Omega-3-rasvahappojen käyttö nivelrikkoisten koirien hoidossa

Nivelrikko on koirilla yleinen sairaus. Sen hoitoon yleisesti käytettävien tulehduskipulääkkeiden rinnalle etsitään hoitomuotoja tulehduskipulääkkeiden pitkäaikaiskäytöstä johtuvien haittavaikutusten takia. Tutkimuksemme tavoite oli selvittää omega-3-rasvahappojen käytön hyötyä nivelrikkoisten koirien hoidossa. Tutkimuksen alkuhetkellä tutkimusta vastaavasta aiheesta koirilla ei ollut tehty. Ihmisillä reumatoidin artriitin hoidossa omega-3-rasvahapoilla on todettu olevan positiivisia vaikutuksia, joten siihen viitaten myös nivelrikkoisilla koirilla saattaisi olla hyötyä omega-3-rasvahappojen käytöstä. Omega-3-rasvahapoilla on todettu olevan positiivisia vaikutuksia useisiin tulehduksellisiin sairauksiin. Tutkimushypoteesimme oli, että kalaöljyä syövän ryhmän kohtisuora maksimaalinen voima askelvoimalevyllä kasvaisi ja ryhmän arvioitu kivuliaisuus laskisi tutkimuksen aikana. Tutkimamme tuote oli omega-3-rasvahapporavintolisä (Doils® Nivelet, Nutraceuticoils, Belgia). Tutkimus oli satunnaistettu, kaksoissokkoutettu ja kontrolloitu kliininen tutkimus. Tutkimukseen haettiin koiria ilmoitusten perusteella. Alkukyselyn ja seulontakäynnin perusteella tutkimuksen aloitti 77 koiraa. Seulontakäynnillä koirille tehtiin kliininen yleistutkimus, ortopedinen tutkimus, suppea neurologinen tutkimus, röntgenkuvaus, askelvoimalevymittaus sekä verinäytteenotto. Koirat kävivät varsinaisen tutkimuksen aikana kahdella lähikäynnillä. Molemmilla kerroilla koirille suoritettiin röntgenkuvausta lukuun ottamatta samat toimenpiteet kuin seulontakäynnillä. Tutkimuksen aikana omistajat täyttivät kyselykaavakkeita yhteensä seitsemän kertaa. Tutkimuksessa arvioitiin nivelrikkoisten koirien kipua sekä omistajan että eläinlääkärin arvioiden avulla sekä askelvoimalevyn avulla. Arviointimenetelmistä saatuja tuloksia olivat omistajan täyttämästä kyselykaavakkeesta kipuindeksin kyselyn tulokset, liikkumisvaikeuksista kertova VAS, elämänlaadusta kertova VAS, varakipulääkkeiden käyttö, vertailevat kysymykset, omistajan arvio valmisteen tehosta ja koiran ryhmästä, eläinlääkärin arvio sekä askelvoimalevyltä saadut kaksi muuttujaa (kohtisuora maksimaalinen voima ja impulssi). Tutkimustuloksissa havaittiin omega-3-rasvahappojen käytössä nivelrikkoisten koirien hoidossa pieni hyöty. Kalaöljyryhmän ja lumeryhmän välillä ei havaittu tilastollisesti merkitsevää eroa. Ryhmien sisällä havaittiin muutamia tilastollisesti merkitseviä muutoksia. Kipuindeksin muutos paremmaksi kalaöljyryhmässä tutkimuksen aikana oli vahvasti tilastollisesti merkitsevä muutos (p=0,002). Myös askelvoimalevyn kohtisuoran maksimaalisen voiman parantuminen oli vahvasti tilastollisesti merkitsevä muutos kalaöljyä syöneessä ryhmässä(p=0,001). Myös lumeryhmässä oli kipuindeksissä ja askelvoimalevyn kohtisuorassa maksimaalisessa voimassa havaittavissa tilastollisesti merkitsevä trendi (p=0,07 & p=0,059), mutta p-arvot eivät yltäneet tilastolliseen merkitsevyyteen. Suuremmalla otoskoolla näissä muuttujissa olisi voitu havaita joko tilastollisesti merkitseviä eroja ryhmien välillä tai sitten olisimme voineet osoittaa molemmissa ryhmissä tapahtuneen positiivisia eli parantavia muutoksia. Tutkimuksessa ei havaittu sivuvaikutuksia kalaöljyryhmässä. Tutkimustulokset todistivat tutkimushypoteesimme heikosti todeksi. Omega-3-rasvahappoja voisi siis hyvin käyttää koirilla, joille ei sovi kipulääkkeet.

Structure of 6,5'-anhydro-6-hydroxy-2',3' O-isopropylideneuridine

CI2HI4N206, Mr=282"3, orthorhombic,P21212 t, a = 10.412 (2), b = 14.936 (2), c =16.651(3),/k, V=2589.46A 3, Z--8, Din= 1.450, D x = 1.447 Mg m -3, 2(Cu Kct) = 1.5418/~, # =0.902mm -~, F(000)-- 1184.00, T= 293 K, R = 0.039, wR--0.038 for 2548 unique reflections with F > 3a(F). The two crystallographically independent molecules in the asymmetric unit have similar geome-tries with the ribose ring having an O(4')-exo, C(4')-endo pucker and the uracil base in the anti conformation.The geometry about the exocyclic C(4')-C(5') bond in both molecules is gauche-gauche. The dioxolane ring assumes twist conformations in both molecules.

Temperature and thiol-induced desensitization of a Ca2+-sensitive cyclic-3',5'-nucleotide phosphodiesterase from sheep lung

Ca2+-sensitivity of sheep lung cyclic-3',5'-nucleotide phosphodiesterase is provided by endogenous tightly bound calmodulin. The calcium sensitivity of a highly purified enzyme was desensitized by increasing the assay temperature. It could also be desensitized to Ca2+-activation by thiols such as dithiothreitol. The thiol-induced desensitization could be partially reversed by dialysis and almost completely reversed by dilution. The results presented in this paper indicate that thiols are possibly involved in the interaction of calmodulin with cyclic-3',5'-nucleotide phosphodiesterase. This is the first report on temperature and thiol-induced desensitization of Ca2+-sensitivity of a cyclic-3',5'-nucleotide phosphodiesterase.

Desensitization to ATP-Mg inhibition of 3-hydroxy-3-methylglutarylCoA reductase by heat treatment of microsomes

HMGCoA reductase is found to be inhibited by palmitylCoA and free CoA. The inhibition of this enzyme by ATP-Mg, but not by palmityl CoA, is lost on preincubation of microsomes at 50°C for 15 min.

Identifying N60D mutation in omega subunit of Escherichia coli RNA polymerase by bottom-up proteomic approach

Escherichia coli RNA polymerase is a multi-subunit enzyme containing alpha(2)beta beta'omega sigma, which transcribes DNA template to intermediate RNA product in a sequence specific manner. Although most of the subunits are essential for its function, the smallest subunit omega (average molecular mass similar to 10,105 Da) can be deleted without affecting bacterial growth. Creating a mutant of the omega subunit can aid in improving the understanding of its role. Sequencing of rpoZ gene that codes for omega subunit from a mutant variant suggested a substitution mutation at position 60 of the protein: asparagine (N) -> aspartic acid (D). This mutation was verified at the protein level by following a typical mass spectrometry (MS) based bottom-up proteomic approach. Characterization of in-gel trypsin digested samples by reverse phase liquid chromatography (LC) coupled to electrospray ionization (ESI)-tandem mass spectrometry (MS/MS) enabled in ascertaining this mutation. Electron transfer dissociation (ETD) of triply charged (M + 3H)(3+)] tryptic peptides (residues 53-67]), EIEEGLINNQILDVR from wild-type and EIEEGLIDNQILDVR from mutant, facilitated in unambiguously determining the site of mutation at residue 60.

Crystallographic identification of a ‘stepped-cubane’ structure for the Cu4O4 core in [Cu4L2(bipy)4(µ3-OH)2][ClO4]4(HL = 5-hydroxy-6-methylpyridine-,4-dimethanol, bipy = 2,2′-bipyridine)

The structure of [Cu4L2(bipy)4(µ3-OH)2][ClO4]4 containing a Vitamin B6 ligand, pyridoxine (5-hydroxy-6-methylpyridine-3,4-dimethanol, HL), and 2,2′-bipyridine (bipy) has been determined by single-crystal X-ray analysis. This is the first report on a copper(II) complex having a ‘stepped-cubane’ structure. The compound crystallizes in the triclinic space group P[1 with combining macron](Z= 1) with a= 11.015(3), b= 11.902(1), c= 13.142(2)Å, α= 105.07(1), β= 102.22(1) and γ= 99.12(1)°; R= 0.054). The co-ordination geometry around each copper is trigonally distorted square pyramidal. Two of the basal sites are occupied by bipyridyl nitrogens in a bidentate fashion. The remaining basal positions for Cu(1) are filled by a phenolic oxygen and a 4-hydroxymethyl oxygen of the L moiety, whereas for Cu(2) they are occupied by two µ3-OH oxygens. The axial sites are occupied by a µ3-OH oxygen and the 4-hydroxymethyl oxygen of the same pyridoxine for Cu(1) and Cu(2), respectively. Both the bridging nature of the 4-hydroxymethyl oxygen of the L moiety and the unsymmetrical bridging nature of the µ3-OH groups with axial–equatorial bridging are novel features. The structure is discussed in relation to stepped-cubane structures reported in the literature. A comparative study is also made with µ3-hydroxo-bridged copper(II) complexes. Both the plasticity effect of CuII and the stacking interactions between the various rings appear to be important in stabilizing this unusual structure.

Conformational properties of hybrid peptides containing alpha and omega-amino acids

This review briefly surveys the conformational properties of guest omega-amino acid residues when incorporated into host alpha-peptide sequences. The results presented focus primarily on the use of beta- and gamma-residues in alphaomega sequences. The insertion of additional methylene groups into peptide backbones enhances the range of accessible conformations, introducing additional torsional variables. A nomenclature system, which permits ready comparisons between alpha-peptides and hybrid sequences, is defined. Crystal structure determination of hybrid peptides, which adopt helical and beta-hairpin conformations permits the characterization of backbone conformational parameters for beta- and gamma-residues inserted into regular alpha-polypeptide structures. Substituted beta- and gamma-residues are more limited in the range of accessible conformation than their unsubstituted counterparts. The achiral beta,beta-disubstituted gamma-amino acid, gabapentin, is an example of a stereochemically constrained residue in which the torsion angles about the C-beta-C-gamma (theta(1)) and C-alpha-C-beta (theta(2)) bonds are restricted to the gauche conformation. Hybrid sequences permit the design of novel hydrogen bonded rings in peptide structures.

Structural Investigations on Poly(4-hydroxy-L-proline). 2. Physicochemical Studies

We report experimental studies which confirm our prediction, namely that the ordered structure of poly(hydroxypro1ine) in solution corresponds to a left-handed helical structure with intrachain hydrogen bonds. The CD studies show that the poly(hydroxypro1ine) molecule has essentially the same conformation in aqueous solution and in the film obtained subsequently by evaporation. X-ray diffraction patterns of the sample in this form (B form) have been recorded at different relative humidities. The patterns recorded at relative humidities over 66% can be interpreted in terms of a helical structure with intrachain hydrogen bonds. These results lead us to conclude that the ordered conformation of poly(hydroxypro1ine) in solution is form B and not form A. This offers a simple explanation for the greater stability of the poly(hydroxypro1ine) helix in solution as compared to the poly(pro1ine) form I1 helix and also for the absence of mutarotation for poly(hydroxypro1ine).

Structural Investigations on Poly(4-hydroxy-L-proline). 1. Theoretical Studies

Model building studies on poly(hydroxypro1ine) indicate that in addition to the well-known helical structure of form A, a left-handed helical structure with trans peptide units and with h = 2.86 A and n = 2.67 (i.e., 8 residues in 3 turns) is also possible. In this structure which is shown to be in agreement with X-ray data of the form B in the next paper, the y-hydroxyl group of an (i + 1)th Hyp residue is hydrogen bonded to the carbonyl oxygen of an (i - 1)th residue. The possibility of a structure with cis peptide units is ruled out. It is shown that both forms A and B are equally favorable from considerations of intramolecular energies. Since form B is further stabilized by intrachain hydrogen bonds, we believe that this is likely to be the ordered conformation for poly(hydroxypro1ine) in water.

Chemical toughening of epoxies. I. Structural modification of epoxy resins by reaction with hydroxy-terminated poly (butadiene-co-acrylonitrile)

In an attempt to toughen the epoxy resin matrix for fiber-reinforced composite applications, a chemical modification procedure of a commercially available bisphenol-A-based epoxy resin using reactive liquid rubber HTBN [hydroxy-terminated poly(butadiene-co-acrylonitrile)] and TDI (tolylene diisocyanate) is described. The progress of the reaction and the structural changes during modification process are studied using IR spectroscopy, viscosity data, and chemical analysis (epoxy value determination). The studies support the proposition that TDI acts as a coupling agent between the epoxy and HTBN, forming a urethane linkage with the former and an oxazolidone ring with the latter. The chemical reactions that possibly take place during the modification are discussed.

On the possibility of an alpha-sq omega-type dynamo in a thin layer inside the sun

If the solar dynamo operates in a thin layer of 10,000-km thickness at the interface between the convection zone and the radiative core, using the facts that the dynamo should have a period of 22 years and a half-wavelength of 40 deg in the theta-direction, it is possible to impose restrictions on the values which various dynamo parameters are allowed to have. It is pointed out that the dynamo should be of alpha-sq omega nature, and kinematical calculations are presented for free dynamo waves and for dynamos in thin rectangular slabs with appropriate boundary conditions. An alpha-sq omega dynamo is expected to produce a significant poloidal field which does not leak to the solar surface. It is found that the turbulent diffusity eta and alpha-coefficient are restricted to values within about a factor of 10, the median values being eta of about 10 to the 10th sq cm/sec and alpha of about 10 cm/sec. On the basis of mixing length theory, it is pointed out that such values imply a reasonable turbulent velocity of the order 30 m/s, but rather small turbulent length scales like 300 km.

Chemical toughening of epoxies. I. Structural modification of epoxy resins by reaction with hydroxy-terminated poly(butadiene-co-acrylonitrile)

In an attempt to toughen the epoxy resin matrix for fiber-reinforced composite applications, a chemical modification procedure of a commercially available bisphenol-A-based epoxy resin using reactive liquid rubber HTBN [hydroxy-terminated poly(butadiene-co-acrylonitrile)] and TDI (tolylene diisocyanate) is described. The progress of the reaction and the structural changes during modification process are studied using IR spectroscopy, viscosity data, and chemical analysis (epoxy value determination). The studies support the proposition that TDI acts as a coupling agent between the epoxy and HTBN, forming a urethane linkage with the former and an oxazolidone ring with the latter. The chemical reactions that possibly take place during the modification are discussed.