The Role of Testosterone in the Elderly: What Do We Know?

Testosterone is the most important hormone in male health. Aging is characterized by testosterone deficiency due to decreasing testosterone levels associated with low testicular production, genetic factors, adiposity, and illness. Low testosterone levels in men are associated with sexual dysfunction (low sexual desire, erectile dysfunction), reduced skeletal muscle mass and strength, decreased bone mineral density, increased cardiovascular risk and alterations of the glycometabolic profile. Testosterone replacement therapy (TRT) shows several therapeutic effects while maintaining a good safety profile in hypogonadal men. TRT restores normal levels of serum testosterone in men, increasing libido and energy level and producing beneficial effects on bone density, strength and muscle as well as yielding cardioprotective effects. Nevertheless, TRT could be contraindicated in men with untreated prostate cancer, although poor findings are reported in the literature. In addition, different potential side effects, such as polycythemia, cardiac events and obstructive sleep apnea, should be monitored. The aim of our review is to provide an updated background regarding the pros and cons of TRT, evaluating its role and its clinical applicability in different domains.     

SOAT1: A Suitable Target for Therapy in High-Grade Astrocytic Glioma?

Targeting molecular alterations as an effective treatment for isocitrate dehydrogenase-wildtype glioblastoma (GBM) patients has not yet been established. Sterol-O-Acyl Transferase 1 (SOAT1), a key enzyme in the conversion of endoplasmic reticulum cholesterol to esters for storage in lipid droplets (LD), serves as a target for the orphan drug mitotane to treat adrenocortical carcinoma. Inhibition of SOAT1 also suppresses GBM growth. Here, we refined SOAT1-expression in GBM and IDH-mutant astrocytoma, CNS WHO grade 4 (HGA), and assessed the distribution of LD in these tumors. Twenty-seven GBM and three HGA specimens were evaluated by multiple GFAP, Iba1, IDH1 R132H, and SOAT1 immunofluorescence labeling as well as Oil Red O staining. To a small extent SOAT1 was expressed by tumor cells in both tumor entities. In contrast, strong expression was observed in glioma-associated macrophages. Triple immunofluorescence labeling revealed, for the first time, evidence for SOAT1 colocalization with Iba1 and IDH1 R132H, respectively. Furthermore, a notable difference in the amount of LD between GBM and HGA was observed. Therefore, SOAT1 suppression might be a therapeutic option to target GBM and HGA growth and invasiveness. In addition, the high expression in cells related to neuroinflammation could be beneficial for a concomitant suppression of protumoral microglia/macrophages.     

Online Portable Microcantilever Biosensors for Salmonella enterica Serotype Enteritidis Detection

The micro- and nano-technologies coupled with a deep knowledge of organic/inorganic interfaces guarantee an exceptional sensitivity and specificity of the sensor, while the lab-on-a-chip platform reduces assay times and limits sampling and/or sample preparation, providing compact and portable objects. Therefore, the development of innovative biosensors such as antibody-immobilized microcantilevers can overcome the evident limits of nowadays technologies, such as time consuming, expensiveness, difficult automation, low sensitivity, accuracy, and precision for quantitative methods. The present study proposes two device designs for the detection of food pathogens, exploiting an antibody-immobilized microcantilever biosensors, a novel class of mass detectors. For the first one, we integrated the mechanical sensors on a microfluidic platform (lab-on-a-chip) to perform online analysis, directly in liquid environment. We showed that our portable biosensors could easily detect the presence of pathogenic bacteria such as Salmonella enterica serotype enteritidis in concentration 10⁵ cfu/mL in just 40 min, without any enrichment and/or sample preparation. To increase the mass sensitivity of our analysis, we also fabricated microstructures optimized for vibrating in vacuum environment. Using a dip-and-dry technique, we showed that, in such configuration, the experimental limit of detection is as low as 10³ cfu/mL. Due to the extremely small volumes needed, our biosensors operating in vacuum have the potentiality of detecting the presence or absence of a single cell.     

Phenolic Substances,Flavor Compounds,and Textural Properties of Three Native Romanian Wine Grape Varieties

In this work, the chemical compositions and texture characteristics of three native Romanian wine grape varieties (Feteasc? regal?, Feteasc? alba, and Feteasc? neagr?) were studied. We assessed the distinct characteristics directly linked to their phenolic compositions, volatile profiles, and mechanical properties and compared these characteristics with those of Pinot noir grapes. The effect of the growing zone was also evaluated. Various spectrophotometric indices directly related to the phenolic compositions of berry skins and seeds were determined. The detailed phenolic compositions (anthocyanins, hydroxycinnamoyl tartaric acids, and stilbenes) of the skins were determined using high-performance liquid chromatography methods. Free and bound volatile compounds in the berries were quantified by gas chromatography/mass spectrometry. The textural properties of the skins and seeds were measured by instrumental texture analysis. The results showed high diversity among the varieties and zones that affected the enological potential. Among the white varieties, Feteasc? alb? grapes could be less susceptible to browning as a consequence of their lower trans-caffeoyltartaric acid concentration, whereas Feteasc? regal? grapes from Cluj had the highest concentrations of total free and bound volatile compounds, particularly terpenes and norisoprenoids. Among the red varieties, Feteasc? neagr? was identified as a promising variety to be exploited in the future for its particular phenolic characteristics, particularly those grapes grown in Mica. Nevertheless, Feteasc? neagr? grapes grown in Cluj had the highest total glycosidically bound terpene concentrations. Finally, differences in the mechanical and/or acoustic properties of the skins and seeds could strongly influence the kinetics and completeness of phenolic compound extractions.     

Non-destructive evaluation of ripening and quality traits in apples using a multiparametric fluorescence sensor

BACKGROUND: The detection of pigments and colourless flavonoids in apples can provide a useful indication of fruit quality. Optical methods are preferable because they are fast and non‐destructive. In this study, a fluorescence‐based portable sensor was used in order to non‐invasively determine the content of chlorophylls, anthocyanins and flavonols in Fuji, Granny Smith and Golden Delicious apple cultivars. The aim was to define new non‐destructive optical indices of apple quality. RESULTS: The anthocyanin index (ANTH) in Fuji was higher in the sunny (i.e. sun‐exposed) side of the fruit compared to the shady side. For all cultivars, the flavonol index (FLAV) was higher in the sunny side compared with the shady side. The chlorophyll index (CHL) for the shady sides of Granny Smith and Golden Delicious was significantly higher than for the sunny sides. Fine linear regressions were found between the ANTH, FLAV and CHL indices and the actual anthocyanin, flavonol and chlorophyll concentrations, respectively, which were determined destructively on the apple peel extracts. A negative correlation was found between the apple sugar content and the chlorophyll fluorescence in the far‐red spectral band. CONCLUSION: Our results indicate that a single multiparametric fluorescence‐based sensor can provide valuable non‐destructive markers of ripening and quality in apples. Copyright © 2012 Society of Chemical Industry     

Potent,Metabolically Stable 2‐Alkyl‐8‐(2H‐1,2,3‐triazol‐2‐yl)‐9H‐adenines as Adenosine A2A Receptor Ligands

Inhibition of adenosine A_2A receptors has been shown to elicit a therapeutic response in preclinical animal models of Parkinson’s disease (PD). We previously identified the triazolo‐9H‐purine, ST1535, as a potent A_2AR antagonist. Studies revealed that ST1535 is extensively hydroxylated at the ω‐1 position of the butyl side chain. Here, we describe the synthesis and evaluation of derivatives in which the ω‐1 position has been substituted (F, Me, OH) in order to block metabolism. The stability of the compounds was evaluated in human liver microsomes (HLM), and the affinity for A_2AR was determined. Two compounds, (2‐(3,3‐dimethylbutyl)‐9‐methyl‐8‐(2H‐1,2,3‐triazol‐2‐yl)‐9H‐purin‐6‐amine ( 3 b ) and 4‐(6‐amino‐9‐methyl‐8‐(2H‐1,2,3‐triazol‐2‐yl)‐9H‐purin‐2‐yl)‐2‐methylbutan‐2‐ol ( 3 c ), exhibited good affinity against A_2AR (K_i=0.4 nM and 2 nM , respectively) and high in vitro metabolic stability (89.5 % and 95.3 % recovery, respectively, after incubation with HLM for two hours).     

Determination of the Hydroxyl Value of Soybean Polyol by Attenuated Total Reflectance/Fourier Transform Infrared Spectroscopy

A rapid method for the quantitative determination of the hydroxyl value (OHV) of hydroxylated soybean oils by HATR/FTIR spectroscopy is described. Calibration standards were prepared by the formic acid/hydrogen peroxide method and OH values were determined by the official method of AOCS Tx 1a-66, covering an analytical range of 3.5–125 mg of KOH/g of sample. A partial least squares (PLS) calibration model for the prediction of the hydroxyl value (OHV) was developed based on eight different spectral subregions between 3,150 and 990 cm⁻¹ and combinations of them. On average, 36 samples were used for the modeling and 17 were used for external validation. The resulting calibration was linear over the analytical range and had a standard deviation of 2.334. Validation of the method was carried out by comparing the OHV of a series of hydroxylated soybean oils predicted by the PLS model to the values obtained by the AOCS standard method. A correlation coefficient of R ² = 0.9843 and RMSEC and RMSEP values of, respectively, 3.393 and 3.643 were obtained. After the calibration of the spectrometer, the OHV could be obtained in 2–3 min per sample, a major improvement over conventional wet chemical methods. The advantages of these methodologies are that they do not destroy the sample, have a lower cost, expedite the analysis and do not produce residues. Therefore, they may yield excellent results when used to quantify OHV of soybean polyols obtained by hydroxylation reaction.     

Prodynorphin and Proenkephalin in Cerebrospinal Fluid of Sporadic Creutzfeldt–Jakob Disease

Proenkephalin (PENK) and prodynorphin (PDYN) are endogenous opioid peptides mainly produced in the striatum and, to a lesser extent, in the cerebral cortex. Dysregulated metabolism and altered cerebrospinal fluid (CSF) levels of PENK and PDYN have been described in several neurodegenerative diseases. However, no study to date investigated these peptides in the CSF of sporadic Creutzfeldt–Jakob disease (sCJD). Using liquid chromatography-multiple reaction monitoring mass spectrometry, we evaluated the CSF PDYN- and PENK-derived peptide levels in 25 controls and 63 patients with sCJD belonging to the most prevalent molecular subtypes (MM(V)1, VV2 and MV2K). One of the PENK-derived peptides was significantly decreased in each sCJD subtype compared to the controls without a difference among subtypes. Conversely, PDYN-derived peptides were selectively decreased in the CSF of sCJD MV2K, a subtype with a more widespread overall pathology compared to the sCJD MM(V)1 and the VV2 subtypes, which we confirmed by semiquantitative analysis of cortical and striatal neuronal loss and astrocytosis. In sCJD CSF PENK and PDYN were associated with CSF biomarkers of neurodegeneration but not with clinical variables and showed a poor diagnostic performance. CSF PDYN and PENK-derived peptides had no significant diagnostic and prognostic values in sCJD; however, the distinct marker levels between molecular subtypes might help to better understand the basis of phenotypic heterogeneity determined by divergent neuronal targeting.