Among all metazoan phyla, sponges are known to produce the largest number of bioactive compounds. However, until now, only one compound, arabinofuranosyladenine, has been approved for application in humans. One major obstacle is the limited availability of larger quantities of defined sponge starting material. Recently, we introduced the in vitro culture of primmorphs from Suberites domuncula, which contain proliferating cells. Now we have established the primmorph culture also from the marine sponge Dysidea avara and demonstrate that this special form of sponge cell aggregates produces avarol, a sesquiterpenoid hydroquinone, known to display strong cytostatic activity especially against mammalian cells. If dissociated sponge cells are transferred into Ca2+- and Mg2+-containing seawater, they form after a period of two to three days round-shaped primmorphs (size of 1 to 3 mm). After longer incubation, the globular primmorphs fuse and form meshes of primmorphs that adhere to the bottom of the incubation chamber. Later, during incubation, freely floating mesh-primmorphs are formed. No bacterial rRNA could be detected in the primmorphs. We were able to prove that the primmorphs produce avarol. Levels (1.4 μg of avarol/100 μg of protein) close to those identified in specimens from the field (1.8 μg/100 μg) are reached. Avarol was extracted from the cells with EtOAc and subsequently purified by HPLC. The identification was performed spectrophotometrically and by thin-layer chromatography. Single cells apparently do not have the potency to produce this secondary metabolite. It is concluded that the primmorph model is a suitable system for the synthesis of bioactive compounds in vitro.
Background— Cell-based therapies are a promising option in patients with acute myocardial infarction or chronic heart failure (CHF). However, administration of cells requires intracoronary or intracardiac instrumentation, which is potentially associated with periprocedural risks. Therefore, we analyzed periprocedural complications and 30-day outcome in 775 consecutive procedures of intracoronary administration of progenitor cells using the stop-flow technique. Methods and Results— Indications for cell administration were acute myocardial infarction (n=126) and CHF of ischemic (n=562) or nonischemic (n=87) etiology. Vessel injury was observed in a total of 9 procedures (1.2%) and could be promptly managed by additional progenitor cell injection (PCI) in all but 1 case. No procedural deaths were observed. A periprocedural increase in troponin T was observed in 3.2% of the CHF procedures, in which no concomitant PCI was performed and troponin levels were not elevated before the procedure. Independent significant predictors of troponin T increase were higher New York Heart Association (NYHA) class (NYHA I versus NYHA IV; P =0.01; NYHA I versus III; P =0.19; NYHA I versus II; P =0.55), concomitant revascularization ( P <0.01), presence of elevated troponin T before the procedure ( P <0.01), and peripheral occlusive disease ( P =0.04). At 30 days, there were 4 deaths (0.5%), 1 stroke (0.13%), 8 acute myocardial infarctions (1%), and 5 hospitalizations for exacerbation of heart failure (0.64%). Conclusions— Intracoronary infusion of progenitor cells can be performed with adequate safety in patients with acute myocardial infarction or CHF, because the safety profile was similar to what is usually expected from a coronary angiogram in the present cohort. Clinical Trial Registration— URL: http://www.clinicaltrials.gov . Unique identifier: NCT00962364, NCT00284713, and NCT00289822.
The paper presents ROSES, its robotic components, the different devices, not necessarily sterile, and its disposables, suitable for any endovascular procedure, both actually performed and presently not assisted by any robotic system, and open in the future for new application yet to come, such as what will be allowed by the new animated catheter. In fact, this is due to the mechanical configuration of the robotic actuators based on a peculiar gear train which presents a big passage hole which allows both the passage of big catheters and even hemostasis valves, as well as full control of very small catheters and guide wires. The system measures forces opposed by the body showing their value both numerically and analogically without the need of any. special tool, measures length of penetration of each catheter and guide wires recording their value. Thus, it may become in future, connected to a work station that will register in real time also the fluoroscopic images, a kind of black box of endovascular surgeries, separating completely doctor and nurses from the patient, using also cameras and microphones to replace the physical contact with the patient.
<i>Objective:</i> Atherosclerosis is characterized by endothelial inflammation and dysfunction. Adipose tissue has increasingly been recognized as an active endocrine organ secreting so-called adipokines. Among these, resistin – recently described, but not yet extensively studied – has been defined as a novel inflammatory marker in atherosclerosis. The pathophysiology underlying this interplay, however, remains to be fully characterized. The aim of the study is to determine whether resistin might affect prothrombotic characteristics of human coronary artery endothelial cells (HCAECs). <i>Methods and Results:</i> Incubation of HCAECs with resistin caused upregulation of tissue factor (TF) expression as demonstrated by FACS analysis. Moreover, TF activity was induced in a dose-dependent manner, as shown by real-time PCR and colorimetric assay. Resistin-induced TF expression was mediated by oxygen free radicals through the activation of the transcription factor nuclear factor-ĸB (NF-ĸB), as demonstrated by electrophoretic mobility shift assay and by suppression of TF expression by superoxide dismutase, catalase, and the NF-ĸB inhibitors PDTC and BAY 11-7082. <i>Conclusions:</i> These data confirm the hypothesis that resistin may contribute to atherothrombosis, exerting direct effects on HCAECs by promoting TF expression; thus, it represents an effector molecule able to induce a prothrombotic phenotype in cells present in the vessel wall.
A new inhibitor of human secretory phospholipase A2 (PLA2), cacospongionolide E (4a), has been isolated from the Tyrrhenian sponge Fasciospongia cavernosa. The structure was proposed on the basis of spectroscopic data and by chemical transformations. The absolute configuration of cacospongionolides 2a−4a was established using the modified Mosher's method. Cacospongionolide E was the most potent inhibitor toward human synovial PLA2, showing higher potency than the reference compound manoalide and exerting no signs of toxicity on human neutrophils. It showed high activity in the Artemia salina bioassay and moderate toxicity in the fish (Gambusia affinis) lethality assay.
Cardiovascular diseases (CVD) are the leading cause of mortality and morbidity in Western Countries. Coronary artery disease is the etiology underlying the most prevalent clinical manifestations of CVD. Atherosclerosis is often diagnosed only at late stages, when it manifests in clinically overt forms. Coronary angiography often does not show critical stenoses. We recently showed that the latency of flow mediated dilation (FMD) correlates with the presence of carotid atherosclerosis and the individual cardiovascular risk. Hence, we aimed at evaluating whether the latency of the vasodilator response at the brachial artery could predict the presence of critical coronary stenoses. We evaluated FMD in 74 consecutive patients, before performing coronary angiography for clinical indication at our hospital. Patients were classified in early (ED), late (LD) and no dilators (ND), based on the latency of the vasodilator response. Briefly, ED showed maximal dilation at 60s after ischemic stimulus, and LD over 60s. Very interestingly, lost of early vasodilator response showed a much better diagnostic performance than maximal FMD for the prediction of critical (>70%) coronary stenoses. In fact, classification match of loss of early vasodilator response with coronary angiography was twice as good as with FMD max (72% vs 39%, p=0.002). Using this approach, the number of false negative results was quite low at 4/74 (0.5%), yielding a 89% specificity. Furthermore, ischemia extension - measured by means of the Gensini score - was progressively larger with longer latency (4.5±13.5 in ED, 17.5±27.1 in LD, 39.7±55.0 in ND; p<0.02). In conclusion, using the lost of early vasodilator response as a diagnostic cutpoint allowed to confidently rule out the presence of critical coronary stenoses be means of a simple non-invasive examination. In our cohort, this could have avoided a useless exposition of patients to the potential complications of an invasive coronary angiography in 42% of cases. Once confirmed in larger studies, measurement of latency in vasodilator response could largely improve the selection of patients to refer for coronary angiography, reducing useless patients’ exposition to a potentially harmful diagnostic procedure and healthcare costs.
BRS represent a new approach to treating coronary artery disease. Beneficial properties of BRS regarding the restoration of vasomotility after resorption make them attractive devices in CTO revascularization. However, experience in this setting is limited.
Abstract Aims Takotsubo syndrome (TTS) is an acute cardiac condition characterized by a temporary wall motion abnormality of the left ventricle that mimics an acute coronary syndrome (ACS). TTS usually occurs following emotionally or physically triggering event. We report a rare case of Takotsubo syndrome following a pacemaker implantation. Methods and results A 77-year-old woman was admitted to our hospital with a third-degree atrioventricular block. She was asymptomatic with a history of hypertension, diabetes, hyperlipidaemia and extrapyramidal syndrome. Laboratory tests reported High-Sensitive cardiac Troponin T (HS-cTnT) 32.9 ng/L (ULN <14), creatine kinase muscle and brain (CK-MB) 4.1 ng/mL (ULN < 4.94) and NT-proB-type Natriuretic Peptide (NT-proBNP) 1465 pg/ml (ULN < 125). Echocardiography showed a normal left ventricular ejection fraction (EF = 58%) (Figure 2A). The patient underwent dual chamber pacemaker implantation without immediate complications. Three days later, a routine ECG showed new T wave inversions (Figure 1), in absence of symptoms. Echocardiography revealed apical akinesia, with ‘apical ballooning’ (EF 30%) (Figure 2B). Serum cardiac markers were increased (CK-MB 8.2 ng/ml, HS-cTnT 189.7 pg/ml, NT-proBNP 15 005 pg/ml. A coronary angiography excluded obstructive coronary artery disease (Figure 3). Given the impossibility of carrying out a cardiac RMI for the recent pacemaker implantation and after exclusion of other diagnoses, pacemaker implantation induced Takotsubo syndrome was suspected. Conclusions The trigger of this case of TTS was the pacemaker implantation, a relatively brief and painless procedure that, in her case could have constitute a considerable emotional and physical stress. To the best of our knowledge 13 cases of TTS after pacemaker implantation have been described to date. Of those cases, four had an asymptomatic course. Therefore, the real incidence of TTS following pacemaker implantation may be underestimated and ECG and echocardiography should always be performed after pacemaker implantation.