Syndecan-1 (CD138) and Ki-67 expression in different subtypes of ameloblastomas

Ameloblastoma is the most frequent odontogenic tumor and is considered a benign, but locally invasive, neoplasm with variable clinico-pathological expression. Syndecan-1 is a cell surface proteoglycan that binds cells to the extracellular matrix and its expression is down-regulated in many cellular transformation models. The aims of this study were to examine the pattern of syndecan-1 expression, to evaluate the proliferating activity in a large series of solid/multicystic (SA) and unicystic ameloblastomas (UA), and to study its possible correlation to their biological behavior. Immunohistochemical studies were performed for syndecan-1 (clone MI15) and Ki-67 (clone MIB-1) in 120 ameloblastomas (75 SA and 45 UA). The salient finding was that expression of syndecan-1 was related to the histological subtype of tumors, as there was a lower expression in SA (40.2%) as compared to UA (49.7%) (p<0.05). These findings did not correlate with Ki-67 expression, as this was similar in both types of ameloblastomas. Our results suggest that the reduced expression of syndecan-1 supports the view that SA has a more aggressive biological behavior than the UA. The lack of correlation between reduction of the syndecan-1 and Ki-67 index may be due to the different histomorphologies of both types of ameloblastoma, and more studies are necessary to better understand the role of this protein in the biological behavior of these tumors.     

The concentration of deoxyribonucleic acid in plasma from 73 patients with colorectal cancer and apparent clinical correlations

Background: Detection of cell-free plasma DNA has considerable potential as a tool for the diagnosis and assessment of the prognosis of many types of cancer. The aim of the present study was to quantify, by spectrophotometry, the cell-free DNA in plasma samples from patients with colorectal cancer at different stages of the disease and to attempt to correlate the resultant values with the clinical picture. Methods: We reviewed the medical reports of 73 patients, who had undergone resection of primary colorectal cancer. Samples of blood had been taken from each patient immediately prior to surgery. DNA was extracted from samples of plasma and quantified, by spectrophotometry, after a storage period of no longer than 2 years in 89% of the cases examined. Results: The mean(±S.D.) concentration of DNA in plasma samples was 108 ± 156 ng/μl. We found a statistically significant correlation between the concentration of DNA and the presence of metastases (mainly liver metastases). Conclusion: The detection and quantitation of cell-free DNA in plasma, using this simple technique, might be of clinical value for the surveillance of colon cancer patients and the detection of metastases.     

The Management of Erectile Dysfunction with Placebo Only: Does it Work?

IntroductionRandomized clinical trials (RCT) remain the gold standard in providing scientific evidence in medical practice in spite of the significant placebo effect in the treatment of several disorders. Although the first‐line therapy for erectile dysfunction (ED) is oral phosphodiesterase type‐5 inhibitor (iPDE5), the placebo effect in RCT of iPDE5 for ED occurs at a rate as high as 50%.AimsTo evaluate the role of therapeutic illusion in the oral treatment for ED.MethodsA prospective, controlled, single‐blind, parallel‐group study was performed at single‐center. One hundred and twenty‐three patients with ED were randomly assigned into three groups and received different letters: Group 1 (G1) was informed to be receiving a substance for ED treatment; Group 2 (G2) was informed that they could be receiving an active drug or placebo; Group 3 (G3) was conscious to be using placebo. Starch capsules were dispensed to all patients. Median follow up was 12 weeks.Main Outcome MeasuresED improvement was assessed after 8 weeks of the intervention by the erectile function domain of the International Index of Erectile Function (IIEF) and the Quality of Erection Questionnaire. ED severity was classified by the IIEF erectile function (IIEF‐EF) domain score into five categories: no ED (score of 26–30), mild (22–25), mild to moderate (17–21), moderate (11–16), and severe (6–10). Improvement in IIEF‐EF domain was considered as a change in category of severity.ResultsED severity improved in all three groups (G1 = 31.7%, P = 0.039; G2 = 36.8%, P = 0.028; G3 = 36.8%, P = 0.002) and no difference was found among groups (P = 0.857). Improvement of quality of erection score was only significant in G2 (P = 0.005) and G3 (P < 0.001).ConclusionsWritten‐suggested therapeutic illusion for patients with ED has no major influence in the outcomes. However, treatment of ED with oral placebo capsules demonstrates clinical effects, improving erectile function and quality of erection. de Araujo AC, da Silva FG, Salvi F, Awad MC, da Silva EA, and Damião R. The management of erectile dysfunction with placebo only: Does it work?     

Melatonin protects the retina from experimental nonexudative age-related macular degeneration in mice

Nonexudative age-related macular degeneration (NE-AMD) represents the leading cause of blindness in the elderly. Currently, there are no available treatments for NE-AMD. We have developed a NE-AMD model induced by superior cervical ganglionectomy (SCGx) in C57BL/6J mice, which reproduces the disease hallmarks. Several lines of evidence strongly support the involvement of oxidative stress in NE-AMD-induced retinal pigment epithelium (RPE) and outer retina damage. Melatonin is a proven and safe antioxidant. Our aim was analysing the effect of melatonin in the RPE/outer retina damage within experimental NE-AMD. The treatment with melatonin starting 48 h after SCGx, which had no effect on the ubiquitous choriocapillaris widening, protected visual functions and avoided Bruch´s membrane thickening, RPE melanin content, melanosome number loss, retinoid isomerohydrolase (RPE65)-immunoreactivity decrease, and RPE and hotoreceptor ultrastructural damage induced within experimental NE-AMD exclusively located at the central temporal (but not nasal) region. Melatonin also prevented the increase in outer retina/RPE oxidative stress markers and a decrease in mitochondrial mass at 6 weeks post-SCGx. Moreover, when the treatment with melatonin started at 4 weeks post-SCGx, it restored visual functions and reversed the decrease in RPE melanin content and RPE65-immunoreactivity. These findings suggest that melatonin could become a promising safe therapeutic strategy for NE-AMD.     

Ebulin from Dwarf Elder (Sambucus ebulus L.): A Mini-Review

Sambucus ebulus L. (dwarf elder) is a medicinal plant, the usefulness of which also as food is restricted due to its toxicity. In the last few years, both the chemistry and pharmacology of Sambucus ebulus L. have been investigated. Among the structural and functional proteins present in the plant, sugar-binding proteins (lectins) with or without anti-ribosomal activity and single chain ribosome-inactivating proteins (RIPs) have been isolated. RIPs are enzymes (E.C. 3.2.2.22) that display N-glycosidase activity on the 28S rRNA subunit, leading to the inhibition of protein synthesis by arresting the step of polypeptide chain elongation. The biological role of all these proteins is as yet unknown. The evidence suggests that they could be involved in the defense of the plant against predators and viruses or/and a nitrogen store, with an impact on the nutritional characteristics and food safety. In this mini-review we describe all the isoforms of ebulin that have to date been isolated from dwarf elder, as well as their functional characteristics and potential uses, whilst highlighting concern regarding ebulin toxicity.     

联合应用经尿道气压碎石和电切治疗前列腺增生并继发膀胱结石

对24例前列腺增生症（BPH）并继发膀胱结石的病人联合应用经尿道气压碎石（TUPL）和经尿道前列腺电切术（TURP）处理，均获满意疗效。其中9例为多发结石，15例为单发结石。发现TUPL不增加TURP手术难度，也不增加电切综合征和术后尿道狭窄等并发症。与开放性膀胱切开取石和前列腺摘除术比较，TUPL和TURP联合应用具有创伤小、效果好和节省费用之优点，应作为BPH继发膀胱结石的首选治疗方法。     

Comparison of behavioral,neuroprotective, and proinflammatory cytokine modulating effects exercised by (+)‐cis‐EC and (−)‐cis‐EC stereoisomers in a PTZ‐induced kindling test in mice

Epoxy‐carvone (EC) has chiral centers that allow generation of stereoisomers, including (+)‐cis‐EC and (?)‐cis‐EC, whose effects in the kindling tests have never been studied. Accordingly, this study aims to comparatively investigate the effect of stereoisomers (+)‐cis‐epoxy‐carvone and (?)‐cis‐epoxy‐carvone on behavioral changes measured in scores, in the levels of cytokines (IL‐1β, IL‐6, and TNFα) and neuronal protection in the face of continuous treatment with pentylenetetrazol. Swiss mice were divided into five groups (n = 10), receiving vehicle, (+) – cis‐EC, (?) – cis‐EC (both at the dose of 30 mg/kg), and diazepam (4 mg/kg). Thirty minutes after the respective treatment was administered to the animals one subconvulsive dose of PTZ (35 mg/kg). Seven subconvulsives treatments were made on alternate days, in which each treatment several parameters were recorded. In the eighth treatment, the animals receiving the highest dose of PTZ (75 mg/kg) and were sacrificed for quantification of cytokines and histopathologic analysis. All drugs were administered by intraperitoneal route. In the kindling test, (+)‐cis‐EC and (?)‐cis‐EC reduced the average scores. The stereoisomer (+)‐cis‐EC decreased levels of proinflammatory cytokines IL‐1β, IL‐6, and TNFα, whereas comparatively (?)‐cis‐EC did not reduce IL‐1β levels. Histopathological analysis of the mice hippocampi undergoing this methodology showed neural protection for treated with (+)‐cis‐EC. The results suggest that the anticonvulsant effect of (+)‐cis‐EC possibly takes place due to reduction of proinflammatory cytokines involved in the epileptogenic process, besides neuronal protection, yet further investigation of the mechanisms involved is required.     

RPF101, a new capsaicin-like analogue,disrupts the microtubule network accompanied by arrest in the G2/M phase,inducing apoptosis and mitotic catastrophe in the MCF-7 breast cancer cells

Breast cancer is the world's leading cause of death among women. This situation imposes an urgent development of more selective and less toxic agents. The use of natural molecular fingerprints as sources for new bioactive chemical entities has proven to be a quite promising and efficient method. Capsaicin, which is the primary pungent compound in red peppers, was reported to selectively inhibit the growth of a variety tumor cell lines. Here, we report for the first time a novel synthetic capsaicin-like analogue, RPF101, which presents a high antitumor activity on MCF-7 cell line, inducing arrest of the cell cycle at the G2/M phase through a disruption of the microtubule network. Furthermore, it causes cellular morphologic changes characteristic of apoptosis and a decrease of Δψm. Molecular modeling studies corroborated the biological findings and suggested that RPF101, besides being a more reactive molecule towards its target, may also present a better pharmacokinetic profile than capsaicin. All these findings support the fact that RPF101 is a promising anticancer agent.