The Rheumatoid Shoulder: Current Surgical Treatments

Background: Rheumatoid arthritis (RA) is an inflammatory disease resulting in pain and decreased functional outcome. Even though most of large joints are widely discussed in literature, shoulder’s surgical treatment options, indications and superiorities to each other were not compared entirely

Synthesis and photophysical properties of phthalocyanines having calixpyrrole units

Zn2+ and Co2+ metallated phthalocyanines having four calixpyrrole units have been prepared from a calixpyrrole phthalonitrile using Zn2+ or Co2+ salts as templates of a phthalocyanine macrocycle. Hostguest complexes between the anions (Cl-, F- and H2PO4-) and the calixpyrrole units are formed as evidenced by NMR, the shift in the reduction potential of the calixpyrrole units by cyclic voltammetry and by observation of two straight lines in the plot of the conductivity versus the amount of halide. While halides do not form complexes with Zn2+ or Co2+ ions of the phthalocyanine core in the ground state as evidenced by the lack of variation in the position of the Q-band in optical spectroscopy, upon 355 nm excitation, the apical metal-halide complex should be formed as a transient as evidenced by the comparison of the transient absorption spectra in the presence and absence of halides.Financial support from the Ministry of Science and Innovation of Spain, (CTQ 2012-2013) is gratefully acknowledged. P.A. also thanks the Spanish Ministry of Science and Innovation by a Ramon y Cajal research associate contract (RYC-2012-10702) and the UPV for the grant PAID-06-12.Erol, ZN.; Atienzar Corvillo, PE.; Arslanoglu, Y.; Hamuryudan, E.; García Gómez, H. (2015). Synthesis and photophysical properties of phthalocyanines having calixpyrrole units. RSC ADVANCES. 5(69):55901-55908. https://doi.org/10.1039/c5ra05830a5590155908569Bottari, G., de la Torre, G., Guldi, D. M., & Torres, T. (2010). Covalent and Noncovalent Phthalocyanine−Carbon Nanostructure Systems: Synthesis, Photoinduced Electron Transfer, and Application to Molecular Photovoltaics. Chemical Reviews, 110(11), 6768-6816. doi:10.1021/cr900254zClaessens, C. G., Hahn, U., & Torres, T. (2008). Phthalocyanines: From outstanding electronic properties to emerging applications. The Chemical Record, 8(2), 75-97. doi:10.1002/tcr.20139Elemans, J. A. A. W., van Hameren, R., Nolte, R. J. M., & Rowan, A. E. (2006). Molecular Materials by Self-Assembly of Porphyrins, Phthalocyanines, and Perylenes. Advanced Materials, 18(10), 1251-1266. doi:10.1002/adma.200502498De la Torre, G., Vázquez, P., Agulló-López, F., & Torres, T. (2004). Role of Structural Factors in the Nonlinear Optical Properties of Phthalocyanines and Related Compounds. Chemical Reviews, 104(9), 3723-3750. doi:10.1021/cr030206tLiddell, P. A., Kuciauskas, D., Sumida, J. P., Nash, B., Nguyen, D., Moore, A. L., … Gust, D. (1997). Photoinduced Charge Separation and Charge Recombination to a Triplet State in a Carotene−Porphyrin−Fullerene Triad. Journal of the American Chemical Society, 119(6), 1400-1405. doi:10.1021/ja9631054Cid, J.-J., García-Iglesias, M., Yum, J.-H., Forneli, A., Albero, J., Martínez-Ferrero, E., … Torres, T. (2009). Structure-Function Relationships in Unsymmetrical Zinc Phthalocyanines for Dye-Sensitized Solar Cells. Chemistry - A European Journal, 15(20), 5130-5137. doi:10.1002/chem.200801778Morimune, T., Kajii, H., & Ohmori, Y. (2006). Photoresponse Properties of a High-Speed Organic Photodetector Based on Copper–Phthalocyanine Under Red Light Illumination. IEEE Photonics Technology Letters, 18(24), 2662-2664. doi:10.1109/lpt.2006.887786Moore, T. A., Gust, D., Mathis, P., Mialocq, J.-C., Chachaty, C., Bensasson, R. V., … Moore, A. L. (1984). Photodriven charge separation in a carotenoporphyrin–quinone triad. Nature, 307(5952), 630-632. doi:10.1038/307630a0Sürgün, S., Arslanoğlu, Y., & Hamuryudan, E. (2014). Synthesis of non-peripherally and peripherally substituted zinc (II) phthalocyanines bearing pyrene groups via different routes and their photophysical properties. Dyes and Pigments, 100, 32-40. doi:10.1016/j.dyepig.2013.07.027Adriaenssens, L., Estarellas, C., Vargas Jentzsch, A., Martinez Belmonte, M., Matile, S., & Ballester, P. (2013). Quantification of Nitrate−π Interactions and Selective Transport of Nitrate Using Calix[4]pyrroles with Two Aromatic Walls. Journal of the American Chemical Society, 135(22), 8324-8330. doi:10.1021/ja4021793Sessler, J. L., Kral, V., Shishkanova, T. V., & Gale, P. A. (2002). Cytosine substituted calix[4]pyrroles: Neutral receptors for 5’-guanosine monophosphate. Proceedings of the National Academy of Sciences, 99(8), 4848-4853. doi:10.1073/pnas.062633799Lee, C.-H., Na, H.-K., Yoon, D.-W., Won, D.-H., Cho, W.-S., Lynch, V. M., … Sessler, J. L. (2003). Single Side Strapping:  A New Approach to Fine Tuning the Anion Recognition Properties of Calix[4]pyrroles. Journal of the American Chemical Society, 125(24), 7301-7306. doi:10.1021/ja029175uYoung, J. G., & Onyebuagu, W. (1990). Synthesis and characterization of di-disubstituted phthalocyanines. The Journal of Organic Chemistry, 55(7), 2155-2159. doi:10.1021/jo00294a032Aydogan, A., & Akar, A. (2012). Tri- and Pentacalix[4]pyrroles: Synthesis, Characterization and Their Use in the Extraction of Halide Salts. Chemistry - A European Journal, 18(7), 1999-2005. doi:10.1002/chem.201101605Alvaro, M., Atienzar, P., de la Cruz, P., Delgado, J. L., Troiani, V., Garcia, H., … Echegoyen, L. (2006). Synthesis, Photochemistry, and Electrochemistry of Single-Wall Carbon Nanotubes with Pendent Pyridyl Groups and of Their Metal Complexes with Zinc Porphyrin. Comparison with Pyridyl-Bearing Fullerenes. Journal of the American Chemical Society, 128(20), 6626-6635. doi:10.1021/ja057742iD’Souza, F., Smith, P. M., Gadde, S., McCarty, A. L., Kullman, M. J., Zandler, M. E., … Ito, O. (2004). Supramolecular Triads Formed by Axial Coordination of Fullerene to Covalently Linked Zinc Porphyrin−Ferrocene(s):  Design, Syntheses, Electrochemistry, and Photochemistry. The Journal of Physical Chemistry B, 108(31), 11333-11343. doi:10.1021/jp0485688Nyokong, T. (2007). Effects of substituents on the photochemical and photophysical properties of main group metal phthalocyanines. Coordination Chemistry Reviews, 251(13-14), 1707-1722. doi:10.1016/j.ccr.2006.11.011Owens, J. W., Smith, R., Robinson, R., & Robins, M. (1998). Photophysical properties of porphyrins, phthalocyanines, and benzochlorins. Inorganica Chimica Acta, 279(2), 226-231. doi:10.1016/s0020-1693(98)00137-6Durmuş, M., & Nyokong, T. (2008). Photophysicochemical and fluorescence quenching studies of benzyloxyphenoxy-substituted zinc phthalocyanines. Spectrochimica Acta Part A: Molecular and Biomolecular Spectroscopy, 69(4), 1170-1177. doi:10.1016/j.saa.2007.06.029Idowu, M., & Nyokong, T. (2009). Photophysicochemical and fluorescence quenching studies of tetra- and octa-carboxy substituted silicon and germanium phthalocyanines. Journal of Photochemistry and Photobiology A: Chemistry, 204(1), 63-68. doi:10.1016/j.jphotochem.2009.02.002J. C. Scaiano , CRC handbook of organic photochemistry, ed. J. C. Scaiano, CRC Press, Boca Raton, Fla, 1989J. Mack and M. J.Stillman, in The Porphyrin Handbook, ed. K. M. Kadish, K. M. Smith and R. Guilard, Academic Press, Amsterdam, 2003, pp. 43–116, 10.1016/b978-0-08-092390-1.50008-4Bohne, C. (2014). Supramolecular dynamics. Chem. Soc. Rev., 43(12), 4037-4050. doi:10.1039/c3cs60352kBarra, M., Bohne, C., & Scaiano, J. C. (1991). STUDY OF XANTHONE-CYCLODEXTRIN INCLUSION COMPLEXES IN THE SOLID STATE USING TIME-RESOLVED DIFFUSE REFLECTANCE-LASER FLASH PHOTOLYSIS. Photochemistry and Photobiology, 54(1), 1-5. doi:10.1111/j.1751-1097.1991.tb01977.xBarra, M. (1997). Deuterium Isotope Effect on the Complexation of β-Cyclodextrin and Triplet Xanthone in Aqueous Solution. Supramolecular Chemistry, 8(4), 263-266. doi:10.1080/10610279708034944Scaiano, J. C. (1980). Solvent effects in the photochemistry of xanthone. Journal of the American Chemical Society, 102(26), 7747-7753. doi:10.1021/ja00546a018Ogunsipe, A., & Nyokong, T. (2004). Effects of substituents and solvents on the photochemical properties of zinc phthalocyanine complexes and their protonated derivatives. Journal of Molecular Structure, 689(1-2), 89-97. doi:10.1016/j.molstruc.2003.10.024D’Souza, F., & Ito, O. (2005). Photoinduced electron transfer in supramolecular systems of fullerenes functionalized with ligands capable of binding to zinc porphyrins and zinc phthalocyanines. Coordination Chemistry Reviews, 249(13-14), 1410-1422. doi:10.1016/j.ccr.2005.01.00

Synthesis of the alkylphthalodinitrile derivatives and phthalocyanines

Bu çalışmada, 4,5-dikloro-ftalonitril ve dietilmalonatın yerdeğiştirme reaksiyonuyla 4-kloro-5-alkil-ftalonitril türevlerinin sentezi için yeni bir yöntem gösterilmektedir. Ayrıca 2 bileşiğindeki klor grubunun reaktivitesini göstermek amacıyla n-hekzantiyol ile reaksiyon gerçekleştirilmiş ve. 3,4- pozisyonunda bir alkilsülfanil ve bir dietilmalonil grubu taşıyan 1-hekziltiyo-3,4-disiyano-6-(1,1-dikarbetoksimetil)benzen (3) isimli yeni ftalonitril bileşiği elde edilmiştir. 1-Kloro-3,4-disiyano-6-(1,1-dikarbetoksi)benzen (2) ve 1-hekziltiyo-3,4-disiyano-6-(1,1-dikarbetoksimetil)benzen (3)’in metal tuzları ile çözücüsüz ortamda siklotetramerizasyonuyla metalli ftalosiyaninler elde edilmiştir). Reaksiyon hekzanol içerisinde ve DBU varlığında gerçekleştirildiğinde transesterifikasyon reaksiyonu gerçekleşmiş ve metalsiz ve metalli ftalosiyaniler elde edilmiştir. 6 bileşiğinin hidrolizi ile kısmen dekarboksile olmuş 2,9,16,23-tetra(karboksimetil)-3,10,17,24-tetrakloro-ftalosiyaninatopaladyum (II) elde edilmiştir. Anahtar Kelimeler: Ftalosiyanin, ftalonitril, paladyum, kobalt, bakır, çinko.In this study, we described for the first time the displacement of chloro group with an acidic CH group in 4,5-dichlorophthalonitrile and show the affect of this substitution pattern in spectral properties after phthalocyanine formation. A new route to the synthesis of 4-chloro-5-alkyl-phthalonitrile (2) derivatives was shown by the displacement reaction of 4,5-dichloro-phthalonitrile and diethylmalonate, a CH-acidic precursor, in the presence of K2CO3.. In order to verify the reactivity of the remaining chloro-group in 2, it was reacted with n-hexane-thiol in DMF by addition of anhydrous K2CO3. The product (3), was a phthalonitrile derivative carrying an alkylsulfanyl and a diethylmalonyl moiety at 3,4-positions. Cyclotetramerization of (2) and (3) with the metal salts without any solvent gave the corresponding metallophthalocyanines (M= Co, Cu, Zn or Pd). Transesterification occurred when the reaction was carried out in hexanol in the presence of DBU to obtain metal-free and metallophthalocyanine derivatives. Treatment of compound (6) with sodium ethoxide at ambient temperature and further acidification resulted with 2,9,16,23-tetra(carboxymethyl)-3,10,17,24-tetrachloro-phthalocyaninatopalladium (II) (15) with partial decarboxylation. Its electronic spectrum in aqueous solution indicated no appreciable change in a pH range from 7 to 12. All componds have been characterized by using elemental analyses, IR, UV-VIS, 1 H NMR, and FAB-MASS spectral data. Keywords: Phthalocyanine, phthalonitrile, palladium, cobalt, copper, zinc

MiRNA and mRNA Profiling in Systemic Lupus Reveals a Novel Set of Cytokine - Related miRNAs and their Target Genes in Cases With and Without Renal Involvement

Background/Aims: MiRNAs transpire as promising elements in molecular medicine for the identification of new diagnostic, prognostic and targeting therapeutic biomarkers. This study consisted of four steps: First, to investigate one or a group of specific diagnostic miRNAs for Systemic Lupus Erythematosus (SLE) disease in patients with and without renal involvement, second, to identify cytokines genes’ expression profiling, third, comparing the profiles with related amounts in the serum and finally, to study target-gene-mediated functional roles of miRNAs, which have been correlated to disease development and progression. Methods: In order to use in microarray assays total RNA and miRNAs were isolated from blood and serum samples that were obtained from 16 SLE patients (9 with renal involvement and 7 without renal involvement). Taking coexistence of factors such as hypocomplementemia, positive ANA and anti-DNA into account, obtained data were processed. For each differentially expressed miRNA, potential target genes were predicted by microRNAorg, TargetScan and PITA prediction tools. Obtained mRNA profiling data were interrogated for the target genes. MiRNA and mRNA microarray results were confirmed by QRT-PCR. Finally, the amounts of cytokines were measured by multiplex ELISA method. Results: The results of study showed that among differentially expressed miRNAs in SLE patients with renal involvement compared to those without renal involvement, hsa-miR-766-3p, may play pivotal roles in PI3K-AKT-mTOR pathway. In addition according to the obtained data it is suggested that blood-borne proinflammatory cytokines such as IL-4, IL-6 and TNF-α alongside with disease stage and severity may contribute to this differential expression of these miRNA which may be leading to insulin resistance. Finally, hsa-miR-621, which was differentially expressed in hypertensive SLE patients without renal involvement and a positive ANA test with its predicted target gene “Kallikrein-related peptidase 9” may play a role in the pathophysiology of hypertension in SLE. Conclusions: We reported some human miRNAs which were differentially expressed in SLE patients according to disease activity and renal involvement. Larger studies are necessary to confirm our findings and detect further biomarkers

Serum Anti-Saccharomyces Cerevisiae Antibodies in Greek Patients with Behcet's Disease

We tested 59 Greek patients with Behcet's Disease (BD) for serum anti-Saccharomyces cerevisiae antibodies. No increase of these antibodies was detected in the cases compared to 55 healthy unrelated blood donors from the same population. This finding is in contrast with the correlation between Saccharomyces cerevisiae antibodies and BD as reported in other populations. It seems that environmental factors may contribute to disease expression in different populations, producing different effects according to the individual's genetic predisposition. Saccharomyces cerevisiae antibodies do not seem to be of any significance in the Greek population

New Insights in the Clinical Understanding of Behçet's Disease

Behçet's disease is a chronic relapsing multisystemic inflammatory disorder characterized by four major symptoms (oral aphthous ulcers, genital ulcers, skin lesions, and ocular lesions) and occasionally by five minor symptoms (arthritis, gastrointestinal ulcers, epididymitis, vascular lesions, and central nervous system symptoms). Although the etiology of Behçet's disease is still unknown, there have been recent advances in immunopathogenic studies, genome-wide association studies, animal models, diagnostic markers, and new biological agents. These advances have improved the clinical understanding of Behçet's disease and have enabled us to develop new treatment strategies for this intractable disease, which remains one of the leading causes of blindness

Phase I study to determine the safety, tolerability and immunostimulatory activity of thalidomide analogue CC-5013 in patients with metastatic malignant melanoma and other advanced cancers

We assessed the safety, tolerability and efficacy of the immunomodulatory drug, CC-5013 (REVIMID(TM)), in the treatment of patients with metastatic malignant melanoma and other advanced cancers. A total of 20 heavily pretreated patients received a dose-escalating regimen of oral CC-5013. Maximal tolerated dose, toxicity and clinical responses were evaluated and analysis of peripheral T-cell surface markers and serum for cytokines and proangiogenic factors were performed. CC-5013 was well tolerated. In all, 87% of adverse effects were classified as grade 1 or grade 2 according to Common Toxicity Criteria and there were no serious adverse events attributable to CC-5013 treatment. Six patients failed to complete the study, three because of disease progression, two withdrew consent and one was entered inappropriately and withdrawn from the study. The remaining 14 patients completed treatment without dose reduction, with one patient achieving partial remission. Evidence of T-cell activation was indicated by significantly increased serum levels of sIL-2 receptor, granulocyte- macrophage colony-stimulating factor, interleukin-12 (IL-12), tumour necrosis factor-alpha and IL-8 in nine patients from whom serum was available. However, levels of proangiogenic factors vascular endothelial growth factor and basic foetal growth factor were not consistently affected, This study demonstrates the safety, tolerability and suggests the clinical activity of CC-5013 in the treatment of refractory malignant melanoma. Furthermore, this is the first report demonstrating T-cell stimulatory activity of this class of compound in patients with advanced cancer

Mucocutaneous Lesions of Behçet's Disease

Behçet's disease is particularly prevalent in "Silk Route" populations, but it has a global distribution. The diagnosis of the disease is based on clinical criteria as there is as yet no pathognomonic test, and mucocutaneous lesions, which figure prominently in the presentation and diagnosis, may be considered the diagnostic hallmarks. Among the internationally accepted criteria, painful oral and genital ulcers, cutaneous vasculitic lesions and reactivity of the skin to needle prick or injection (the pathergy reaction) are considered hallmarks of Behçet's disease, and often precede other manifestations. Their recognition may permit earlier diagnosis and treatment, with salutary results. This paper describes the various lesions that constitute the syndrome and focuses on those that may be considered characteristic

Thrombosis in vasculitis: from pathogenesis to treatment

In recent years, the relationship between inflammation and thrombosis has been deeply investigated and it is now clear that immune and coagulation systems are functionally interconnected. Inflammation-induced thrombosis is by now considered a feature not only of autoimmune rheumatic diseases, but also of systemic vasculitides such as Behçet’s syndrome, ANCA-associated vasculitis or giant cells arteritis, especially during active disease. These findings have important consequences in terms of management and treatment. Indeed, Behçet’syndrome requires immunosuppressive agents for vascular involvement rather than anticoagulation or antiplatelet therapy, and it is conceivable that also in ANCA-associated vasculitis or large vessel-vasculitis an aggressive anti-inflammatory treatment during active disease could reduce the risk of thrombotic events in early stages. In this review we discuss thrombosis in vasculitides, especially in Behçet’s syndrome, ANCA-associated vasculitis and large-vessel vasculitis, and provide pathogenetic and clinical clues for the different specialists involved in the care of these patients