Differential scanning calorimetric study of antibiotic distamycin A binding with chromatin within isolated rat liver nuclei

Context: Natural oligopeptide antibiotic distamycin A (Dst) biosynthesized by Streptomyces distallicus is traditionally used in medical practice as an anti-inflammatory and antitumour drug.

Objective: Dst was investigated for its effect on the structural components of native chromatin directly within isolated rat liver nuclei in the presence of physiologically significant cations (magnesium or spermine and spermidine).

Materials and methods: Differential scanning calorimetry (DSC) was used to study the Dst action at molar ratio Dst/DNA?=?0.1 and 0.15?mM Dst on the melting profile of nuclei suspension in different conditions.

Results: Results showed that the thermodynamic parameters of control nuclei in the presence of polyamines or Mg^2+?were different. The incubation of nuclei with Dst raised transition temperatures of relaxed (peak II) and topologically constrained DNA (peak III) by 6–8?°C and decreased by 2–4?°C that of core-histones (peak I). The total excess transition enthalpy (ΔH_exc) in buffer with polyamines (24.7?kJ/mol DNA nucleotides) increased by1.5 times versus control but in buffer with Mg²⁺, the value of ΔH_exc (35.8?kJ/mol DNA nucleotides) remained unchanged.

Conclusions: The association of Dst with chromatin in the nucleus weakens histone-DNA contacts and causes additional strengthening of interaction between two complementary DNA chains. Our results contribute towards validation of DSC to test drug ability to modulate chromatin structure in the physiological environment and to clarify the mechanism of these modulations.     

Facial expression recognition in Alzheimer’s disease: A systematic review

Introduction: It is well established that behavioral variant frontotemporal dementia can impair social and emotional function. However, there is no consensus regarding how Alzheimer’s disease can affect facial expression recognition. We aim to systematically review all the literature addressing this issue over the last 10 years.

Method: We conducted a search based on the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). The search for literature was undertaken on 19 September 2017, using Pubmed, SciELO, BIREME, and Thomson Reuters Web of Science electronic databases. The key terms for the search were: Alzheimer’s disease, dementia, and facial expression recognition.

Results: We screened 173 articles, and 22 of them were selected. The most common methodology involved showing participants photographs of people expressing the six basic emotions—fear, anger, sadness, disgust, surprise, and happiness. Results were ambiguous. Among people with mild Alzheimer’s disease, happiness was easier to recognize than the other five basic emotions, with sadness and anger the most difficult to recognize. In addition, the intensity level of the emotions presented seems to be important, and facial expression recognition is related to specific cognitive capacities, including executive function and visuoperceptual abilities. Impairment in facial expression recognition does not appear to be a consistent neuropsychological finding in Alzheimer’s disease.

Conclusions: The lack of standardized assessment instruments and the heterogeneity of the methods and samples used across studies hamper comparisons. Future researches should investigate facial expression recognition through more ecological and standardized methods.     

Melatonin and Metformin Failed to Modify the Effect of Dacarbazine in Melanoma

Lessons Learned

• Melatonin did not increase the efficacy of systemic chemotherapy in melanoma.
• Metformin did not increase the efficacy of systemic chemotherapy in melanoma.

     

S-Nitrosoglutathione formation at gastric pH is augmented by ascorbic acid and by the antioxidant vitamin complex,Resiston

Context: Exogenous nitrogen oxides must be made bioavailable to sustain normal physiology because nitric oxide synthase (NOS) deficient mice are viable. In the stomach, S-nitrosoglutathione (GSNO) is formed from ingested nitrite and high levels of airway glutathione (GSH) that are cleared and swallowed. However, gastric GSNO may be broken down by nutrients like ascorbic acid (AA) before it is absorbed.

Objective: To study the effect of AA on GSNO formation and stability.

Materials and methods: GSH and nitrite were reacted with or without 5?mM AA or Resiston (5?mM AA with retinoic acid and α-tocopherol). GSNO was measured by reduction/chemiluminescence and HPLC. AA and reduced thiols were measured colorimetrically. O-Nitrosoascorbate and AA were measured by gas chromatography–mass spectrometry (GC–MS).

Results: GSNO was formed in saline and gastric samples (pH ～4.5) from physiological levels of GSH and nitrite. Neither AA nor Resiston decreased [GSNO] at pH >3; rather, they increased [GSNO] (0.12?±?0.19?μM without AA; 0.42?±?0.35?μM with AA; and 0.43?±?0.23?μM with Resiston; n?=?4 each; p?≤?0.05). However, AA compounds decreased [GSNO] at lower pH and with incubation >1?h. Mechanistically, AA, but not dehydroascorbate, increased GSNO formation; and the O-nitrosoascorbate intermediate was formed.

Conclusions: AA, with or without other antioxidants, did not deplete GSNO formed from physiological levels of GSH and nitrite at pH >3. In fact, it favoured GSNO formation, likely through O-nitrosoascorbate. Gastric GSNO could be a NOS-independent source of bioavailable nitrogen oxides.     

Acute effects of aerobic exercise on mood and hunger feelings in male obese adolescents: a crossover study

ABSTRACT: BACKGROUND: The aim of this study was to determine the acute effects of exercise intensity on anxiety, mood states and hunger in obese adolescents. METHODS: Subjects were eight male obese adolescents (age 15.44 +/- 2.06y; BMI 33.06 +/- 4.78 kg/m2). Each subject underwent three experimental trials: 1) Control, seated for 30 min; 2) Low intensity exercise (LIE) - exercise at 10% below ventilatory threshold (VT); 3) High intensity exercise (HIE) - exercise at 10% above VT. Anxiety (STAI Trait/State), mood (POMS) and hunger (VAS) were assessed before and immediately after the experimental sessions. Comparisons between trials and times were assessed using Kruskal-Wallis and Wilcoxon tests, respectively. Associations between variables were described using a Spearman test. RESULTS: The largest increase in hunger was observed after LEI (914.22%). Both exercise sessions increased anxiety, fatigue and decreased vigor (p < 0.05). CONCLUSIONS: Acute exercise bouts are associated with negative changes in anxiety and mood, and with increases in hunger in obese adolescents.     

The chicken chorioallantoic membrane model in biology,medicine and bioengineering

The chicken chorioallantoic membrane (CAM) is a simple, highly vascularized extraembryonic membrane, which performs multiple functions during embryonic development, including but not restricted to gas exchange. Over the last two decades, interest in the CAM as a robust experimental platform to study blood vessels has been shared by specialists working in bioengineering, development, morphology, biochemistry, transplant biology, cancer research and drug development. The tissue composition and accessibility of the CAM for experimental manipulation, makes it an attractive preclinical in vivo model for drug screening and/or for studies of vascular growth. In this article we provide a detailed review of the use of the CAM to study vascular biology and response of blood vessels to a variety of agonists. We also present distinct cultivation protocols discussing their advantages and limitations and provide a summarized update on the use of the CAM in vascular imaging, drug delivery, pharmacokinetics and toxicology.     

Nocardiosis: an overview and additional report of 28 cases in cattle and dogs

Phenotypic characteristics, antimicrobial susceptibility profile, and clinical-epidemiological features of 28 Nocardia strains isolated from 19 cases of bovine mastitis, eight cutaneous-subcutaneous lesions and one case of pneumonia in dogs were evaluated. Microbiological, biochemical, cytological and scanning electron microscopy methods were used in diagnosis. Nocardia asteroides type IV, Nocardia otitidiscaviarum,Nocardia nova (type III) and Nocardia farcinica (type V) were isolated from bovine milk, bronchial lavage and/or cutaneous-subcutaneous abscesses in dogs. Nocardial bovine mastitis was diagnosed predominantly in clinical cases, in dairy herds with poor environmental hygienic conditions between milking and inappropriate intramammary therapy. Canine nocardiosis was observed commonly in animals co-infected with distemper virus. Sulphamethoxazole-trimethoprim (92.8%), amikacin (92.8%) and ceftiofur (92.8%) were the most effective drugs in 28 isolates. Multiple drug resistance to three or more and five or more antimicrobials was observed in ten (35.7%) and three (10.7%) strains, respectively, predominantly with use of cloxaxillin, cefoperazone and ampicillin. The species (type) classification, clinical-epidemiological characteristics, diagnosis, multiple-drug resistance and public health considerations in Nocardia strains isolated from cattle and dogs in Brazil are discussed, with special reference to report of bovine mastitis by N. otitidiscaviarum by first time in Brazil and the similarity between Nocardia species isolated from human and animal origin.     

A randomized trial of amodiaquine and artesunate alone and in combination for the treatment of uncomplicated falciparum malaria in children from Burkina Faso

Combining artesunate (AR) with existing antimalarial drugs may improve cure rates, delay emergence of resistance and reduce parasite clearance time. In order to investigate the latter, we conducted a randomized clinical trial testing the AR plus amodiaquine (AQ) combination for the treatment of uncomplicated Plasmodium falciparum malaria in Burkina Faso. Children aged 1-15 years were randomly assigned to either AQ (10 mg/kg) or AR (4 mg/kg first day then half dose) or AQ + AR (AQAR) as a single daily dose under supervision for three consecutive days for all groups. Follow-up lasted 28 days. Primary endpoints were parasite and fever clearance time. Eighty-seven children were evaluated: 27 received AQ, 27 AR and 33 AQAR. Using an intention to treat analysis, fever clearance time was similar in the three groups. However, it was significantly faster in the AR (1.21 days; P = 0.02) and AQAR groups (1.19 days; P < 0.01) than in the AQ group (1.46 days) when excluding other concomitant causes of fever. Parasite clearance time was faster in AR (1.13 days; P = 0.008) and AQAR groups (1.13 days; P < 0.01) than in the AQ group (1.6 days). All children cleared their parasites by day 14, including the child with Late Parasitological Failure (LPF) at day 7 after rescue treatment. Only one child (4%) from the AR group and one (4%) from the AQ group presented with asymptomatic parasitaemia at day 7 and day 21, respectively (LPF). Gametocyte carriage was not detectable in any group during follow-up nor was any adverse reaction observed. While resistance to first-line treatment (chloroquine) is already established in the country, AQ and AR used alone or in combination therapy proved highly efficacious in our study. Burkina Faso stands in a very good situation for an internationally recommended switch to AR-containing combination as first-line treatment for uncomplicated malaria. Including AQ in this regimen seems the best option.