Nitric Oxide Induction in Peritoneal Macrophages by a 1,2,3-Triazole Derivative Improves Its Efficacy upon Leishmania amazonensis In Vitro Infection.

1,2,3-Triazole is one of the most flexible chemical scaffolds broadly used in various fields. Here, we report the antileishmanial activity of 1,2,3-triazole derivatives, the ultrastructural alterations induced by their treatment, and the nitric oxide (NO) modulation effect on their efficacy against Leishmania amazonensis in vitro infection. After the screening of eleven compounds, compound 4 exhibited better results against L. amazonensis promastigotes (IC50 = 15.52 ± 3.782 µM) and intracellular amastigotes (IC50 = 4.10 ± 1.136 µM), 50% cytotoxicity concentration at 84.01 ± 3.064 µM against BALB/c peritoneal macrophages, and 20.49-fold selectivity for the parasite over the cells. Compound 4 induced ultrastructural mitochondrial alterations and lipid inclusions in L. amazonensis promastigotes, upregulated tumor necrosis factor α, interleukin (IL)-1ß, IL-6, IL-12, and IL-10 messenger RNA expressions, and enhanced the NO production, verified by nitrite (p = 0.0095) and inducible nitric oxide synthase expression (p = 0.0049) quantification, which played an important role in its activity against intramacrophagic L. amazonensis. In silico prediction in association with antileishmanial activity results showed compound 4 as a hit compound with promising potential for further studies of new leishmaniasis treatment options.

Inhibitory Effect of Catechin-Rich Açaí Seed Extract on LPS-Stimulated RAW 264.7 Cells and Carrageenan-Induced Paw Edema.

Açaí berry is a fruit from the tree commonly known as açaízeiro (Euterpe oleracea Mart.) originated from the Amazonian region and widely consumed in Brazil. There are several reports of the anti-inflammatory activity of its pulp and few data about the seed's potential in inflammation control. This work aimed to evaluate the effect of catechin-rich açaí extract on lipopolysaccharide (LPS)-stimulated RAW 264.7 cells and carrageenan-induced paw edema. The treatment with E. oleracea ethyl acetate extract (EO-ACET) was used in an in vitro model performed with macrophages stimulated by LPS, in which pro-inflammatory markers were evaluated, and in an in vivo model of acute inflammation, in which edema inhibition was evaluated. EO-ACET showed an absence of endotoxins, and did not display cytotoxic effects in RAW 264.7 cells. LPS-stimulated cells treated with EO-ACET displayed low levels of nitrite and interleukins (IL's), IL-1ß, IL-6 and IL-12, when compared to untreated cells. EO-ACET treatment was able to inhibit carrageenan-induced paw edema at 500 and 1000 mg/kg, in which no acute inflammatory reaction or low mast cell counts were observed by histology at the site of inoculation of λ-carrageenan. These findings provide more evidence to support further studies with E. oleracea seeds for the treatment of inflammation.

Expansion of arbitrary electromagnetic fields in terms of vector spherical wave functions.

Since 1908, when Mie reported analytical expressions for the fields scattered by a spherical particle upon incidence of plane-waves, generalizing his analysis for the case of an arbitrary incident wave has been an open question because of the cancellation of the prefactor radial spherical Bessel function. This cancellation was obtained before by our own group for a highly focused beam centered in the objective. In this work, however, we show for the first time how these terms can be canceled out for any arbitrary incident field that satisfies Maxwells equations, and obtain analytical expressions for the beam shape coefficients. We show several examples on how to use our method to obtain analytical beam shape coefficients for: Bessel beams, general hollow waveguide modes and specific geometries such as cylindrical and rectangular. Our method uses the vector potential, which shows the interesting characteristic of being gauge invariant. These results are highly relevant for speeding up numerical calculation of light scattering applications such as the radiation forces acting on spherical particles placed in an arbitrary electromagnetic field, as in an optical tweezers system.

Atrial tachycardia originating from the pulmonary vein: importance of the stimulation sites.

The introduction of percutaneous ablative treatments for atrial fibrillation led to new information regarding the region of the left atrium and pulmonary veins, which electrophysiologists had previously overlooked. Initially, procedures for treating atrial fibrillation involved ablation and then the isolation of specific points in the pulmonary veins; this technique is still in use. Subsequent variations have included the use of multiple lines that are guided by electroanatomic mapping. All of these techniques have produced encouraging results, and the importance of stimulation sites in inducing various arrhythmias is known. Nevertheless, pacing maneuvers have rarely been used to evaluate electrophysiologic properties around the target areas.In a 53-year-old man who presented with a focal atrial tachycardia that originated from a pulmonary vein, we used different stimulation sites to induce arrhythmias in the region of the left atrium and pulmonary veins. The resultant unique arrhythmogenic values enabled successful ablation of the culprit pulmonary vein in this patient.

Long-term follow-up after cryothermic ostial pulmonary vein isolation in paroxysmal atrial fibrillation.

OBJECTIVES: This study was designed to evaluate the long-term effect of segmental pulmonary vein (PV) cryoablation in patients with recent-onset paroxysmal atrial fibrillation (PAF). BACKGROUND: Patients with PAF have more triggers to initiate and less substrate to sustain atrial fibrillation (AF). Elimination of the potential initiators alone may be sufficient to abolish the arrhythmia. METHODS: Patients with PAF were prospectively recruited from July 2001 to July 2005. If the triggers for AF were identified, PV cryoisolation of the arrhythmogenic vein(s) was performed. Otherwise, all PVs were isolated. RESULTS: Seventy patients with minimal or no heart disease (54 men; age 40 +/- 10 years) were enrolled. The duration of AF was 4 +/- 1 year. The left ventricular ejection fraction and left atrial size were 59 +/- 8% and 41 +/- 5 mm, respectively. An arrhythmogenic PV was found in 10 patients (14%). Complications occurred in 3 patients (4%). No PV stenosis or esophageal injury was detected during a mean follow-up of 33 +/- 15 months. Thirty-four patients (49%) achieved complete success (no AF and no antiarrhythmic drugs [AAD]); 15 patients (22%) had no recurrences with AAD; and 8 patients (11%), still with sporadic bursts of AF, improved >50% with AAD. Overall, 82% of the patients benefited from the procedure. Patients in whom the arrhythmogenic PV was identified and isolated had no recurrences. CONCLUSIONS: Pulmonary vein cryoisolation is effective in 82% of patients with recent-onset PAF during a mean follow-up of 33 +/- 15 (range 15 to 60) months. If the arrhythmogenic PV is identified and isolated, the long-term outcome is excellent, indicating no need to isolate all PVs.

Long term outcome of cavotricuspid isthmus cryoablation for the treatment of common atrial flutter in 180 patients: a single center experience.

OBJECTIVE: Recent literature has shown that common type atrial flutter (AFL) can recur late after cavotricuspid isthmus (CTI) catheter ablation using radiofrequency energy (RF). We report the long term outcome of a large group of patients undergoing CTI ablation using cryothermy for AFL in a single center. METHODS: Patients with AFL referred for CTI ablation were recruited prospectively from July 2001 to July 2006. Cryoablation was performed using a deflectable, 10.5 F, 6.5 mm tip catheter. CTI block was reassessed 30 min after the last application during isoproterenol infusion. Recurrences were evaluated by 12-lead ECG and 24 h Holter recording every clinic visit (1/3/6/9 and 12 months after the procedure and yearly thereafter) or if symptoms developed. RESULTS: The 180 enrolled patients had the following characteristics: 39 women (22%), mean age 58 years, no structural heart disease in 86 patients (48%), mean left atrium diameter 44+/-7 mm and mean left ventricular ejection fraction 57+/-7%. The average number of applications per patient was 7 (3 to 20) with a mean temperature and duration of -88 degrees C and 3 min, respectively. Acute success was achieved in 95% (171) of the patients. There were no complications. After a mean follow-up of 27+/-17 (from 12 to 60) months, the chronic success rate was 91%. The majority of the recurrences occurred within the first year post ablation. One hundred and twenty three patients had a history of atrial fibrillation (AF) prior to CTI ablation and 85 (69%) of those remained having AF after cryoablation. In 20 of 57 (35%) patients without a history of AF prior to CTI ablation, AF occurred during follow-up. CONCLUSIONS: This prospective study showed a 91% chronic success rate (range 12 to 60 months) for cryoablation of the CTI in patients with common type AFL and ratified the frequent association of AF with AFL.

Can common-type atrial flutter be a sign of an arrhythmogenic substrate in paroxysmal atrial fibrillation? Clinical and ablative consequences in patients with coexistent paroxysmal atrial fibrillation/atrial flutter.

BACKGROUND: The coexistence of atrial fibrillation (AF) and atrial flutter (AFL) is well recognized. AF precedes the onset of AFL in almost all instances. We evaluated the effect of 2 ablation strategies in patients with paroxysmal AF (PAF) and AFL. METHODS AND RESULTS: Ninety-eight patients with PAF/AFL were prospectively recruited to undergo pulmonary vein cryoisolation (PVI). Those with at least 1 episode of sustained common-type AFL were assigned to cavotricuspid isthmus cryoablation followed by a 6-week monitoring period and a subsequent PVI (n=36; group I). Patients with PAF only underwent PVI (n=62; group II). The study included 76 men with a mean age of 50+/-10 years. Most patients (76 [78%]) had no structural heart disease. When the 2 groups were compared, residual AF after a blanking period of 3 months after PVI occurred in 24 patients (67%) in group I versus 7 (11%) in group II (P<0.05). CONCLUSIONS: In patients with PAF and no documented common-type AFL, PVI alone prevented the occurrence of AF in 82%, whereas in patients with AFL/PAF, cavotricuspid isthmus cryoablation and PVI were used successfully to treat sustained common-type AFL but appeared to be insufficient to prevent recurrences of AF. In this population, AFL can be a sign that non-pulmonary vein triggers are the culprit behind AF or that sufficient electrical remodeling has already occurred in both atria, and thus a strategy that includes substrate modification may be required.

Daughter, you broke my heart: accidental thrombosis at a muscular bridge.

We report the case of a 59-year-old trained runner, who sustained an acute myocardial infarction, with residual effort angina, following extreme exertion while experiencing severe anxiety. Coronary angiography revealed that this patient had a myocardial bridge at the mid-left anterior descending artery, and an occlusive clot had developed at the proximal end of the muscular bridge. We discuss the possible relationships between the various circumstances of this sudden event. We argue that, under exceptional conditions, myocardial bridges can lead to myocardial infarction by clot formation.

Effects of pulmonary vein ablation on regional atrial vagal innervation and vulnerability to atrial fibrillation in dogs.

INTRODUCTION: Pulmonary vein (PV) isolation has proven to be an effective therapy for atrial fibrillation (AF). However, clinical evidence suggests that suppression of AF after PV isolation could not be fully attributed to the interruption of electrical conduction in and out of the PVs. Furthermore, little is known regarding the effects of ablation around the PVs on the atrial electrophysiological properties. We aimed to study the changes in atrial response to vagal stimulation (VS) after PV ablation (PVA). METHODS: We studied 11 adult mongrel dogs under general anesthesia. Bilateral cervical sympathovagal trunks were decentralized. Propranolol was given to block sympathetic effects. Multipolar catheters were placed into right atrial appendage (RAA), distal and proximal coronary sinus (CSD, CSP), and left atrial free wall (LAFW). PVA was performed via trans-septal approach. Atrial effective refractory period (AERP) and vulnerability window (VW) of AF were measured with and without VS before and after ablation to isolate the PVs. RESULTS: After ablation, AERP shortening in response to VS significantly decreased in the left atrium (43.64 +/- 21.57 vs 11.82 +/- 9.82 msec, P < 0.001 at LAFW; 50.91 +/- 26.25 vs 11.82 +/- 14.01 msec, P < 0.001 at CSP; 50 +/- 31.94 vs 17.27 +/- 20.54 msec, P < 0.005 at CSD), while the response to VS did not change significantly at RAA (58.18 +/- 28.22 vs 50.91 +/- 22.12 msec, P = 0.245). After ablation, atrial fibrillation VW during VS narrowed (20.63 +/- 11.48 vs 5.63 +/- 8.63 msec, P < 0.03 at LAFW; 26.25 +/- 12.46 vs 5.00 +/- 9.64 msec, P = 0.001 at CSP; 28.75 +/- 18.47 vs 6.88 +/- 7.53 msec, P < 0.02 at CSD, and 33.75 +/- 24.5 vs 16.25 +/- 9.91 msec, P = 0.03 at RAA). CONCLUSIONS: Ablation around the PV ostia diminishes left atrial response to VS and decreases the atrial VW. The attenuated vagal response after ablation may contribute to the suppression of AF.