sets in rapidly. From this observation one can conclude that the impact of the relatively small Me.PEG chains on Me.PEG5-PLA45 erosion is not pronounced. This is beneficial for all those applications that require the stability of the polymer matrix and in which the Me.PEG chain is intended to bring about other effects such as the modification of the surface properties of PLA polymers.     

The unique endometrial expression and genomic organization of the porcine IGFBP-2 gene

Nisin was first introduced commercially as a food preservative in the UK approximately 30 years ago. First established use was as a preservative in processed cheese products and since then numerous other applications in foods and beverages have been identified. It is currently recognised as a safe food preservative in approximately 50 countries. The established uses of nisin as a preservative in processed cheese, various pasteurised dairy products, and canned vegetables will be briefly reviewed. More recent applications of nisin include its use as a preservative in high moisture, hot baked flour products (crumpets) and pasteurised liquid egg. Renewed interest is evident in the use of nisin in natural cheese production. Considerable research has been carried out on the antilisterial properties of nisin in foods and a number of applications have been proposed. Uses of nisin to control spoilage lactic acid bacteria have been identified in beer, wine, alcohol production and low pH foods such as salad dressings. Further developments of nisin are likely to include synergistic action of nisin with chelators and other bacteriocins, and its use as an adjunct in novel food processing technology such as higher pressure sterilisation and electroporation. Production of highly purified nisin preparations and enhancement by chelators has led to interest in the use of nisin for human ulcer therapy, and mastitis control in cattle.     

Influence of the microencapsulation method and peptide loading on poly(lactic acid) and poly(lactic-co-glycolic acid) degradation during in vitro testing

Three methods were used, namely spray drying, w/o/w solvent evaporation and the aerosol solvent extraction system (ASES), for the preparation of microparticles having the same size range, to study the influence of the preparation method on polymer degradation in vitro (PBS, 37 degrees C, one month). The following five polymers of the biodegradable poly(lactic acid) (PLA) and poly(lactic-co-glycolic acid) (PLGA) group were selected: L-PLA, MW 81 200; DL-PLGA 75:25, MW 64-300; DL-PLGA 50:50 MW 52 600; DL-PLGA 50:50 MW 14 500, AND DL-PLGA 50:50, MW 3400, to prepare drug-free and drug-loaded microparticles. Tetracosactide was selected as model peptide. When microparticles were prepared by solvent evaporation, the mean diameter and, more markedly, the drug encapsulation efficiency tended to decrease when decreasing the molecular weight and increasing the proportion of glycolic acid in the polymer. In contrast, no direct influence of the polymer nature on these parameters was observed in spray dried microparticles. Polymer degradation was heterogenous in L-PLA and DL-PLGA 75:25 microparticles and was not influenced by the presence of the drug at a nominal loading of 1% (w/w), when prepared by the three methods (note that with ASES, only L-PLA could be used for microencapsulation). In batches made of DL-PLGA 50:50 MW 52 600, the degradation rate decreased slightly when increasing the drug loading. Only in the case of DL-PLGA 50:50 MW 14 500, the polymer degradation rate for spray dried microparticles was higher compared to that for microparticles prepared by the w/o/w solvent evaporation method. Generally, the degradation rates of the different microparticles followed the expected order: L-PLA相似文献   

Solvent extraction and separation of light rare earth elements (La,Pr and Nd) in the presence of lactic acid as a complexing agent by Cyanex 272 in kerosene and the effect of citric acid,acetic acid and Titriplex III as auxiliary agents

At present, the use of rare earth elements (REEs) has become an inevitable necessity in many modern industries. In general, liquid extraction is the best commercial method for extracting REEs due to its ability to control high volumes of liquids with electrical load. With the aim of improving a separation technology that would be superior to the existing extraction systems, the extraction behaviors of La(III), Pr(III), and Nd(III) from an HCl medium with Cyanex 272 in the presence of the complexing agent lactic acid (HLac) and auxiliary agents citric acid (H₃Cit), acetic acid (HAc), and Titriplex III have been reported. The effect of pH and lactic acid concentration has been examined. The use of lactic acid as a complexing agent leading to a high extraction of REEs with Cyanex 272 at pH = 5 was compared with systems without lactic acid. The results show that the use of acetic acid along with lactic acid leads to an increase in the extraction percentage of LREEs. While use of citric acid and Titriplex III reduces the extraction percentage of LREEs. Finally, the presence of Titriplex III together with lactic acid could lead to an increase in the separation factor of Pr and Nd.     

聚乳酸/羟基磷灰石复合型多孔状可降解生物材料

以乳酸和乙醇酸为原料分别合成了丙交酯(LA)和乙交酯(GA)2种单体,并用单体聚合成了聚丙交酯(PLA)和丙交酯乙交酯共聚物(PLGA),结合用粉末冶金的方法制得的纳米羟基磷灰石粉末(HA),制得了聚乳酸/羟基磷灰石复合型生物可降解的多孔材料。研究结果表明,PLA和PLGA聚合物的产率同聚合过程中的氮压有关,控制造孔剂的粒度,可以得到理想的多孔材料。     

Use of high-precision gas isotope ratio mass spectrometry to determine natural abundance 13C in lutein isolated from C3 and C4 plant sources

Previous studies have shown that cholesterol esterification activity by lecithin:cholesterol acyltransferase (LCAT) is progressively inhibited as up to three acidic acid residues are chemically modified. The purpose of this study was to determine whether three glutamic acid residues in LCAT (154, 155, and 165), that align exactly with three acidic acid residues (270, 271, and 281) in the amphipathic phospholipid binding region of apoE, were necessary for enzymatic activity. Site-directed mutagenesis was used to generate mutant constructs of LCAT in which glutamic acid residues 154, 155, and 165 were replaced with glutamine or lysine. Media harvested from transiently transfected COS cells was used as a source of LCAT for cholesterol esterification and phospholipase A2 (PLA2) assays. Cholesterol esterification for all mutant constructs (11-26 nmol CE/h/microg) was similar to or greater than that of wild type LCAT (16 nmol CE/h/microg), except for a triple mutant, in which glutamic acid residues 154, 155, and 165 were changed to lysines (5 nmol CE/h/microg). PLA2 activity followed a similar trend. There was a significant decrease in the cholesterol esterification to PLA2 activity ratio when residue 165 was mutated from its wild type negative charge (E) to an uncharged (Q) or positive (K) charged residue (10.2 vs. 6.0 vs. 4.3, respectively). We conclude that glutamic acid residues 154, 155, and 165 individually or collectively are not necessary for LCAT activity and that residue 165 may be in a region of LCAT that is involved with cholesterol binding or is sensitive to cholesterol binding at the active site of the enzyme.     

Controlled overproduction of proteins by lactic acid bacteria

Lactic acid bacteria are widely used in industrial food fermentations, contributing to flavour, texture and preservation of the fermented products. Here we describe recent advances in the development of controlled gene expression systems, which allow the regulated overproduction of any desirable protein by lactic acid bacteria. Some systems benefit from the fact that the expression vectors, marker genes and inducing factors can be used directly in food applications since they are all derived from food-grade lactic acid bacteria. These systems have also been employed for the development of autolytic bacteria, suitable for various industrial applications.     

Lactic acid production from molasses by Sporolactobacillus cellulosolvens

Sporolactobacillus cellulosolvens (NCIMB 12173) isolated from an anaerobic digester and characterised biochemically is being reported for homofermentative lactic acid production from molasses in a batch culture. The effect of various process parameters on lactic acid production were optimized. A maximum lactic acid (24.2 g/l) and yield coefficient (0.79) was achieved using 3% (v/v) inoculum of 36 h old culture in molasses medium containing sugars (5%; w/v) supplemented with peptone (2.5 g/l) and (NH4)2SO4 (7.5 g/l), pH 6.5 at 40 degrees C after 72 h of fermentation.     

Taurine in rat posterior pituitary: localization in astrocytes and selective release by hypoosmotic stimulation

The design of biomaterials containing specific ligands on the surface offers the possibility of creating materials that can interact with and potentially control mammalian cell behavior. Biodegradable materials further provide the significant advantage that the polymer will disappear in vivo, obviating long-term negative tissue responses as well as the need for retrieval. In earlier studies we synthesized and characterized arginine-glycine-aspartic acid (RGD) peptide-modified poly(lactic acid-co-lysine) (PLAL). In this study, both bulk properties and surface features have been characterized, with a focus on surface analysis as a means of interpreting observed changes in cell behavior. Bulk peptide attachments were performed using 1,1'-carbonyldiimidazole (CDI). Amino groups were measured using colorimetric assays and X-ray photoelectron spectroscopy (XPS). Peptides were measured by incorporating iodine into the peptide as a distinct elemental marker for use with XPS. Typical samples contained 13 +/- 4 pmol/cm2 of amino groups and 4 +/- 0.2 pmol/ cm2 of peptides, as calculated from XPS measurements of nitrogen and iodine. The wettability and crystallinity of the samples were determined by contact angles and differential scanning calorimetry, respectively. Wettability and crystallinity were not altered by the incorporation of lysine or peptides. After incubating bovine aortic endothelial (BAE) cells for 4 h on surfaces with RGD-containing peptides, the mean spread cell area increased from 77 +/- 2 microns2 to 405 +/- 29 microns2 compared to 116 +/- 11 microns2 on poly(lactic acid), 87 +/- 4 microns2 on PLAL, and 105 +/- 4 microns2 on surfaces with RDG-containing (control) peptides. The significance of this work is that the first synthetic interactive, resorbable biomaterial has been developed, and use of this material to control cell behavior has been demonstrated.     

Undetected cardiogenic shock in patients with congestive heart failure presenting to the emergency department

The purpose of this study was to examine the use of lactic acid levels and continuous central venous oxygen saturation (central venous oximetry) to stratify and treat patients with acutely decompensated end-stage chronic congestive heart failure (CHF) presenting to the emergency department. This prospective, convenience, non-outcome study was performed at an urban tertiary care hospital. Patients with end-stage CHF with an ejection fraction <30% presenting in decompensated CHF were eligible for the study. Patients were assessed using the Killip classification and New York Heart Association criteria. After lactic acid levels were obtained, patients were managed according to a standardized protocol guided by central venous oximetry. The patients were divided into high lactic acid (n = 22), low lactic acid (n = 5), and control groups (stable patients presenting to a cardiology clinic, n = 17) for comparison. There was no statistical difference in vital signs, or Killip and New York Heart Association criteria among the 3 groups. Central venous oxygen saturation was significantly lower in the high lactic acid group (32 +/- 12%) than in the normal lactic acid (51 +/- 13%) and control groups (60 +/- 6%) (p < 0.001). After treatment there was a significant decrease in lactic acid (-3.65 +/- 3.65 mM/L) and an increase in central venous oxygen saturation (32 +/- 13%) in the high lactic acid group compared with the normal lactic acid group (p < 0.001). A significant subset of patients with decompensated end-stage CHF present to the emergency department in occult shock and are clinically indistinguishable from patients with mildly decompensated CHF and stable CHF. Once identified, these patients require aggressive alternative management and disposition. Further study is necessary to identify whether this intervention impacts morbidity, mortality, and health care resource consumption.     

Predictive models of the effect of temperature, pH and acetic and lactic acids on the growth of Listeria monocytogenes

The combined effect of temperature (1-20 degrees C), pH (4.5-7.2) and acetic acid (0-10,000 mg/l; model 1) or lactic acid (0-20,000 mg/l; model 2) on growth of Listeria monocytogenes in laboratory media was studied. Growth curves at various combinations of temperature, pH and acid concentration were fitted by the model of Baranyi and Roberts (1994), and specific growth rates derived from the curve fit were modelled. Predictions of growth from the models were compared with data in the literature, and this showed the models to be suitable for use in predicting growth of L. monocytogenes in a range of foods including meat, poultry, fish, egg and milk and dairy products. The two models are compatible, i.e. they give similar predictions for cases when no acid is present.     

Injectable microcapsules prepared with biodegradable poly(alpha-hydroxy) acids for prolonged release of drugs

In this paper, microencapsulation techniques for the preparation of drug-containing monolithic microcapsules for prolonged release using biodegradable poly(alpha-hydroxy) acids, such as polylactic acid, poly(lactide-co-glycolide) and copoly(lactic/glycolic) acid are reviewed. Phase separation, solvent evaporation, and spray drying procedures are discussed. In order to achieve controlled-release formulations of highly water-soluble drugs that are entrapped efficiently, various manufacturing techniques and procedures have been developed. Degradation of poly(alpha-hydroxy) acids is altered by the copolymer ratio and molecular weight of the polymer used to make microcapsules and the amounts of released microencapsulated drugs correlate almost linearly with polymer degradation, indicating that controlled-release formulations, which release drugs over different times, can be prepared using suitable poly(alpha-hydroxy) acids with different degradation rates.     

Inhibition of type I and type II phospholipase A2 by phosphatidyl-ethanolamine linked to polymeric carriers

We have previously shown that cell surface proteoglycans protect the cell membrane from the action of extracellular phospholipase A2 (PLA2) enzymes [Dan, P., Nitzan, D. W., Dagan, A., Ginsburg, I., and Yedgar, S. (1996) FEBS Lett. 383, 75-78]. Cell-impermeable PLA2 inhibitors (ExPLIs) were prepared by linking phosphatidylethanolamine (PE) to polymeric carriers, specifically, carboxymethylcellulose, heparin, or hyaluronic acid. The structure of these inhibitors enables the incorporation of their PE moiety into the membrane while the polymer remains at the membrane surface. In the present study, we show that the ExPLIs are effective inhibitors of the hydrolysis of different phospholipids in biological (Escherichia coli) and model (phospholipid vesicle) membranes, by diverse types of PLA2 enzymes, specifically human recombinant synovial fluid and C. atrox (type II), as well as Naja mocambique and porcine pancreatic (type I) PLA2. It is proposed that the external polymers of the ExPLIs, which are anchored to the membrane by the PE, mimic the naturally occurring cell surface proteoglycans and similarly protect membranes from the action of exogenous PLA2.     

Influence of nicotine and cotinine on retinal phospholipase A2 and its significance to macular function

The macula is a constituent of the sensory retina that is necessary for sharp contrast and color vision. A significant relationship has been found between tobacco smoking and age-related macular degeneration. Opsin, rhodopsin and phospholipase A2 (PLA2) are located in excitable membranes of retina which are enriched with polyunsaturated fatty acids (PUFA). A question may arise as to whether nicotine and its major metabolite cotinine influence PLA2 so that arachidonic acid (AA) and proinflammatory prostaglandins (PG) are produced in the retina. Therefore, the effects of nicotine and cotinine on the retinal PLA2 were studied. PLA2 activity of rat retinal sonicates was assayed using 1-palmitoyl-2[1-14C]arachidonyl-Phosphatidylethanolamine (PE, 2.2 nmol) as a substrate in Tris buffer (10 mM, pH 7.4) at 37 degrees C with and without nicotine or cotinine in the assay medium. These studies gave the following results: (1) Rat retinal PLA2 activity was 4.2+/-0.8 pmol PE hydrolyzed/100 ng protein/hr. (2) Nicotine in low concentrations (1-150 nM) activated PLA2 (EC50 5 nM). (3) Cotinine also activated PLA2 (EC50 300 nM). (4) Only high concentrations of nicotine (> 1.0 microM) and cotinine (> 25 microM) exhibit inhibition of PLA2. (5) All three known PLA2 inhibitors, mepacrine, 4-bromophenacyl bromide and bromoacetylcholine bromide (IC50: 0.5mM, 88 microM, 30 mM, respectively) inhibited retinal PLA2 activity. These observations suggest that polyunsaturated fatty acids are cleaved, and arachidonic acid, the precursor for prostaglandins and related pro-inflammatory mediators, is liberated by nicotine and cotinine. Oxidative stress (reduced levels of antioxidants), vascular insufficiency, as well as activation of PLA2 by nicotine and cotinine may contribute for retinal degeneration in smokers during aging.     

Characterization and evolution of a gene encoding a Trimeresurus flavoviridis serum protein that inhibits basic phospholipase A2 isozymes in the snake's venom

The proteins that bind phospholipase A2 (PLA2) isozymes of Trimeresurus flavoviridis (habu snake, crotalinae) venom were fractionated from sera on four columns, each conjugated with one of four PLA2 isozymes. Five proteins, termed PLA2 inhibitors (PLI) I-V, were obtained as the binding components. The combinations of the binding components differed depending on the PLA2 isozymes. PLI-IV and PLI-V correspond to PLI-A and PLI-B, respectively, which were known to bind to a major [Asp49]PLA2, PLA2, and contained a segment similar to the carbohydrate-recognition domain of C-type lectins. PLI-I, which is a major component of inhibitory proteins against three basic PLA2 isozymes, PLA-B (a basic [Asp49]PLA2) and basic proteins I and II (both [Lys49]PLA2s), has been isolated, and its partial amino acid sequence has been determined. A cDNA encoding PLI-I was isolated from a T. flavoviridis liver cDNA library and sequenced. PLI-I cDNA encoded 200 amino acid residues, including a signal peptide of 19 amino acid residues. One sugar chain was predicted to occur at position 157. A gene coding for PLI-I was isolated. It is 9.6-kb long and consists of five exons and four introns. Comparison of the exon-intron structure of the PLI-I gene with those of genes encoding urokinase-type-plasminogen-activator receptor (uPAR), Ly-6, CD59 and neurotoxins showed that they have characteristic unit encoding approximately 90 amino acid residues, which is divided over two exons. This strongly suggests that the PLI-I gene belongs to the uPAR, Ly-6, CD59 and neurotoxin gene family. There are two types of structurally different inhibitors against PLA2 isozymes in T. flavoviridis serum with different evolutionary origins.     

Emerging quinolone-resistant Salmonella in the United States

We conducted a national survey of antimicrobial resistance in human clinical isolates of Salmonella between July 1, 1994, and June 30, 1995. Every tenth nontyphoidal Salmonella isolate received at state public health laboratories in the United States during this period was tested for resistance to 12 antimicrobial agents, including two quinolones, nalidixic acid, and ciprofloxacin. Emerging quinolone resistance was detected; of 4,008 isolates tested, 21 (0.5%) were resistant to nalidixic acid, and one (0.02%) was resistant to ciprofloxacin. Continued surveillance for quinolone-resistant Salmonella is necessary, particularly after the recent approval of a fluoroquinolone for use in animals intended for food in the United States.     

Poly(alpha-hydroxyacids) for application in the spinal cord: resorbability and biocompatibility with adult rat Schwann cells and spinal cord

Future surgical strategies to restore neurological function in the damaged human spinal cord may involve replacement of nerve tissue with cultured Schwann cells using biodegradable guiding implants. We have studied the in vitro and in vivo degradability of various aliphatic polyesters as well as their effects on rat Schwann cells in vitro and on spinal cord tissue in vivo. In vitro, cylinders made of poly(D,L-lactic-co-glycolic acid) 50:50 (PLA25GA50) started to degrade at 7 days, compared with 28 days for cylinders made of poly(D,L-lactic acid) (PLA50). This faster degradation of PLA25GA50 was reflected by a much higher absorption of water. In vivo, after implantation of PLA25GA50 or PLA50 cylinders between the stumps of a completely transected adult rat spinal cord, the decrease in molecular weight of both polymers was similar to that found in vitro. In vitro degradation of poly(L-lactic acid) (PLA100) mixed with increasing amounts of PLA100 oligomers also was determined. The degradation rate of PLA100 mixed with 30% oligomers was found to be similar to that of PLA50. In vitro, PLA25GA50 and the breakdown products had no adverse effect on the morphology, survival, and proliferation of cultured rat Schwann cells. In vivo, PLA25GA50 cylinders were integrated into the spinal tissue 2 weeks after implantation, unlike PLA50 cylinders. At all time points after surgery, the glial and inflammatory response near the lesion site was largely similar in both experimental and control animals. At time points later than 1 week, neurofilament-positive fibers were found within PLA25GA50 cylinders or the remains thereof. Growth-associated protein 43, which is indicative of regenerating axons, was observed in fibers in the vicinity of the injury site and in the remains of PLA25GA50 cylinders. The results suggest that poly(alpha-hydroxyacids) are likely candidates for application in spinal cord regeneration paradigms involving Schwann cells.     

The benefits and risks of n-3 polyunsaturated fatty acids

There is a growing number of animal models and clinical trials of n-3 polyunsaturated fatty acid (PUFAs) supplementation in disease. Epidemiologic and biochemical studies have suggested beneficial effects of n-3 PUFAs. But also, the use of n-3 PUFAs has some potential toxicological risks that can be circumvented by careless processing, storing, and preserving the PUFAs. The use of n-3 PUFAs is safe if appropriate preparations and dosages are selected. Much research is needed to clarify their use under different disease conditions. The newly established clinical and nutritional facts on n-3 PUFAs will induce industry to develop food products based on this knowledge.