Bilateral profunda femoris artery and left common femoral artery aneurysms presenting as lower limb ischemia

We report a rare case of bilateral profunda femoris artery aneurysms (PFAAs) and a left common femoral artery aneurysm (CFAA) presenting as lower limb ischemia. An 84-year-old man presented with a sense of coldness and intermittent claudication of his left lower limb. Ultrasonography and computed tomography angiography showed bilateral PFAAs, a left CFAA, and an occlusion of the left popliteal artery. Thrombectomy of the left popliteal artery, exclusion of the bilateral PFAAs, replacement of the left CFAA, and bypass grafting of the right profunda femoris artery were performed. The patient had an uneventful postoperative course and was discharged from hospital on the postoperative day 14.     

Tributyltin impairs the coronary vasodilation induced by 17β-estradiol in isolated rat heart

Triorganotins, such as tributyltin (TBT), are environmental contaminants that are commonly used as antifouling agents for boats. However, TBT is also known to alter mammalian reproductive functions. Although the female sex hormones are primarily involved in the regulation of reproductive functions, 17β-estradiol also protects against cardiovascular diseases, in that this hormone reduces the incidence of coronary artery disease via coronary vasodilation. The aim of this study was to examine the influence of 100 ng/kg TBT administered daily by oral gavage for 15 d on coronary functions in female Wistar rats. Findings were correlated with changes in sex steroids concentrations. Tributyltin significantly increased the baseline coronary perfusion pressure and impaired vasodilation induced by 17β-estradiol. In addition, TBT markedly decreased serum 17β-estradiol levels accompanied by a significant rise in serum progesterone levels. Tributyltin elevated collagen deposition in the heart interstitium and number of mast cells proximate to the cardiac vessels. There was a positive correlation between the increase in coronary perfusion pressure and incidence of cardiac hypertrophy. In addition, TBT induced endothelium denudation (scanning electron microscopy) and accumulation of platelets. Moreover, TBT impaired coronary vascular reactivity to estradiol (at least in part), resulting in endothelial denudation, enhanced collagen deposition and elevated number of mast cells. Taken together, the present results demonstrate that TBT exposure may be a potential risk factor for cardiovascular disorders in rats.     

Fructose-1,6 diphosphate as a protective agent for experimental ischemic acute renal failure

Cold ischemia time is a risk factor for the development of acute renal failure in the immediate post-transplant period. In this study, we aimed to determine if intravenous fructose-1,6-diphosphate (FDP), given before nephrectomy, attenuates renal cell injury in a cold ischemia model. Male adult Wistar rats were subjected to infusion of either FDP 350 mg/kg (group F, n=6), an equal volume of 0.9% NaCl (group S, n=6), an equal volume/osmolality of mannitol (group M, n=6) or no infusion (group C, n=7). Kidneys were then perfused in situ with Collins solution and nephrectomy was performed. Other kidney slices were stored in Collins solution at 4 degrees C. Adenosine triphosphate (ATP) levels and lactate dehydrogenase (LDH) release were examined at 0, 24, 48 and 72 h. Other slices, obtained after 50 min immersion in Collins solution at 37 degrees C, were frozen for characterization of cytoskeletal preservation using phalloidin-FITC staining. Apical fluorescence intensity of proximal tubule cells, indicative of the F-actin concentration, was measured in a fluorescence microscope interfaced with computer image analysis system. Adenosine triphosphate levels, after up to 72 h of tissue incubation, were higher (P<0.05) in the FDP group when compared to other groups. In addition, LDH release was smaller (P<0.0001) in the FDP group. The F-actin concentration of proximal tubule cells cells was greater in the FDP group (P<0.0001). Results indicate that FDP is a useful tool to increase tissue viability in a rat kidney subjected to cold ischemia, by maintaining ATP cell content, decreasing LDH release and preventing microfilament disruption of proximal tubule cells.     

Safety and efficacy of eletriptan in the treatment of acute migraine

Eletriptan is a new selective serotonin agonist approved for the treatment of acute migraine headaches. To review the pharmacologic, pharmacodynamic, pharmacokinetic, safety, and clinical efficacy data for eletriptan, we searched the literature in PubMed/MEDLINE, EMBASE, International Pharmaceutical Abstracts, and Science Direct databases to gather all published reports from January 1996-October 2004. All English-language reports (abstract or full trial reports) about the pharmacology, pharmacokinetics, clinical efficacy, and safety of eletriptan were reviewed. Eletriptan's pharmacokinetic and pharmacodynamic parameters translate into a favorable safety and efficacy profile. The drug is rapidly absorbed when administered orally, has good bioavailability and central nervous system penetration due to its lipophilicity, and has a long half-life, which contributes to its ability to prevent recurrent headaches. Compared with other serotonin agonists, eletriptan has a longer duration of action and greater lipophilicity. Eletriptan is metabolized through the cytochrome P450 3A4 system; therefore, it does have the potential for clinically significant drug interactions. In clinical trials, eletriptan demonstrated efficacy superior to that of placebo and similar or superior efficacy to that of other serotonin agonists, with limited adverse effects. With clinical use, headache and pain-free responses and headache recurrence rates were similar to those of other serotonin agonists, but the agent is superior to ergotamine tartrate-caffeine. Based on pharmaco-economic data, eletriptan is more cost-effective than other agents in its class. Eletriptan is a safe and cost-effective option for the treatment of migraine headaches.     

LASSBio-468: a new achiral thalidomide analogue which modulates TNF-alpha and NO production and inhibits endotoxic shock and arthritis in an animal model

As part of a program researching the synthesis and immunopharmacological evaluation of novel synthetic compounds, we have described the immune modulatory profile of the new achiral thalidomide analogue LASSBio-468 in the present work. This compound was planned as an N-substituted phthalimide derivate, structurally designed as a hybrid of thalidomide and aryl sulfonamides, which were previously described as tumor necrosis factor-alpha (TNF-alpha) and PDE4 inhibitors. LASSBio-468 was recently demonstrated to inhibit the TNF-alpha production induced by lipopolysaccharide (LPS), in vivo. Here, we investigated whether this compound would affect chronic inflammation processes associated with the production of this pro-inflammatory cytokine. Treatment with LASSBio-468 before a lethal dose injection of LPS in animals greatly inhibited endotoxic shock. This effect seems to be mediated by a specific down regulation of TNF-alpha and nitric oxide production, regulated mainly at the RNA level. In another model, histopathological analysis indicated that this compound also inhibited adjuvant-induced arthritis in rats. Taken together, our data demonstrated a potent anti-inflammatory effect of LASSBio-468, suggesting its use as a potential drug against chronic inflammatory diseases.     

Histopathologic analysis of hamster hepatocytes submitted to experimental infection with Leishmania donovani

Hepatocytes from different vertebrates are used increasingly as models of environmentally driven cell structure plasticity and for the investigation of ultrastructural pathological patterns induced by cell injury. The present study was carried out to assess the morphological changes in hamster hepatocytes subjected to chronic infection by amastigote forms of Leishmania donovani. Liver fragments were processed for routine light and transmission electron microscopy. For cytochemical visualization of peroxisomes, liver slices were incubated in alkaline 3,3'-diaminobenzidine (DAB) medium at pH 10.0. The results showed that the presence of Leishmania donovani induced distinct ultrastructural changes in the liver acinus (zone 2). The significant pathological changes in hepatocytes consisted of disruption of the endomembrane system and alterations of both the peroxisomal compartment and the distribution of hepatic glycogen. Particularly, hepatic peroxisomes exhibited different shapes and sizes, with modifications of the peroxisomal matrix, including absence of the catalase reaction. These observations suggest an adaptive response of hepatocytes, with cytological reorganization after parasitic infection. The presence of DAB-negative peroxisomes could be morphological evidence of a metabolic disturbance of this organelle. The parasitic infection, through deregulation of the cytokene network, is probably responsible for those structural alterations, since similar changes have been observed in vivo and in vitro.     

A motif within the N-terminal domain of TSP-1 specifically promotes the proangiogenic activity of endothelial colony-forming cells

Thrombospondin-1 (TSP-1) gives rise to fragments that have both pro- and anti-angiogenic effects in vitro and in vivo. The TSP-HepI peptide (2.3kDa), located in the N-terminal domain of TSP-1, has proangiogenic effects on endothelial cells. We have previously shown that TSP-1 itself exhibits a dual effect on endothelial colony-forming cells (ECFC) by enhancing their adhesion through its TSP-HepI fragment while reducing their proliferation and differentiation into vascular tubes (tubulogenesis) in vitro. This effect is likely mediated through CD47 binding to the TSP-1 C-terminal domain. Here we investigated the effect of TSP-HepI peptide on the angiogenic properties of ECFC in vitro and in vivo. TSP-HepI peptide potentiated FGF-2-induced neovascularisation by enhancing ECFC chemotaxis and tubulogenesis in a Matrigel plug assay. ECFC exposure to 20μg/mL of TSP-HepI peptide for 18h enhanced cell migration (p<0.001 versus VEGF exposure), upregulated alpha 6-integrin expression, and enhanced their cell adhesion to activated endothelium under physiological shear stress conditions at levels comparable to those of SDF-1α. The adhesion enhancement appeared to be mediated by the heparan sulfate proteoglycan (HSPG) syndecan-4, as ECFC adhesion was significantly reduced by a syndecan-4-neutralising antibody. ECFC migration and tubulogenesis were stimulated neither by a TSP-HepI peptide with a modified heparin-binding site (S/TSP-HepI) nor when the glycosaminoglycans (GAGs) moieties were removed from the ECFC surface by enzymatic treatment. Ex vivo TSP-HepI priming could potentially serve to enhance the effectiveness of therapeutic neovascularisation with ECFC.     

Influence of Lycopene on Cell Viability,Cell Cycle,and Apoptosis of Human Prostate Cancer and Benign Hyperplastic Cells

Prostate cancer is the most common malignancy in men and the second leading cause of cancer-related mortality in men of the Western world. Lycopene has received attention because of its expcted potential to prevent cancer. In the present study, we evaluated the influence of lycopene on cell viability, cell cycle, and apoptosis of human prostate cancer cells and benign prostate hyperplastic cells. Using MTT assay, we observed a decrease of cell viability in all cancer cell lines after treatment with lycopene, which decreased the percentage of cells in G0/G1 phase and increased in S and G2/M phases after 96 h of treatment in metastatic prostate cancer cell lineages. Flow citometry analysis of cell cycle revealed lycopene promoted cell cycle arrest in G0/G1 phase after 48 and 96 h of treatment in a primary cancer cell line. Using real time PCR assay, lycopene also induced apoptosis in prostate cancer cells with altered gene expression of Bax and Bcl-2. No effect was observed in benign prostate hyperplasia cells. These results suggest an effect of lycopene on activity of human prostate cancer cells.     

Immunohistochemical detection of Ki‐67 is not associated with tumor‐infiltrating macrophages and cyclooxygenase‐2 in oral squamous cell carcinoma

J Oral Pathol Med (2010) 39 : 565–570 Background: An inflammatory component consisting of cells and chemical mediators may influence the proliferation and dissemination of the oral squamous cell carcinoma (OSCC). In the present study, we evaluated the possible relationship between Ki‐67, tumor‐associated macrophages (TAMs), and COX‐2 in OSCCs. In addition, the immunodetection of these proteins was associated with different histological grades of malignancy, including invasive and in situ tumors. Methods: Twenty‐seven OSCC cases were examined by light microscopy using criteria adopted WHO, and immunohistochemistry for Ki‐67, CD68, and COX‐2 using EnVision System in invasive and in situ lesions. Immunohistochemical detection of these proteins was assessed and scored for COX‐2, and results were compared with their histological grades of malignancy. Results: A correlation between Ki‐67, COX‐2, and CD68 was not found. Histological grade of malignancy (HDM) was associated with the Ki‐67 immunostaining (P = 0.00), but this was not observed regarding both CD68 (P = 0.51) and COX‐2 (P = 0.89). Furthermore, there was a COX‐2 overexpression in 62.96% of the sample, and a high density of TAMs in both OSCCs and in situ carcinomas. Conclusions: Imunolabeling for Ki‐67 was directly correlated with less‐differentiated tumors, suggesting that this marker may contribute to understand the biological behavior of OSCC, and help to distinguish risk groups of OSCC. Furthermore, the lack of correlation between Ki‐67, COX‐2, and CD68 indicates that the latter two markers may play a pivotal role in oral carcinogenesis. However, further studies are needed to clarify their contribution for cell proliferation and tumor differentiation.