Ocular and systemic bio-distribution of rhodamine-conjugated liposomes loaded with VIP injected into the vitreous of Lewis rats.

PURPOSE: Local delivery of therapeutic molecules encapsulated within liposomes is a promising method to treat ocular inflammation. The purpose of the present study was to define the biodistribution of rhodamine-conjugated liposomes loaded with vasoactive intestinal peptide (VIP), an immunosuppressive neuropeptide, following their intravitreal (IVT) injection in normal rats. METHODS: Healthy seven- to eight-week-old Lewis male rats were injected into the vitreous with empty rhodamine-conjugated liposomes (Rh-Lip) or with VIP-loaded Rh-Lip (VIP-Rh-Lip; 50 mM of lipids with an encapsulation efficiency of 3.0+/-0.4 mmol VIP/mol lipids). Twenty-four h after IVT injection, the eyes, the cervical, mesenteric, and inguinal lymph nodes (LN), and spleen were collected. The phenotype and distribution of cells internalizing Rh-Lip and VIP-Rh-Lip were studied. Determination of VIP expression in ocular tissues and lymphoid organs and interactions with T cells in cervical LN was performed on whole mounted tissues and frozen tissue sections by immunofluorescence and confocal microscopy. RESULTS: In the eye, 24 h following IVT injection, fluorescent liposomes (Rh-Lip and VIP-Rh-Lip) were detected mainly in the posterior segment of the eye (vitreous, inner layer of the retina) and to a lesser extent at the level of the iris root and ciliary body. Liposomes were internalized by activated retinal Müller glial cells, ocular tissue resident macrophages, and rare infiltrating activated macrophages. In addition, fluorescent liposomes were found in the episclera and conjunctiva where free VIP expression was also detected. In lymphoid organs, Rh-Lip and VIP-Rh-Lip were distributed almost exclusively in the cervical lymph nodes (LN) with only a few Rh-Lip-positive cells detected in the spleen and mesenteric LN and none in the inguinal LN. In the cervical LN, Rh-Lip were internalized by resident ED3-positive macrophages adjacent to CD4 and CD8-positive T lymphocytes. Some of these T lymphocytes in close contact with macrophages containing VIP-Rh-Lip expressed VIP. CONCLUSIONS: Liposomes are specifically internalized by retinal Müller glial cells and resident macrophages in the eye. A limited passage of fluorescent liposomes from the vitreous to the spleen via the conventional outflow pathway and the venous circulation was detected. The majority of fluorescent liposomes deposited in the conjunctiva following IVT injection reached the subcapsular sinus of the cervical LN via conjuntival lymphatics. In the cervical LN, Rh-Lip were internalized by resident subcapsular sinus macrophages adjacent to T lymphocytes. Detection of VIP in both macrophages and T cells in cervical LN suggests that IVT injection of VIP-Rh-Lip may increase ocular immune privilege by modulating the loco-regional immune environment. In conclusion, our observations suggest that IVT injection of VIP-loaded liposomes is a promising therapeutic strategy to dampen ocular inflammation by modulating macrophage and T cell activation mainly in the loco-regional immune system.

Classical parameters of Shadowlands by Richard Attenborough (On C. S. Lewis's Life and Work)

The aim of this article is to show the classical parameters of Shadowlands by R. Attenborough, with a screenplay by W. Nicholson, on C. S. Lewis's life and work. Based upon an accurate reading of Lewis's works, the author of this article proposes to interpret the opposition Lewis / Gresham as the translation into the real life of the opposition between the Platonic or idealistic and the Aristotelian or materialistic temperaments which was already maintained by Coleridge. In any case, there are many classical references which must be taken into account in order to understand to what extent C. S. Lewis's Christianity is also a classic Christianity, that is, a Greek and Latin one.

Cocoa flavonoid-enriched diet modulates systemic and intestinal immunoglobulin synthesis in adult Lewis rats

Previous studies have reported that a diet containing 10% cocoa, a rich source of flavonoids, has immunomodulatory effects on rats and, among others effects, is able to attenuate the immunoglobulin (Ig) synthesis in both systemic and intestinal compartments. The purpose of the present study was focused on investigating whether these effects were attributed exclusively to the flavonoid content or to other compounds present in cocoa. To this end, eight-week-old Lewis rats were fed, for two weeks, either a standard diet or three isoenergetic diets containing increasing proportions of cocoa flavonoids from different sources: one with 0.2% polyphenols from conventional defatted cocoa, and two others with 0.4% and 0.8% polyphenols, respectively, from non-fermented cocoa. Diet intake and body weight were monitored and fecal samples were obtained throughout the study to determine fecal pH, IgA, bacteria proportions, and IgA-coated bacteria. Moreover, IgG and IgM concentrations in serum samples collected during the study were quantified. At the end of the dietary intervention no clear changes of serum IgG or IgM concentrations were quantified, showing few effects of cocoa polyphenol diets at the systemic level. However, in the intestine, all cocoa polyphenol-enriched diets attenuated the age-related increase of both fecal IgA and IgA-coated bacteria, as well as the proportion of bacteria in feces. As these effects were not dependent on the dose of polyphenol present in the diets, other compounds and/or the precise polyphenol composition present in cocoa raw material used for the diets could be key factors in this effect.

Studies of the association of the A, B and Lewis Blood group antigens with carcinoembryonic antigen (CEA).

Carcinoembryonic antigen (CEA) was purified from primary tumour or from hepatic metastases obtained from ten cases of carcinoma of the colon. In nine cases the blood group antigens A, B, Lea or Leb were detected in CEA preparations by the binding of 125I-labelled CEA by blood group antibodies. The extent of binding appeared to preclude simple contamination of CEA preparations by blood group glycoprotein. In all cases the blood group antigens detected were consistent with the patients' known blood groups. Blood group I and i activities were not detected. It is concluded that the determinants of A, B and Lewis antigens and of CEA share the same glycoprotein carrier molecules.

Applications of optically active metallacycles: new useful materials for the determination of the enantiomeric excess of Lewis bases and as resolving agents for monodentate phosphines

Es descriu la síntesi de nous compostos ciclopal·ladats derivats d'imines i amines primàries, òpticament actius, així com les seves aplicacions per a la determinació de l'excés enantiomèric i per a la resolució de bases de Lewis. També es comenta la síntesi i resolució de noves fosfines P-quirals, així com la seva aplicació a processos de catàlisi asimètrica. A més, es descriu la preparació d'algunes fosfines secundàries quirals i s'estudia la seva estabilitat configuracional.

Strain-dependent effects of diazepam and the 5-HT2B/2C receptor antagonist SB 206553 in spontaneously hypertensive and Lewis rats tested in the elevated plus-maze

The 5-HT2B/2C receptor antagonist SB 206553 exerts anxiolytic effects in rat models of anxiety. However, these effects have been reported for standard rat strains, thus raising the issue of SB 206553 effects in rat strains displaying different levels of anxiety. Herein, the effects of SB 206553 in a 5-min elevated plus-maze test of anxiety were compared to those of the reference anxiolytic, diazepam, in two rat strains respectively displaying high (Lewis rats) and low (spontaneously hypertensive rats, SHR) anxiety. Diazepam (0.37, 0.75, or 1.5 mg/kg; 30 min before testing) increased in a dose-dependent manner the behavioral measures in SHR, but not in Lewis rats. On the other hand, SB 206553 (1.25, 2.5, or 5 mg/kg; 30 min before testing) failed to alter the anxiety parameters in both strains, whereas it increased closed arm entries in Lewis rats, suggesting that it elicited hyperactivity in the latter strain. Accordingly, the hypolocomotor effect of the nonselective 5-HT2B/2C receptor agonist m-chlorophenylpiperazine (1.5 mg/kg ip 20 min before a 15-min exposure to an activity cage) was prevented by the 1.25 and 2.5 mg/kg doses of SB 206553 in Lewis rats and SHR, respectively. Compared with SHR, Lewis rats may display a lower response to benzodiazepine-mediated effects and a more efficient control of locomotor activity by 5-HT2B/2C receptors.

Iron(III) as Lewis acid catalyst in organosilicon and carbonyl chemistry

Iron is one of the most common elements in the earth’s crust and thus its availability and economic viability far exceed that of metals commonly used in catalysis. Also the toxicity of iron is miniscule, compared to the likes of platinum and nickel, making it very desirable as a catalyst. Despite this, prior to the 21st century, the applicability of iron in catalysis was not thoroughly investigated, as it was considered to be inefficient and unselective in desired transformations. In this doctoral thesis, the application of iron catalysis in combination with organosilicon reagents for transformations of carbonyl compounds has been investigated together with insights into iron catalyzed chlorination of silanes and silanols. In the first part of the thesis, the synthetic application of iron(III)-catalyzed chlorination of silanes (Si-H) and the monochlorination of silanes (SiH2) using acetyl chloride as the chlorine source is described. The reactions proceed under ambient conditions, although some compounds need to be protected from excess moisture. In addition, the mechanism and kinetics of the chlorination reaction are briefly adressed. In the second part of this thesis a versatile methodology for transformation of carbonyl compounds into three different compound classes by changing the conditions and amounts of reagents is discussed. One pot reductive benzylation, reductive halogenation and reductive etherification of ketones and aldehydes using silanes as the reducing agent, halide source or cocatalyst, were investigated. Also the reaction kinetics and mechanism of the reductive halogenation of acetophenone are briefly discussed.

Captain Lewis Warrington and others : memorial of Lewis Warrington, Captain in the U.S. Navy, (in behalf of himself and the officers and crew of the U.S. sloop-of-war Peacock); praying that the one half of the proceeds of the Epervier and goods which went into the officers and crew of said vessel, it having been decreed to them by the United States court as captors. April 26, 1848.--

Caption title.

Grant of Permission for lease of military lands from Sir Robert Prescott to Thomas Clark, 1798-1801.

Transcript (original spelling and grammar retained): By His Excellency Robert Prescott Esquire, Captain General and Governor in Chief in and over His Majestys Provinces of Upper and Lower Canada, General and Commander in Chief of all His Majesty’s forces in the Provinces of Upper and Lower Canada, Nova Scotia, New Brunswick and their several Dependencies and in the Island of Newfoundland &ca. &ca. &ca. I do hereby authorise and permit Thomas Clark of Queenstown in the County of Lincoln in the Province of Upper Canada merchant to take possession of all that Lot, piece and parcel of Land (being part of the land reserved by his Majesty for Military purposes) situate, lying and being at Queenstown in the Township of Newark, in the Home District in the said Province of Upper Canada, bounded and abutted as follows, that is to say beginning at the Distance of two Chains and ninety links from the South East End of his Majesty’s Store House, the said distance being measured along the Bank up Stream, thence South thirty nine degrees and an half West one Chain and fifty links thence south fifty degrees and an half East one Chain and thirty links thence North thirty nine degrees and an half East to the Edge of the Bank and from thence along the Bank to the place of beginning, containing thirty one perches and one hundred and twenty five square links and to occupy and hold the said Lot, piece and parcel of Land during pleasure subject nevertheless to the provisoes and Conditions herein after contained, that is to say. First on condition that it shall and may be lawful to and for His Majesty his Heirs and Successors and to and for the Commander in Chief of His Majesty Forces for the time being and to and for the Officer commanding his Majesty’s Forces in Upper Canada for the time being and to and for either of them to determine and make void this present permission to occupy during pleasure the said Lot, Piece or Parcel of Land above described at any time hereafter whenever he or they shall see fit so to do without any compensation or indemnification to the said Thomas Clark or any other Person or Persons whosoever for any Loss Injury or Damage which he the said Thomas Clark or any other Person or Persons whosoever may thereby sustain. Secondly on this further Condition that it shall and may be lawful to and for His Majesty his Heirs and Successors and to and for his and their Officers, Soldiers and Servants at any time hereafter by order of the Commander in Chief of His Majesty’s Forces for the time being or by order of the Officer commanding his Majesty’s forces in Upper Canada for the time being or by order of the Officer of His Majesty’s Corps of Royal Engineers commanding in the said Province of Upper Canada for the time being to enter upon the said Lot Piece and parcel of Land which the said Thomas Clark is hereby permitted to occupy during pleasure or upon any part thereof and to take down and from the said Lot piece and parcel of Land or from any part thereof to remove any dwelling House Store or other Buildings on the said Lot, piece or Parcel of Land or any part thereof erected and to remove any goods or Chattels on the said Lot piece and parcel of Land or on any part thereof or on any such dwelling House Store or other building found or being and that His Majesty his Heirs and Successors or any other Person or Persons whosoever shall not be liable or responsible to the said Thomas Clark or to any other Person or Persons whosoever for any Loss, Injury or Damage which he or they shall or may in such case sustain. Thirdly on this further Condition that the said Thomas Clark shall not erect on the said Lot Piece or Parcel of Land which the said Thomas Clark is hereby permitted to occupy during pleasure or upon any part thereof at any time or times hereafter any dwelling House store or other Building whatsoever of Stone or brick or of any other materials wood only exccepted and that if any dwelling House or Store or other building of Stone or brick or of any other materials except wood shall at any time be erected on the said Lot, piece or parcel of Land or upon any part thereof, then and in such case, this present permission and every Clause and Article thereof shall from thenceforth cease and determine and be absolutely and entirely null and void. And lastly on this further Condition that the said Thomas Clark or any other Person whosoever shall not assign this permission to occupy the said Lot, Piece or Parcel of Land above described to any Person of Persons whosoever, and if any such assignment shall be made by the said Thomas Clark or by any other Person in his right, or on his behalf, that then and in such case such assignment and this permission to occupy during pleasure the said Lot piece and parcel of Land above described, and every Clause and Article thereof shall from thenceforth cease and determine and be absolutely and entirely null and void. Given under my hand at the Castle of St. Lewis in the City of Quebec in the Province of Lower Canada this Ninth day of July in the year of our Lord one thousand seven hundred and ninety eight and in the thirty eighth year of His Majesty’s Reign. [Signed here by Robert Prescott] By Order of the Commander in Chief [Signed here by James Green (Illegible signature)] I the said Thomas Clark above named do hereby accept the above written Permission to occupy during pleasure the said Lot piece and parcel of Land above described upon and subject to the several Provisioes and Conditions above written and each and every of them severally and respectively. In witness whereof I have hereunto set my hand the Sixteenth day of August in the year of our Lord one thousand seven hundred and ninety eight and in the thirty eighth year of His Majesty’s Reign. [Signed here by Thomas Clark] Signed in the presence of [Illegible signature – looks like J. M Donell Lt. Col.] [Illegible – looks like 2d. Battn R. C. Sm?] [Signed here by C. Anderson] Whereas Inconveniences did arise from the peculiar situation of the Ground contiguous to the above described Lot of Land and the occupation thereof, if estimated by the above Limits would prove highly disadvantageous to Mr. Thomas Clark be it known that in consideration thereof we do permit the above Lot to extend one half Chain more in length up stream so as to comprehend the space allowed for the Road between Lots Two + Three, and we do hereby appropriate the said additional space wholly to the use of the said Thomas Clark. In witness whereof we have hereunto subscribed this Thirteenth Day of October in the Year of our Lord one thousand Eight Hundred and one. [Signed here by J. M’Donell Lt. Col] 2d. Battn. R. C. [in?] Com of Fort George + Dependencies Robt. Pilkington Captain Royal Engineers

Probate (copy) of the Last Will and Testament of Thomas Clark Street of Stamford Township

Probate (copy) of the Last Will and Testament of Thomas Clark Street of Stamford Township. This is a printed copy which is signed by Charles A. Mittleberger, student at law, Oct. 18, 1872.

Indenture Land Sold by Thomas Clark to Lewis Clement, 1817

Indenture regarding land sold by Thomas Clark of Stamford Township to Lewis Clement of Niagara Township. The land includes 50 acres in the northern half of Lot 58 in Niagara Township - instrument no. 5356, January 17, 1817.