Adrenal hemorrhage and non-ST elevation myocardial infarction: an antiphospholipid syndrome dilemma.

Antiphospholipid syndrome (APS) can affect different organ systems, including the heart and adrenal glands. Despite being known for its prothrombotic characteristics, APS can have serious bleeding complications. Occasionally, thrombotic and bleeding episodes can present simultaneously in an APS patient. Whenever these events co-occur, resuming anticoagulation becomes a topic of debate. As such, we present the case of a 43-year-old male with triple positive antiphospholipid antibodies, indicating APS, who presented with chest pain. Anticoagulants were switched one month before presentation from warfarin to a direct oral anticoagulant, rivaroxaban. Non-ST elevation myocardial infarction, as well as new-onset left-sided adrenal hemorrhage, were diagnosed. The patient developed adrenal insufficiency; therefore, corticosteroids were administered, and warfarin was resumed to prevent further thrombotic episodes.

Enhanced antitumor effect of L-buthionine sulfoximine or ionizing radiation by copper complexes with 2,2´-biquinoline and sulfonamides on A549 2D and 3D lung cancer cell models.

Two ternary copper(II) complexes with 2,2'-biquinoline (BQ) and with sulfonamides: sulfamethazine (SMT) or sulfaquinoxaline (SDQ) whose formulae are Cu(SMT)(BQ)Cl and Cu(SDQ)(BQ)Cl·CH3OH, in what follows SMTCu and SDQCu, respectively, induced oxidative stress by increasing ROS level from 1.0 µM and the reduction potential of the couple GSSG/GSH2. The co-treatment with L-buthionine sulfoximine (BSO), which inhibits the production of GSH, enhanced the effect of copper complexes on tumor cell viability and on oxidative damage. Both complexes generated DNA strand breaks given by-at least partially-the oxidation of pyrimidine bases, which caused the arrest of the cell cycle in the G2/M phase. These phenomena triggered processes of apoptosis proven by activation of caspase 3 and externalization of phosphatidylserine and loss of cell integrity from 1.0 µM. The combination with BSO induced a marked increase in the apoptotic population. On the other hand, an improved cell proliferation effect was observed when combining SDQCu with a radiation dose of 2 Gy from 1.0 µM or with 6 Gy from 1.5 µM. Finally, studies in multicellular spheroids demonstrated that even though copper(II) complexes did not inhibit cell invasion in collagen gels up to 48 h of treatment at the higher concentrations, multicellular resistance outperformed several drugs currently used in cancer treatment. Overall, our results reveal an antitumor effect of both complexes in monolayer and multicellular spheroids and an improvement with the addition of BSO. However, only SDQCu was the best adjuvant of ionizing radiation treatment.

6-Methoxyquinoline complexes as lung carcinoma agents: induction of oxidative damage on A549 monolayer and multicellular spheroid model.

The aim of this work was to study the antitumor effects and the mechanisms of toxic action of a series of 6-methoxyquinoline (6MQ) complexes in vitro. The Cu(II) and Zn(II) complexes (Cu6MQ and Zn6MQ) are formulated as M(6MQ)2Cl2; the Co(II) and Ag(I) compounds (Co6MQ and Ag6MQ) are ionic with formulae [Ag(6MQ)2]+NO3- and H(6MQ)+[Co(6MQ)Cl3]- (where H(6MQ)+ is the protonated ligand). We found that the copper complex, outperformed the Co(II), Zn(II) and Ag(I) complexes with a lower IC50 (57.9 µM) in A549 cells exposed for 24 h. Cu6MQ decreased cell proliferation and induced oxidative stress detected with H2DCFDA at 40 µM, which reduces GSH/GSSG ratio. This redox imbalance induced oxidative DNA damage revealed by the Micronucleus test and the Comet assay, which turned into a cell cycle arrest at G2/M phase and induced apoptosis. In multicellular spheroids, the IC50 values tripled the monolayer model (187.3 µM for 24 h). At this concentration, the proportion of live/dead cells diminished, and the spheroids could not proliferate or invade. Although Zn6MQ also decreased GSH/GSSG ratio from 200 µM and the cytotoxicity is related to oxidative stress, the induction of the hydrogen peroxide levels only doubled the control value. Zn6MQ induced S phase arrest, which relates with the increased micronucleus frequency and with the induction of necrosis. Finally, our results reveal a synergistic activity with a 1:1 ratio of both complexes in the monolayer and multicellular spheroids.

Descripción anatómica de la musculatura intrínseca del miembro torácico de león (Panthera leo) / Anatomical description of the intrinsic muscle of thoracic limb of lion (Panthera leo)

El presente estudio tuvo como objetivo el describir la musculatura intrínseca del miembro torácico del león africano (Panthera leo). Para tal efecto se utilizó un ejemplar hembra, donado por el Zoológico Metropolitano de Santiago-Chile, fijado y conservado. La disección se llevó a cabo, de proximal a distal, considerando las cuatro regiones topográficas de dicho miembro: Cintura Escapular, Brazo, Antebrazo y Mano. Se discuten y comparan los hallazgos anatómicos observados, con lo descrito para el gato doméstico y trabajos realizados por otros autores en Ocelote (Leopardus pardalis), Puma (Puma concolor) y en la propia especie en estudio. La finalidad del presente trabajo fue aportar al conocimiento de la anatomía de especies exóticas, con proyección médico quirúrgica.

The objective of this study was to describe the intrinsic muscles of the thoracic limb of the African lion (Panthera leo). For this purpose a fixed and preserved female specimen donated by the Metropolitan Zoo in Santiago, Chile, was used. The dissection was carried out, from proximal to distal, considering the four topographical regions of that limb: Scapular girdle, arm, forearm and hand. Anatomical findings observed are discusses and compared to those described for the domestic cat and works by other authors in ocelot (Leopardus pardalis), puma (Puma concolor) and the species under study. The purpose of this work was to contribute to the knowledge of the anatomy of this exotic species, with medical and surgical projections.

Oxidovanadium(IV) complexes with chrysin and silibinin: anticancer activity and mechanisms of action in a human colon adenocarcinoma model.

Vanadium compounds were studied during recent years to be considered as a representative of a new class of nonplatinum metal antitumor agents in combination to its low toxicity. On the other hand, flavonoids are a wide family of polyphenolic compounds synthesized by plants that display many interesting biological effects. Since coordination of ligands to metals can improve the pharmacological properties, we report herein, for the first time, a exhaustive study of the mechanisms of action of two oxidovanadium(IV) complexes with the flavonoids: silibinin Na2[VO(silibinin)22]·6H2O (VOsil) and chrysin [VO(chrysin)2EtOH]2(VOchrys) on human colon adenocarcinoma derived cell line HT-29. The complexes inhibited the cell viability of colon adenocarcinoma cells in a dose dependent manner with a greater potency than that the free ligands and free metal, demonstrating the benefit of complexation. The decrease of the ratio of the amount of reduced glutathione to the amount of oxidized glutathione were involved in the deleterious effects of both complexes. Besides, VOchrys caused cell cycle arrest in G2/M phase while VOsil activated caspase 3 and triggering the cells directly to apoptosis. Moreover, VOsil diminished the NF-kB activation via increasing the sensitivity of cells to apoptosis. On the other hand, VOsil inhibited the topoisomerase IB activity concluding that this is important target involved in the anticancer vanadium effects. As a whole, the results presented herein demonstrate that VOsil has a stronger deleterious action than VOchrys on HT-29 cells, whereby suggesting that Vosil is the potentially best candidate for future use in alternative anti-tumor treatments.

Oxidative stress in diabetic rats induced by streptozotocin: protective effects of melatonin.

We have studied the effect of the administration of two doses of melatonin (melatonin 100 and melatonin 200 microg/kg bw) on diabetes and oxidative stress experimentally induced by the injection of streptozotocin (STZ) in female Wistar rats. STZ was injected as a single dose (60 mg/kg i.p. in buffered citrate solution, pH 4.0) and melatonin (melatonin 100, 100 microg/kg/day i.p.; melatonin 200, 200 microg/kg/day i.p.) beginning 3 days before diabetes induction and continuing until the end of the study (8 weeks). The parameters analysed to evaluate oxidative stress and the diabetic state were a) for oxidative stress, changes of lipoperoxides (i.e., malondialdehyde, MDA) in plasma and erythrocytes and the changes in reduced glutathione (GSH) in erythrocytes and b) for diabetes, changes in glycemia, lipids (triglycerides: TG; total cholesterol: TC; HDL-cholesterol, HDL-c), percentage of glycosylated hemoglobin (Hb%), and plasma fructosamine. The injection of STZ caused significant increases in the levels of glycemia, percentage of glycosylated hemoglobin, fructosamine, cholesterol, triglycerides, and lipoperoxides in plasma and erythrocytes, whereas it decreased the levels of HDL-c and the GSH content in erythrocytes. The melatonin 100 dose reduced significantly all these increases, except the percentage of glycosylated hemoglobin. With regard to the decreases of plasma HDL-c and GSH content in erythrocytes, this melatonin dose returned them to normal levels. The melatonin 200 dose produced similar changes, though the effects were especially noticeable in the decrease of glycemia (55% vs. diabetes), percentage of hemoglobin (P < 0.001 vs diabetes), and fructosamine (31% vs. diabetes). This dose also reversed the decreases of HDL-c and GSH in erythrocytes. Both doses of melatonin caused significant reduction of the percentage of glycosylated hemoglobin in those groups that were non-diabetic. These illustrate the protective effect of melatonin against oxidative stress and the severity of diabetes induced by STZ. In particular, this study confirms two facts: 1) the powerful antioxidant action of this pineal indole and 2) the importance of the severity of oxidative stress to maintain hyperglycemia and protein glycosylation, two pathogenetic cornerstones indicative of diabetic complications. Melatonin reduces remarkably the degree of lipoperoxidation, hyperglycemia, and protein glycosylation, which gives hope to a promising perspective of this product, together with other biological antioxidants, in the treatment of diabetic complications where oxidative stress, either in a high or in a low degree, is present.

[Postoperative hyperuricemia of cyanotic and acyanotic congenital cardiopathies]. / Hiperuricemia en el post-quirúrgico de cardiopatías congénitas cianóticas y acianóticas.

In a prospective study, 10 children with congenital heart disease were studied before and after surgery (24-48 h). Mean age and weight, type of disease and surgery performed are described in Table 1. Six patients had acyanotic disease and 4 were cyanotic. Before surgery, the acyanotic group (AG) showed hyperuricemia compared to normal children of the same chronological age (mean +/- SE: 5.53 +/- 0.42 vs 4.27 +/- 0.22, p less than 0.02). Initial seric creatinine (sCr), increased in 3 patients of the AC and in the 4 patients of the cyanotic group (CG) compared to normal values of sCr for height (AG: 0.47 +/- 0.05 vs 0.34 +/- 0.03, p less than 0.05; CG: 0.63 +/- 0.05 vs 0.38 +/- 0.05, p less than 0.01). Post-surgery, sCr and serum uric acid (sUA) increased significantly at 24 and 48 h in both groups (Fig 1); at 24 h the increment in sUA in the AG was higher than that in the CG (p less than 0.05). There was a direct and significant correlation between the increment in sUA and sCr in the AG (Fig. 2). The urine excretion of uric acid paralleled the increment of sUA in the CG (Table 2). Fractional excretion of, sodium (FENa) was less than 1% and greater than 1% in the AG and the CG, respectively, being the basal FENa of the AG significantly lower (Table 3).(ABSTRACT TRUNCATED AT 250 WORDS)

Hiperuricemia en el post-quirurgico de cardiopatias congenitas cianoticas y acianoticas / Postoperative hyperuricemia of cyanotic and acyanotic congenital cardiopathies

En forma prospectiva, se estudiaron 10 niños con cardiopatías congénitas antes de la cirugía y en el post-operatorio inmediato(24-48 h). La edad promedio de los pacientes fue de 2,81 años (0,5-8,75). Seis de los 10 niños eran portadores de una cardiopatía acianótica (CA) y 4 de cardiopatías cianóticas (CC). Antes de la cirugía, el grupo acianótico (GA) presentaba hiperuricemia significativa con respecto a niños sanos de igual edad cronológica. En el mismo perído de estudio 3 de los 6 pacientes del GA y los 4 pacientes de GC, mostraban caída de la filtración glomerular expresada por un aumento de la creatinina suérica (Crs) en relación al valor normal de Crs por talla. En el post-operatorio inmediato, la Crs aumentó en forma significativa con respecto a los valores basales (pre-quirúrgicos), tanto en el GA como en el GC. El ácido úrico suérico (AUs), mostró en los dos grupos de pacientes el mismo comportamiento que la Crs, siendo el aumento del SAUs sa las 24 h significativamente mayor en el GA. Este aumento del AUs en el GA, se correlacionó en forma directa y significativa con el aumento de la Crs. En el GC, el aumento del AUs se acompañó de un aumento tanto en la excreción fraccional de ácido úrico como en la excreción de ácido úrico ajustada a la filtración glomerular; esta respuesta no fue observada en el GA, a pesar de una hiperuricemia significativamente mayor. En el GA, la excreción fraccional de sodio tanto antes de la cirugía como en el post-operatorio fue < de 1% y en el período basal, esta fue significativamente menor que la del GC. A las 24 h de la cirugía, el aumento significativo del U/P de úrea en el GA con respecto al basal y al del GC, se acompaño de un aumento también significativo del U/P de potasio y de la actividad de la aldosterona. Nuestros datos indicarían que la hiperuricemia en el post-quirúrgico de las cardiopatías congénitas no está limitada a las CC y puede estar presente antes de la cirugía. En las CA, además de una disminución de la excreción por caída de la filtración glomerular, existiría una alteración en el transporte tubular bidireccional del ácido úrico. En las CC, los datos sugerirían que la hiperuricemia obedecería a una disminucuón de la excreción como consecuencia de una disminución de la masa funcionante renal. La sobreproducción de ácido úrico, no puede ser descartada en los dos grupos

Hiperuricemia en el post-quirúrgico de cardiopatías congénitas cianóticas y acianóticas. / [Postoperative hyperuricemia of cyanotic and acyanotic congenital cardiopathies]

In a prospective study, 10 children with congenital heart disease were studied before and after surgery (24-48 h). Mean age and weight, type of disease and surgery performed are described in Table 1. Six patients had acyanotic disease and 4 were cyanotic. Before surgery, the acyanotic group (AG) showed hyperuricemia compared to normal children of the same chronological age (mean +/- SE: 5.53 +/- 0.42 vs 4.27 +/- 0.22, p less than 0.02). Initial seric creatinine (sCr), increased in 3 patients of the AC and in the 4 patients of the cyanotic group (CG) compared to normal values of sCr for height (AG: 0.47 +/- 0.05 vs 0.34 +/- 0.03, p less than 0.05; CG: 0.63 +/- 0.05 vs 0.38 +/- 0.05, p less than 0.01). Post-surgery, sCr and serum uric acid (sUA) increased significantly at 24 and 48 h in both groups (Fig 1); at 24 h the increment in sUA in the AG was higher than that in the CG (p less than 0.05). There was a direct and significant correlation between the increment in sUA and sCr in the AG (Fig. 2). The urine excretion of uric acid paralleled the increment of sUA in the CG (Table 2). Fractional excretion of, sodium (FENa) was less than 1

and greater than 1

in the AG and the CG, respectively, being the basal FENa of the AG significantly lower (Table 3).(ABSTRACT TRUNCATED AT 250 WORDS)

Hiperuricemia en el post-quirurgico de cardiopatias congenitas cianoticas y acianoticas / Postoperative hyperuricemia of cyanotic and acyanotic congenital cardiopathies

En forma prospectiva, se estudiaron 10 niños con cardiopatías congénitas antes de la cirugía y en el post-operatorio inmediato(24-48 h). La edad promedio de los pacientes fue de 2,81 años (0,5-8,75). Seis de los 10 niños eran portadores de una cardiopatía acianótica (CA) y 4 de cardiopatías cianóticas (CC). Antes de la cirugía, el grupo acianótico (GA) presentaba hiperuricemia significativa con respecto a niños sanos de igual edad cronológica. En el mismo perído de estudio 3 de los 6 pacientes del GA y los 4 pacientes de GC, mostraban caída de la filtración glomerular expresada por un aumento de la creatinina suérica (Crs) en relación al valor normal de Crs por talla. En el post-operatorio inmediato, la Crs aumentó en forma significativa con respecto a los valores basales (pre-quirúrgicos), tanto en el GA como en el GC. El ácido úrico suérico (AUs), mostró en los dos grupos de pacientes el mismo comportamiento que la Crs, siendo el aumento del SAUs sa las 24 h significativamente mayor en el GA. Este aumento del AUs en el GA, se correlacionó en forma directa y significativa con el aumento de la Crs. En el GC, el aumento del AUs se acompañó de un aumento tanto en la excreción fraccional de ácido úrico como en la excreción de ácido úrico ajustada a la filtración glomerular; esta respuesta no fue observada en el GA, a pesar de una hiperuricemia significativamente mayor. En el GA, la excreción fraccional de sodio tanto antes de la cirugía como en el post-operatorio fue < de 1% y en el período basal, esta fue significativamente menor que la del GC. A las 24 h de la cirugía, el aumento significativo del U/P de úrea en el GA con respecto al basal y al del GC, se acompaño de un aumento también significativo del U/P de potasio y de la actividad de la aldosterona. Nuestros datos indicarían que la hiperuricemia en el post-quirúrgico de las cardiopatías congénitas no está limitada a las CC y puede estar presente antes de la cirugía. En las CA, además de una disminución de la excreción por caída de la filtración glomerular, existiría una alteración en el transporte tubular bidireccional del ácido úrico. En las CC, los datos sugerirían que la hiperuricemia obedecería a una disminucuón de la excreción como consecuencia de una disminución de la masa funcionante renal. La sobreproducción de ácido úrico, no puede ser descartada en los dos grupos (AU)

Anapsos, an antipsoriatic drug, in atopic dermatitis.

An open, controlled study was carried out in young patients with atopic dermatitis, who during one month received oral anti-psoriatic drug, anapsos (n = 46), or antihistamines (n = 30), simultaneously with topic applications. The activity and extension of the cutaneous lesions improved under both treatments, but more markedly with anapsos in spite of the fact that topical applications did not contain steroids in the group treated with anapsos, and the effect was still appreciable several months after interruption of medication. Anapsos, which was well tolerated, considerably relieved the respiratory symptoms of all patients with asthma. Studies performed on patients with atopic dermatitis have shown high IgE levels, eosinophils and T4 counts, and a marked decrease in T8 suppressor cells in peripheral blood. Our data also show a slight decrease in T8 cells (%), a significant increase in T4 sub-sets (%) and a high T4/T8 ratio as a previously reported by several authors. Such an imbalance between helper and suppresor cells may cause alterations in the response to extrinsic and intrinsic antigens, as shown in particular by the abnormally high IgE levels observed in atopic dermatitis. Anapsos was associated with a correction in T lymphocytes imbalances, specifically through the increase of the initially low T8 cells levels and subsequent normalization of the mean T4/T8 index. The tolerance and promising therapeutic activity of this antipsoriatic drug deserve further research in other conditions characterized by a deficit of suppressor cells.