Physical exercise on the rat ventral prostate: Steroid hormone receptors,apoptosis and cell proliferation

Studies have investigated the effect of exercise on prostate cancer risk. However, there are still doubts regarding the correlation between physical activity and the steroid hormones with respect to the reduction of the risk for prostatic lesions. We evaluated the levels of corticosterone, dihydrotestosterone (DHT), testosterone, estradiol, and steroid hormone receptors, and investigated the relationship between apoptosis and cell proliferation in the rat ventral prostate after training. Two groups were included in this study: control and trained. The trained group was submitted to training for 13 weeks (1 week of adaptation). Two days after the last training session, all animals were euthanized, and the intermediate and distal regions of the ventral prostate were collected and processed for immunohistochemistry, Western blotting and hormonal analyses. Physical exercise increased the corticosterone plasma, DHT and testosterone. In addition, androgen receptor expression was lower and estrogen receptor (ER) α and ER β expression were higher in the trained group. However, the trained group showed disruption of the ratio of apoptotic to proliferating cells, indicating a predominance of apoptosis. We conclude that physical exercise alters the sex hormones and their receptors and is associated with the disruption of the balance between apoptosis and cell proliferation in the rat ventral prostate.     

Norfloxacin versus thiamphenicol for treatment of uncomplicated gonorrhea in Rwanda.

In an open prospective study, single oral doses of norfloxacin (800 mg) and thiamphenicol (2.5 g) were used to treat, respectively, 122 and 46 consecutive patients with uncomplicated gonorrhea. Neisseria gonorrhoeae was eradicated from 119 (97.5%) patients treated with norfloxacin and from 35 (76.0%) patients treated with thiamphenicol. Norfloxacin treatment failure was not related to drug resistance or to insufficient absorption of the drug. Thiamphenicol failure correlated with low in vitro susceptibility of the infecting strain. In a single oral dose of 800 mg, norfloxacin appeared to be an excellent alternative treatment regimen for uncomplicated gonorrhea in an area with a high prevalence of penicillin-resistant gonococci.     

Effects of Iron Chelators on the Formation and Development of Aspergillus fumigatus Biofilm

Iron acquisition is crucial for the growth of Aspergillus fumigatus. A. fumigatus biofilm formation occurs in vitro and in vivo and is associated with physiological changes. In this study, we assessed the effects of Fe chelators on biofilm formation and development. Deferiprone (DFP), deferasirox (DFS), and deferoxamine (DFM) were tested for MIC against a reference isolate via a broth macrodilution method. The metabolic effects (assessed by XTT [2,3-bis[2-methoxy-4-nitro-5-sulfophenyl]-2H-tetrazolium-5-carboxanilide inner salt]) on biofilm formation by conidia were studied upon exposure to DFP, DFM, DFP plus FeCl₃, or FeCl₃ alone. A preformed biofilm was exposed to DFP with or without FeCl₃. The DFP and DFS MIC₅₀ against planktonic A. fumigatus was 1,250 μM, and XTT gave the same result. DFM showed no planktonic inhibition at concentrations of ≤2,500 μM. By XTT testing, DFM concentrations of <1,250 μM had no effect, whereas 2,500 μM increased biofilms forming in A. fumigatus or preformed biofilms (P < 0.01). DFP at 156 to 2,500 μM inhibited biofilm formation (P < 0.01 to 0.001) in a dose-responsive manner. Biofilm formation with 625 μM DFP plus any concentration of FeCl₃ was lower than that in the controls (P < 0.05 to 0.001). FeCl₃ at ≥625 μM reversed the DFP inhibitory effect (P < 0.05 to 0.01), but the reversal was incomplete compared to the controls (P < 0.05 to 0.01). For preformed biofilms, DFP in the range of ≥625 to 1,250 μM was inhibitory compared to the controls (P < 0.01 to 0.001). FeCl₃ at ≥625 μM overcame inhibition by 625 μM DFP (P < 0.001). FeCl₃ alone at ≥156 μM stimulated biofilm formation (P < 0.05 to 0.001). Preformed A. fumigatus biofilm increased with 2,500 μM FeCl₃ only (P < 0.05). In a strain survey, various susceptibilities of biofilms of A. fumigatus clinical isolates to DFP were noted. In conclusion, iron stimulates biofilm formation and preformed biofilms. Chelators can inhibit or enhance biofilms. Chelation may be a potential therapy for A. fumigatus, but we show here that chelators must be chosen carefully. Individual isolate susceptibility assessments may be needed.     

APOE ɛ4 constrains engagement of encoding‐related compensatory networks in amnestic mild cognitive impairment

People with amnestic mild cognitive impairment (aMCI), compared to healthy older adults (HO), benefit less from semantic congruent cues during episodic encoding. The presence of the apolipoprotein E (APOE) ?4 makes this congruency benefit smaller, but the neural correlates of this deficit are unknown. Here, we estimated the source generators of EEG oscillatory activity associated with successful encoding of face‐location associations preceded by semantically congruent and incongruent cues in HO (N = 26) and aMCI subjects (N = 34), 16 of which were ?4 carriers (?4⁺) and 18 ?4 noncarriers (?4^?). Source estimation was performed in those spectrotemporal windows where the power of low‐alpha, high‐alpha, and beta oscillatory activity differed either between congruent and incongruent faces or between groups. Differences in high‐alpha and beta‐oscillatory dynamics indicated that aMCI ?4⁺ are unable to activate lateral regions of the temporal lobe involved in associative memory and congruency benefit in HO. Interestingly, and regardless of APOE genotype, aMCI activated additional regions relative to HO, through alpha oscillations. However, only activation in a distributed fronto‐temporo‐parietal network in ?4 noncarriers was paralleled by enhanced memory. On the contrary, the redundant prefrontal activation shown by aMCI ?4⁺ did not prevent performance from decreasing. These results indicate that the effect of aMCI‐related degeneracy on functional networks is constrained by the presence of APOE ?4. Whereas individuals with aMCI ?4^? activate attentional, perceptual and semantic compensatory networks, aMCI ?4⁺ show reduced processing efficiency and capacity. © 2015 Wiley Periodicals, Inc.     

Identification of Nucleoside Analogs as Inducers of Neuronal Differentiation in a Human Reporter Cell Line and Adult Stem Cells

Nucleoside analogs (NSAs) were among the first chemotherapeutic agents and could also be useful for the manipulation of cell fate. To investigate the potential of NSAs for the induction of neuronal differentiation, we developed a novel phenotypic assay based on a human neuron‐committed teratocarcinoma cell line (NT2) as a model for neuronal progenitors and constructed a NT2‐based reporter cell line that expressed eGFP under the control of a neuron‐specific promoter. We tested 38 structurally related NSAs and determined their activity to induce neuronal differentiation by immunocytochemistry of neuronal marker proteins, live cell imaging, fluorometric detection and immunoblot analysis. We identified twelve NSAs, which induced neuronal differentiation to different extents. NSAs with highest activity carried a halogen substituent at their pyrimidine nucleobase and an unmodified or 2′‐O‐methyl substituted 2‐deoxy‐β‐D‐ribofuranosyl residue as glyconic moiety. Cladribine, a purine nucleoside with similar structural features and in use to treat leukemia and multiple sclerosis, induced also differentiation of adult human neural crest‐derived stem cells. Our results suggest that NSAs could be useful for the manipulation of neuronal cell fate in cell replacement therapy or treatment of neurodegenerative disorders. The data on the structure and function relationship will help to design compounds with increased activity and low toxicity.