Use of Possible Synergistic Expression of p53 and p185 as a Prognostic Tool for Stage I Non-small-cell Lung Cancer

The possible interaction between the quantified overexpression of the oncoproteins p53 and p185 was evaluated. These proteins have already been independently defined as prognostic factors in non-small-cell lung cancer (NSCLC). p53 and p185 levels were determined in stage I patients (n= 40) from a sample of 102 NSCLC sufferers who underwent surgery for precocious disease during the period October 1991 to June 1994. The resected tumors were histologically classified and included 15 adenocarcinomas (37.5%), 1 large-cell carcinoma (2.5%), and 24 epidermoid (60%) carcinomas. The p53 concentration of tumor specimens was determined by luminescence immunoanalysis and was defined as positive if it was above the minimum value detectable by the method (0.01 ng/mg). The p185 protein was quantified by enzyme-linked immunoassay, and the 80th percentile of the frequency distribution was used as the reference cutoff value (348.8 U/mg). Survival and disease-free-survival (DFS) rates were estimated at 24 months after intervention. There were no significant differences in survival or DFS of patients with adenocarcinoma-type tumors for subjects with independent p185 values < 348.8 U/mg and those showing values ≥ 348.8 U/mg. Neither were there differences observed between patients with positive and negative p53 values. In patients with epidermoid-type tumors the cumulative survival was significantly higher in p53-negative than in p53-positive patients (p= 0.03) and was also higher in patients with p185 levels < 348.8 U/mg than in those with values ≥ 348.8 U/mg (p= 0.00001). These patients showed no significant differences with respect to recurrence rate. The possible synergistic behavior of p53 and p185 levels as a prognostic factor was evaluated in patients with epidermoid-type tumors. p53-negative and p53-positive patients were grouped according to a p185 level of less than or more than 348.8 U/mg. Significant differences were seen in both survival rates and DFS between groups. Individual analysis of relative risks showed an increased risk of death and greater recurrence rate in patients with p185 levels ≥ 348.8 U/mg and a greater recurrence rate in patients with p53-positive values. Multivariate analysis established that the multiplicative, synergistic, prognostic effect of p53 and p185 was not significant. The existence of a significant, synergistic, prognostic effect of the p185 and p53 proteins in NSCLC could not be proven. However, a greater prognostic potential of the quantified overexpression of p185 with respect to that of p53 was established. An additive effect in the prognostic potential of both proteins was also observed (stratified analysis).     

West Nile virus associated with equid encephalitis in Brazil, 2018

Mosquito‐borne arboviruses are a major public health concern worldwide and are responsible for emerging and re‐emerging diseases. Taken together, the arboviruses have a strong impact on public health and are the most common causes of equine encephalitis. In‐depth diagnostic investigation of equine viral encephalitis is of utmost importance for the epidemiological surveillance and control of this disease. Regarding neurological disorders in equids, in April–May 2018, at least 12 cases of equid mortality with acute neurological signs were reported in six farms from Espirito Santo state, Brazil. To investigate the aetiological agent of this neurological disease outbreak, central nervous system (CNS) fragments from two horses and two donkeys were submitted for virologic diagnosis. Rabies, equine herpesvirus‐1, and arbovirus‐associated encephalomyelitis were investigated using differential diagnosis techniques. West Nile virus (WNV) was detected by nested RT‐PCR in CNS fragments from each of the four animals in the study and confirmed by nucleotide sequencing. This is the first case of neurological disease in equids confirmed to be associated with WNV infection in Brazil. This finding unveils a new and urgent field of research and the need to understand the epidemiological and clinical characteristics of the disease and the risk to public health.     

Peptides stimulating synthesis of extracellular matrix used in anti-ageing cosmetics: Are they clinically tested? A systematic review of the literature

Peptides stimulating synthesis of extracellular matrix are now commonly used in the production of anti-ageing cosmetics. However, much uncertainty still exists about the methodology of their clinical assessment. The aim of the study was to review the literature for clinical study designs assessing the efficacy of these peptides. The authors searched systematically publications indexed in PubMed, Scope and Web of Science, according to the PRISMA protocol. Altogether 12 scientific papers, reporting results of 15 independent studies were identified. Out of these 15 studies, only six used a placebo control. Double-blinding was applied in five out of 15 studies. Nine studies were based on female-only populations. For the product performance evaluation, most of the studies (10 out of the 15) used image-based methods. The literature on the topic is sparse. The studies carried out so far have many methodological limitations. Most of the clinical experiments hitherto conducted were non-double-blind and used no placebo control. There is a need for better planned and controlled clinical trials in this area.     

Antinociceptive effect of the monoterpene R-(+)-limonene in mice

In the present study were studied the antinociceptives properties of monoterpene R-(+)-limonene (LM) in chemical and thermal models of nociception in mice. The R-(+)-limonene was administered, intraperitoneally (i.p.), at doses of 25 and 50 mg/kg. The results showed significant inhibition produced on chemical nociception induced by intraperitoneal acetic-acid and in the second phase of subplantar formalin test, but did not manifest a significant effect in hot-plate test. The R-(+)-limonene-induced antinociception in second phase of formalin test was insensitive to naloxone (1 mg/kg, s.c.). It was also demonstrated that R-(+)-limonene (25, 50 mg/kg) neither significantly enhanced the pentobarbital-sleeping time nor impaired the motor performance in rota-rod test, indicating that the observed antinociception is unlikely to be due to sedation or motor abnormality. In conclusion it may be suggested that the R-(+)-limonene presented antinociceptive activity and that, probably, this action can be related with peripheral analgesia, but, not with the stimulation of opioids receptors.     

Changes in purines concentration in the cerebrospinal fluid of patients experiencing pain: A case-control study

This study analyzes the relationship between extracellular purines and pain perception in humans. Cerebrospinal fluid (CSF) levels of purines and their metabolites were compared between patients displaying acute and/or chronic pain syndromes and control subjects. The CSF levels of IMP, inosine, guanosine and uric acid were significantly increased in the chronic pain group and correlated with pain severity (P < 0.05). Patients displaying both chronic and acute pain presented similar changes in the CSF purines concentration (P < 0.05). However, in the acute pain group, only CSF inosine and uric acid levels were significantly increased (P < 0.05). These findings suggest that purines, in special inosine, guanosine and uric acid, are associated with the spinal mechanisms underlying nociception.