António Freitas

Synthesis and analgesic properties of 5-acyl-arylhydrazone 1-H pyrazolo [3,4-b] pyridine derivatives

A series of 5-acyl-arylhydrazone 1-H pyrazolo [3,4-b] pyridine derivatives (1), planned by applying classical ring isosterism, were synthesized in order to evaluate the structure-activity relationship (SAR), especially the participation of the structural acyl-arylhydrazone subunit in the analgesia. The synthetic route used produced the derivatives 1 in approximately 40% overall yield, using 9 as key intermediate. The results obtained from this study showed that in general the compounds of this series present a powerful analgesic activity in the test of abdominal contortions induced by acetic acid i.p. in albino mice, indicating the participation of the acyl-arylhydrazone moiety, as well the relevance of the substituent of the aryl ring, in the activity.

Synthesis and analgesic properties of new 4-arylhydrazone 1-H pyrazole [3,4-b] pyridine derivatives

Based on the principle of bioisosterism, a successful strategy in the planning of new drugs, we describe in this work the synthesis and the analgesic activity of the new functionalized arylcarbaldehyde 4-(1-phenyl-3-methylpyrazolo[3,4-b]pyridine) hydrazone derivatives 5a-m. These derivatives (5a-m) were synthesized in ca. 45% overall yield, using 4-(1-phenyl-3-methylpyrazolo[3,4-b]pyridinyl) hydrazine 6, as key intermediate. by applying classical synthetic methods to construct the aryl-hydrazone unit at C-4 of the heterocyclic system. Compound 6 was prepared from the corresponding 4-chloro-(N-phenyl-3-methylpyrazolo[3,4-b]pyridine) derivative 7 in very high yield. The antinociceptive activity of these new compounds 5a was evaluated by a test of abdominal contortions induced by 0.6% acetic acid solution i.p. in albino mice. The compounds 5f, 5g, 5j and 5k were strongly active showing a good analgesic profile.

Antinociceptive, anti-inflammatory and antipyretic effects of 1.5-diphenyl-1H-Pyrazole-3-carbohydrazide, a new heterocyclic pyrazole derivative

AIMS Heterocyclic pyrazole derivative has been described for the treatment of pain and inflammatory diseases. This study evaluated the in vivo, antinociceptive, anti-inflammatory and antipyretic effects of 1.5-diphenyl-1H-Pyrazole-3-carbohydrazide (1.5-DHP) and the in vivo or in vitro mechanism of action. MAIN METHODS Acetic acid-induced writhing, hot-plate and formalin-induced nociception tests were used to evaluate the antinociceptive effect, while the rota-rod test was used to assess the motor activity. Croton oil-induced ear edema and carrageenan-induced peritonitis tests were used to investigate the anti-inflammatory effect of 1.5-DHP. The antipyretic effect was assessed using the LPS-induced fever model. The mechanism of action was evaluated by PGE2 and TNF-α measurement and cyclooxygenase inhibition assay. KEY FINDINGS Oral administration (p.o.) of 1.5-DHP (1, 3, 10 mg/kg) caused a dose-related inhibition of the acetic acid-induced writhing, however the highest dose was not effective on the hot-plate and rota-rod. In the formalin-induced nociception, 1.5-DHP (10mg/kg, p.o.) inhibited only the late phase of nociception. This same dose of 1.5-DHP also reduced the croton oil-induced ear edema. 1.5-DHP (3, 10, 30 mg/kg, p.o.) produced a dose-related reduction of leukocyte migration on the carrageenan-induced peritonitis. 1.5-DHP (60 mg/kg, p.o.) reduced the fever and the increase of PGE2 concentration in the cerebrospinal fluid induced by LPS. 1.5-DHP inhibited both COXs in vitro. Finally, 1.5-DHP (10 mg/kg, p.o.) reduced the TNF-α concentration in peritoneal exudates after carrageenan injection. SIGNIFICANCE These results indicate that 1.5-DHP produces anti-inflammatory, antinociceptive and antipyretic effects by PGE2 synthesis reduction through COX-1/COX-2 inhibition and by TNF-α synthesis/release inhibition.

New pyrazolylhydrazone derivatives as inhibitors of platelet aggregation.

Abstract— A series of 5‐pyrazolylhydrazone derivatives was designed to be mixed hybrid isosteres of both BW755C and CBS‐1108, which belong to the class of dual cyclo‐oxygenase and 5‐lipoxygenase inhibitors. Some derivatives of this series inhibit the in‐vitro platelet aggregation of citrated platelet‐rich rabbit plasma induced by ADP (5 μm), collagen (5 μg mL−1) and arachidonic acid (100 μm). The structure‐activity relationships of this class of compounds were determined from these results. When ADP is used as the aggregation inducer, the presence of free oxygenated substituents at the p‐position in the phenyl subunit of the hydrazone moiety favours inhibitory activity; p‐methoxyformylbenzene‐5‐(1‐phenyl‐3‐methyl‐4‐nitropyrazolyl)hydrazone (100 μm), which has a methoxy group at this position was the most active with 62·8% inhibition of aggregation. In contrast, substitution in the aryl ring does not affect the aggregation induced by collagen, whereas the non‐substituted compound, formylbenzene‐5‐(1‐phenyl‐3‐methyl‐4‐nitropyrazolyl)hydrazone, showed similar activity to those of substituted derivatives. In the arachidonic acid assays, the presence of an aryl ring linked to the hydrazone moiety, with an adequate electronic density at the ring due to the nature of its substitutents, is an important structural requirement for inhibitory activity.

Symptomatic charcoal heart

A 47-year-old woman with a past history of left choroidal malignant melanoma submitted to eye enucleation 13 years before presented to the emergency department because of pleuritic chest pain, shortness of breath, and tiredness. Transthoracic echocardiography revealed pericardial thickening and multiple confluent hypoechoic nodular images, extending into …

Contrast-enhanced CT and MRI for detecting neck metastasis of oral cancer: comparison between analyses performed by oral and medical radiologists

OBJECTIVES The aim of the study was to verify the concordance of contrast-enhanced CT (CECT) and MRI evaluation among four radiologists in detecting metastatic cervical lymph nodes of oral cancer patients. METHODS Ten patients underwent clinical and imaging examinations (CECT and MRI). Four radiologists, two oral and maxillofacial radiologists (OMRs) and two medical radiologists (MRs), independently analysed the images twice. Cohens kappa index and Wilcoxon signed-rank test were used to verify the concordance between all analyses. RESULTS Regarding the interobserver agreement, the OMRs presented excellent kappa values for determining the regional lymph nodes (N-stage) in both CECT and MRI. The MRs presented moderate agreement for CECT evaluation at the first reading, but no concordance was found for the other analyses. When each imaging modality was analysed separately, kappa values were higher between all examiners. Greater variability was demonstrated between N-stage evaluation using different examinations. All radiologists were able to identify a greater number of metastatic lymph nodes in CECT than in MRI, except one MR, but no significant difference was found for all readers. The differences between the number of metastatic lymph nodes among all radiologists were not statistically significant. Moderate intraobserver agreement was observed for CECT and MRI evaluation, except for one MR. CONCLUSIONS The differences found between the N-stage performed by OMRs and MRs support the necessity of a multidisciplinary approach in the imaging evaluation of metastatic nodes. Further studies are necessary to confirm which imaging modality should be employed when evaluating neck areas.

Acute coronary syndrome of paradoxical origin

We describe a rare case of acute myocardial infarction secondary to paradoxical embolism complicating acute pulmonary embolism. A 44-year-old woman presented to the emergency department with chest pain. The physical examination was unremarkable except for oxygen saturation of 75%, and the electrocardiogram showed ST-segment elevation in the inferior leads. Urgent coronary angiography showed a distal occlusion of the right coronary artery and multiple thrombi were aspirated. Despite relief of chest pain and electrocardiogram normalization, her oxygen saturation remained low (90%) with high-flow oxygen by mask. The transthoracic echocardiogram showed a mass in the left atrium and dilatation of the right chambers, while the transesophageal echocardiogram showed a thrombus attached to the interatrial septum in the region of the foramen ovale. Color flow imaging was consistent with a patent foramen ovale. Thoracic computed tomography angiography documented thrombi in both branches of the pulmonary trunk. After five days on anticoagulation, the patient underwent surgical foramen ovale closure.

Double orifice mitral valve in an asymptomatic adult with an unusual combination of congenital malformations: a case report

http://dx.doi.org/10.1016/j.rppnen.2017.02.006 2173-5115/© 2017 Sociedade Portuguesa de Pneumologia. Published by CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4 Physical examination and chest X-ray were unremarkble. A chest high resolution computed tomography (HRCT) howed diffuse ground glass opacities and ground glass entrilobular opacities, besides lobular air trapping on he expiratory acquisition (Fig. 1A and B). Bronchoscopy

Pseudoaneurisma ventricular esquerdo – um desafio diagnóstico

Left ventricular pseudoaneurysm is a rare complication of acute myocardial infarction, associated with high mortality. However, it can present in a non-specific manner, complicating and delaying the diagnosis. The authors present the case of a 65-year-old patient, hypertensive, with no other known relevant medical history, who presented with chest pain, cough and left pleural effusion, initially attributed to a pulmonary process. However, these were in fact the result of a left ventricular pseudoaneurysm following silent acute myocardial infarction. The diagnosis was suspected on echocardiography and confirmed by cardiac magnetic resonance imaging, and the patient underwent successful surgical pseudoaneurysm repair. This case illustrates an atypical presentation of a left ventricular pseudoaneurysm, in which the manifestations resulted from pericardial and pleural extension of the inflammatory process associated with contained myocardial rupture. The case demonstrates the need for a high index of suspicion, and the value of imaging techniques to confirm it, in order to proceed with appropriate surgical treatment, and thus modify the course of the disease.

Adult Congenital Heart Disease: a Substrate for Infective Endocarditis

CIV Os autores apresentam o caso de um homem de 39 anos de idade, com historia de cardiopatia congenita nao especificada, assintomatico, nao submetido a qualquer intervencao e sem seguimento cardiologico. Foi internado por quadro insidioso de perda ponderal, cansaco e febre. Apresentava sopro sistolico IV/VI em todo o precordio, hepatoesplenomegalia e edema dos membros inferiores. Nas hemoculturas isolou-se Streptococcus viridans e identificaram-se multiplos focos de embolizacao pulmonar e esplenica. Os ecocardiogramas transtoracico e transesofagico revelaram comunicacao interventricular (CIV) restritiva subpulmonar e estenose pulmonar infundibular (Figura 1, Video 1), com multiplas vegetacoes em relacao com a CIV, que envolviam a cuspide coronaria direita da valvula aortica e faziam protusao na câmara de saida do ventriculo direito (CSVD) (Figura 2, Videos 2 e 3). Observavam-se ainda vegetacoes aderentes a valvula pulmonar e na parede da arteria pulmonar, por provavel lesao de jato (Figura 3, Video 4). Foi estabelecido o diagnostico de endocardite infeciosa e o doente foi submetido a cirurgia, onde se