Position dependent right ventricular dysfunction caused by a giant right coronary artery aneurysm

We describe an instructive case of a 79-year-old patient with a giant coronary aneurysm and a second smaller aneurysm with an uncommon symptomatology. Giant coronary artery aneurysms (>2 cm diameter) are rare pathologic entities with a prevalence of 0.02%. They either can be congenital malformations or are atherosclerotic in origin. Although spontaneous rupture of giant coronary artery aneurysms has been reported, they generally remain silent or induce myocardial ischemia. Our patient, however, showed no signs of myocardial malperfusion but transient position-dependent pre-syncope. The cardiologic work-up and the intraoperative considerations regarding patient management are described. During surgery, manipulation of the giant coronary artery aneurysm caused impairment of right ventricular function and regional wall hypokinesia, as assessed by transesophageal echocardiography. Venous cannulation of the right atrium was thus abandoned and extracorporeal circulation was established via the femoral vein. Subsequent dissection and surgical repair were uneventful and further recovery of the elderly patient was uncomplicated. This case underlines that once the diagnosis is established, proper perioperative management enables successful surgical treatment even of patients of advanced age.     

Combinatorial optimization of multiple MALDI matrices on a single tissue sample using inkjet printing

Taking advantage of the drop-on-demand capabilities of inkjet printing, the first example of a single tissue being used as a substrate for preparing combinatorial arrays of different matrix-assisted laser desorption/ionization (MALDI) matrices in multiple concentrations on a single chip is reported. By varying the number of droplets per spot that were printed, a gradient array of different amounts of matrix material could be printed on a single chip, while the selection of matrices could be adjusted by switching different matrix materials. The result was a two-dimensional array of multiple matrices on a single tissue slice, which could be analyzed microscopically and by MALDI to elucidate which combination of matrix and printing conditions offered the best resolution in terms of spot-to-spot distance and signal-to-noise ratios for proteins in the recorded MS spectra. This combinatorial approach enables the efficient optimization of possible matrices in an organized, side-by-side array format, which can particularly be useful for the detection of specific protein markers.     

Dichloroacetate (DCA) sensitizes both wild-type and over expressing Bcl-2 prostate cancer cells in vitro to radiation

BACKGROUND: Bcl-2 protects cells from apoptosis and provides a survival advantage to cells over-expressing this oncogene. In addition, over expression of Bcl-2 renders cell resistant to radiation therapy. Recently, dichloroacetate (DCA) was proven to potentiate the apoptotic machinery by interacting with Bcl-2. In this study, we investigated whether treating human prostate cancer cells with DCA could modulate Bcl-2 expression and if the modulation in Bcl-2 expression could render the Bcl-2 over expressing cells more susceptible to cytotoxicity effects of radiation. METHODS: PC-3-Bcl-2 and PC-3-Neo human prostate cancer cells treated with DCA in addition to irradiation were analyzed in vitro for changes in proliferation, clonogenic survival, apoptosis, cell cycle phase distribution, mitochondrial membrane potential, and expression of Bcl-2, Bcl-xL, Bax, or Bak proteins. RESULTS: DCA alone produced significant cytotoxic effects and was associated with G1 cell cycle arrest. Furthermore, DCA was associated with an increased rate of apoptosis. The combination of DCA with irradiation sensitized both cell lines to radiation's killing effects. Treatment of PC-3-Bcl-2 or PC-3-Neo with DCA and irradiation resulted in marked changes in various members of the Bcl-2 family. In addition, DCA therapy resulted in a significant change in mitochondria membrane potential, thus supporting the notion that DCAs effect is on the mitochondria. CONCLUSIONS: This is the first study to demonstrate DCA can effectively sensitize wild-type and over expressing Bcl-2 human prostate cancer cells to radiation by modulating the expression of key members of the Bcl-2 family. Together, these findings warrant further evaluation of the combination of DCA and irradiation.     

Pyridazinoquinolinetriones as NMDA glycine-site antagonists with oral antinociceptive activity in a model of neuropathic pain

A series of 7-chloro-2,3-dihydro-2-[1-(pyridinyl)alkyl]-pyridazino[4,5-b]quinoline-1,4,10(5H)-triones were synthesized and found to have potent activity at the glycine site of the NMDA receptor. In some cases, these compounds possessed poor aqueous solubility that may have contributed to poor rat oral bioavailability. Subsequently, compounds have been identified with improved aqueous solubility and oral bioavailability. Several of these compounds were examined in a rat chronic constrictive injury (CCI) model of neuropathic pain and found to have potent activity when dosed orally.     

Focus from superior vena cava and atypical atrioventricular nodal reentrant tachycardia in patient with paroxysmal atrial fibrillation--selective RF ablation

We describe a case of a 34-year-old woman with atrial fibrillation induced by focal frequent tachycardias from superior vena cava and atypical atrioventricular nodal reentrant tachycardia. Selective isolation of SVC and slow pathway RF ablation cured all types of atrial arrhythmias. The slow pathway was localised in the postero-septal mitral anulus and ablated from the left atrium.