Cervicogenic headache: Josey's cases revisited

Before Sjaastad coined the term cervicogenic headache (CH) 15 years ago, neck-related headaches have been considered by different authors for many years. Even after the publication of diagnostic criteria, dispute on the clinical picture, differential diagnosis, pathophysiology and treatment of CH still persists. A paper published in 1949 by Josey reports on 6 "illustrative" cases of cervical-related headaches. Indeed, looked from a more recent perspective, those cases could eventually correspond to CH. Important topics such as the relatively high frequency, fixed unilaterality of the pain, relation to previous trauma, irradiation from the back to the forehead, normal or slightly abnormal roentgenograms, and the mechanical precipitation of attacks are some of the topics considered by Josey. The female gender was not prevalent in Josey's series. Traction and analgesics were basically the recommended treatment. CH is probably a common disorder, an idea already considered by a clinician in 1949. This syndrome was not adequately described before Sjaastad's group papers in the 80's.Muitos autores escreveram sobre cefaléias relacionadas ao pescoço antes da descrição da cefaléia cervicogênica (CH) por Sjaastad e col. Mesmo após a publicação de critérios diagnósticos, há controvérsias em relação ao quadro clínico, diagnóstico diferencial, fisiopatologia e tratamento da CH. Um artigo publicado em 1949 por Josey relata 6 casos "ilustrativos" de cefaléia relacionada ao pescoço, cujo quadro pode corresponder ao que hoje consideramos ser CH. Aspectos importantes como sua frequência relativamente elevada, unilateralidade fixa, relação a traumas prévios, irradiação póstero-anterior, normalidade de exames radiológicos e os mecanismos de precipitação foram considerados por Josey. O sexo feminino não foi predominante na sua casuística. Tração e analgésicos foram os tratamentos recomendados. CH é provavelmente uma desordem comum, o que já havia sido considerado neste estudo de 1949. A síndrome, entretanto, não foi completa e adequadamente descrita antes de Sjaastad

Sulfation of glycosaminoglycans and its Implications in human health and disorders

Sulfation is a dynamic and complex posttranslational modification process. It can occur at various positions within the glycosaminoglycan (GAG) backbone and modulates extracellular signals such as cellâ cell and cellâ matrix interactions; different sulfation patterns have been identified for the same organs and cells during their development. Because of their high specificity in relation to function, GAG sulfation patterns are referred to as the sulfation code. This review explores the role of GAG sulfation in different biological processes at the cell, tissue, and organism levels. We address the connection between the sulfation patterns of GAGs and several physiological processes and discuss the misregulation of GAG sulfation and its involvement in several genetic and metabolic disorders. Finally, we present the therapeutic potential of GAGs and their synthetic mimics in the biomedical field.info:eu-repo/semantics/publishedVersio

Lipid-Coated Cisplatin Nanoparticles Induce Neighboring Effect and Exhibit Enhanced Anticancer Efficacy

Encapsulation of cisplatin (CDDP) into nanoparticles (NPs) with high drug loading and encapsulation efficiency has been difficult due to the poor solubility of CDDP. However, this barrier has been overcome with a reverse microemulsion method appropriating CDDP’s poor solubility to our advantage promoting the synthesis of a pure cisplatin nanoparticle with a high drug loading capacity (approximately 80.8wt%). Actively targeted CDDP NPs exhibited significant accumulation in human A375M melanoma tumor cells in vivo. In addition, CDDP NPs achieved potent anti-tumor efficacy through the neighboring effect at a dose of 1 mg/kg when injected weekly via IV without inducing nephrotoxicity. The neighboring effect regards an observation made in vivo when the tumor cells that took up CDDP NPs released active drug following apoptosis. Via diffusion, surrounding cells that were previously unaffected showed intake of the released drug and their apoptosis soon followed. This observation was also made in vitro when A375M melanoma tumor cells incubated with CDDP NPs exhibited release of active drug and induced apoptosis on untreated neighboring cells. However, the neighboring effect was unique to rapidly proliferating tumor cells. Liver functional parameters and H&E staining of liver tissue in vivo failed to detect any difference between CDDP NP treated and control groups in terms of tissue health. By simultaneously promoting an increase in cytotoxicity and a lesser degree of side effects over free CDDP, CDDP NPs show great therapeutic potential with lower doses of drug while enhancing anti-cancer effectiveness

Anti-Invasive and Anti-Proliferative Synergism between Docetaxel and a Polynuclear Pd-Spermine Agent

The present work is aimed at evaluating the antitumour properties of a Pd(II) dinuclear complex with the biogenic polyamine spermine, by investigating: i) the anti-angiogenic and anti-migration properties of a Pd(II) dinuclear complex with spermine (Pd2Spm); ii) the anti-proliferative activity of Pd2Spm against a triple negative human breast carcinoma (MDA-MB-231); and finally iii) the putative interaction mediated by combination of Pd2Spm with Docetaxel. Anti-invasive (anti-angiogenic and anti-migratory) as well as anti-proliferative capacities were assessed, for different combination schemes and drug exposure times, using the CAM assay and VEGFR2 activity measurement, the MatrigelTM method and the SRB proliferation test. The results thus obtained evidence the ability of Pd2Spm to restrict angiogenesis and cell migration: Pd2Spm induced a marked inhibition of migration (43.8±12.2%), and a higher inhibition of angiogenesis (81.8±4.4% for total length values, at 4 μM) as compared to DTX at the clinical dosage 4x10-2 μM (26.4±14.4%; n = 4 to 11). Combination of Pd2Spm/DTX was more effective as anti-invasive and anti-proliferative than DTX or Pd2Spm in sole administration, which is compatible with the occurrence of synergism: for the anti-angiogenic effect, IC50(Pd2Spm/DTX) = 0.5/0.5x10-2 μM vs IC50(DTX) = 1.7x10-2 μM and IC50(Pd2Spm) = 1.6 μM. In conclusion, the reported effects of Pd2Spm on angiogenesis, migration and proliferation showed that this compound is a promising therapeutic agent against this type of breast cancer. Moreover, combined administration of Pd2Spm and DTX was found to trigger a substantial synergetic effect regarding angiogenesis inhibition as well as anti-migratory and anti-proliferative activities reinforcing the putative use of Pd(II) complexes in chemotherapeutic regimens. This is a significant outcome, aiming at the application of these combined strategies towards metastatic breast cancer (or other type of resistant cancers), justifying further studies that include pre-clinical trials

In situ generated D‐peptidic nanofibrils as multifaceted apoptotic inducers to target cancer cells

Nanofibrils of small molecules, as a new class of biofunctional entities, exhibit emergent properties for controlling cell fates, but the relevant mechanism remains to be elucidated and the in vivo effect has yet to be examined. Here, we show that D-peptide nanofibrils, generated by enzyme-instructed self-assembly (EISA), pleiotropically activate extrinsic death signaling for selectively killing cancer cells. Catalyzed by alkaline phosphatases and formed in situ on cancer cells, D-peptide nanofibrils present autocrine proapoptotic ligands to their cognate receptors in a juxtacrine manner, as well as directly cluster the death receptors. As multifaceted initiators, D-peptide nanofibrils induce apoptosis of cancer cells without harming normal cells in a co-culture, kill multidrug-resistant (MDR) cancer cells, boost the activities of anticancer drugs, and inhibit tumor growth in a murine model. Such a supramolecular cellular biochemical process (consisting of reaction, assembly, and binding) for multi-targeting or modulating protein–protein interaction networks ultimately may lead to new ways for combating cancer drug resistance