Anti–Trypanosoma cruzi effect of the photodynamic antiparasitic chemotherapy using phenothiazine derivatives as photosensitizers

Lasers in Medical Science - Chagas disease is endemic in Latin America and increasingly found in non-endemic countries. Its treatment is limited due to the variable efficacy and several side...     

Left subclavian artery stenting: an option for the treatment of the coronary-subclavian steal syndrome

Introduction

The subclavian steal syndrome is characterized by the vertebral artery flow inversion, due to a stenotic lesion in the origin of the subclavian artery. The Coronary-subclavian Steal Syndrome is a variation of the Subclavian Steal Syndrome and is characterized by inversion of flow in the Internal Thracic artery that has been used as conduct in a myocardial revascularization. Its diagnosis must be suspected in patients with difference in pulse and arterial pressure in the upper limbs, that present with angina pectoris and that have done a myocardial revascularization. Its treatment must be a surgical bypass or a transluminal angioplasty.

Objective

The objective is to show the left subclavian artery stenting as a safe and effective method to treat the coronary-subclavian steal syndrome.

Methods

Historical prospective, non-randomized trial, through revision of the hospital records of the patients treated with the stenting of the left subclavian artery, from January 2006 to September 2012.

Results

In the mentioned period, 4.291 miocardial revascularizations were performed with the use of the left mammary artery, and 16 patients were identified to have the Coronary-subclavian steal syndrome. All of them were submitted to endovascular treatment. The success rate was 100%; two patients experienced minor complications; none of them presented with major complications. Eleven of the 16 patients had ultrassonographic documentation of patent stent for at least one year; two patients lost follow up and other two died.

Conclusion

The stenting of the left subclavian artery is a good option for the treatment of the Coronary-subclavian Steal Syndrome, with high level of technical and clinical success.     

Influence of valve prosthesis type on early mortality in patients undergoing valve surgery

Objective

To evaluate the influence of the type of prosthesis in-hospital mortality in the post-operative period in patients who had valve replacement.

Methods

A cross-sectional data, such as gender, origin, age, etiology, echocardiograph data, the type of surgery performed and the prosthesis used in cases of valve replacement were analyzed retrospectively.

Results

We reviewed 353 charts of patients who underwent valve replacement surgery. The mean age was 41.87±17.9 years. Regarding gender, 52.8% were female. As for the origin, 61.1% came from small cities within the state. Of all patients, 58.5% suffered from rheumatic disease. Assessing the type of prosthesis implanted, 70% held replace by bioprosthesis and 30% metallic. The hospital mortality in this study was 11%, with no significant difference between the types of prosthesis utilized.

Conclusion

The type of implant used had no effect on in-hospital mortality.     

Kidney Retransplantation: Removal or Persistence of the Previous Failed Allograft?

A significant percentage of patients with failed renal graft are candidates for retransplantation. The outcomes of retransplantation are poorer than those of primary transplantation and sensitization is documented to be a major reason. The management of a failed allograft that is not immediately symptomatic is still very controversial. The aim of this study was to determine the impact of the failed allograft nephrectomy on a subsequent transplantation and its importance in the sensitization. We performed a retrospective analysis of the local prospective transplantation registry of the outcome of 126 second kidney transplantations among 2438 transplantations performed in our unit between June 1980 and March 2013, comparing those who underwent allograft nephrectomy prior to retransplantation with those who retained the failed graft. Primary endpoints were graft and patient survival. The levels of panel-reactive antibodies (PRA) and rate of acute rejections on retransplantation outcomes were also studied. Among the 126 patients who underwent a second renal transplantation, 76 (60.3%) had a prior graft nephrectomy (Group A), whereas 50 (39.7%) kept their failed graft (Group B). Group A showed significantly more positive PRA levels when compared with the other group (38% vs 10%; P < .001), as measured before the most recent transplantation, and a higher rate of acute rejection (19% vs 5.6%; P = .016). There were 28 (36%) renal allograft losses for Group A and 18 (36%) for those who had not had transplantectomy (P = not significant [NS]). One-, 3-, and 5-year graft survival rates were 96.6%, 90.7%, and 83.4%, respectively, in Group A and 95%, 82%, and 68.4%, respectively, in Group B, with no statistical differences (P = .19). Five-year actuarial patient survival rates in the 2 groups was 89.3% and 82.8%, respectively (P = .55). Multivariate analysis showed that PRA level and delayed graft function (DGF) had a statistically significant influence on graft survival (P = .028; odds ratio [OR] = 1.029; and P = .024; OR = 8.6), irrespective of whether the patient had graft nephrectomy or not. The allosensitization indicated by PRA increases after transplantectomy and leads to a higher incidence of acute rejection after retransplantation. Nephrectomy of failed allograft does not seem to significantly influence the survival of a subsequent graft. The decision to remove or retain a failed graft in the context of retransplantation should thus be based on known clinical indications for the procedure.     

Changes in the serum levels of brain-derived neurotrophic factor in adults with attention deficit hyperactivity disorder after treatment with atomoxetine

Rationale

Atomoxetine (ATX) is a non-stimulant drug approved for the treatment of attention deficit hyperactivity disorder (ADHD). Although animal models have provided evidence that brain-derived neurotrophic factor (BDNF) is involved in the effects of ATX in the brain, there are no studies of BDNF in ADHD patients undergoing treatment with ATX.

Objectives

The aim of this study was to evaluate the possible changes in serum levels of BDNF in adults treated with ATX and its relationship with clinical improvement.

Methods

A total of 54 adults with ADHD (age 33.43?±?8.99 years) without any medical or psychiatric comorbidities were treated with ATX for 3 months; 35 of them completed the protocol. The clinical data for ADHD diagnosis, including Conners’ ADHD Rating Scale and blood samples, were collected at baseline (V1) and at the end of the treatment (V2).

Results

Adults with ADHD who completed ATX treatment for 3 months showed a significant improvement in their clinical symptoms. No significant differences were found in BDNF levels before and after treatment with ATX in the whole group of patients (p?=?0.15). The inattentive subgroup of ATX responders showed a decrease of serum BDNF after 3 months of ATX treatment (p?=?0.05) not present in the combined subtype (p?=?0.82).

Conclusions

These results suggest that BDNF is not directly involved in the neurobiological mechanisms of ATX-induced improvement of clinical symptoms of ADHD. The differences between the combined and inattentive subtypes in serum BDNF changes suggest selective ATX-induced effects in the function of brain circuitry.     

Potential risk of biochar-amended soil to aquatic systems: an evaluation based on aquatic bioassays

It is vital to address potential risks to aquatic ecosystems exposed to runoff and leachates from biochar-amended soils, before large scale applications can be considered. So far, there are no established approaches for such an assessment. This study used a battery of bioassays and representative aquatic organisms for assessing the acute toxicity of water-extractable fractions of biochar-amended soil, at reported application rates (80 t ha^?1). Biochar-amended aqueous soil extracts contained cadmium (Cd), cobalt (Co), chromium (Cr), copper (Cu), manganese (Mn), zinc (Zn), nickel (Ni), lead (Pb), arsenic (As) and mercury (Hg) (Σmetals 96.3 µg l^?1) as well as the 16 priority PAHs defined by the U.S. Environmental Protection Agency (Σ₁₆PAHs 106 ng l^?1) at contents in the range of current EU regulations for surface waters. Nevertheless, acute exposure to soil-biochar (SB) extracts resulted in species-specific effects and dose–response patterns. While the bioluminescent marine bacterium Vibrio fischeri was the most sensitive organism to aqueous SB extracts, there were no effects on the growth of the microalgae Pseudokirchneriella subcapitata. In contrast, up to 20 and 25 % mobility impairment was obtained for the invertebrate Daphnia magna upon exposure to 50 and 100 % SB extract concentrations (respectively). Results suggest that a battery of rapid and cost-effective aquatic bioassays that account for ecological representation can complement analytical characterization of biochar-amended soils and risk assessment approaches for surface and groundwater protection.     

The expression patterns and prognostic significance of pleckstrin homology-like domain family A (PHLDA) in lung cancer and malignant mesothelioma

BackgroundPleckstrin homology domain family A (PHLDA) genes play important roles in cancer cellular processes, including inhibiting Akt activation, repressing growth factor signaling, inhibiting the negative feedback of EGFR/ErbB2 signaling cells, and inducing apoptosis. However, the prognostic significance of PHLDA in non-small cell lung cancer (NSCLC) and malignant pleural mesothelioma (MM) remains unclear. The present study investigates the associations between PHLDA expression patterns and their prognostic value in lung adenocarcinoma (LUAD) and MM.MethodsWe analyzed PHLDA family members at the genomic level in silico to explore their mRNA expression pattern and predictive significance in LUAD and MM. We then created a PHLDA–drug interaction network and a protein-protein interaction (PPI) network using different databases. Finally, we immunohistochemically assessed the protein expression of each PHLDA family member on tissue microarrays (TMAs) in both LUAD and MM cohorts with long-term follow-up.ResultsWhile PHLDA1 mRNA expression in both LUAD and MM was lower than that of normal tissue, PHLDA2 mRNA was significantly overexpressed in LUAD, and PHLDA3 mRNA was overexpressed in MM. In NSCLC, both low PHLDA1 mRNA expression and high PHLDA3 mRNA expression correlated with worse overall survival (OS) (P<0.01), whereas high PHLDA2 mRNA expression was associated with better OS (P<0.01). In MM, patients presenting high PHLDA1 and PHLDA2 mRNA expression had poor OS (P=0.01 and P<0.01, respectively). In addition, the PHLDA-drug interaction network indicated that several common drugs could potentially modulate PHLDA expression, and the PPI network suggested that PHLDA1 interacts with Notch family members, whereas PHLDA3 interacts with TP53. Our results also showed that the expression of PHLDA2 and PHLDA3 was significantly higher in LUAD and MM than that of PHLDA1 (P<0.05) and was associated with the risk of death. While patients with PHLDA2 >85.09 cells/mm² had a low risk of death (P=0.01) and a median survival time of 48 months, those with PHLDA3 <70.38 cells/mm² had a high risk of death (P=0.03) and a median survival time of 34 months.ConclusionsWe shed light on the role of the PHLDA family as promising predictive biomarkers and potential therapeutic targets in LUAD and MM.     

The transverse aortic constriction heart failure animal model: a systematic review and meta-analysis

Heart Failure Reviews - The transverse aortic constriction (TAC) model is frequently used to study adverse cardiac remodeling upon pressure overload. We set out to define the most important...     

Novel Selective Inhibitor of Leishmania (Leishmania) amazonensis Arginase

Arginase is a glycosomal enzyme in Leishmania that is involved in polyamine and trypanothione biosynthesis. The central role of arginase in Leishmania (Leishmania) amazonensis was demonstrated by the generation of two mutants: one with an arginase lacking the glycosomal addressing signal and one in which the arginase‐coding gene was knocked out. Both of these mutants exhibited decreased infectivity. Thus, arginase seems to be a potential drug target for Leishmania treatment. In an attempt to search for arginase inhibitors, 29 derivatives of the [1,2,4]triazolo[1,5‐a]pyrimidine system were tested against Leishmania (Leishmania) amazonensis arginase in vitro. The [1,2,4]triazolo[1,5‐a]pyrimidine scaffold containing R₁ = CF₃ exhibited greater activity against the arginase rather than when the substituent R₁ = CH₃ in the 2‐position. The novel compound 2‐(5‐methyl‐2‐(trifluoromethyl)‐[1,2,4]triazolo[1,5‐a]pyrimidin‐7‐yl)hydrazinecarbothioamide (30) was the most potent, inhibiting arginase by a non‐competitive mechanism, with the Ki and IC₅₀ values for arginase inhibition estimated to be 17 ± 1 μm and 16.5 ± 0.5 μm , respectively. These results can guide the development of new drugs against leishmaniasis based on [1,2,4]triazolo[1,5‐a]pyrimidine derivatives targeting the arginase enzyme.