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The present invention involves a process for producing fine powder suitable for the preparation of antifungal polyene microlide-containing liposomes upon suspension in an aqueous solution. This process comprises the following steps. Quantities of polyene macrolide and phospholipids are dissolved respectively in a first solvent and a second solvent to form a first solution and a second solution. The first solution and the second solution are mixed in a desired ratio to form a mixture. The first solvent and the second solvent are then removed from the mixture, for example by evaporation, to form a residue. The residue is then dissolved in a third solvent comprising tertiary butanol and methylene chloride to form a third solution. The third solvent is then removed from the third solution to form a remnant. The remnant is then dissolved in a solvent consisting essentially of tertiary butanol to form a fourth solution. The fourth solution is then filtered through a filter having orifices of between about 0.05 and 0.5 micrometers in diameter to produce a filtrate. The filtrate is lyophilized to remove the tertiary butanol and a fine powder remains. This fine powder may be used to form polyene macrolide-containing liposomes by simple incubation or suspension in an aqueous solution.
1. A process for producing a powder which forms liposomes comprising an antifungal polyene macrolide upon suspension in an aqueous solution, said process comprising the steps of:
(a) dissolving antifungal polyene macrolide and phospholipids in a quantity of first organic solvent and a quantity of second organic solvent respectively, to form a first solution and a second solution;
(b) mixing the first solution and the second solution to form a mixture;
(c) removing the first organic solvent and the second organic solvent from the mixture to form a residue;
(d) dissolving the residue in a quantity of a third organic solvent to form a third solution, wherein the third organic solvent comprises tertiary butanol and methylene chloride;
(e) extracting the third organic solvent from the third solution to leave a remnant;
(f) forming a fourth solution by dissolving the remnant in a solvent consisting essentially of tertiary butanol;
(g) passing the fourth solution through a filter having orifices with diameters of between about 0.05 um and about 0.5 um to produce a filtrate; and
(h) lyophilizing the filtrate to remove the solvent consisting essentially of tertiary butanol.
2. The process of claim 1 wherein the antifungal polyene macrolide is nystatin, amphotericin B, partricin or a derivative thereof.
3. The process of claim 1 wherein the antifungal polyene macrolide is nystatin or amphotericin B.
4. The process of claim 1 wherein the antifungal polyene macrolide is amphotericin B.
5. The process of claim 1 wherein the antifungal polyene macrolide is nystatin.
6. The process of claim 1 wherein the phospholipids are one or more of phosphatidylcholine, phosphatidylserine, phosphatidylglycerol, sphingomyelin and phosphatidic acid.
7. The process of claim 1 wherein the phospholipids comprise DMPC and DMPG.
8. The process of claim 1 wherein the phospholipids consist essentially of DMPC and DMPG in 7:3 ratio.
9. The process of claim 1 wherein the first solvent is methanol.
10. The process of claim 1 wherein the second solvent is chloroform.
11. The process of claim 1 wherein step (b) is defined further as:
mixing the first solution and the second solution to form a first mixture having a ratio of antifungal polyene macrolide to phospholipid between about 1:5 and about 1:50.
12. The process of claim 1 wherein step (b) is defined further as:
mixing the first solution and the second solution to form a first mixture having a ratio of antifungal polyene macrolide to phospholipid of about 1:10.
13. The process of claim 1 wherein step (c) is defined further as:
removing the first solvent and the second solvent from the first mixture by subjecting the first mixture to solvent evaporation under reduced pressure and at a temperature between about 35� C. and about 45� C.
14. The process of claim 1 wherein, prior to the passing step, the fourth solution is clarified by warming to between about 50� C. and about 70� C.
15. The process of claim 1 wherein the third organic solvent comprises tertiary butanol and methylene chloride in a ratio between about 2:1 and about 1:40.
16. The process of claim 1 defined further wherein the filter has orifices of about 0.2 um.
17. The process of claim 1 wherein the antifungal polyene macrolide and phospholipids are in a ratio of between about 1:5 and about 1:20.
18. The process of claim 1 wherein the antifungal polyene macrolide and phospholipids are in a ratio of about 1 to 10.
The present invention relates to a composition of matter usable to form liposomes comprising antifungal polyene macrolides and the production thereof.
Clinical observations and animal experimental studies have added to the understanding of host-fungal interactions. It is becoming recognized that host defense against fungal disease is multifactorial and may vary, depending on the etiologic agent. The mechanisms of resistance are not well defined in most instances, but various innate barriers and cell-mediated immune responses seem to be of primary importance. Clearly, debilitation of innate defenses and of cell-mediated immune responses can increase an individual's susceptibility to severe fungal disease from opportunistic agents such as Cryptococcus neoformans and species of Candida and Aspergillus, as well as from fungal pathogens such as Histoplasma capsulatum and Coccidioides immitis. The difficulty in gaining a complete understanding of the critical host defenses has been further complicated by many studies that show fungi may affect various host immune functions adversely. Although it is too early to evaluate the clinical importance of many of these experimental findings, investigators have demonstrated that fungi impair neutrophil function, induce IgE responses, and cause suppression of cell-mediated immune responses.
Host changes likely to be associated with increased susceptibility may be accidentally induced, as in traumatic injuries (such as burns or puncture wounds); selfinduced, as in chronic alcoholism; naturally occurring, as in diabetes mellitus, various congenital immune deficiencies, collagen diseases, lyaphoreticular neoplastic disease, and other types of tumors; or iatrogenically induced by instrumentation (such as catheterization), surgical procedures (such as open heart surgery), or by use of cytotoxic drugs (as in an attempt to prevent graft rejection and to treat neoplastic disease), corticosteroid therapy, and long-term use of broad-spectrum antibiotics.
Chemical factors that aid resistance to fungal diseases are poorly defined. Knowledge of these substances is based primarily on circumstantial evidence at the clinical level and in vitro observations at the experimental level. Hormonally associated increases in lipid and fatty acid content on the skin occurring at puberty have been correlated with increased resistance to tinea capitis caused by the dermatophyte Microsporum audouinii, although pubescent changes are not the sole factors in resistance. Substances in serum, cerebrospinal fluid, and saliva may limit growth of Cryptococcus neoformans, and basic peptides in body fluids have been shown to inhibit Candida albicans.
Results of clinical and experimental studies indicate that C. albicans, C. neoformans, Aspergillus fumigatus, and C. immitis activate the alternative pathway of the complement cascade. Because of the polysaccharide nature of fungal cell walls, it is expected that all medically important fungi activate complement. Such activation may be important in defense against some mycoses; a positive correlation has been demonstrated between animals deficient in late-acting complement components (C3-C9) and increased susceptibility to fungi such as C. neoformans and C. albicans. Assuming that phagocytic cells are important in resistance to fungi, complement activation may play a role by provoking an acute inflammatory response on generation of complement fragments C3a and C5a, and by coating the fungal elements with opsonic fragments C3b and C3d for ingestion by phagocytic cells.
The systemic mycoses of humans and other animals are caused by some fungi that are pathogenic and cause disease in the healthy host, and by other fungi (opportunistic pathogens) that are usually innocuous but cause disease in patients whose immune defenses are impaired. Some of these fungi may be saprophytes in nature (soil, bird droppings), whereas others are a part of the normal human flora (commensals). In no case are humans the solitary or necessary host.
An example of a soil saprophyte is Histoplasma capsulatum, which commonly causes infection in endemic areas; 80%-90% of adults react positively to histoplasmin in delayed cutaneous hypersensitivity tests. An example of an opportunistic pathogen is Candida albicans, normally present in the oral cavity, gastrointestinal tract, and probably the skin. In the patient with acute leukemia, however, C. albicans is commonly present in blood, causing a fulminant, usually fatal, septicemia. Other opportunistic infections are seen in patients with diabetic acidosis (mucormycosis) and Hodgkin's disease (for example, cryptococcosis and histoplasmosis). The pathogenesis of these mechanisms is obscure, but cell-mediated immunity seems to be essential for a good prognosis.
Neither active vaccines nor passive immune serum immunization has been sufficiently successful to result in commercially available preparations.
Treatment of active disease may be symptomatic (for example, pain relief), sometimes surgical (resection of irremedially damaged tissue and correction of hydrocephalus), and, most successfully, chemotherapeutic (Table 1). Among the chemotherapeutic agents commonly used are hydroxystilbamidine isethionate, amphotericin B, 5-fluorocytosine (Flucytosine), miconazole, and ketoconazole. Response to these drugs varies according to the fungus, type of disease, and course of illness. For example, response is good in most B. dermatitidis infections, but is poor in most diseases caused by A. fumigatus. Response is better for skin lesions caused by B. dermatitidis than for meningitis due to C. immitis; response is better in chronic cryptococcosis than in fulminant candidiasis. Table 1 shows a listing of some systemic mycoses and generally accepted chemotherapeutic agents.
TABLE 1______________________________________CHEMOTHERAPEUTIC AGENTS FORSYSTEMIC MYCOSESDisease First Choice Second Choice______________________________________Aspergillosis Amphotericin B KetoconazoleBlastomycosis Amphotericin B Hydroxystilbamidine isethionateCandidiasis Amphotericin B Flucytosine or ketoconazoleCoccidioidomycosis Amphotericin B KetoconazoleCryptococcosis Amphotericin B Either drug alone* FlucytosineHistoplasmosis Amphotericin B Ketoconazole*Mucormycosis Amphotericin B Miconazole*Paracoccidioidomycosis Amphotericin B Sulfonamides, Ketoconazole*______________________________________ *Depending on minimal inhibitory concentration necessary for the fungus.
Infection is the cause of death in 51% of patients with lymphoma and 75% of patients with leukemia. Although bacteria are the causative organisms of many such infections, fungi account for 13% of the fatal infections in patients with lymphoma and for more than 20% of patients with leukemia. The fungus Candida albicans causes more than 80% of these infections, and Aspergillus spp. is also a frequent cause of such infections. In addition, fungal infection is a major cause of morbidity and mortality in patients with congenital and acquired deficiencies of the immune system. Much concerted effort has been expended in search of agents useful in treating fungal infections of humans. As a result, many compounds have been isolated and shown to have antifungal activity, but problems associated with solubility, stability, absorption, and toxicity have limited the therapeutic value of most of them in human infections. The most useful antifungal antibiotics fall into one of two categories: those that affect fungal cell membranes and those that are taken up by the cell and interrupt vital cellular processes such as RNA, DNA, or protein synthesis. Table 2 lists some useful antifungal agents and their mechanisms of action.
TABLE 2______________________________________SOME USEFUL ANTIFUNGAL AGENTS,THEIR CHEMICAL CLASSIFICATION,AND THEIR MECHANISMS OF ACTIONClass Compounds Mechanism______________________________________Polyene Amphotericin B Interacts with sterols Nystatin (ergosterol) in fungal cell membrane, render ing cells selectively permeable to the outflow of vital constituents, e.g. potassiumImidazole Miconazole Inhibits demethylation of Clotrimazole lanosterol thus Ketoconazole preventing formation of ergosterol, a vital component of fungal cell membrane; also has a direct cidal effect on fungal cellsPyrimidine 5-Fluorocytosine Is taken up and deaminated by susceptible cell to form 5-fluorouracil, which in turn inhibits RNA synthesis; also thought to inhibit thymidylate synthetase and DNA synthesisGrisan Griseofulvin Binds to tubulin and inhibits microtubule assembly3-Arylpyrrole Pyrrolnitrin Appears to inhibit terminal electron transport between succinate or NADH and coenzyme QGlutaramide Cycloheximide Inhibits protein synthesis at 80S ribosomal level preventing transfer of aminoacyl tRNA to the ribosome______________________________________
The polyene macrolide antibiotics are secondary metabolites produced by various species of Streptomyces. Several common features of these compounds are useful in classifying the more than 80 different polyenes that have been isolated. All are characterized by a macrolide ring, composed of 26-38 carbon atoms and containing a series of unsaturated carbon atoms and hydroxyl groups. These features of the molecule contribute to the polyenes' amphipathic properties (those relating to molecules containing groups with different properties, for example, hydrophilic and hydrophobic). The ring structure is closed by the formation of an internal ester or lactone bond (FIG. 1). The number of conjugated double bonds vary with each polyene, and the compounds are generally classified according to the degree of unsaturation.
Toxic effects of polyene macrolides appear to be dependent on binding to cell membrane sterols. Thus, they bind to membranes of fungus cells as well as to those of other eukaryotic cells (human, plant, and protozoa), but not to bacterial cell membranes, which do not contain membrane sterols. The interaction of polyene macrolides with mammalian and fungal membrane sterols results in transmembrane channels that allow the leakage of intracellular components leading to cell deaths.
The usefulness of an antibiotic is usually measured by the differential sensitivity of the pathogen and host. Two polyene macrolides agents, nystatin and amphotericin B, are relatively specific for fungi and have thusfar proven to have therapeutic usefulness in humans. The relative specificity of these two polyene macrolides may be based on their greater avidity for ergosterol, the principal sterol of fungal membranes, compared to cholesterol, the principal sterol of human cell membranes.
Amphotericin B is a heptaene macrolide with seven resonating carbon bonds. The compound was first isolated from broth filtrates of S. nodosum in 1956. Like other polyene macrolide antibiotics, amphotericin B is insoluble in water. The problem of its solubility has been circumvented by combining the antibiotic with sodium deoxycholate and sodium phosphate and hydrating the mixture with sterile water or saline. Amphotericin B is the polyene antibiotic thusfar most sufficiently nontoxic to humans that it has been used parenterally at effective doses against various fungi.
Nystatin, first isolated from S. noursei, is structurally related to amphotericin B, but is not classified as a heptaene because the conjugated portion of the ring is interrupted and thus forms a tetraene and a diene. Tolerated well both orally and topically, the drug is not available for intravenous use because of its presumed high toxicity and aqueous insolubility. Nystatin is available as oral tablets (500,000 units) or as an ointment for topical use (100,000 units/g). It is used in the management of cutaneous and mucocutaneous candidiasis.
It has recently been shown that the encapsulation of certain drugs in liposomes before administration to the patient can markedly alter the pharmacokinetics, tissue distribution, metabolism and therapeutic efficacy of these compounds. Liposomes may be defined as lipid vesicles which are formed spontaneously on addition of an aqueous solution to a dry lipid film. Further, the distribution and pharmacokinetics of these drugs can be modified by altering the lipid composition, size, charge and membrane fluidity of the liposome in which they are encapsulated.
Recently, liposomes have been used as carriers of amphotericin B for treatment of murine leishmaniasis (New, R.R.C., et al., "Antileishmanial Activity of Amphotericin and Other Antifungal Agents Entrapped in Liposomes." J. Antimicrob. Chemother., Vol. 8 (1981), pp. 371-381), histoplasmosis (Taylor, R.L., et al., "Amphotericin B in Liposomes: A Novel Therapy for histoplasmosis." Am. Rev. Respir. Dis., Vol. 125 (1982), pp. 610-611), cryptococosis (Graybill, J.R., et al., "Treatment of Murine Cryptococosis with Liposome-Associated Amphotericin B." J. Infect. Dis., Vol. 145 (1982), pp. 748-752). and candidiasis (Tremblay, C., et al., "Comparative Efficacy of Amphotericin B (AMB) and Liposomal AMB (lip-AMB) in Systemic Candidiasis in Mice." Abstr. 1983 ICAAC, No. 755 (1983), p. 222). Liposome-encapsulated Amphotericin B has also been used for treatment of coccidioidomycosis in the Japanese macaque (Graybill, J.R., et al., "Treatment of Coccidioidomydosis (cocci) in Primates Using Liposome Associated Amphotericin B (Lipo-AMB)." Abstr. 1982 ICCAC, No. 492 (1982), p. 152).
The treatment of fungal infections remains a major problem in spite of the availability of effective antifungal drugs such as the polyenes. Most of the available polyene antibiotics have toxic side effects that limit their clinical application. Nystatin, a tetraene-diene polyene macrolide antibiotic, has high hydrophobicity, which has precluded its effective systemic administration. It has been used as suspensions prepared in various ways and administered to the patients orally. However, these studies have generally failed to document a beneficial effect of nystatin administration against systemic fungal infections.
The present inventors have recently demonstrated that liposome-encapsulated amphotericin B may be used to treat experimental murine candidiasis (Lopez-Berestein et al., J. Infect. Dis., Vol. 150, pp 278-283 (1984) and in the treatment of fungal infections in patients with leukemia and lymphoma (Lopez-Berestein et al., J. Infect. Dis., Vol. 151, pp 704-71 (1985).
The present invention involves a process for producing fine powder suitable for the preparation of antifungal polyene microlide-containing liposomes upon suspension in an aqueous solution. This process comprises the following steps. Quantities of polyene macrolide and phospholipids are dissolved respectively in a first solvent and a second solvent to form a first solution and a second solution. The first solution and the second solution are mixed in a desired ratio to form a mixture. The first solvent and the second solvent are then removed from the mixture, for example by evaporation, to form a residue. The residue is then dissolved in a third solvent comprising tertiary butanol and methylene chloride to form a third solution. The third solvent is then extracted by evaporation from the third solution to form a remnant. The remnant is then dissolved in a solvent consisting essentially of tertiary butanol to form a fourth solution. The fourth solution is then filtered through a filter having orifices of between about 0.05 and 0.5 micrometers in diameter to produce a filtrate. The filtrate is lyophilized to remove the tertiary butanol and a fine powder remains. This fine powder may be used to form polyene macrolide-containing liposomes by simple incubation or suspension in an aqueous solution.
A stable powder suitable for the direct preparation of liposome-incorporated antifungal polyene macrolides may be made by a process of the present invention. While the conditions described herein are specifically applicable to nystatin and amphotericin B, other polyene macrolide antifungals may be likewise used, but with minor modifications of procedure apparent to those skilled in the art upon a minimal amount of experimentation.
The process for pre-liposomal polyene macrolide powder formation of the present invention involves dissolution of an antifungal polyene macrolide such as nystatin or amphotericin B in a first organic solvent such as methanol to form a first solution. Phospholipids are dissolved in a second organic solvent such as, for example, chloroform, to form a second solution. The first solution and the second solution are mixed to form a first mixture having a ratio of antifungal polyene macrolide to phospholipid between about 1:5 and about 1:50, preferably of about 1:10. The organic solvents are removed from the mixture, for example, by solvent evaporation under reduced pressure and at a temperature between about 35� C. and about 45� C., until a residue such as a dry film is formed. The residue is then dissolved in a quantity of a third organic solvent such as a mixture of tertiary butanol and methylene chloride in a ratio between about 2:1 (preferred for nystatin) and about 1:40 (preferred for amphotericin B) and the solvent evaporated to leave a remnant. The remnant is dissolved in a solvent consisting essentially of tertiary butanol to form a fourth solution which is warmed, if necessary for clarification, and passed through a filter having orifices of between about 0.05 and 0.5 micrometers (um) in diameter. If warming is desired to clarify the fourth solution, particularly with amphoterecin B, the warming is preferably to a temperature between about 50� C. and about 70� C. The filtrate is subjected to freezing, for example, with dry ice-acetone. The frozen material is then lyophilized until essentially all solvent is removed. After lyophilization, a fine pre-liposomal polyene macrolide powder is produced. This powder is readily and stably stored under commonly available dry and cool storage conditions.
The above-described pre-liposomal polyene macrolide powder may be easily used to reconstitute a liposome suspension according to the following general procedure. The powder is added to an aqueous solution such as pyrogen-free saline, and allowed to incubate at 25� C. to 45� C. for 1-10 minutes for a liposome suspension to form. Polyene macrolide content may be measured by dissolution of the liposomes in methanol and monitoring of optical density at a wavelength characteristic for polyene macrolide absorption.
Representative, suitable phospholipids in the present invention are phosphatidylcholine, both naturally occurring and synthetically prepared, phosphatidic acid, phosphatidylserine, phosphatidylethanolamine, sphingolipids, phosphatidyglycerol, spingomyelin, cardiolipin, glycolipids, gangliosides, cerebrosides and the like used either singularly or intermixed such as in soybean phospholipids.
More particularly useful phospholipids include egg phosphatidylcholine, dilaurylphosphatidylcholine, dimyristoylphosphatidylcholine, dipalmitoylphosphatidylcholine, distearoylphosphatidylcholine, 1-myristoyl-2palmitoylphosphatidylcholine, 1-palmitoyl-2-myristoyl phosphatidylcholine, 1-stearoyl-2-palmitoyl phosphatidylcholine, dioleoylphosphatidylcholine, dilauryloylphosphatidylglycerol, dimyristoylphosphatidylglycerol, dipalmitoylphosphatidylglycerol, distearoylphosphatidylglycerol, dioleoylphosphatidylglycerol, dimyristoyl phosphatidic acid, dipalmitoyl phosphatidic, dimyristoyl phosphatidylethanolamine, dipalmitoyl phosphatidylethanolamine, dimyristoyl phosphatidylserine, dipalmitoyl phosphatidylserine, brain phosphatidylserine, brain sphingomyelin, dipalmitoyl sphingomyelin, and distearoyl sphingomyelin.
The lipid composition of both the initial powdered composition of matter and the resultant liposomes, formed in accordance with the present method, is normally the same. Where the resultant liposomes are intended for in vivo applications (such as drug delivery), then it is normally desirable that the lipid composition have a transition temperature below body temperature. Liposomes composed of phospholipids which have transition temperatures below the characteristic gel-liquid crystalline phase transition temperature of biological membranes, i.e. about 37� C., are considered fluid and those which have transition temperature above 37� C. are considered solid. Another consideration in selecting the composition of lipid or lipids for liposome applications is that alkyl-ether linked lipids (rather than ester linked) are more stable to hydrolysis, and hence alkylether linked lipids for the resultant liposomes may be particularly desirable for therapeutic application.
In addition, other lipid-like substances such as steroids, cholesterol, aliphatic amines or acids such as long chain aliphatic amines or carboxylic acids, long chain sulfates and phosphates, dicetyl phosphate, butylated hydroxytoluene, tocopherol, and isoprenoid compounds may be intermixed with the phospholipid components to confer certain desired and known properties on the initial liposomes and hence the resultant liposomes. Further, synthetic phospholipids containing either altered aliphatic portions, such as hydroxyl groups, branched carbon chains, cycloderivatives, aromatic derivatives, ethers, amides, polyunsaturated derivatives, halogenated derivatives, or altered hydrophillic portions containing carbohydrate, glycol, phosphate, phosphonate, quaternary amine, sulfate, sulfonate, carboxy, amine, sulfhydryl, imidazole groups and combinations of such groups, can be either substituted or intermixed with the phospholipids.
The antifungal polyene macrolides of the present invention include nystatin, amphotericin B, partricin and derivatives thereof such as methyl esters.
These examples are presented to illustrate preferred embodiments and utilities of the present invention and are not meant to limit the present invention unless otherwise stated in the claims appended hereto.
A solution of 25 mg nystatin in 25 ml methanol was mixed with a solution of 175 dimyristoylphosphatidylcholine (DMPC) and 75 mg dimyristoylphosphatidylglycerol (DMPG) in 10 ml chloroform. The DMPC:DMPG ration was 7:3 and the nystatin:DMPC+DMPG ration was 1:10. The organic solvents were then evaporated at 40� C. under partial vacuum in a rotary evaporator until a dried lipid film was formed. Thirty ml of 2:1 mixture of tertiary butanol and methylene chloride were added to dissolve the dried lipid film. The organic were then evaporated from the solution at 40� C. and under partial vacuum to form a lipid residue. The lipid residue was dissolved in tertiary butanol and the solution passed through a 0.2 um filter. The nystatin concentration was measured from an aliquot of the filtrate. The filtrate was frozen by immersion of a container in dry ice-acetone. The frozen material was subjected to overnight lyophilization and a fine preliposomal nystatin powder produced.
A 100 mg sample of the fine powder (containing about 10 mg nystatin) was suspended with 10 ml of pyrogen-free saline. When the powder suspension was warmed at 40� C. for 2-5 minutes, liposomes were formed therein. As determined by microscopic examination, the suspended materials were 100% liposomes were formed therein. As determined by microscopic examination, the suspended materials Were 100% liposomes and no crystals were found. The suspension was centrifuged at 20,000 rpm (40,700�g) for one hour and the resultant pellet removed and resuspended in saline. The nystatin remaining in the resuspended pellet was determined to be 70-80 percent of the original amount added, by dissolution in methanol and measurement of optical density at 306 nm. The encapsulation efficiency of the liposomes, as measured after the filtration step, was observed to be >99%. (No detectable free drug was left after formation of liposomes from the powder). The resuspended pellet was a liposome preparation substantially free of soluble lipids or other materials and was suitable for clinical administration.
Amphotericin B in methanol and phospholipids (DMPC:DMPG, 7:3) in chloroform were mixed together in a ratio of 1:10. The organic solvents were then evaporated at 40� C. using a rotary evaporator under vacuum.
Tertiary butanol and methylene chloride in a 1:30-40 ratio were added to solubilize the dried lipid film. The organic solvents were then evaporated.
The residue in the flask was then dissolved in tertiary butanol, warmed to temperatures above 52� C., and filtered through a 0.2 um filter. An aliquot from this filtrate was taken to determine the amphotericin B concentration.
The above mixture was then frozen (using dry ice with acetone) and lyophilized overnight. A fine powder was obtained.
The powder obtained as described above was suspended in pyrogen-free saline. The liposomes did not form until the suspension was warmed in a water bath at about 40� C. for about 2-5 minutes. The suspension then formed 100% liposomes (no crystals), as they appeared under a microscope. The suspension was centrifuged at 20,000 rpm for one hour and the pellet removed and resuspended in saline. An aliquot was taken from this final suspension and the amount of amphotericin B incorporated into liposomes quantitated by dissolving in methanol and measuring O.D. at 405 nm. The encapsulation efficiency of drug from the powder to liposomes was 99-100%.
Changes may be made in the elements and methods described herein or in the steps or the sequence of steps of the method described herein without departing from the concept and scope of the invention as defined in the following claims.
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Chad Mendes will not be fighting Jose Aldo at UFC 133 in August, but the UFC's top featherweight contender still intends to compete on the card. Read More >> read news >>
Chad Mendes has only ever lost a fight to UFC featherweight champion Jose Aldo, and it sticks in his craw. He wants that fight again, and he wants it bad. read news >>
Jose Aldo hasn't withdrawn from anything, according to his manager, Ed Soares.
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Al read news >>
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But the UFC's first-time defending featherweight champion did enough to read news >>
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Jose Aldo is the best featherweight in the world. And it's hard to say Chad Mendes is not a close second. Mendes proved that again by knocking out Ricardo Lamas at 2:45 of the first round in the main read news >>
Check out Chad Mendes' full UFC Fight Night 63 media scrum, where he spent most of his time fielding questions about Jose Aldo and Conor McGregor. read news >>
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Holly Madison engaged to Pasquale Rotella: See her ring
First comes baby, then comes marriage! Three months after welcoming daughter Rainbow Aurora, Holly Madison announced via her official blog on Monday that she is ready to wed her boyfriend, Pasquale Rotella . "I got engaged on Sunday," the former Playboy model wrote. "My fiance was so wonderful in creating such a romantic night! He proposed to me at the top of the Ferris wheel at EDC Las Vegas."
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Madison posted several pictures of Rotella's proposal on her blog. "I was so happy that so many of our close friends were there to share the wonderful moment with us," she wrote. "We rode around the festival on the art car until the sun came up! I couldn't have asked for a more wonderful or magical proposal!"
The former "Peepshow" performer had previously revealed that she hopes to tie the knot on Aug. 14. At the Tao Beach opening in Las Vegas May 5, Madison, 33, opened up to Us Weekly about her new life as a mom.
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"The last few months have been really great just getting to know her," she said of Rainbow, who was born on March 5. "I'm now just starting to slowly reintroduce my old life into this new life, but it's all about her."
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As for her daughter's other milestones? "She's definitely sleeping through the night," Madison shared. "She's also starting to talk a little bit -- starting to babble. She rolls over. She's doing really well."
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This is the first engagement for Madison, who was previously in a long-term relationship with Playboy founder Hugh Hefner. She has been dating event planner Rotella since the fall of 2011.
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I am married (38 years), we enjoy being outdoors, fishing, going for drives on the back-roads. I enjoy taking pictures of everything and I really enjoy seeing everyones pictures they put on this site. We live in a very small town that is where the White and Black Rivers meet. The town has a State Park here, has a lot of history, there is a video that was made for AETN TV, if you click on Visit My Website, you can see it. Create your own visitor map!
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Caption: Okay okay, I'm thorwing you the corn! This little guy looked mean coming toward me instead of the cute look from the side, lol. I don't know what kind of duck it is. We checked out Magness Lake to see if the Trumpter Swans were back for the winter and they are, plus these cute little ducks.
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News flash, Cecile: Abortion is not and never has been #WhatWomenNeed.(Our pipes have been frozen for a few days, and my hair is in desperate need of washing; so my vanity won't let me post a picture of myself holding a #WhatWomenNeed placard. But if you want to join in the fun with New Wave Feminists, where you can find a template for the placard, my suggestion for What Women Need is "PEACE IN THE WOMB.") … [Read more...]
At the Register: What Planned Parenthood Needs
February 13, 2014 by Leave a Comment


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Definitions for maga
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Maga is a musical group.
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text:
I actually have several big news things!
The first thing is that my boyfriend and I will be moving apartments, away from horrible Roommate! Our new apartment will be a one bedroom with all new appliances, on the second floor (instead of the third that we currently live on).
The move in date is set at the end of August and I'm beyond excited, but that leads me to my next news.
Also in August, I will be taking my first vacation since moving out! I'll be going to see my grandparents in Texas, right before the moving date. I haven't seen them in six years so I'm pretty excited about it, though I will probably not be online much at all while there (but will get pictures to share).
On my final big news, that is actually child related... I'm going to be a Godmother!
I, for uncontrollable reasons I don't care to discuss, wasn't able to get to know my dad's sisters as I was growing up. They recently came back into my life and for the first time, I have aunts as a part of my life and it makes me beyond happy. One of those aunts is expecting her third child in roughly a month and she's already asked if I would accept the honor of being Godmother (with full legal paperwork and everything).
I said yes and promptly spent all of my money, sending my unborn Godson as many gifts as I could think of.
For about two weeks, I was tagged in a new photo on Facebook every day with her thanking me for all the stuff I sent. Then I ran out of spending money and decided that I should probably pay rent and also eat food so I stopped sending stuff...for now. I still have carts full of stuff ready to be paid for online to send. It could actually be a problem. Somebody set up an intervention.
So, what's going on in your lives?
Also, I need a super cool nickname for my Godson here. Because as much as I love saying "my Godson", I want it to be a more unique name in case (if I am so blessed) I were to be given that honor a second time.


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Book your room at Dahab Bay Hotel
Double RoomMax Occupancy: 2 guests (up to 1 child, 1 infant)
StudioMax Occupancy: 2 guests (up to 1 child, 1 infant)
Triple RoomMax Occupancy: 3 guests (up to 2 children, 2 infants)
Single RoomMax Occupancy: 1 guest
Get an overview of this hotel3-star hotel with free breakfast and restaurant
Collect 200 extra points
Just enter your Nectar card number when you book and you'll receive 400 points credited to your account 30 days after you return from your trip.
Situated near the beach, this hotel is 0.5 mi (0.9 km) from Dahab Beach and 2.4 mi (3.9 km) from Dahab Bay. Blue Hole is 5.6 mi (9 km) away.
Hotel Features
This hotel features a restaurant, a bar/lounge, and a coffee shop/café. Self parking is free. Other amenities include a snack bar/deli, a rooftop terrace, and massage/treatment rooms.
Room Amenities
All 25 rooms boast deep soaking tubs and offer free WiFi and balconies. Other amenities available to guests include 24-hour room service, TVs, and refrigerators.Information missing or incorrect? Tell us!
Hotel Amenities
Hotel Amenities
Dining options at the hotel include a restaurant, a coffee shop/café, and a snack bar/deli. A bar/lounge is on site where guests can unwind with a drink. Guests can enjoy a complimentary breakfast.
This Dahab hotel also offers a rooftop terrace, a library, and tour/ticket assistance. Complimentary self parking is available on site.
- 24-hour front desk
- Total number of rooms - 25
- Number of floors - 2
- Babysitting or childcare
- Bar/lounge
- Coffee shop or café
- Free breakfast
- Express check-in
- Express check-out
- Tours/ticket assistance
- Snack bar/deli
- Rooftop terrace
- Luggage storage
- Dry cleaning/laundry service
- Barbecue grill(s)
- ATM/banking
- Library
- Laundry facilities
- Spa treatment room(s)
- Multilingual staff
- Garden
- Restaurant
- Safe-deposit box at front desk
- Free self parking
- Number of buildings/towers - 2
Family Friendly Amenities
- Free Wi-Fi
- Snack bar/deli
- Laundry facilities
- Babysitting or childcare
- Refrigerator
Available in all rooms: Free WiFi
Free self parking
Room Amenities
- Balcony
- Air conditioning
- Free newspaper
- Free local calls
- Refrigerator
- Minibar
- Daily housekeeping
- Private bathroom
- Free toiletries
- Deep soaking bathtub
- Rainfall showerhead
- Bathtub or shower
- Iron/ironing board (on request)
- Television
- Free WiFi
- In-room massage available
- Climate control
- In-room safe
- Room service (24 hours)
Where to Eat
A complimentary breakfast is served between 7:00 AM and 10:30 AM.
Dahab Bay Hotel has a restaurant on site.
Late night fare is available from 24-hour room service.
Nearby Things to Do
The recreational activities listed below are available either on site or nearby; fees may apply.
- Bicycle rentals nearby
- Scuba diving nearby
- Windsurfing nearby
- Safari on site
- Snorkeling nearby
- Rock climbing nearby
- Boat tours nearby
Spa Services
- Massages on beach
- Massages
Hotel Policies
Check-in time starts at 12:30 PM
Check-in time ends at noon
Check-out time is 12:30 PM
Payment types
You need to know
Extra-person charges may apply and vary depending on hotel policy.
Government-issued photo identification and a credit card or cash deposit are required at check-in for incidental charges.
Special requests are subject to availability upon check-in and may incur additional charges. Special requests cannot be guaranteed.
- The name on the credit card used at check-in to pay for incidentals must be the primary name on the guestroom reservation.
No pets or service animals allowed
We should mention
Children 6 years old and younger stay free when occupying the parent or guardian's room, using existing bedding. No pets and no service animals are allowed at this property.


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Great location, everything else sucks. Rooms ard small old anx glummy. Breakfast is 99% starch. The pool is actually a large bathtub. The gym consist of a few old and dangerous machines. Service is proper but not friendly. Single beds are the width of millitary cots. The price, including 21% VAT was $130 dollars, a fair price for a 4... More
Top-rated Attractions Nearby
Top-rated Restaurants Nearby


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Jason Aldean and Kristen Bell to Host the 2013 CMT Music Awards
Jason Aldean is following in his good friend Luke Bryan's footsteps, announcing Thursday that he'll be hosting a country music awards show.
Jason Aldean is following in his good friend Luke Bryan's footsteps, announcing Thursday that he'll be hosting a country music awards show.
Kristen Bell returns as host of this year's "CMT Music Awards", but TOBY KEITH was NOT asked back as her co-host. It doesn't sound like Kristen will miss him though. She Tweeted, "Yay! Heading back to Nashville to host the
Toby Keith gave a fantastic performance at the Stagecoach Country Music Festival the same day that his old friend George Jones sadly passed away at the age of 81. Halfway through his set, the singer paid tribute to the iconic entertainer in a heartfelt way.
Songs that are amongst the biggest of Lee Brice and Lady Antebellum's careers make a return to the ToC Top 10 Video Countdown this week -- in a big way. 'I Drive Your Truck' was a chart-topper for Brice, while Lady A's 'Downtown' sits at the top of the charts just this week. However, neither of these videos were No. 1 on this list, as decided explicitly by country music fans.
Can anyone stop Carrie Underwood? 'Two Black Cadillacs' has built a house on top of the ToC Top 10 Video Countdown, but there are more than a few big bad wolves looking to blow it down. New videos from Florida Georgia Line and Taylor Swift enter the voting poll this week, in addition to returning Top-10ers from Miranda Lambert, Blake Shelton and Toby Keith.
Alabama have certainly earned the right to be known as one of the best country bands of all time, with 21 Gold, Platinum, and multi-Platinum albums, 43 No. 1 singles, eight Entertainer of the Year Awards, and over 73 million records sold. It's been 40 years since their start, and they'll be combining their legendary greatness with some of country's biggest stars for a collaborative album called 'Alabama & Friends.'
Two country family trios found their way back into the Taste of Country Top 10 Video Countdown this week! The Band Perry's 'Better Dig Two' video and the Henningsens' fan-favorite 'American Beautiful' both waltzed back in, giving Jason Aldean and Kip Moore's latest clips the boot.
Sammy Kershaw's home in Lafayette, La. was damaged in a fire that broke out in the kitchen on Thursday (April 4). The property sustained heavy smoke damage, but thankfully, no one was injured in the blaze.
Women continue to rule the Taste of Country Top 10 Video Countdown. For a third straight week, a video for a song sung by a female topped the weekly countdown. It was Carrie Underwood's 'Two Black Cadillacs' last week, and prior to that, 'American Beautiful' by the Henningsens. Can new clips by Jason Aldean, Blake Shelton or Eric Church best the country superstar? It's up to fans to decide the weekly Top 10.
There is comedy in Blake Shelton singing with Pistol Annies, as he does on his new single 'Boys 'Round Here.' One imagines a country Hugh Hefner surrounded by his beauties. In real life, the Annies likely (very likely) don't attend to his every need and agree with him at all costs, but they do on this song, and it's absolutely charming.
The three-day outdoor Watershed Music Festival is only two years in the making, but it's drawing some big names to headline the performances. Luke Bryan, Toby Keith and Brad Paisley are among the talented country crooners who will take the stage at The Gorge Amphitheatre August 2-4. Sounds like this is a "can't miss" experience!
Fans of Eric Church and Kix Brooks made strong statements this week. 'Like Jesus Does' and 'Moonshine Road' both cracked the weekly Top 10 video countdown, the only countdown decided entirely by fan votes. Additionally, some familiar videos battled for the No. 1 spot, which was decided by a narrow margin of less than one percent.


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Bryan Adams' Hit-Heavy Fox Show
By Jeremy Essig
Lightning Bolt's Sharp New Sound
By Jason Robinson
Fleetwood Mac Back with Classic Lineup
By Hans Morgenstern
Here's Who's Making STL Noisy This Spring
By Joseph Hess
Beatles Sister Louise Harrison Departs the Midwest
By Peter Gilstrap
By Julia Burch
Working Class Dogs to Honor Rick Springfield
By Jeremy Essig
Torche Gets Back Into Its Heavy Groove With Restarter
By Nathan Smith
Make something of yourself, or hit the snooze button. That was the directive in the title of Ghosty's first album, 2005's Grow Up or Sleep In. Even though Grow Up didn't make the Kansas City band famous, the new LP Answers proves that Ghosty is grown up, and it does not sleep in — or, for that matter, sleep much at all. Produced in large part by Paul Malinowski (who also did Riddle of Steel's 1985), Answers captures Ghosty's live sound; the album maintains an intimate, spontaneous feel, its songs sounding fresh despite the fact that the band has been working on them for so long. Opener "Dumbo Wins Again" starts sparsely, a tumbling drum pattern interlocking with a quirky guitar chord, over which vocalist Andrew Connor unloads the complaints of a hypothetical Kansas Citian who's tired of his surroundings: "Well I'd like nothing more than to leave your sad monuments and dumb fountains behind."
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James Quadra's Legal Cases
4 total
James Quadra
In Re Complete® Cases, J.C.C.P. 4521 (Lazar et al vs. AMO, Inc. et al., O.C.S.C. No. 07-CC-01296).
Practice Area:
Class Action
Mar 23, 2012
The action has been certified and is currently scheduled for trial in June 2011 before Judge David Velasquez in Orange County Superior Court. Jim Quadra is co-lead counsel.
Calvo Fisher & Jacob represents a class of consumers throughout the California who purchased AMO's Complete Moisture Plus contact lens solution, alleging violations of California's Unfair Competition Law (Cal. Bus. & Prof. Code section 17200 et seq.), False Advertising Act (Cal. Bus. & Prof. Code section 17500 et seq.) and California's Consumer Legal Remedies Act.
Vienna Hall, et al., v. Cinema 7, Inc., et al., S.F. Sup. Ct. No. 02-409105.
Practice Area:
Class Action
Sep 01, 2008
The Class obtained a judgment regarding liability at trial in 2007 which led to a $3,740,000 settlement.
Jim Quadra was lead class counsel representing a class of approximately 400 current and former performers who alleged that their employer violated provisions of the California Labor and Business & Professions Codes.
John LaBriola v. Bank of America, N.A. et al., No. 12-0079 (CW) (U.S.D.C., N.D. Cal)
Practice Area:
Class Action
The case was removed to federal court and is currently in the initial pleadings stage
John LaBriola v. Bank of America, N.A. et al., No. 12-0079 (CW) (U.S.D.C., N.D. Cal). Quadra & Coll are counsel for a named plaintiff acting on behalf of himself and a putative class of financial advisors who worked for Merrill Lynch and/or Bank of America, who left employment and were not paid their final commission wages within the time allowed by law. .
Old Republic Title Company Cases, J.C.C.P. No. 4111; (Wisper v. Old Republic Title Company, et al.)
Practice Area:
Class Action
Mar 08, 2002
The class settled a portion of the case for more than $3 million. The trial regarding the remaining claims resulted in judgment for customers of escrow services throughout California of $14 million. Mr. Quadra was one of trial attorneys who tried the case
James Quadra represented a class comprised of customers of escrow services throughout California who were charged reconveyance fees for services not provided and who did not receive interest on escrow funds. .


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Minimalist in menu and décor, this 40-seat relative newcomer to DC serves up exciting Japanese dishes created by Chef Hiroshi Seki, who co-owns Izakaya with his daughter, Cizuka. Chef Seki has been carving fish since he was a boy. Try the raw tuna or yellowtail with sake; ask your server to recommend the perfect pairing.
Read or Share this story: http://usat.ly/1magcxg


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1 Review
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I have made this recipe several times and it is spectacular. The combination of honey and the pistahios I used- which were slightly salty is perfect. The texture of the cheesecake is creamier because of the mascarpone. Expensive to make but worth it if you are going to really impress.


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After spending several years in a mental institute Charlie (Michael Douglas) is sent home, reuniting with his teenage daughter Miranda (Evan Rachel Wood). Charlie becomes obsessed with the notion that a long-lost Spanish treasure is buried underneath their local suburban California Costco. Disconnected from reality and his daughter's life, Charlie's erratic behavior further strains their relationship and completely disrupts her peaceful existence.
Initially skeptical, Miranda soon finds herself joining in Charlie's questionable antics in an effort to believe in her father and give him one last shot at accomplishing his dreams in this darkly funny, exciting and surprisingly hopeful take on the modern family and the American dream.


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DGO Jet
From Wikipedia, the free encyclopedia
|This article relies largely or entirely upon a single source. (October 2010)
DGO Jet was a Mexican charter airline and was based in Mexico City.
The airline was established in 1995 with a fleet of a sole Boeing 737-300. The next year more 737s were incorporated. In 1997 was incorporated the first wide-body aircraft, an Airbus A300 for regional routes and to middle of year was incorporated Douglas DC-10 for flights to US, Canada and Spain. In 1998, the airline had a debt of US$60,000, and due to their incapability for pay the debt, the airline ceased operations. Airline code IATA was DGO[1]
|This article relating to a Mexican airline is a stub. You can help Wikipedia by expanding it.


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Social Justice Day: A Nyack College Tradition
Nyack College will host its annual Social Justice Day Luncheon on Friday, January 14 at 12:15 p.m. in Shuman Hall on the Rockland County campus. This year the Social Justice Award will be presented to the Honorable Harriet Cornell, chairperson of the Rockland County Legislature and the first woman to serve in this role for four consecutive terms. A second Social Justice award will be presented to Dr. Stella Marrs, community liasion specialist for Rockland County's Human Rights Commission. Dr. Marrs was the former executive director and CEO of the Martin Luther King Multipurpose Center in Spring Valley, NY for 21 years and is a Rockland County Human Rights Hall of Fame inductee.
Two posthumous tributes will be announced at the luncheon. The late New York State Senator Thomas P. Morahan will be recognized. His lengthy career in local government began in 1977. He served Rockland resident as a member of the 96th district of the New York State Assembly and the Rockland County Legislature. In 1999 he won the race for the New York State Senator in the 38th senatorial district and served for five terms. Senator Morahan passed away in July 2010. A second posthumous tribute will also be paid to the Honorable William "Bill" Darden, vice chairman of the Rockland County Legislature, who passed away in October 2010. He served Rockland citizens in a number of civic and community roles. Mr. Darden retired as an educator from the East Ramapo School District in 2000.
The Social Justice Day Luncheon is a Nyack College tradition that exemplifies the institutional core value of social relevance. This platform gathers bridge-builders in Rockland County who join the campus community in a celebration that serves as a prelude to the Martin Luther King Jr. holiday.
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Presumed GuiltySeries Website »
Episode Guide »
Imagine being picked up off the street, told you have committed a murder you know nothing about and then finding yourself sentenced to 20 years in jail. In December 2005 this happened to Tono Zuniga in Mexico City and, like thousands of other innocent people, he was wrongfully imprisoned. "Presumed Guilty" is the story of two young lawyers and their struggle to free Zuniga. With no background in film, Roberto HernAˇndez and Layda Negrete set about recording the injustices they were witnessing, enlisting acclaimed director Geoffrey Smith ("The English Surgeon") to tell this dramatic story.
Tough LoveTough Love: Filmmaker InterviewStoryCorps Shorts: A More Perfect UnionThe OvernightersOut in the NightStoryCorps Shorts: Clean StreetsStoryCorps Shorts: 1st Squad, 3rd PlatoonStoryCorps Shorts: The Last ViewingStoryCorps Shorts: The Nature of War20/NothingStoryCorps Shorts: A Good ManGood SoilListening Is an Act of Love: A StoryCorps SpecialStoryCorps Shorts: Making ItStoryCorps Shorts: The Road HomeStoryCorps Shorts: Me and YouStoryCorps Shorts: Marking the DistancexoxosmsGrounded By RealityStoryCorps Shorts: Sundays at Rocco'sSound of Vision
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'Spider-Man' Reboot Will Be About Peter Parker, Won't Be an Origin Story
Posted on Sunday, April 12th, 2015 by Angie Han
Sony's plans to reboot the Spider-Man franchise are coming into clearer focus. According to new reports, the new film will center on a teenaged Peter Parker — not Miles Morales or another character as some have speculated.
What will be different this time around, though, is we won't be starting with an origin story. At this point, even Marvel Studios figures there's no need to rehash the same old tale. Read Kevin Feige's comments about the Spider-Man reboot Peter Parker after the jump. Read More »


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text: Conflict ConflictMiddle EastLillian Rizzo on Oct 25, 2011 @ 12:32 PMOct 25, 2011 @ 12:32 PM PublishedSyrian hospitals accused of tortureAmnesty International released a report today accusing government-run hospitals of torturing wounded protesters.The Syrian government has been accused by Amnesty International of torturing wounded protesters at state-run hospitals, CNN International reports.Amnesty International has accused the government of using the medical facilities and staff as "instruments of repression," CNN reports. The report released Tuesday claims this is a latest trend by Syria's security forces to crack down on protesters against President Bashar al-Assad.Read more at GlobalPost: US ambassador to Syria withdrawn after threatsThe human rights group's report states that wounded patients in at least four government-run hospitals have been subjected to torture, Reuters reports. The report also included that some hospital workers suspected of treating protesters injured from protests have faced either arrest or torture."It is deeply alarming that the Syrian authorities seem to have given the security forces a free rein in hospitals, and that in many cases hospital staff appear to have taken part in torture and ill treatment of the very people they are supposed to care for," said Cilina Nasser, an Amnesty researcher, Reuters reports.Read more at GlobalPost: Syria: The cost of repressionThe 39-page report also states that protesters and victims have avoided going to government hospitals and instead seek treatment at private facilities or "poorly equipped" makeshift field hospitals, the Los Angeles Times reports. The Syrian government has yet to respond to the allegations.About 3,000 people have died since the protests against Assad started in mid-March, the L.A. Times reports.Read more at GlobalPost: Syria: The sanctions effect


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Although the Mets lost in the NLCS to the Phillies in the 2016 season of MLB: The Show '11, there were some surprises.
Also the Mets Police are not happy in 2016
And here is your everyday 8
I like that OF better than the real one.
A podcast about the Mets and Star Wars I'd Just As Soon Kiss A Mookiee
Bored with Sports Talk Radio? Try Alternative Sports Talk via TuneIn


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Good morning!
Our early headlines:
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LITTLEST PET SHOP TEENSIES Keychain – Snail and Flamingo
Approx. Retail $3.99Where To Buy
CHOKING HAZARD-Small Parts. Not For Children Under 3 Years.
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full description
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Ages 4 and up.


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We use acid-free papers and canvases with archival inks to guarantee that your prints last a lifetime without fading or loss of color. Paper prints include a 1" white border around the image to allow for future framing and matting. Canvas prints include a 2.5" white border to allow for future stretching on stretcher bars.
Prints ship within 3 - 4 business days in durable cardboard tubes.
Here is an arial view of Las Vegas.
When I started my photography career, I knew that I wanted to take my images further than the click of a shutter so I built a darkroom in my home and explored my creativity under a red light. When digital photography arrived on the scene, I came out of the dark and into the world of pixels and possibilities. Today, I take my images even further with paint and mixed media. I use layers, texture and contrast to create complex images of every day things, places and people. Hints of the past and the present play together to tell my visional stories. For inquiries on usage rights or signed, personally inspected fine art on paper or wood panels please contact me directly at firstname.lastname@example.com. Please visit...
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June 16, 2015 @ 1:00 PM EDT Videos
Rescue Me.
Rescue Me.
Class Of Their Own
You might want to think twice when double-crossing these three.
The collective Czarface consisting of Inspectah Deck, 7L and Esoteric will be releasing their self-titled project on February 19 and pair up with Action Bronson for this offering. Pre-order Czarface here.


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We have divided our commodity market news under the categories as mentioned above. To read more miscellaneous uncategorized commodity market news click here...
Equity news contains all the news pertaining to the Indian corporate sector, and their equity.
Click on respective link above to read latest news & updates.
Indian-commodity.com works out to be an optimum marketing platform for finance and investment market products, for we reach out to thousands of unique visitors daily. We do offer options of text links and text+image links on our website. You can opt for only home page link, or category page link, or category-wide links, or even full website links. Your site-wide or category-wide links, are listed on the old news articles as well. Sounds tempting!!
For any business queries or custom needs, please write us at email@example.com
ICICI Prudential Mutual Fund has launched the New Fund Offer (NFO) of ICICI Prudential Fixed Maturity Plan-Series 66-368 Days Plan B, a close ended income scheme.
The NFO opens for subscription on February 11, 2013 and closes on February 14, 2013. No entry load will be applicable for the scheme; being a listed scheme, no exit load will be applicable. Investors shall note that the brokerage on sales of the units of the scheme on the stock exchanges shall be borne by the investors. The minimum subscription amount is Rs 5000.
The scheme's performance will be benchmarked against CRISIL Short Term Bond Fund Index and its fund manager is Manish Banthia.
The investment objective of the scheme is to generate income by investing in a portfolio of fixed income securities/debt instruments maturing on or before the maturity of the scheme. However, there can be no assurance that the investment objective of the scheme will be realized.
Domestic rating agency ICRA has said that the Indian economy will grow in the range of 7.6-7.8 percent in the current fiscal, despite the headwinds posed by muted global growth and an unfavourable monsoon......click on news to read complete article.
Finance Minister Arun Jaitley has expressed his confidence that Goods and Services Tax (GST) regime would come into force from April 2016. He said, 'GST bill is a constitutional amendment bill.... We hope......click on news to read complete article.
The country's largest iron ore miner NMDC has charted out a growth plan to take its iron ore production to 100 million tonnes (MT) by 2022. The state-run company's production, at present, stands at about......click on news to read complete article.
The US markets closed lower on Tuesday, with the S&P 500 and Dow suffering their biggest one-day declines in three weeks. A sharp increase in the dollar spurred global investors to dump riskier......click on news to read complete article.
US markets ended in red terrain on Friday after hawkish remarks from Federal Reserve Chair Janet Yellen, who said the central bank will likely raise interest rates this year, as long as economic activity......click on news to read complete article.
The US markets closed higher on Thursday, sending the S&P 500 to a fresh record. Investors mostly brushed off a flurry of weaker-than-expected economic data a day after minutes from Federal Reserve's......click on news to read complete article.


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The Norland Vikings basketball team won Thursday's neutral playoff game against Fort Lauderdale by a score of 51-35.
This game is a part of the 2012 Florida Boys State Basketball Playoff Brackets: FHSAA - Class 6A tournament.
(February 16, 2012: Fort Lauderdale, FL 33305) Norland Vikings (Miami, FL) backers were pleased Thursday as they saw their basketball squad overcome the host Fort Lauderdale Flying L's (Fort Lauderdale, FL), 51-35 in a non-league bout.
With the victory, Norland upgrades its record to 25-3 on the campaign. The Vikings travel to Pembroke Pines Charter (Pembroke Pines, FL) to play the Jaguars in a non-league bout on Tuesday, February 21. The Jaguars come into the bout with a record of 17-4. Pembroke Pines Charter won 70-66 in their recent non-league bout against Central (Miami, FL)


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The Center for Southwest Research and Special Collections (CSWR) specializes in interdisciplinary subjects relating to New Mexico, the Southwestern U.S., Mexico and Latin America, as well as rare materials from around the world. Our strengths include Native American, Chicano/Hispano, Latin American, Spanish Colonial, and environmental history, plus a wide range of locally published and archival materials documenting the region.
Use the tools to the left to find CSWR collections in the library catalog, archival finding aids, and digital resources.
Books from the CSWR can be requested in the Anderson Reading Room, and do not circulate.
The Rocky Mountain Online Archive includes information about archival collections in Colorado, New Mexico, and Wyoming. Finding aids give detailed descriptions of primary source materials located at twenty-seven different repositories. Materials held in the Center for Southwest Research can be requested in the Anderson Reading Room.
New Mexico's Digital Collections are digitized materials from libraries, archives, and museums in New Mexico.
LoboVault is UNM's Institutional Repository. It hosts scholarly publications from UNM faculty, graduate student theses and dissertations from 2009 through the present, UNM administrative records, and more.
Research Guides cover a variety of subject areas. A great place to start your research.Celebrating New Mexico Statehood
Cultural heritage materials from 12 New Mexico institutions are available here, including photographs, documents, maps, posters, art, music and video.Tony Hillerman Portal
This portal hosts digital reproductions of Hillerman's manuscripts, screenplays and papers, as well as a complete catalog of his published works.New Mexico Digital Newspapers
Over 200,000 pages of historical newspapers from New Mexico can be found here.
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Jul. 14, 12:00 PM - Jul. 14, 1:00 PM
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Tony Hillerman on Film
Jul. 24, 2:45 PM - Jul. 24, 3:45 PM
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Graduate Student Stephanie Mack discusses Tony Hillerman's novels
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Scholars working in the humanities will see immediate benefit
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Wall, Pierce get Wiz past Raptors 106-99 for 3-0 series lead
Latos has best outing of year to help Marlins top Nats 3-2
Holt's 8th-inning HR lifts Red Sox past skidding Orioles 7-5
Hutchison gets win, Blue Jays beat Orioles 7-6
Capitals beat Islanders, Halak 5-1 for 3-2 series lead
Apr. 23rd Sportstalk: Doug Speaks
Super Bowl MVP Doug Williams joins Alex Parker to discuss the Dare to Care event, plus his thoughts on Robert Griffin III. Plus, Washington Post reporter Jorge Castillo on if the Wizards can close out their series vs. Toronto.
Wacha outdoes Scherzer as Cardinals beat Nationals 4-1
DC Sports; Hogan's Decisions; Dulles Airport Losing PassengersComment
Today on NewsTalk:
DC Pro Sports reporter Tom Threlkeld discussed last night's big wins for the Caps, Wizards, and Nats,
Montgomery County Executive Ike Leggett talked about the hit MCPS will take if Gov. Hogan withholds funds approved by the General Assembly.
And Washington Post reporter Lori Aratani weighed in on why Dulles Airport is losing passengers to National and BWI.
Watch today's full hour in the clips below.
Wong's tiebreaking double in 8th helps Cardinals top Nats
Travis and Smoak homer, Blue Jays beat Orioles 4-2
Apr. 22nd Sportstalk: Earth Gray
Radio show host, and local sports journalist Mark Gray joins Alex Parker to discuss the DC sports 'trifecta' on April 21st. Plus, finally for Terps vs. Hoyas!
Local youth basketball team loses nearly $2K after travel league folds
Apr. 19th Sportstalk: DC Legends
Alex Parker has 1-on-1 interviews from the Washington Sports Hall of Fame induction day at Nationals Park. Plus, who are your favorite DC sports Legends?
Wall has 26 points, 17 assists, Wizards rout Raptors 117-106
Encarnacion hits 2 home runs, Blue Jays beat Orioles 13-6
Escobar's HR in 10th lifts Nationals over Cardinals 2-1
Backstrom seals Capitals' 2-1 overtime win over Isles
Apr. 20th Sportstalk: Upsets or Chalk?
Glenn Harris is joined by Howard Head Basketball Coach Kevin Nickelberry to breakdown the 1st Round of the NBA Playoffs. Plus, a recap on Howard basketball.
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Inside Toronto.CTVNews.ca
Latest News
- Teen in critical condition after falling off bike in Etobicoke
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PICTURES: Thousands gathered on Saturday night to watch the Bloor Viaduct light up in celebration of the upcoming Pan Am...Posted by CTV Toronto on Sunday, 5 July 2015