Clinical and histopathological profile of primary or secondary osteosarcoma of the jaws

Osteosarcoma of the jaw is a rare disease; we report two cases, one in which the primary osteosarcoma had occurred in the sacrum and ileum, the second at the mandible. Dissemination of osteosarcoma to other organs, especially early dissemination to the lung, is common, but metastasis to the jaw has only rarely been reported. About 10% of osteosarcomas occur in the head and neck, most in the mandible or maxilla. Clinically, both patients presented swelling, and pain at the jaw in the premolar-molar region. At radiography, extensive bone erosion and soft-tissue swelling were apparent. A biopsy was taken and a diagnosis of osteosarcoma rendered in both cases. Histological examination revealed a proliferation of atypical osteoblast-like cells with hyperchromatic nuclei and formation of scattered neoplastic osteoid tissue. Immunohistochemistry for a panel of antibodies showed strong positivity for CD99, weak positivity for S-100, but was negative for desmin, vimentin, and cytokeratins. The diagnosis for both cases was of osteogenic osteosarcoma, chondroblastic subtype. Unfortunately, both patients died, one before the planned chemotherapy regime could begin, the second during the chemotherapy course. Our report aims to highlight the importance of the diagnostic profile in formulating a diagnosis of osteosarcoma, and that this tumor, although very rare, may be primary or may metastasize to the jaws.     

Synthesis, biological evaluation, and docking studies of tetrahydrofuran- cyclopentanone- and cyclopentanol-based ligands acting at adrenergic α₁- and serotonine 5-HT1A receptors

A series of aralkylphenoxyethylamine and aralkylmethoxyphenylpiperazine compounds was synthesized and their in vitro pharmacological profile at both 5-HT(1A) receptors and α(1)-adrenoceptor subtypes was measured by binding assay and functional studies. The results showed that the replacement of the 1,3-dioxolane ring by a tetrahydrofuran, cyclopentanone, or cyclopentanol moiety leads to an overall reduction of in vitro affinity at the α(1)-adrenoceptor while both potency and efficacy were increased at the 5-HT(1A) receptor. A significant improvement of 5-HT(1A)/α(1) selectivity was observed in some of the cyclopentanol derivatives synthesized (4acis, 4ccis and trans). Compounds 2a and 4ccis emerged as novel and interesting 5-HT(1A) receptor antagonist (pK(i) = 8.70) and a 5-HT(1A) receptor partial agonist (pK(i) = 9.25, pD(2) = 9.03, E(max) = 47%, 5-HT(1A)/α(1a) = 69), respectively. Docking studies were performed at support of the biological data and to elucidate the molecular basis for 5-HT(1A) agonism/antagonism activity.     

In vitro and in vivo antitumor effects of the essential oil from the leaves of Guatteria friesiana

Guatteria friesiana (W. A. Rodrigues) Erkens & Maas (synonym Guatteriopsis friesiana W. A. Rodrigues), popularly known as "envireira", is a medicinal plant found in the Brazilian and Colombian Amazon basin that is used in traditional medicine for various purposes. Recent studies on this species have demonstrated antimicrobial activity. In this study, the antitumor activity of the essential oil from the leaves of G. friesiana (EOGF) and its main components ( α-, β-, and γ-eudesmol) were determined using experimental models. In the in vitro study, EOGF and its components α-, β-, and γ-eudesmol displayed cytotoxicity against tumor cell lines, showing IC?? values in the range of 1.7 to 9.4 μg/mL in the HCT-8 and HL-60 cell lines for EOGF, 5.7 to 19.4 μg/mL in the HL-60 and MDA-MB-435 cell lines for α-eudesmol, 24.1 to > 25 μg/mL in the SF-295 and MDA-MB-435 cell lines for β-eudesmol, and 7.1 to 20.6 μg/mL in the SF-295 and MDA-MB-435 cell lines for γ-eudesmol, respectively. In the in vivo study, the antitumor effect of EOGF was evaluated in mice inoculated with sarcoma 180 tumor cells. Tumor growth inhibition rates were 43.4-54.2 % and 6.6-42.8 % for the EOGF treatment by intraperitoneal (50 and 100 mg/kg/day) and oral (100 and 200 mg/kg/day) administration, respectively. The treatment with EOGF did not significantly affect body mass, macroscopy of the organs, or blood leukocyte counts. Based on these results, we can conclude that EOGF possesses significant antitumor activity and has only low systemic toxicity. These effects could be assigned to its components α-, β-, and γ-eudesmol.     

Comparative assessment of vascular function in autoimmune rheumatic diseases: considerations of prevention and treatment

Numerous autoimmune-inflammatory rheumatic diseases have been associated with accelerated atherosclerosis or other types of vasculopathy leading to increased cardio- and cerebrovascular disease risk. Traditional risk factors, as well as the role of systemic inflammation including cytokines, chemokines, proteases, autoantibodies, adhesion receptors and others have been implicated in the development of these vascular pathologies. The characteristics of vasculopathies may significantly differ depending on the underlying disease. While classical accelerated atherosclerosis has been associated with rheumatoid arthritis (RA), systemic lupus erythematosus (SLE) or spondyloarthropathies (SpA), obliterative vasculopathy may rather be characteristic for systemic sclerosis (SSc) or mixed connective tissue disease (MCTD). Antiphospholipid antibodies have been implicated in vasculopathies underlying SLE, antiphospholipid syndrome (APS), RA and MCTD. There is also heterogeneity with respect to inflammatory risk factors. Cytokines, such as tumor necrosis factor-α (TNF-α) or interleukin 6 (IL-6) and immune complexes are primarily involved in arthritides, such as RA, SpA, as well as in SLE. On the other hand, autoantibodies including anti-oxLDL anti-cardiolipin and anti-β2GPI are rather involved in SLE- and APS-associated vasculopathies. Regarding the non-invasive assessment of vascular function, endothelial dysfunction, overt atherosclerosis and vascular stiffness may be indicated by brachial artery flow-mediated vasodilation (FMD), common carotid intima-media thickness (ccIMT) and aortic pulse-wave velocity (PWV), respectively. These abnormalities have been described in most inflammatory rheumatic diseases. While ccIMT and stiffness are relatively stable, FMD may be influenced by many confounding factors. In addition to traditional vasculoprotection, immunosuppressive agents including corticosteroids, traditional and biologic DMARDs may have significant vascular and metabolic effects. The official EULAR recommendations on the assessment and management of cardiovascular disease in arthritides have just been published, and similar recommendations in connective tissue diseases are to be developed soon.     

N-valproyl-L-tryptophan for CNS-targeting: synthesis, characterization and efficacy in vitro studies of a new potential antiepileptic drug

A new aminoacidic derivative of valproic acid (VPA) has been synthesized and characterized by analytical and spectral data. The rationale for the preparation of such potential antiepileptic agent is based on the observation that chemical combination of the anticonvulsant pharmacophore, VPA with essential aminoacids could afford more effective and less toxic actives. The synthesis, characterization, physico-chemical parameters functional for crossing Blood Brain Barrier of N-valproyl-L-tryptophan (4) are reported. The Log D (pH7.4) (0.3) indicates that (4) is adequate to cross biological membranes. Its chemical and enzymatic stability were assessed. The experiments indicate high stability of compound (4) at pH conditions of physiological fluids. Moreover, both in plasma and in cerebral enzymatic environments compound (4) doesn't undergo cleavage after 24 h. The anticonvulsant activity of the new compound was assessed against epileptic burst discharges evoked in vitro in rat hippocampal slices (Seizure like events - SLEs) and compared with that of the widely used VPA. Compound (4), even at the lower tested concentration, when compared to VPA, showed an improved protective effect against hippocampal seizures. The collected data suggest that compound (4) could be considered a very valuable candidate for subsequent in vivo evaluation as new potential antiepileptic drug.