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Chagas disease causes more deaths in the Americas than any other parasitic disease. Initially confined to the American continent, it is increasingly becoming a global health problem. In fact, it is considered to be an "exotic" disease in Europe, being virtually undiagnosed. Benznidazole, the only drug approved for treatment, effectively treats acute-stage Chagas disease, but its effectiveness for treating indeterminate and chronic stages remains uncertain. Previously, our research group demonstrated that 4-thiazolidinones presented anti-T. cruzi activity including in the in vivo assays in mice, making this fragment appealing for drug development. The present work reports the synthesis and anti-T. cruzi activities of a novel series of 4-thiazolidinones derivatives that resulted in an increased anti-T. cruzi activity in comparison to thiosemicarbazones intermediates. Compounds 2c, 2e, and 3a showed potent inhibition of the trypomastigote form of the parasite at low cytotoxicity concentrations in mouse splenocytes. Besides, all the 2c, 2e, and 3a tested concentrations showed no cytotoxic activity on macrophages cell viability. When macrophages were submitted to T. cruzi infection and treated with 2c and 3a, compounds reduced the release of trypomastigote forms. Results also showed that the increased trypanocidal activity induced by 2c and 3a is independent of nitric oxide release. Flow cytometry assay showed that compound 2e was able to induce necrosis and apoptosis in trypomastigotes. Parasites treated with the compounds 2e, 3a, and 3c presented flagellum shortening, retraction and curvature of the parasite body, and extravasation of the internal content. Together, these data revealed a novel series of 4-thiazolidinones fragment-based compounds with potential effects against T. cruzi and lead-like characteristics., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Background: Patients with Prader-Willi syndrome (PWS) often have comorbidities, especially obesity, that may constitute a risk factor for severe forms of COVID-19. We aimed to assess prevalence and medical course of SARS-CoV-2 infection in children and adults with PWS. From November 2020 to January 2021, we performed a detailed medical survey on 342 adults and 305 children with PWS followed in the French reference center., Results: We obtained responses from 288 adults (84%) and 239 children (78%). From March 2020 to January 2021, 38 adults (13.2%) and 13 children (5.4%) with PWS had SARS-CoV-2 infection. Mean age of adults was 34.1 ± 11.9 years and mean body mass index was 40.6 ± 12.7 kg/m 2 ; 82% had obesity and 37% had diabetes. Only 3 children (23%) had obesity and none had diabetes. Similar to the general population, the most frequent symptoms of COVID-19 were asthenia, fever, cough, headache and shortness of breath. All patients had a favorable outcome., Conclusion: PWS itself is not a risk factor for severe COVID-19 in children and adults. On the contrary, evolution of SARS-CoV-2 infection in adults with PWS seems more favorable than expected, given their comorbidities., (© 2021. The Author(s).)

The aim of this study was to evaluate the efficacy and safety of outpatient antimicrobial therapy with piperacillin-tazobactam in continuous infusion using elastomeric pumps and to evaluate the economic impact compared with conventional hospital treatment in patients with Pseudomonas aeruginosa (PA) infections. This is an observational study. Patients with PA infection treated with continuous piperacillin-tazobactam infusion using elastomeric pumps in our hospital between January 2015 and December 2017 were included. Primary outcomes were mortality during antibiotic treatment and mortality at 30 days. Secondary outcomes were reinfection or relapse at 30 days and clinical cure rate. The cost of each episode was compared with theoretical cost of the same treatment using conventional hospitalization. 35 patients were included. One patient (2.9%) died during the treatment. Overall 30-day mortality was 5.7%. No death was related to infection by PA. One patient (2.9%) had a reinfection at 30 days. Cure was achieved in 93% of patients at the end of treatment. There were no severe complications related to elastomeric pumps. Treatment cost with outpatient antimicrobial therapy was 67% lower than theoretical cost with conventional hospital treatment. Oupatient antimicrobial therapy with piperacillin-tazobactam in continuous infusion using elastomeric pumps in patients with PA infections is safe and effective with lower costs.

Among the different biomarkers predicting response in chronic lymphocytic leukemia (CLL), the most influential parameters are the mutational status of the IGHV genes and the presence of TP53 gene disruptions. Nevertheless, these important assessments are not readily available in most centers dealing with CLL patients. To provide this molecular testing across the country, the Spanish Cooperative Group on CLL (GELLC) established a network of four analytical reference centers. A total of 2153 samples from 256 centers were analyzed over a period of 30 months. In 9% of the patients, we found pathological mutations in the TP53 gene, whereas 48.96% were classified as IGHV unmutated. Results of the satisfaction survey of the program showed a Net Promoter Score of 85.15. Building a national network for molecular testing in CLL allowed the CLL population a broad access to complex biomarkers analysis that should translate into a more accurate and informed therapeutic decision-making.

Background: Little is known about radiofrequency electromagnetic fields (RF) from mobile technology and resulting dose in young people. We describe modeled integrated RF dose in European children and adolescents combining own mobile device use and surrounding sources., Methods: Using an integrated RF model, we estimated the daily RF dose in the brain (whole-brain, cerebellum, frontal lobe, midbrain, occipital lobe, parietal lobe, temporal lobes) and the whole-body in 8358 children (ages 8-12) and adolescents (ages 14-18) from the Netherlands, Spain, and Switzerland during 2012-2016. The integrated model estimated RF dose from near-field sources (digital enhanced communication technology (DECT) phone, mobile phone, tablet, and laptop) and far-field sources (mobile phone base stations via 3D-radiowave modeling or RF measurements)., Results: Adolescents were more frequent mobile phone users and experienced higher modeled RF doses in the whole-brain (median 330.4 mJ/kg/day) compared to children (median 81.8 mJ/kg/day). Children spent more time using tablets or laptops compared to adolescents, resulting in higher RF doses in the whole-body (median whole-body dose of 81.8 mJ/kg/day) compared to adolescents (41.9 mJ/kg/day). Among brain regions, temporal lobes received the highest RF dose (medians of 274.9 and 1786.5 mJ/kg/day in children and adolescents, respectively) followed by the frontal lobe. In most children and adolescents, calling on 2G networks was the main contributor to RF dose in the whole-brain (medians of 31.1 and 273.7 mJ/kg/day, respectively)., Conclusion: This first large study of RF dose to the brain and body of children and adolescents shows that mobile phone calls on 2G networks are the main determinants of brain dose, especially in temporal and frontal lobes, whereas whole-body doses were mostly determined by tablet and laptop use. The modeling of RF doses provides valuable input to epidemiological research and to potential risk management regarding RF exposure in young people., (Copyright © 2020. Published by Elsevier Inc.)

Aims: The aims of this study were (a) to know the kinetics of antitumor necrosis factor (TNF) drug serum levels during the induction phase in patients with Crohn's disease; (b) to identify variables associated with these levels; and (c) to assess the relation between these levels and short-term effectiveness in Crohn's disease patients., Methods: Patients with Crohn's disease naïve to anti-TNF treatment were prospectively included. Remission was defined as a Crohn's disease activity index (CDAI) score <150 after 14 weeks of treatment. Blood samples were obtained at baseline and at weeks 4, 8, and 14. Adalimumab and infliximab levels were measured, receiver operating characteristic (ROC) curves were constructed, and the area under the ROC curve was calculated., Results: One-hundred fifty patients with Crohn's disease were included, 79 (53%) received infliximab and 71 (47%) had CDAI > 150 at study entry. At week 14, 52 out of 71 patients with CDAI > 150 at baseline (73%) had clinical remission. There were no differences in infliximab levels between patients with and without remission (8 vs. 9.1 μg/mL, P > 0.05) or with and without response (7 vs. 11 μg/mL, P > 0.05) at week 14. There was a trend to higher levels of adalimumab concentration in responders in comparison with nonresponders (13 vs. 6.7 μg/mL, P = 0.05) and in patients who achieved remission in comparison with nonremitters (13.5 vs. 8.4 μg/mL, P = 0.06). In the multivariate analysis, no variable was predictive of short-term remission, including infliximab and adalimumab serum levels., Conclusion: Determining anti-TNF serum levels during the induction phase is not useful for predicting short-term remission in patients with Crohn's disease.

Niemann-Pick type C (NP-C) disease is a neurovisceral atypical lysosomal lipid storage disorder with a poor prognosis. We present the 5-year neuropsychological follow-up of a patient with juvenile onset NP-C, spanning the pre-diagnostic stage to the period after treatment with miglustat (Actelion Pharmaceuticals Inc., CA, US). In the initial stages of the disease, the patient presented behavioral dysexecutive symptoms resembling those frequently observed in adult-onset forms and frontotemporal dementia, which frequently makes early diagnosis difficult in children. After 4 years of treatment, the impaired cognitive function and behavioral dysexecutive syndrome had been completely reversed. The variability of NP-C disease makes early diagnosis challenging. Evaluations of long-term neuropsychological development can help diagnose this neurodegenerative disease and document its progression.

Ethnopharmacological Relevance: Cocoa extracts rich in polyphenols are used as potential agent for treating diabetes. Cocoa polyphenols have been proved to ameliorate important hallmarks of type-2 diabetes (T2D). They can regulate glucose levels by increasing insulin secretion, promoting β-cell proliferation and a reduction of insulin resistance. In addition, epidemiological evidence indicates that consumption of flavonoid decreases the incidence of T2D., Aim of the Study: T2D is preceded by a prediabetic state in which the endocrine-metabolic changes described in T2D are already present. Since epidemiological evidence indicates that consumption of flavonoid decreases its incidence, we evaluated possible preventive effects of polyphenol-enriched cocoa extract on a model of prediabetes induced by sucrose., Materials and Methods: We determined circulating parameters and insulin sensitivity indexes, liver protein carbonyl groups and reduced glutathione, liver mRNA expression levels of lipogenic enzymes, expression of different pro-inflammatory mediators, fructokinase activity and liver glycogen content. For that, radioimmunoassay, real-time polymerase chain reaction, Western blot, spectrophotometry, and immunohistochemistry were used., Results: We demonstrated that sucrose administration triggered hypertriglyceridemia, insulin-resistance, and liver increased oxidative stress and inflammation markers compared to control rats. Additionally, we found an increase in glycogen deposit, fructokinase activity, and lipogenic genes expression (SREBP-1c, FAS and GPAT) together with a decrease in P-Akt and P-eNOS protein content (P < 0.05). Sucrose-induced insulin resistance, hepatic carbohydrate and lipid dysmetabolism, oxidative stress, and inflammation were effectively disrupted by polyphenol-enriched cocoa extract (PECE) co-administration (P < 0.05)., Conclusion: Dietary administration of cocoa flavanols may be an effective and complementary tool for preventing or reverting T2D at an early stage of its development (prediabetes)., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Chitin is an abundant polysaccharide primarily produced as an industrial waste stream during the processing of crustaceans. Despite the limited applications of chitin, there is interest from the medical, agrochemical, food and cosmetic industries because it can be converted into chitosan and partially acetylated chitosan oligomers (COS). These molecules have various useful properties, including antimicrobial and anti-inflammatory activities. The chemical production of COS is environmentally hazardous and it is difficult to control the degree of polymerization and acetylation. These issues can be addressed by using specific enzymes, particularly chitinases, chitosanases and chitin deacetylases, which yield better-defined chitosan and COS mixtures. In this review, we summarize recent chemical and enzymatic approaches for the production of chitosan and COS. We also discuss a design-of-experiments approach for process optimization that could help to enhance enzymatic processes in terms of product yield and product characteristics. This may allow the production of novel COS structures with unique functional properties to further expand the applications of these diverse bioactive molecules., Competing Interests: The authors declare no conflict of interest.

The marine unicellular green cyanobacterium Prochlorococcus marinus MIT9313 belongs to the most abundant and photosynthetically productive genus of cyanobacteria in the oceans. This monophyletic genus use divinyl chlorophyll a (Chl a 2 ) and b (Chl b 2 ) to build the photosystems and the membrane-intrinsic Pcb-type antennae. We used the mild detergent n-dodecyl β D-maltopyranoside to solubilize the thylakoid membranes. Gel electrophoresis and sucrose gradient ultracentrifugation was then used to separate the complexes of the photosynthetic apparatus. The proteins and the pigments were identified by mass spectrometry. Protein complexes were characterized biochemically, and the distribution of Chl a 2 and Chl b 2 was determined. The photosynthetic apparatus was shown as supercomplexes formed by Photosystem II dimers with up to eight PcbB proteins; Photosystem I was present as trimers. A heterogeneous distribution of pigments was shown using sucrose gradient-enriched fractions with ratios of [Chl b 2 ]/[Chl a 2 ] of 2.16 ± 0.13, 1.86 ± 0.08, and 2.61 ± 0.07, for Photosystem I, Photosystem II, and PcbB, respectively. These ratios of Chl b / a are without precedent in organisms with oxygenic photosynthesis. Diaphorase activity was measured in the fractions of the sucrose gradient. Gel electrophoresis, immunodetection, and mass spectrometry were used to conclude that the commonly soluble protein ferredoxin-NADP + reductase (FNR) is a membrane-anchored protein (probably associated to cytochrome b 6 f complex) in the low-light adapted Prochlorococcus marinus MIT9313.

Aim: Hypothalamic obese rats are characterized by pre-diabetes, dyslipidemia, hyperadiposity, inflammation and, liver dysmetabolism with oxidative stress (OS), among others. We studied endocrine-metabolic dysfunctions and, liver OS and inflammation in both monosodium l-glutamate (MSG)-neonatally damaged and control litter-mate (C) adult male rats, either chronically treated with N-Acetyl-l-Cysteine since weaned (C-NAC and MSG-NAC) or not., Methodology: We evaluated circulating TBARS, glucose, insulin, triglycerides, uric acid (UA) and, aspartate and alanine amino-transferase; insulin sensitivity markers (HOMA indexes, Liver Index of Insulin Sensitivity -LISI-) were calculated and liver steps of the insulin-signaling pathway were investigated. Additionally, we monitored liver OS (protein carbonyl groups, GSH and iNOS level) and inflammation-related markers (COX-2 and TNFα protein content; gene expression level of Il1b, Tnfα and Pai-1); and carbohydrate and lipid metabolic functions (glucokinase/fructokinase activities and, mRNA levels of Srebp1c, Fas and Gpat)., Key Findings: Chronic NAC treatment in MSG rats efficiently decreased the high circulating levels of triglycerides, UA, transaminases and TBARS, as well as peripheral (high insulinemia and HOMA indexes) and liver (LISI and the P-AKT:AKT and P-eNOS:eNOS protein ratio values) insulin-resistance. Moreover, NAC therapy in MSG rats prevented liver dysmetabolism by decreasing local levels of OS and inflammation markers. Finally, NAC-treated MSG rats retained normal liver glucokinase and fructokinase activities, and Srebp1c, Fas and Gpat (lipogenic genes) expression levels., Significance: Our study strongly supports that chronic oral antioxidant therapy (NAC administration) prevented the development of pre-diabetes, dyslipidemia, and inflamed-dysmetabolic liver in hypothalamic obese rats by efficiently decreasing high endogenous OS., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Aims and Objectives: The objective of this integrative review is to identify the factors that contribute to diet adherence in people suffering from kidney disease who are receiving haemodialysis treatment., Background: Adherence to the therapeutic regimen determines therapeutic success, quality of life and survival in patients on haemodialysis. Lack of diet adherence ranges from 25%-86% in patients receiving haemodialysis treatment and affects patient morbidity and mortality., Design: An integrative literature review was conducted based on the criteria of Whittemore & Knafl., Methods: A literature review was performed by two members of the team using twelve databases including PubMed, CUIDEN, CINAHL, The Cochrane Library and ScienceDirect., Results: The main issues identified after analysing the results were as follows: the intrinsic barriers (age, dialysis time, motivation, perceived benefit, distorted perception of adherence) and facilitators (self-efficacy, perception of disease, perception of control), extrinsic barriers (family dysfunction, lack of social support, cultural patterns of consumption of food) and facilitators (social support, relationship with healthcare providers), and interventions to encourage diet adherence, such as the use of motivational interviewing in educational interventions, and the training and education of relevant professionals in communication skills., Conclusions: Diet nonadherence remains a serious health problem and suffers from a lack of solid criteria to identify this condition. The onset of depression signs and the level of social support available to the patient should be assessed, because these are important factors that determine adherence to treatment., Relevance to Clinical Practice: Professionals should be trained in health education and communication techniques to contribute to the patient's self-management and motivation for diet adherence. Controlled and randomised clinical studies involving predialysis stages should be performed to investigate the impact of the assessment and control of barriers to diet adherence., (© 2017 John Wiley & Sons Ltd.)

Melatonin is synthesized from serotonin and it is excreted as sulphatoxymelatonin in urine. We aim to evaluate urinary sulphatoxymelatonin as a biomarker of brain serotonin status in a cohort of patients with mutations in genes related to serotonin biosynthesis. We analized urinary sulphatoxymelatonin from 65 healthy subjects and from 28 patients with genetic defects. A total of 18 patients were studied: 14 with autosomal dominant and recessive guanosine triphosphate cyclohydrolase-I deficiency; 3 with sepiapterin reductase deficiency; and 1 with aromatic L-amino acid decarboxylase deficiency. Further 11 patients were studied after receiving serotoninergic treatment (serotonin precursors, monoamine oxidase inhibitors, selective serotonin re-uptake inhibitors): 5 with aromatic L-amino acid decarboxylase deficiency; 1 with sepiapterin reductase deficiency; 3 with dihydropteridine reductase deficiency; and 2 with 6-pyruvoyltetrahydropterin synthase deficiency. Among the patients without therapy, 6 presented low urinary sulphatoxymelatonin values, while most of the patients with guanosine triphosphate cyclohydrolase-I deficiency showed normal values. 5 of 11 patients under treatment presented low urine sulphatoxymelatonin values. Thus, decreased excretion of sulphatoxymelatonin is frequently observed in cases with severe genetic disorders affecting serotonin biosynthesis. In conclusion, sulphatoxymelatonin can be a good biomarker to estimate serotonin status in the brain, especially for treatment monitoring purposes.

The aim of this work was to assess the influence of treatment with U-Caspofungin, on the quality of diagnostic scintigraphic images of induced lesions in nude mice undergoing both bacterial and fungal infections and to determine the level of specificity of 99mTc-tricarbonyl-Caspofungin to discriminate between fungal or bacterial infections. In vitro studies on the behaviour of the 99mTc-tricarbonyl-Caspofungin complex binding percentage at different yeast concentrations of Candida albicans or Staphyolococcus aureus were determined. The incubation was performed with and without U-Caspofungin. In vivo evaluation was performed of 6 groups of athymic mice: sham, inflammation (LPS), fungal infection with Candida albicans (CA) and bacterial infection with Staphylocuccus aureus (SA). In vitro studies showed that the uptake of the complex by both yeasts and bacteria, depends on the concentration of colony forming units (cfu), and that this uptake is favoured by the presence of UCaspofungin that increases the membrane permeability to the 99mTc-tricarbonyl-Caspofungin complex. In vivo evaluation showed low uptake in sterile inflammation model and moderate to high uptake in infections models both treated or not with U-Caspofungin. The results of biodistributions were compatible with scintigraphic images., Conclusion: The uptake of the complex depends on the load of microorganisms, but it presents high sensibility, even at low concentrations of the infecting agent. The treatment with U-Caspofungin has no influence on the quality of the scintigraphic images used for diagnosis and localization of infection foci., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.)

Plant organs are typically organized into three main tissue layers. The middle ground tissue layer comprises the majority of the plant body and serves a wide range of functions, including photosynthesis, selective nutrient uptake and storage, and gravity sensing. Ground tissue patterning and maintenance in Arabidopsis are controlled by a well-established gene network revolving around the key regulator SHORT-ROOT ( SHR ). In contrast, it is completely unknown how ground tissue identity is first specified from totipotent precursor cells in the embryo. The plant signaling molecule auxin, acting through AUXIN RESPONSE FACTOR (ARF) transcription factors, is critical for embryo patterning. The auxin effector ARF5/MONOPTEROS (MP) acts both cell-autonomously and noncell-autonomously to control embryonic vascular tissue formation and root initiation, respectively. Here we show that auxin response and ARF activity cell-autonomously control the asymmetric division of the first ground tissue cells. By identifying embryonic target genes, we show that MP transcriptionally initiates the ground tissue lineage and acts upstream of the regulatory network that controls ground tissue patterning and maintenance. Strikingly, whereas the SHR network depends on MP, this MP function is, at least in part, SHR independent. Our study therefore identifies auxin response as a regulator of ground tissue specification in the embryonic root, and reveals that ground tissue initiation and maintenance use different regulators and mechanisms. Moreover, our data provide a framework for the simultaneous formation of multiple cell types by the same transcriptional regulator.

Subcutaneous fat necrosis of the newborn (SCFN) is a rare, self-limited disorder of the panniculus which appears in the first few weeks of life. SCFN generally follows an uncomplicated course. However, there are important complications for which the patient must be regularly monitored, including thrombocytopenia, hypoglycemia, hypertriglyceridemia, and most importantly, hypercalcemia. We report five infants with SCFN. All children were born at term. The onset of lesions was between 1 day and 20 days after birth. The back was the most frequent location. Birth hypoxia was the most frequent risk factor. Complications included hypercalcemia, hypoglycemia, and metastatic calcifications (disseminated subcutaneous calcifications, nephrocalcinosis, and myocardial calcifications). This study provides the first case of SCFN in the context of hypoxic encephalopathy and refractory septic shock that required extracorporeal membrane oxygenation (ECMO)., (Copyright © 2014. Published by Elsevier B.V.)

Genomic selection can be applied prior to phenotyping, enabling shorter breeding cycles and greater rates of genetic gain relative to phenotypic selection. Traits measured using high-throughput phenotyping based on proximal or remote sensing could be useful for improving pedigree and genomic prediction model accuracies for traits not yet possible to phenotype directly. We tested if using aerial measurements of canopy temperature, and green and red normalized difference vegetation index as secondary traits in pedigree and genomic best linear unbiased prediction models could increase accuracy for grain yield in wheat, Triticum aestivum L., using 557 lines in five environments. Secondary traits on training and test sets, and grain yield on the training set were modeled as multivariate, and compared to univariate models with grain yield on the training set only. Cross validation accuracies were estimated within and across-environment, with and without replication, and with and without correcting for days to heading. We observed that, within environment, with unreplicated secondary trait data, and without correcting for days to heading, secondary traits increased accuracies for grain yield by 56% in pedigree, and 70% in genomic prediction models, on average. Secondary traits increased accuracy slightly more when replicated, and considerably less when models corrected for days to heading. In across-environment prediction, trends were similar but less consistent. These results show that secondary traits measured in high-throughput could be used in pedigree and genomic prediction to improve accuracy. This approach could improve selection in wheat during early stages if validated in early-generation breeding plots., (Copyright © 2016 Rutkoski et al.)

We evaluated the effects of intracerebroventricular administration of ouabain on the antinociception induced by five μ-opioid receptor agonists in a tail flick test on female CD-1 mice and the effects of these μ-opioid receptor agonists on mice forebrain synaptosomal ouabain-sensitive Na(+),K(+)-ATPase activity. The subcutaneous administration of the μ-opioid receptor agonists tested produced a dose-dependent antinociceptive effect. The antinociception induced by morphine (1-32 mg/kg), levorphanol (0.4-6.4 mg/kg), and buprenorphine (0.02-0.64 mg/kg) was antagonised in a dose-dependent manner by ouabain (0.001-10 ng, i.c.v.), whilst the antinociception produced by fentanyl (0.02-0.16 mg/kg) and methadone (2-10 mg/kg) was not influenced significantly by ouabain (1-100 ng, i.c.v.). Incubation in vitro of forebrain synaptosomes with morphine (10(-9)-10(-4) M), levorphanol (10(-10)-10(-4) M), buprenorphine (10(-10)-10(-5) M), or fentanyl (10(-10)-10(-5) M) stimulated significantly ouabain-sensitive Na(+),K(+)-ATPase activity in a concentration-dependent way. The order of efficacy (using the Emax as a measure of intrinsic efficacy) was: morphine (29.83±0.56%)>levorphanol (18.61±1.26%)>buprenorphine (14.91±0.74%)>fentanyl (10.10±1.73%). On the other hand, methadone (10(-10)-10(-5) M) did not significantly modify the ouabain-sensitive Na(+),K(+)-ATPase activity (Emax=5.11±0.92%). These results suggest that Na(+),K(+)-ATPase activity is involved in the antinociceptive effects of morphine, levorphanol and buprenorphine, but not in that produced by fentanyl and methadone. Thus, we can conclude that at least two subgroups can be distinguished among the μ-opioid receptor agonists taking into consideration the role of Na(+),K(+)-ATPase in their antinociceptive effects., (Copyright © 2016 Elsevier B.V. All rights reserved.)

Background: Growth hormone secretagogues (GHS), among other factors, regulate the release of GH. The biological activity of the secretagogue peptide A233 as a promoter of growth and innate immunity in teleost fish has previously been demonstrated, but its role in the immune system of mammals is not well understood., Methods: The effect of the peptide was investigated in J774A.2 macrophage cells using a comparative proteomics approach after 6 and 12 h of peptide stimulation., Results: The functional analysis of differentially modulated proteins showed that A233 peptide treatment appears to promote activation and ROS-dependent cytotoxic functions in macrophages and enhanced expression of antiviral protein complexes such as MAVS. In accordance with this hypothesis, we found that A233 treatment enhanced superoxide anion production and the IFN-γ level in J774A.2 cells and mouse splenocytes, respectively, and reduced viral load in a dengue virus mouse model of infection., Conclusions: The growth hormone secretagogue A233 peptide promotes activation of ROS-dependent cytotoxic functions and exerts immunomodulatory effects that enable an antiviral state in a dengue virus mouse model., General Significance: The increase of IFN-γ level and the differential modulation of antiviral proteins by the A233 peptide suggest that the molecule could activate an innate immune response with a possible further impact in the treatment of acute and chronic diseases.

A Gas Chromatography (GC) method has been developed for the separation and characterization of the different fatty acids in anhydrous milk fat (AMF) by means of an ionic liquid stationary phase, characterized by a monocationic imidazolium salt derived from L-phenylalanine. The inner surface of a fused silica capillary column was modified using this ionic liquid functionality and 3-aminopropyldiethoxymethyl silane. This coated GC column, which exhibited good thermal stability (270°C) and good efficiency (2700 plates/m), has been characterized using the Abraham solvation parameter model. The intra-day and inter-day precision of the method have been evaluated, obtaining relative standard deviations (RSD) from 0.99% to 4.0% and from 2.8% to 9.2%, respectively. Furthermore, recoveries from 90% and 99% have been achieved., (Copyright © 2015 Elsevier B.V. All rights reserved.)

Aims: Fructose administration induces hepatic oxidative stress, insulin resistance, inflammatory and metabolic changes. We tested their potential pathogenic relationship and whether these alterations can be prevented by R/S-α-lipoic acid., Main Methods: Wistar rats received during 21days a commercial diet or the same diet supplemented with 10% fructose in drinking water without/with R/S-α-lipoic acid injection. After this period, we measured a) serum glucose, triglyceride, insulin, homeostasis model assessment-insulin resistance (HOMA-IR), insulin glucose ratio (IGR) and Matsuda indexes and b) liver oxidative stress, inflammatory markers and insulin signaling pathway components., Key Findings: Fructose fed rats had hyperinsulinemia, hypertriglyceridemia, higher HOMA-IR, IGR and lower Matsuda indices compared to control animals, together with increased oxidative stress markers, TNFα, IL1β and PAI-1 gene expression, and TNFα and COX-2 protein content. Whereas insulin receptor level was higher in fructose fed rats, their tyrosine-residue phosphorylation was lower. IRS1/IRS2 protein levels and IRS1 tyrosine-phosphorylation rate were lower in fructose fed rats. All changes were prevented by R/S-α-lipoic acid co-administration., Significance: Fructose-induced hepatic oxidative stress, insulin resistance and inflammation form a triad that constitutes a vicious pathogenic circle. This circle can be effectively disrupted by R/S-α-lipoic acid co-administration, thus suggesting mutual positive interaction among the triad components., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Background: Oesophagoscopy with biopsy is considered the gold standard for diagnosing and monitoring eosinophilic oesophagitis (EoE). Therefore is important to discover less-invasive diagnostic methods., Methods: Cytology specimens were obtained in patients with active EoE (AEoE) (≥15 eos/hpf) and EoE in remission (EoER) (<15 eos/hpf). The samples were assessed by two independent pathologists and were compared with biopsy samples. EoE cytology specimens were compared with specimens obtained from patients with GERD., Results: Specimens of 36 patients (69.4% male, mean age 30.88 years) were included. AEoE (17, 47.2%), EoER (11, 30.5%) and GERD (22.2%). eos/hpf in cytology (AEoE 9.23 vs. EoER 1.54 vs. GERD 2, p = 0.01). Linear correlation between eos/hpf average biopsy and cytology eos/hpf: r = 0.57, p < 0.001. For diagnosis of EoE ≥3 eos/hpf in cytology obtained a sensitivity of 70%, specificity 81%, PPV 86% and NPV 60% (AUC = 0.81, p = 0.01). For detection of AEoE, ≥3 eos/hpf in LBC obtained a sensitivity of 70%, specificity 82%, PPV 81% and NPV 66% (AUC = 0.87, p = 0.001)., Conclusions: LBC in oesophageal aspirate seems to be effective for the diagnosis and monitoring activity in EoE. These results support the usefulness of non-invasive methods for the diagnosis and monitoring of EoE.

Vanishing white matter (VWM) leukoencephalopathy is one of the most prevalent hereditary white matter diseases. It has been associated with mutations in genes encoding eukaryotic translation initiation factor (eIF2B). We have compiled a list of all the patients diagnosed with VWM in Spain; we found 21 children. The first clinical manifestation in all of them was spasticity, with severe ataxia in six patients, hemiparesis in one child, and dystonic movements in another. They suffered from progressive cognitive deterioration and nine of them had epilepsy too. In four children, we observed optic atrophy and three also had progressive macrocephaly, which is not common in VWM disease. The first two cases were diagnosed before the 1980s. Therefore, they were diagnosed by necropsy studies. The last 16 patients were diagnosed according to genetics: we found mutations in the genes eIF2B5 (13 cases), eIF2B3 (2 cases), and eIF2B4 (1 case). In our report, the second mutation in frequency was c.318A>T; patients with this mutation all followed a slow chronic course, both in homozygous and heterozygous states. Previously, there were no other reports to confirm this fact. We also found some mutations not described in previous reports: c.1090C>T in eIF2B4, c.314A>G in eIF2B5, and c.877C>T in eIF2B5.

Penicillium digitatum is the most important postharvest pathogen of citrus fruits. Along disease progression, the infected citrus peel tissue is acidified due to the accumulation of organic acids. So far, relatively little is known about the environmental factors that regulate pathogenicity in this fungus. In this study, the role of the pH signaling transcription factor PacC in the pathogenesis of P. digitatum was investigated. We identified the pacC ortholog (PdpacC) in P. digitatum and found that its transcript levels were elevated under alkaline conditions (pH ≥ 7) in vitro, as well as during the infection of citrus fruits in spite of the low pH (about 3.0 to 3.5) of the macerated tissue. Na(+) and pectin also induced the expression of PdpacC. Disruption of PdpacC resulted in impaired mycelial growth under neutral or alkaline pH conditions and on synthetic medium supplemented with pectin as the sole carbon source, and attenuated virulence towards citrus fruits. Introducing the full length of PdpacC into the ΔPdpacC mutant restored all these phenotypes. The expression of the polygalacturonase gene Pdpg2 and pectin lyase gene Pdpnl1 in P. digitatum was upregulated in the wild type strain but not or weakly upregulated in the ΔPdpacC mutant during infection. Disruption of Pdpg2 also resulted in attenuated virulence of P. digitatum towards citrus fruits. Collectively, we conclude that PdPacC plays an important role in pathogenesis of P. digitatum via regulation of the expression of cell wall degradation enzyme genes, such as Pdpg2 and Pdpnl1.

Because of evidence of causal association between antibiotic use and bacterial resistance, the implementation of national policies has emerged as a interesting tool for controlling and reversing bacterial resistance. The aim of this study was to assess the impact of public policies on antibiotic use in Europe using a differences-in-differences approach. Comparable data on systemic antibiotics administered in 21 European countries are available for a 11-year period between 1997 and 2007. Data on national campaigns are drawn from the public health literature. We estimate an econometric model of antibiotic consumption with country fixed effects and control for the main socioeconomic and epidemiological factors. Lagged values and the instrumental variables approach are applied to address endogeneity aspects of the prevalence of infections and the adoption of national campaigns. We find evidence that public campaigns significantly reduce the use of antimicrobials in the community by 1.3-5.6 defined daily doses per 1,000 inhabitants yearly. This represents an impact of roughly 6.5-28.3 % on the mean level of antibiotic use in Europe between 1997 and 2007. The effect is robust across different measurement methods. Further research is needed to investigate the effectiveness of policy interventions targeting different social groups such as general practitioners or patients.

Purpose: Pyridoxine-dependent epilepsy seizure (PDE; OMIM 266100) is a disorder associated with severe seizures that can be controlled pharmacologically with pyridoxine. In the majority of patients with PDE, the disorder is caused by the deficient activity of the enzyme α-aminoadipic semialdehyde dehydrogenase (antiquitin protein), which is encoded by the ALDH7A1 gene. The aim of this work was the clinical, biochemical, and genetic analysis of 12 unrelated patients, mostly from Spain, in an attempt to provide further valuable data regarding the wide clinical, biochemical, and genetic spectrum of the disease., Methods: The disease was confirmed based on the presence of α-aminoadipic semialdehyde (α-AASA) in urine measured by liquid chromatography tandem mass spectrometry (LC-MS/MS) and pipecolic acid (PA) in plasma and/or cerebrospinal fluid (CSF) measured by high performance liquid chromatography (HPLC)/MS/MS and by sequencing analysis of messenger RNA (mRNA) and genomic DNA of ALDH7A1., Key Findings: Most of the patients had seizures in the neonatal period, but they responded to vitamin B6 administration. Three patients developed late-onset seizures, and most patients showed mild-to-moderate postnatal developmental delay. All patients had elevated PA and α-AASA levels, even those who had undergone pyridoxine treatment for several years. The clinical spectrum of our patients is not limited to seizures but many of them show associated neurologic dysfunctions such as muscle tone alterations, irritability, and psychomotor retardation. The mutational spectrum of the present patients included 12 mutations, five already reported (c.500A>G, c.919C>T, c.1429G>C c.1217&#95;1218delAT, and c.1482-1G>T) and seven novel sequence changes (c.75C>T, c.319G>T, c.554&#95;555delAA, c.757C>T, c.787 + 1G>T, c.1474T>C, c.1093-?&#95;1620+?). Only one mutation, p.G477R (c.1429G>C), was recurrent; this was detected in four different alleles. Transcriptional profile analysis of one patient's lymphoblasts and ex vivo splicing analysis showed the silent nucleotide change c.75C>T to be a novel splicing mutation creating a new donor splice site inside exon 1. Antisense therapy of the aberrant mRNA splicing in a lymphoblast cell line harboring mutation c.75C>T was successful., Significance: The present results broaden our knowledge of PDE, provide information regarding the genetic background of PDE in Spain, afford data of use when making molecular-based prenatal diagnosis, and provide a cellular proof-of concept for antisense therapy application., (Wiley Periodicals, Inc. © 2013 International League Against Epilepsy.)

Background: Flax (Linum usitatissimum L.) is an important crop for the production of bioproducts derived from its seed and stem fiber. Transposable elements (TEs) are widespread in plant genomes and are a key component of their evolution. The availability of a genome assembly of flax (Linum usitatissimum) affords new opportunities to explore the diversity of TEs and their relationship to genes and gene expression., Results: Four de novo repeat identification algorithms (PILER, RepeatScout, LTR&#95;finder and LTR&#95;STRUC) were applied to the flax genome assembly. The resulting library of flax repeats was combined with the RepBase Viridiplantae division and used with RepeatMasker to identify TEs coverage in the genome. LTR retrotransposons were the most abundant TEs (17.2% genome coverage), followed by Long Interspersed Nuclear Element (LINE) retrotransposons (2.10%) and Mutator DNA transposons (1.99%). Comparison of putative flax TEs to flax transcript databases indicated that TEs are not highly expressed in flax. However, the presence of recent insertions, defined by 100% intra-element LTR similarity, provided evidence for recent TE activity. Spatial analysis showed TE-rich regions, gene-rich regions as well as regions with similar genes and TE density. Monte Carlo simulations for the 71 largest scaffolds (≥ 1 Mb each) did not show any regional differences in the frequency of TE overlap with gene coding sequences. However, differences between TE superfamilies were found in their proximity to genes. Genes within TE-rich regions also appeared to have lower transcript expression, based on EST abundance. When LTR elements were compared, Copia showed more diversity, recent insertions and conserved domains than the Gypsy, demonstrating their importance in genome evolution., Conclusions: The calculated 23.06% TE coverage of the flax WGS assembly is at the low end of the range of TE coverages reported in other eudicots, although this estimate does not include TEs likely found in unassembled repetitive regions of the genome. Since enrichment for TEs in genomic regions was associated with reduced expression of neighbouring genes, and many members of the Copia LTR superfamily are inserted close to coding regions, we suggest Copia elements have a greater influence on recent flax genome evolution while Gypsy elements have become residual and highly mutated.

Introduction: Celiac disease (EC) not diagnosed or treated affect histological, immunological and nutritional status of patients who suffer it. These changes allow infection by parasites that cause no symptoms in immunocompetent patients, such as Blastocystis hominis (Bh). OBJETIVE. To analyze the presence of Bh in symptomatic celiac patients and describe the clinical, histological, immune and nutritional status in these patients. MATERIAL AND METHOD An observational descriptive cross sectional study was performed. Thirty symptomatic celiac patients (18 women, mean age 41 years old, range 19-68 years), assisted at the Institute of Gastroenterology of Cuba from January to December 2009, entered the study., Results: Diarrhea and chronic anemia were the most commonly reported clinical manifestations (22 and 4 patients, respectively). The analysis of more than five Bh per field was more frequent in the group ofpatients studied (63.3%), with statistically significant difference in patients with vilous atrophy and low weight (P < 0.03) compared to cases with less than five Bh per feld. No significant differences were found when the immune status of patients was analyzed. CONCLUSIONS. In symptomatic celiac patients with subtotal-total villous atrophy and low weight the finding of more than five Bh perfield should be considered as opportunistic.

Introduction: Hysterical disorder has had different interpretations and therapeutic approaches according to the different cultural contexts. In the Middle Ages, hysteria was conceived as devilish possessions whose symptoms became a sort of veracity certificate for the era's cultural pillar: the Bible. During Renaissance, hysteria obeys a new master: Science, dramatizing the neurological degenerative injuries to give reputation to physicians of the time. There is a kind of consensus: hysteria is an ever less observable disorder in consultation. It has practically disappeared in the North American Diagnosis Manual, DSM-IV. We wonder, has hysteria as such disappeared? Has it gotten new expressions?, Methods: Psychoanalytic review of hysteria, followed by a qualitative, historical and hermeneutic study., Development: In these days of globalization, science is not the master anymore; instead, science is at the service of computing and market. The market biggest sellers are: depressive and anxious disorders, bulimia, anorexia, fibromyalgia, sexual drawbacks, somatoform disorders and extreme exhaustion disorder. Hysteria, raising bewilderment in modern medicine, comes back, cut up into pieces, in the form of these multiple disorders. Not only hysteria has not disappeared, but it has increased in consultation, almost perfect simulation of the disorders most promoted by capitalistic markets, granting power to the new master. Subsequently, its powerlessness is denounced, nothing alleviates said disorders. As Freud stated, the problem lies in the fact that this word does not have a receiver to decipher it., (Copyright © 2012 Asociación Colombiana de Psiquiatría. Publicado por Elsevier España. All rights reserved.)

Purpose: In our series of endoscopic third ventriculostomy (ETV), we sought to establish the relationship between the preoperative prediction using the Endoscopic Third Ventriculostomy Success Score (ETVSS) and the postsurgical success rate., Materials and Methods: This descriptive analytical study comprised 50 pediatric patients who underwent 58 ETV procedures between 2003 and 2011. Data regarding clinical, surgical, and radiological findings were obtained from a continuously updated database. For each patient, we calculated the ETVSS, based on the patient's age, hydrocephalus etiology, and presence of a previous shunt. We considered success to be an established or improved clinical state and at least one of the following radiological criteria: (a) reduction in ventricular size or stable ventricles with disappearance of periventricular edema and increased subarachnoid space over cerebral convexities, (b) flow artifact in sagittal T2FSE MR, or (c) bidirectional flow signal in 2D-CPC MR. Statistical significance was set at p < 0.05. Six months was the minimum postoperative follow-up required., Results: The ETV was successful in 29 patients (58 %). Patients aged over 1 year achieved the best results (p < 0.019). For those who underwent successful ETV, the mean ETVSS was 71.03 (95 % CI, 66.23-75.84). In those for whom the ETV was not successful, the mean ETVSS was 60 (95 % CI, 53.09-66.90); (p < 0.007)., Conclusions: The success of ETV in our series could have been predicted by ETVSS. Predictability could help establish stricter surgical selection criteria, thereby obtaining higher success rates, as well as preparing the patients and their families for expected outcomes.

The surface properties of porous silicon (PSi) evolve rapidly in phosphate-buffered saline. X-ray photoelectron spectra indicate the formation of a Si-OH and C-O enriched surface, which becomes increasingly hydrophilic with aging time. Multiscale stripe micropatterns of Si and PSi have been fabricated by means of a high-energy ion-beam irradiation process. These micropatterns have been aged in physiological conditions and used to analyze human mesenchymal stem cell (hMSC) adhesion. The actin cytoskeleton of hMSCs orients following the uniaxial micropatterns. In the wider Si stripes, hMSCs are dominantly located on Si areas. However, for reduced Si widths, adhesion is avoided on PSi by a split assembly of the actin cytoskeleton on two parallel Si areas. These results confirm that nanostructured Si-OH/C-O-rich surfaces with hydrophilic character are specially adapted for the creation of cell adhesion surface contrasts., (Copyright © 2012 Wiley Periodicals, Inc.)

Antiepileptic hypersensitivity syndrome (AHS) is a potentially life-threatening syndrome in pediatric cases. It is associated with aromatic anticonvulsivant drugs and others antibiotics with or without associated reactivation of virus. The pathogenesis of the process is not clear. Clinical feature of this syndrome include cutaneous reactions, fever and lymphadenopathies, but different organs can be involved. In laboratory analyses we can find leucocytosis, eosinophilia, and increase in transaminase levels. Significant elevation of procalcitonin (PCT) has been described in two adults patients. This study we report two cases of a 14-year-old male and a 13-year-old female with a AHS and a high level of the PCT. These are the first cases described in pediatric age. Establishing a diagnosis of AHS is important to avoid the use of the involved drug. The treatment is based on the withdrawal of the drugs that are supposed and if there is no improvement or a deterioration of the patient, the use of systemic corticosteroids is often useful., (Copyright © 2011 European Paediatric Neurology Society. Published by Elsevier Ltd. All rights reserved.)

Several lines of evidence suggest that σ(1) receptors regulate intracellular calcium concentration [Ca(2+)](i). However, no previous studies have demonstrated a consistent role for these receptors in the modulation of extracellular calcium entry through plasmalemmal voltage-dependent calcium channels (VDCCs). To search for evidence of such a role we compared [Ca(2+)](i) under basal conditions and after depolarization with KCl in fura-2-loaded synaptosomes from wild-type and σ(1) receptor knockout (σ(1)R-KO) mice. We also tested the effects of the selective σ(1) receptor agonists PRE-084 and (+)-pentazocine and antagonists BD-1047 and NE-100 on the increase in [Ca(2+)](i) induced by depolarization with 60mM KCl. Mibefradil, a nonselective blocker of VDCCs, was used as a positive control. Basal [Ca(2+)](i) and the increase in [Ca(2+)](i) caused by KCl-induced depolarization were similar in brain synaptosomes from both wild-type and σ(1)R-KO mice. Mibefradil (1-30 μM) and all σ(1) receptor ligands studied (3-100 μM) inhibited the KCl-induced increase in [Ca(2+)](i) in a concentration-dependent way. The order of maximum inhibition for the ligands compared here was NE-100>BD-1047=PRE 084>(+)-pentazocine. There were no appreciable differences in their effects between wild-type and σ(1)R-KO mice. These findings indicate that σ(1) receptors are not involved in calcium influx through VDCCs or in the inhibitory effects of these σ(1) ligands on Ca(2+) channels., (Copyright © 2012 Elsevier B.V. All rights reserved.)

Cryopreservation introduces extreme temperature and osmolality changes that impart lethal and sublethal effects on spermatozoa. Additionally, there is evidence that the osmotic stress induced by cryopreservation causes oxidative stress to spermatozoa. The main sources of reactive oxygen species in mammalian sperm are the mitochondria. In view of this, the aim of our study was to test whether or not osmotic stress was able to induce mitochondrial damage and to explore the osmotic tolerance of the mitochondria of stallion spermatozoa. Ejaculates from 7 stallions were subjected to osmolalities ranging from 75 to 1500 mOsm/kg, and the effect on sperm membrane integrity and mitochondrial membrane potential was studied. Additionally, the effects of changes in osmolality from hyposmotic to isosmotic and from hyperosmotic to isosmotic solutions were studied (osmotic excursions). The cellular volume of stallion spermatozoa under isosmotic conditions was 20.4 ± 0.33 μm(3). When exposed to low osmolality, the stallion spermatozoa behaved like a linear osmometer, whereas exposure to high osmolalities up to 900 mOsm/kg resulted in decreased sperm volume. Although sperm membranes were relatively resistant to changes in osmolality, mitochondrial membrane potential decreased when osmolalities were low or very high (10.7 ± 1.74 and 16.5 ± 1.70 at 75 and 150 mOsm/kg, respectively, and 13.1 ± 1.83 at 1500 mOsm/kg), whereas in isosmolar controls the percentage of stallion sperm mitochondria with a high membrane potential was 41.1 ± 1.69 (P < .01). Osmotic excursions induced greater damage than exposure of spermatozoa to a given nonphysiologic osmolality, and again the mitochondria were more prone to damage induced by osmotic excursions than was the sperm plasma membrane. In search of intracellular components that could mediate these changes, we have detected for the first time the c-Jun N-terminal kinase 1/2 in stallion spermatozoa, which are apparently involved in the regulation of the viability of these cells.

Objective. The study explores the applicability of the multiple-cause-of-death analysis for cervical-uterine cancer. Methods. A proportional mortality hazard design and the analysis of all causes of death due to cervical-uterine cancer from 367 death certificates of women older than 18 years of age from the State of Mexico, and 515 age and year adjusted sample of death certificates of women from the same region who died from other causes. Results. A basic multiple cause of death of 2.9 was observed in the death certificates, i.e., for every basic cause there were 2.9 multiple causes. When adjusting the multiple-causes-of-death analysis for cervical-uterine cancer by age, education, marital and insurability status, the most contributing and associated causes of death were malignant tumors from unspecified sites [OR=18.98 (2.28-157.56) and OR=14.25 (1.67-121.0)] respectively; Diabetes Mellitus as a contributing [OR=1.82 (1.02-3.27) and associated cause [OR=7.78 (1.46-41.37], and systemic arterial hypertension as an associated cause [OR=3.00 (1.40-6.47)]. Conclusions. The multiple-cause-of-death analysis is an adequate to observe the diseases that contribute condition and are associated to the cervical-uterine cancer.

Tuberculosis is one of the leading causes of mortality produced by an infectious agent. Different strategies including bioinformatics are currently being tested to identify and improve vaccines against tuberculosis. Comparative genome analysis between Streptomyces coelicolor and Mycobacterium tuberculosis suggest that both descend from a common Actinomycete ancestor. In this work, we suggest the use of Streptomyces as a live vector and explore the capacity of Streptomyces immunization to induce a protective response against mycobacterial infection. First, we compared the theoretical proteomes of S. coelicolor A3(2) with those of M. tuberculosis H37Rv and Mycobacterium bovis AF2122/97. This study showed a high similarity at the level of individual genes sequences with both bacteria sharing several membrane proteins. Then, we administered Streptomyces intraperitoneally to mice and determined its distribution by histopathology and culture; we did not find systemic dissemination. After administration of Streptomyces through different routes, we identified the most immunogenic, inducing strong humoral response, as denoted by the high serum antibody titers against this organism with cross reactivity to mycobacterial antigens. Finally, we evaluated the level of protection elicited by the inoculation of Streptomyces in Balb/c mice challenged with BCG. In these animals, lung bacillary loads were significantly lower than the control non-sensitized group.. These observations, along with Streptomyces' potential for expressing foreign proteins, suggest that Streptomyces could be an advantageous vector in the design of new tuberculosis vaccines.

Novel enantiomers and diastereoisomers structurally related to σ ligand (+)-MR200 were synthesized to improve σ(1)/σ(2) subtype selectivity. The selective σ(1) ligand (-)-8 showed an antagonist profile determined by phenytoin differential modulation of binding affinity in vitro, confirmed in vivo by an increase of κ opioid analgesia. The σ(2) ligand (-)-9 displayed agonist properties in an in vitro isolated organ bath assay and antiproliferative effects on LNCaP and PC3 prostate cancer cell lines.

Lipids were extracted from ejaculated spermatozoa from seven individual stallions to distinguish neutral lipids (NL) and polar lipids (PL) and determine their variation among stallions and their relationship with sperm quality and sperm susceptibility to lipid peroxidation. The isolated fatty acids were correlated with sperm quality (membrane integrity, mitochondrial membrane potential (ΔΨm) and expression of active caspases) and the sensitivity of the sperm plasma membrane to LPO. The miristic (C14: 0), palmitic (C16: 0), stearic (C18: 0) and oleic (C18: 1n9) acids were predominant among the NLs. Within the phospholipid fraction, the docosapentanoic acid (C22: 5n6) was dominant, albeit varying among stallions. Surprisingly, the percentage of polyunsaturated fatty acids was positively correlated with sperm quality and a low propensity for LPO, probably because these particular fatty acids provide a higher fluidity of the plasma membrane. The stallion showing the poorest sperm membrane integrity plus a high level of LPO in his ejaculate had a lower percentage (p<0.05) of this fatty acid in his sperm plasma membranes., (© 2010 Blackwell Verlag GmbH.)

Lipid peroxidation (LPO) of dog spermatozoa was assessed in fresh semen and in samples of the same ejaculates after freezing and thawing. Particular attention was paid to individual differences in the susceptibility to LPO and its possible relationship with freezeability. Innate levels of LPO were low in fresh spermatozoa but increased after thawing in one of the dogs included in our study. The level of lipid peroxidation in fresh spermatozoa was not correlated with that of thawed spermatozoa. Negative correlations were detected between the activity in seminal plasma of GPx and sperm velocities post thaw (P < 0.01), however SOD activity was positively correlated with the percentage of linear motile sperm post thaw (P < 0.05)., (Copyright © 2011 Elsevier Inc. All rights reserved.)

Objective: To report a case of congenital adrenal hyperplasia due to CYP17 deficiency caused by a novel CYP17A1 mutation., Methods: We describe the clinical, biochemical, genetic, and radiologic findings of a sporadic case of congenital adrenal hyperplasia due to CYP17 deficiency in a young patient., Results: An 18-year-old woman presented with hypogonadism and progressive muscle weakness and had not yet undergone thelarche, adrenarche, and menarche. Blood pressure was 155/90 mm Hg, she had no axillary or pubic hair, breasts were Tanner stage 1, and female genitalia were Tanner stage 1. Further laboratory studies showed hypokalemia with metabolic alkalosis, hypergonadotropic hypogonadism, a 46, XY karyotype, a low 17-hydroxyprogesterone level, and a high deoxycorticosterone level. Sequencing of the CYP17A1 gene demonstrated homozygous transversion of cytosine to adenine (TCA→TAA) in exon 5, which causes a premature stop codon at position 288 (Ser288X). Imaging studies showed large adrenal glands, cystic picture in the inguinal canal (suggestive of intra-abdominal testes), and absent Müllerian structures. Exploratory laparotomy was performed to remove the remaining gonads, and the final histologic examination showed atrophic testes., Conclusions: Congenital adrenal hyperplasia due to CYP17 deficiency should be suspected in patients with hypertension, hypokalemic alkalosis, and hypogonadism. In such cases, it is mandatory to assess the karyotype and perform hormonal and molecular genetic studies.