Lethal Morel-Lavallée lesion: A forensic radiology-pathology correlation.

Morel Lavallée lesion or closed degloving injury is normally associated with severe trauma and occurs when the skin and subcutaneous fatty tissue traumatically and abruptly separated from the underlying fascia thus creating a potential space filled with fluid. MVA is the commonest etiology but large or lethal Morel Lavallée is extremely rare. A 35 years old, female pillion rider was involved in a motor vehicle accident and sustained injuries to the left pelvis and thigh. Emergency laparotomy and intra-op abdominal and bilateral lower limb arteriogram revealed no significant finding. Her general condition and vital signs continued to deteriorate despite aggressive resuscitation and eventually died. Post-Mortem Computed Tomography and Post-Mortem Computed Tomography Angiogram was performed and revealed a large cavity in the left thigh suggestive of a lethal Morel Lavallée lesion. Findings were confirmed by conventional autopsy.

Overexpression of paralogues of the wheat expansin gene TaEXPA8 improves low-temperature tolerance in Arabidopsis.

Low temperature is one of the important factors limiting wheat yield in cold regions. Expansins are nonenzymatic proteins that loosen cell walls and play important roles in diverse biological processes related to cell wall modification, including development and stress tolerance. Many studies have shown that expansins are involved in resistance to various abiotic stresses, such as heat and drought. However, the role of expansins in response to low-temperature stress remains unclear. Based on our previous transcriptome data of a winter wheat cultivar Dongnongdongmai 2 (DN2), we found that one of the expansin genes, TaEXPA8, was significantly induced by low temperature, indicating a role for TaEXPA8 in cold resistance. In this study, the paralogous TaEXPA8 genes TaEXPA8-A, TaEXPA8-B and TaEXPA8-D were cloned by RT-PCR. These three genes were then transformed into Arabidopsis by the floral dip method. Expression patterns of TaEXPA8 genes in different tissues and in response to several abiotic stresses and hormones were detected by quantitative real-time PCR (qRT-PCR). The results showed that TaEXPA8-A and TaEXPA8-B were expressed mainly in roots, while TaEXPA8-D was expressed predominantly in flowers. TaEXPA8 genes were induced by low-temperature and drought. The overexpression of TaEXPA8-B and TaEXPA8-D enhanced low-temperature resistance and had increased superoxide dismutase (SOD), peroxidase (POD) and catalase (CAT) activity and soluble protein, MDA and proline content. In summary, our study suggested that the expansins TaEXPA8-B and TaEXPA8-D are involved in the response to low temperature and possibly play a role in cold resistance by activating the protective enzyme system.

Methoxy poly(ethylene glycol)-poly(lactide) (MPEG-PLA) nanoparticles for controlled delivery of anticancer drugs.

Methoxy poly(ethylene glycol)-poly(lactide) copolymer (MPEG-PLA) was synthesized and used to make nanoparticles by the nanoprecipitation method for clinical administration of antineoplastic drugs. Paclitaxel was used as a prototype drug due to its excellent efficacy and commercially great success. The size and size distribution, surface morphology, surface charge and surface chemistry of the paclitaxel-loaded nanoparticles were then investigated by laser light scattering, atomic force microscopy, zeta-potential analyzer and X-ray photoelectron spectroscopy (XPS). The drug encapsulation efficiency (EE) and in vitro release profile were measured by high-performance liquid chromatography. The effects of various formulation parameters were evaluated. The prepared nanoparticles were found of spherical shape with size less than 100 nm. Zeta potential measurement and XPS analysis demonstrated the presence of PEG layer on the particle surface. Viscosity of the organic phase was found to be one of the main process factors for the size determination. The EE was found to be greatly influenced by the drug loading. The drug release pattern was biphasic with a fast release rate followed by a slow one. The particle suspension exhibited good steric stability in vitro. Such a nanoparticle formulation of paclitaxel can be expected to have long-circulating effects in circulation.

Fabrication, characterization and in vitro release of paclitaxel (Taxol) loaded poly (lactic-co-glycolic acid) microspheres prepared by spray drying technique with lipid/cholesterol emulsifiers.

Spray dry technique was applied to produce paclitaxel loaded microspheres of biodegradable poly (lactic-co-glycolic acid) (PLGA) as an alternative delivery system. Various emulsifiers such as L-alpha-dipalmitoyl-phosphatidylcholine (DPPC), cholesterol, polyvinyl alcohol (PVA), gelatin were incorporated in order to achieve high encapsulating efficiency of paclitaxel in the microspheres and desired properties for a sustained release. Atomic force microscopy (AFM) and scanning electron microscopy (SEM) showed that the surface of the microspheres with high ratio of lipid was spherical and smooth. Those made with other emulsifiers had rougher surface with pores. Incorporation of lipid, cholesterol or gelatin can significantly increase the drug content in the microspheres. The differential scanning calorimetry (DSC) result indicated that the paclitaxel trapped in the microspheres existed in an amorphous or disordered-crystalline status in the polymer matrix. The zeta potential of the microspheres was negative in general and was strongly influenced by the type of the emulsifiers used in fabrication. The system formulated with cholesterol was most stable. The release profiles of various formulations with PVA, gelatin as well as low ratio of DPPC showed almost zero-order release kinetics in the first 3 weeks after an initial burst less than 5% in the first day. The release rate then gradually decreased. The microspheres fabricated with high ratio of DPPC exhibited large initial burst. When cholesterol was combined together with DPPC as an emulsifier, the release became faster.

A novel controlled release formulation for the anticancer drug paclitaxel (Taxol): PLGA nanoparticles containing vitamin E TPGS.

Paclitaxel (Taxol) is one of the best antineoplastic drugs found from nature in the past decades. Like many other anticancer drugs, there are difficulties in its clinical administration due to its poor solubility. Therefore an adjuvant called Cremophor EL has to be employed, but this has been found to cause serious side-effects. However, nanoparticles of biodegradable polymers can provide an ideal solution to the adjuvant problem and realise a controlled and targeted delivery of the drug with better efficacy and fewer side-effects. The present research proposes a novel formulation for fabrication of nanoparticles of biodegradable polymers containing d-alpha-tocopheryl polyethylene glycol 1000 succinate (vitamin E TPGS or TPGS) to replace the current method of clinical administration and, with further modification, to provide an innovative solution for oral chemotherapy. In the modified solvent extraction/evaporation technique employed in this research, the emulsifier/stabiliser/additive and the matrix material can play a key role in determining the morphological, physicochemical and pharmaceutical properties of the produced nanoparticles. We found that vitamin E TPGS could be a novel surfactant as well as a matrix material when blended with other biodegradable polymers. The nanoparticles composed of various formulations and manufactured under various conditions were characterised by laser light scattering (LLS) for size and size distribution, scanning electron microscopy (SEM) and atomic force microscopy (AFM) for morphological properties, X-ray photoelectron spectroscopy (XPS) for surface chemistry and differential scanning calorimetry (DSC) for thermogram properties. The drug encapsulation efficiency (EE) and the drug release kinetics under in vitro conditions were measured by high performance liquid chromatography (HPLC). It was concluded that vitamin E TPGS has great advantages for the manufacture of polymeric nanoparticles for controlled release of paclitaxel and other anti-cancer drugs. Nanoparticles of nanometer size with narrow distribution can be obtained. A drug encapsulation efficiency as high as 100% can be achieved and the release kinetics can be controlled.

Vitamin E TPGS used as emulsifier in the solvent evaporation/extraction technique for fabrication of polymeric nanospheres for controlled release of paclitaxel (Taxol).

The D-alpha-tocopheryl polyethylene glycol 1000 succinate (vitamin E TPGS) was applied in the present investigation as surfactant stabiliser to fabricate paclitaxel-loaded PLGA nanospheres in the solvent evaporation/extraction technique with successful achievement. Laser light scattering system (LLS), scanning electron microscopy (SEM), atomic force microscopy (AFM), differential scanning calorimetry (DSC), Fourier transform infra-red spectroscopy (FTIR), and X-ray photoelectron spectroscopy (XPS) were employed to characterise the nanopsheres fabricated in various recipes under various preparation conditions for size and size distribution, surface morphology, thermogram property and surface chemistry. Encapsulation efficiency and in vitro release was measured by the high-performance liquid chromatography (HPLC). The outcomes were discussed with respect to the development of polymeric nanospheres delivery system of the anticancer drug, paclitaxel (Taxol((R))). The produced nanospheres were found in fine spherical shape with smooth surfaces and without aggregation or adhesion. There was no significant difference in morphology between the vitamin E TPGS emulsified and PVA emulsified PLGA nanospheres. However, it was found that, in comparison with the traditional chemical emulsifier PVA, the TPGS could significantly improve the encapsulation efficiency of the drug in the PLGA nanospheres, which could be as high as 100%. The size of the vitamin E TPGS emulsified nanospheres ranged from 300 to 800 nm and the size distribution was narrow with polydispersity of 0.005-0.045. XPS investigation demonstrated that there were residual surfactant molecules remained on the surface although the TPGS could be washed out relatively thoroughly in the process of nanospheres formation. This finding was also confirmed by FTIR-PAS investigation of the nanospheres. The in vitro release indicated that the release property of paclitaxel from the nanospheres strongly depends on the emulsifier type employed in the fabrication. Our research shows that vitamin E TPGS could be an ideal and effective emulsifier.

The dynamics of shear disaggregation of red blood cells in a flow channel.

Red blood cell (RBC) rouleaux were formed in a flow channel in the presence of 2 g/dl dextran (molecular weight 76,000). The partial separation of RBC rouleau doublets adhering to the floor of the flow channel in response to small oscillatory shear stresses was observed experimentally. Theoretical analyses on displacement and drag force were performed to determine whether the motion of the cell involves membrane rotation (i.e., rolling) or sliding. From the experimental data and the results of theoretical analyses, it is concluded that, under the conditions of the experiments, the RBCs in a doublet separate from each other by rolling, rather than sliding of the sheared cell.

Nanospheres of biodegradable polymers: a system for clinical administration of an anticancer drug paclitaxel (Taxol).

INTRODUCTION: Paclitaxel is a natural antineoplastic drug. It has been approved by the Food and Drug Administration (FDA) for the treatment of various cancers, especially ovarian and breast cancers with the best effect over other anticancer agents. Due to its high hydrophobicity however, an excipient such as Cremophor EL has to be used, which causes additional serious side effects. This study was intended to investigate the feasibility to apply nanospheres of biodegradable polymers as an alternative system to achieve best results with least side effects. MATERIALS AND METHODS: FDA-approved biodegradable polymers such as poly(D, L-lactic-co-glycolic acid) (PLGA) and poly(D, L-lactic acid) (PLA) were used to fabricate paclitaxel-loaded nanospheres by the solvent extraction/evaporation technique. The nanospheres fabricated in various conditions were characterised by laser light scattering for size and size distribution, scanning electron microscopy (SEM) and atomic force microscopy (AFM) for surface morphology, X-ray photoelectron spectroscopy (XPS) for the chemical structure of the surface. The drug encapsulation efficiency (EE) and the in vitro release kinetics were measured by HPLC. RESULTS: The products ranged from 300 nm to 700 nm with low polydispersity. The in vitro drug release can last more than 6 months at an approximately constant rate after an initial burst. The release kinetics can be fully controlled by the material used and the fabrication conditions. CONCLUSIONS: Nanospheres of biodegradable polymers can be an ideal carrier for pacitaxel to eliminate the side effects caused by the excipient currently used in clinical administration. The technique developed can also be applied to other anticancer drugs.

[Clinicopathologic studies of 100 cases of lymph node metastasis in cardiac carcinoma].

The specimens of 100 cases of carcinoma of the gastric cardiac were studied after curative resection between 1985 and 1988. A total of 2213 lymph nodes were obtained, which were then divided into 23 group and 3 station in accordance with the Japanese staging system for esophageal and gastric carcinoma. Our data were as follow: (1) Eighty eight out of the hundred had lymph nodes metastasis, giving a metastatic rate of 88%: (2) 647 of 2213 lymph nodes were positive for metastasis. The degree of metastasis was 29.2%. The degree of metastasis of station 1,2,3 were 32%, 32.82%, and 14.65% respectively. That of group 1,2,3,4,7 and 110 were 42.5%, 32%, 36%, 11%, 39%, and 20.5% respectively. The lymph nodes of group 12, 14, 15, 16 and 17 were not involved; (3) The extent of lymph nodes metastasis of cardiac carcinoma were closely related the bulk of carcinoma, gross appearance, depth of infiltration and histological type (P less than 0.05). The authors consider that abdominal lymph node metastasis were of importance for cardiac carcinoma. The group 7 should be cleaned first. Lymph nodes dissection would be started from the level of inferior pulmonary vein and ended at the pylorus region.

Sulfatide-tenascin interaction mediates binding to the extracellular matrix and endocytic uptake of liposomes in glioma cells.

Tenascin-C is an extracellular matrix glycoprotein, whose expression is highly restricted in normal adult tissues, but markedly up-regulated in a range of tumors, and therefore serves as a potential receptor for targeted anticancer drug or gene delivery. We describe here a liposomal carrier system in which the targeting ligand is sulfatide. Experiments with tenascin-C-expressing glioma cells demonstrated that binding of liposomes to the extracellular matrix relied essentially on the sulfatide-tenascin-C interaction. Following binding to the extracellular matrix, the sulfatide-containing liposomes were internalized via both caveolae/lipid raft- and clathrin-dependent pathways, which would ensure direct cytoplasmic release of the cargoes carried in the liposomes. Such natural lipid-guided intracellular delivery targeting at the extracellular matrix glycoproteins of tumor cells thus opens a new direction for development of more effective anticancer chemotherapeutics in future.

Halofantrine-phospholipid interactions: monolayer studies.

The antimalarial agent halofantrine penetrates dipalmitolylphosphatidylcholine (DPPC) monolayers resulting in an increase in surface pressure and an expansion in area occupied by the lipid components of the monolayer. This phenomenon is observed at concentrations (0.05-0.2 microm) of halofantrine that have no surface activity. Penetration increases with drug concentration and is greatest at low initial surface pressures of the monolayer. A critical surface pressure of the DPPC monolayer has been determined from constant area and constant pressure conditions. The magnitude of these values support the hypothesis that halofantrine readily penetrates the DPPC monolayers. The presence of cholesterol in the DPPC monolayer hampers penetration and a lower critical surface pressure is obtained under such conditions. Even then, a slower rate of penetration is observed only in monolayers maintained at high initial surface pressures (10, 15 mN/m), corresponding to the liquid condensed phase of the monolayer, and not at low surface pressures (2.5, 5.0 mN/m). These results help to give a better understanding of the dynamics of the halofantrine-phospholipid interaction as well as the pharmacodynamic character of the drug.

Effects of chain unsaturation on the equation of state for lipid monolayers at the air-water interface.

An equation of state for lipid monolayers at the air-water interface is presented, which takes into account the effects of the conformation and the number and position of double bonds of the hydrocarbon chains. The total Hamiltonian of the monolayer is assumed to consist of three terms. Two of them are calculated exactly within the limitations of the formulation. These are the two-dimensional entropy of mixing of the lipid and water molecules at the surface and the conformational entropy of the chains using a model available from the literature. These two terms give rise to positive surface pressure. The third term, which includes all energies that are not amenable to calculation, was obtained as the difference between the sum of the two calculated terms and experimental data and is found to represent an approximately area-independent tension. The effects of chain unsaturation on the equation of state were modeled in the present theory in two ways; the chain bend caused by cis double bonds increases the minimal molecular area, and the double bond linkage on a chain decreases the degrees of freedom of the chain. Calculations revealed that the former is highly significant whereas the latter is negligible. The deduced equation of state reproduces experimental data with appropriate values for three parameters, which represent the collapse area, the overlap of adjacent chains, and the combined effects of the intra- and intermolecular interactions other than the surface mixing entropy and the chain conformational energy.

Velocity distribution on the membrane of a tank-treading red blood cell.

The kinematics of an area-conserving tank-treading disk-shaped red blood cell membrane is studied using the stream function method suggested by Secomb and Skalak (Q. Jl Mech. appl. Math. 35, Pt 2, 233-247, 1982). Two simple area-conserving velocity fields are superimposed to satisfy the continuity condition at the curved edges of the disk. A differential equation for the trajectory of any material point of the membrane is derived. The requirement of synchrony of the cycle for all membrane points leads to an integral equation which determines a magnitude function. An approximate solution is made possible by assuming small trajectory deflections.

Study of synthesis and cardiovascular activity of some furoxan derivatives as potential NO-donors.

A series of hybrid molecules incorporating the furoxan and nicorandil moieties were designed as potential NO donors with cardiovascular and cerebrovascular activities. Thirty-six target molecules were successfully synthesized by conventional methods and characterized by infrared spectroscopy, 1H-NMR spectroscopy and high resolution mass spectra. The compounds were tested for their effects on KCl-induced contraction of rabbit thoracic aorta whose endothelium was denuded. Eight compounds were found to reduce KCl-induced contraction by more than 30% at 10 microM. All except one of these compounds are characterized by the presence of electron withdrawing groups in the phenyl ring attached via an amide or ester linkage to the furoxan moiety. The nature of the terminal carbonyl linkage (ester or amide) and the length or type of the alkyl chain bridging the two carbonyl functions have little effect on the activity. One of the active compounds, N-(4-methoxy-benzoyl)-N'-[3-methylfuroxanyl-4-carbonyl)piperazine (17i) was tested for hypotensive effects on anaesthesized rats at 1.5 mg/kg, and found to demonstrate a gradual and sustained hypotensive effect. The results suggest that the furoxan-nicorandil derivatives are a useful lead in the design of NO-donor compounds for hypertension.

Effects of polymer, organic solvent and mixing strength on integrity of proteins and liposomes encapsulated in polymeric microspheres fabricated by the double emulsion process.

The double emulsion process has commonly been applied to encapsulate water-soluble bioactive agents into polymeric microspheres. However, the integrity of many of these agents may be destroyed by the highly energetic procedures such as sonication that are routinely used to produce stable water-in-oil (w/o) emulsion. The aim of this research was to pursue the possibility of replacing the sonication by a mild emulsification procedure such as vortex mixing, with the use of certain materials to help to obtain stable w/o emulsion. The following materials were examined: poly(lactide-co-ethylene glycol) (PELA) as the polymer, ethyl acetate and acetone as the solvents, poly(vinyl alcohol) (PVA) and d-alpha tocopheryl polyethylene glycol 1000 succinate (Vitamin E TPGS) as the emulsifiers in w/o emulsion. The experimental results, with human serum albumin (HSA) as the encapsulated agent, showed that, when vortex mixing was used, these materials could significantly improve w/o emulsion stability and help to obtain satisfactory encapsulation effects, i.e. high encapsulation efficiency (EE) and low initial release burst. A delicate structure, i.e. liposomes, which is very sensitive to sonication, was then incorporated into microspheres by the 'modified double emulsion process'. It was found that the liposomes were intact and the encapsulation effects were good. Therefore, it can be concluded that the modified double emulsion process could be advantageous for the encapsulation of delicate substances.

Release of paclitaxel from polylactide-co-glycolide (PLGA) microparticles and discs under irradiation.

Paclitaxel is a promising anti-cancer drug as well as a radiosensitizer for chemotherapy and radiotherapy applications. Because of the poor solubility of paclitaxel in water and most pharmaceutical reagents, it is usually formulated with an adjuvant called Cremophor EL, which causes severe side effects. This work develops new dosage forms of paclitaxel for controlled release application, which do not require the adjuvant and, thus, can avoid its associated side effects. Paclitaxel was encapsulated into the PLGA matrix with various additives such as polyethylene glycol (PEG), isopropyl myristate (IPM) and d-alpha tocopheryl polyethylene glycol (Vitamin E TPGS). These additives were used to enhance the release rate of paclitaxel from the polymer matrix. Spray-drying and an hydraulic press were used to prepare paclitaxel-PLGA microspheres and discs. The microspheres and discs were given different irradiation doses to investigate their effects on the surface morphology (characterized by SEM, AFM and XPS) and in vitro release properties. There seems to be a small effect of the ionizing radiation on various formulations. Although the irradiation did not cause observable changes on the morphology of the polymer matrix, the release rate can be enhanced by a few per cent. It was found that PEG has the highest enhancement effect for release rate among all the additives investigated in this study.

Identification of novel regions of allelic loss from a genomewide scan of esophageal squamous-cell carcinoma in a high-risk Chinese population.

Esophageal cancer is one of the most common fatal cancers worldwide. Deletions of genomic regions are thought to be important in esophageal carcinogenesis. We conducted a genomewide scan for regions of allelic loss using microdissected DNA from 11 esophageal squamous-cell carcinoma patients with a family history of upper gastrointestinal tract cancer from a high-risk region in north central China. Allelic patterns of 366 fluorescently labeled microsatellite markers distributed at 10-cM intervals over the 22 autosomal chromosomes were examined. We identified 14 regions with very high frequency (>/= 75%) loss of heterozygosity (LOH), including broad regions encompassing whole chromosome arms (on 3p, 5q, 9p, 9q, and 13q), regions of intermediate size (on 2q, 4p, 11p, and 15q), and more discrete regions identified by very high frequency LOH for a single marker (on 4q, 6q, 8p, 14q, and 17p). Among these 14 regions were 7 not previously described in esophageal squamous-cell carcinoma as having very high frequency LOH (on 2q, 4p, 4q, 6q, 8p, 14q, and 15q). The very high frequency LOH regions identified here may point to major susceptibility genes, including potential tumor suppressor genes and inherited gene loci, which will assist in understanding the molecular events involved in esophageal carcinogenesis and may help in the development of markers for genetic susceptibility testing and screening for the early detection of this cancer. Genes Chromosomes Cancer 27:217-228, 2000. Published 2000 Wiley-Liss, Inc.