Chloroquine and Sulfadoxine Derivatives Inhibit ZIKV Replication in Cervical Cells

Despite the severe morbidity caused by Zika fever, its specific treatment is still a challenge for public health. Several research groups have investigated the drug repurposing of chloroquine. However, the highly toxic side effect induced by chloroquine paves the way for the improvement of this drug for use in Zika fever clinics. Our aim is to evaluate the anti-Zika virus (ZIKV) effect of hybrid compounds derived from chloroquine and sulfadoxine antimalarial drugs. The antiviral activity of hybrid compounds (C-Sd1 to C-Sd7) was assessed in an in-vitro model of human cervical and Vero cell lines infected with a Brazilian (BR) ZIKV strain. First, we evaluated the cytotoxic effect on cultures treated with up to 200 µM of C-Sds and observed CC₅₀ values that ranged from 112.0 ± 1.8 to >200 µM in cervical cells and 43.2 ± 0.4 to 143.0 ± 1.3 µM in Vero cells. Then, the cultures were ZIKV-infected and treated with up to 25 µM of C-Sds for 48 h. The treatment of cervical cells with C-Sds at 12 µM induced a reduction of 79.8% ± 4.2% to 90.7% ± 1.5% of ZIKV–envelope glycoprotein expression in infected cells as compared to 36.8% ± 2.9% of infection in vehicle control. The viral load was also investigated and revealed a reduction of 2- to 3-logs of ZIKV genome copies/mL in culture supernatants compared to 6.7 ± 0.7 × 10⁸ copies/mL in vehicle control. The dose–response curve by plaque-forming reduction (PFR) in cervical cells revealed a potent dose-dependent activity of C-Sds in inhibiting ZIKV replication, with PFR above 50% and 90% at 6 and 12 µM, respectively, while 25 µM inhibited 100% of viral progeny. The treatment of Vero cells at 12 µM led to 100% PFR, confirming the C-Sds activity in another cell type. Regarding effective concentration in cervical cells, the EC₅₀ values ranged from 3.2 ± 0.1 to 5.0 ± 0.2 µM, and the EC₉₀ values ranged from 7.2 ± 0.1 to 11.6 ± 0.1 µM, with selectivity index above 40 for most C-Sds, showing a good therapeutic window. Here, our aim is to investigate the anti-ZIKV activity of new hybrid compounds that show highly potent efficacy as inhibitors of ZIKV in-vitro infection. However, further studies will be needed to investigate whether these new chemical structures can lead to the improvement of chloroquine antiviral activity.     

Leucine Supplementation Accelerates Connective Tissue Repair of Injured Tibialis Anterior Muscle

This study investigated the effect of leucine supplementation on the skeletal muscle regenerative process, focusing on the remodeling of connective tissue of the fast twitch muscle tibialis anterior (TA). Young male Wistar rats were supplemented with leucine (1.35 g/kg per day); then, TA muscles from the left hind limb were cryolesioned and examined after 10 days. Although leucine supplementation induced increased protein synthesis, it was not sufficient to promote an increase in the cross-sectional area (CSA) of regenerating myofibers (p > 0.05) from TA muscles. However, leucine supplementation reduced the amount of collagen and the activation of phosphorylated transforming growth factor-β receptor type I (TβR-I) and Smad2/3 in regenerating muscles (p < 0.05). Leucine also reduced neonatal myosin heavy chain (MyHC-n) (p < 0.05), increased adult MyHC-II expression (p < 0.05) and prevented the decrease in maximum tetanic strength in regenerating TA muscles (p < 0.05). Our results suggest that leucine supplementation accelerates connective tissue repair and consequent function of regenerating TA through the attenuation of TβR-I and Smad2/3 activation. Therefore, future studies are warranted to investigate leucine supplementation as a nutritional strategy to prevent or attenuate muscle fibrosis in patients with several muscle diseases.     

Extraneural ependymoma: Distant bone,lung, liver,and lymph node metastases following bevacizumab

Extraneural metastases of ependymoma are rare, and have been reported in the lungs, lymph nodes, pleura, mediastinum, liver, diaphragmatic muscle, and bone. We report a case of anaplastic ependymoma with distant metastases to the vertebral bones, lungs, liver, and lymph nodes following treatment with bevacizumab. Recent research has hypothesized that angiogenic tumors may develop means of resistance to antiangiogenic therapies, and some evidence suggests potential for antiangiogenic therapies to promote additional means for cancer spread. Nevertheless, antiangiogenic therapies continue to demonstrate potential as potent therapies for the treatment of many cancers, and should continue to be researched for future uses. Pediatr Blood Cancer 2013; 60: 143–145. © 2012 Wiley Periodicals, Inc.     

Response to atomoxetine in boys with high-functioning autism spectrum disorders and attention deficit/hyperactivity disorder

Aim: To study the efficacy and tolerability of atomoxetine in high‐functioning boys with autism spectrum disorders (ASD) and comorbid attention deficit/hyperactivity disorder (AD/HD). Methods: Fourteen boys (age 7–17) participated in a 10‐week open‐label study. Atomoxetine doses were 0.5 mg/kg/day in week 1 and 1.2–1.4 mg/kg/day in weeks 2–10. Changes in AD/HD symptoms were measured by the AD/HD Rating Scale, and global improvements by the Clinical Global Improvement Scale. Both measures were used to assess drug response. Assessments were done at baseline and at weeks 2, 4, 6 and 10. Teacher ratings were done at baseline and 10 weeks. Results: There were significant reductions in AD/HD symptoms rated by parents (p < 0.005) and by teachers (p < 0.05). One participant was rated as ‘Much improved’, five as ‘Moderately improved’, seven as ‘Minimally improved’, and one as ‘Unchanged or worse’. Seven subjects were classified as clinical responders. The most common adverse events were nausea and headache. Two participants discontinued treatment. Conclusion: Seven out of 14 boys with high‐functioning ASD and comorbid AD/HD showed significant reductions in AD/HD symptoms and were classified as responders to atomoxetine. Most children tolerated the drug well.     

Kiddie-SADS Reveals High Rates of DSM-IV Disorders in Children and Adolescents with Autism Spectrum Disorders

Prevalence of current comorbid DSM-IV disorders was assessed in a special school population of children and adolescents with ASD (N = 71, age 6.0–17.9 years), representing all cognitive levels and main ASD subgroups. Symptoms were assessed through parent interview and association to child characteristics was explored. Seventy-two percent was diagnosed with at least one comorbid disorder. Anxiety disorders (41%) and attention deficit/hyperactivity disorder (31%) were most prevalent. Obsessive–compulsive disorder was more common in older children, and oppositional defiant disorder/conduct disorder more prevalent in pervasive developmental disorder, not otherwise specified. Our results show high rates of comorbid DSM-IV disorders and underscore the importance of such evaluation in children ASD. However, diagnostic challenges are present and future research on the diagnostic validity of comorbid psychiatric disorders is needed.     

La vérité dans le contexte de la garde à vue

Today, the gendarmerie in France is equipped with a specialist service to help with inquiries, the Department of Behavioural Science. This department assists with inquiries involving homicide and serial rape by looking purely at the psychological, and focusing in particular upon a suspect's behaviour during police interviews. It is in this constrained environment where a suspect is most likely to lie or clam up that the interviewer must obtain the truth from a suspect, a truth which can only be subjective. In preparation for a hearing, a criminological evaluation of the facts and a study of the personality of the suspect are conducted. The frequent absence of an element of proof in the case handled means that adopting a more rigorous approach including the psychological profile of the suspect is necessary. It is therefore crucial that between the interviewer and the suspect a relationship in which confidences are exchanged is cultivated. In this context, the search for the truth depends upon the detection of a lie. But lies can only be detected by those who help an inquiry. Currently, the search for the truth is still very often in convincing a suspect to confess, the aim being for the interviewer to ‘make the suspect talk’. Although the truth, it can be argued, is independent of a confession. In fact, to base evidence upon the lies, contradictions and inconsistencies in a case can sometimes provide more proof than the confession itself. To receive a truthful interview and confession from a suspect in a limited amount of time to provide evidence for a case is a difficult exercise. Knowing the dynamic of a case, it seems illusory to look for an absolute truth, especially during an interview with a suspect. It would be better to open up the possibilities without making errors and so that the truth may be eventually found.