Analysis of male reproductive parameters in a murine model of mucopolysaccharidosis type I (MPS I)

Mucopolysaccharidosis (MPS) I is a lysosomal storage disorder (LSD) that is characterised by alpha-L-iduronidase (Idua) deficiency and continuous deposition of glycosaminoglycans (GAGs), which consequently interferes with cell signalling mechanisms and results in multisystemic and progressive symptoms. The animal model of MPS I (Idua-/-) has been widely studied to elucidate the consequences and progression of the disorder; however, studies specifically assessing the male reproductive tract are lacking. The aim of this study was to evaluate some of the reproductive characteristics of male MPS I mice in two phases of life. Reproductive organ biometry, sperm counts, sperm morphological evaluation, plasma testosterone measurements and histopathological, histomorphometrical and immunohistochemical analysis were performed in 3- and 6-month-old C57BL/6 Idua+/+ and Idua-/- mice. Seminal vesicle weights were decreased in both the 3- and 6-month-old Idua-/- mice. Decrease in sperm counts and the majority of the histopathological signs were observed in the 6-month-old Idua-/- mice. No differences were detected in the sperm morphological analysis. Immunohistochemistry revealed that seminiferous tubules from 3-month-old Idua-/- mice were more intensely stained with anti-caspase-3 than 3-month-old Idua+/+ mice, but no difference was found at 6 months. These results suggest that MPS I interferes with male reproductive parameters both in 3 and 6-month-old animals and histopathological signs are more pronounced in 6-month-old mice, indicating that the effects of the disorder may intensify with the disease progression.     

Subchronic administration of nandrolone decanoate in acetylcholinesterase activity in Wistar rats

Health sciences have recently discovered the medical uses of nandrolone decanoate (ND), an androgenic anabolic steroid (AAS), and reported its use in human and animal patients. Clinical evidences suggest that the AAS excess may affect the cholinergic system, which is responsible for several vital functions like learning, memory, and the organization of the movements. Thus, our aim is to research the subchronic effect of ND when administered in varying doses on the acetylcholinesterase (AChE) activity in these brain structures: cerebellum (CE), hippocampus, striatum (ST), and cortex of adult rats. We used 36 male Wistar rats, which were divided into six groups (n?=?6). The groups were divided into: G1—control (physiologic solution), G2—diluents control (only an oleaginous vehicle of vegetal origin—olive oil), G3—0.42?mg?kg^?1 of ND, G4—1.8?mg?kg^?1 of ND, G5—4.6?mg?kg^?1 of ND, and G6—10.0?mg?kg^?1 of ND. We applied the doses once every week during a 3-week period. The values obtained demonstrated a significant increase in the AChE activity (referring to ST and CE for the 4.6 and 10.0?mg?kg^?1 doses of ND). The ND causes increase in AChE activity, which could impair neurotransmission and cholinergic modulation.     

Phenotypic characterization and predictive analysis of p.Asp47Asn LDL receptor mutation associated with Familial Hypercholesterolemia in a Chilean population

BackgroundFamilial hypercholesterolemia (FH) is an inherited disorder mainly caused by mutations in the LDL receptor (LDL-R) and characterized by elevation of low-density lipoprotein cholesterol (LDL-C) levels and premature cardiovascular disease.ObjectiveIn this study, we evaluated the clinical phenotype of the p.Asp47Asn, described as an uncertain pathogenic variant, and its effect on the structure of LDL-R and ligand interactions with apolipoproteins.Methods27 children and adolescents with suspected FH diagnosis were recruited from a pediatric endocrinology outpatient clinic. Blood samples were collected after 12 h fasting for lipid profile analysis. DNA sequencing was performed for six FH-related genes by Ion Torrent PGM platform and copy number variation by MLPA. For index cases, a familial cascade screening was done restricted to the same mutation found in the index case. In silico analysis were developed to evaluate the binding capacity of LDL-R to apolipoproteins B100 and E.ResultsLipid profile in children and adolescents demonstrated higher LDL-C levels in p.Asp47Asn carriers compared to the wild type genotype. In silico analysis predicted a reduction in the binding capacity of the ligand-binding modules LA1-2 of p.Asp47Asn LDL-R for ApoB100 and ApoE, which was not produced by local structural changes or folding defects but as a consequence of a decreased apparent affinity for both apolipoproteins.ConclusionThe clinical phenotype and the structural effects of p.Asp47Asn LDL-R mutation suggest that this variant associates to FH.     

Drug trajectories among youth undergoing treatment: The influence of psychological problems and delinquency

Previous research has documented associations of addiction with delinquency and psychological problems. However, few studies have evaluated their influence on adolescent's drug use trajectories. The current study aims to examine the influence of these factors on the recovery trajectories of 199 youths aged 15.6 years on average admitted to inpatient and outpatient addiction treatment centers, followed up three and six months later. Results indicate that youth who show higher severity of drug abuse exhibit greater improvement than youth with a lower severity of drug abuse at the onset of treatment. Although psychological problems were associated with baseline drug use, they did not influence drug use trajectory over time. Only delinquency influenced the recovery trajectories of these youth. Results suggest that a high level of delinquency can have a significant effect on the drug recovery process of adolescents and that interventions should attempt to reduce both drug use and delinquency.     

NTPDase and 5′-nucleotidase activities from synaptosomes and platelets of rats exposed to cadmium and treated with N-acetylcysteine

The purpose of the present investigation was to evaluate the hydrolysis of adenine nucleotides on synaptosomes and platelets obtained from rats exposed to cadmium (Cd) and treated with N-acetylcysteine (NAC). Rats received Cd (2 mg/kg) and NAC (150 mg/kg) by gavage every other day for 30 days. Animals were divided into four groups (n = 4–6): control/saline, NAC, Cd, and Cd/NAC. The results of this study demonstrated that NTPDase and 5′-nucleotidase activities were increased in the cerebral cortex synaptosomes of Cd-poisoned rats, and NAC co-treatment reversed these activities to the control levels. In relation to hippocampus synaptosomes, no differences on the NTPDase and 5′-nucleotidase activities of Cd-poisoned rats were observed and only the 5′-nucleotidase activity was increased by the administration of NAC per se. In platelets, Cd-intoxicated rats showed a decreased NTPDase activity and no difference in the 5′-nucleotidase activity; NAC co-treatment was inefficient in counteracting this undesirable effect. Our findings reveal that adenine nucleotide hydrolysis in synaptosomes and platelets of rats were altered after Cd exposure leading to a compensatory response in the central nervous system and acting as a modulator of the platelet activity. NAC was able to modulate the purinergic system which is interesting since the regulation of these enzymes could have potential therapeutic importance. Thus, our results reinforce the importance of the study of the ecto-nucleotidases pathway in poisoning conditions and highlight the possibility of using antioxidants such as NAC as adjuvant against toxicological conditions.     

Urethral stromal tumor with pacemaker cell phenotype

Penile malignancies are rare in developed countries. The authors present a case of a penile urethral mesenchymal tumor occurring in a 51-year-old Caucasian male and displaying light microscopic, immunohistochemical, and ultrastructural features suggestive of a pacemaker cell type, combined with a lack of diagnostic features of any other established tumor category. The immunohistochemical profile was intensely positive for vimentin, PKC θ, and NSE and weakly positive to nonreactive for CD34 and smooth muscle actin, and entirely negative for CD117 (c-kit), S-100, and other markers. C-kit and PDGFRA gene analysis showed no mutations. Electron microscopy revealed tumor cells with plentiful cytoplasm and cytoplasmic processes/filopodia, both filled with intermediate filaments and occasional solitary focal densities. There were also prominent smooth endoplasmic reticulum cisternae, caveolae, neurosecretory granules, particularly concentrated in cytoplasmic processes, and synaptic-type structures. Poorly formed basal lamina, gap junctions, and intercellular collagen aggregates, consistent with skeinoid-type fibers, were also noted. Interstitial cells with potential pacemaker function have been recently described in the lower urinary tract, including the urethra, and this tumor may be related to this cellular phenotype.     

Enamel microhardness and shear bond strength after treatment with an 18% carbamide peroxide bleaching varnish

PURPOSE: To evaluate the microhardness and shear bond strength of human enamel treated with an 18% carbamide peroxide bleaching varnish. METHODS: 40 dental enamel slabs were embedded and ground flat, dividing them into four groups (n=10) which received the varnish application for 14 consecutive days: (G1) one daily varnish application; (G2) two daily varnish applications with an interval of 15 minutes; (G3) two daily varnish applications with an interval of 5 hours. After varnish application, the slabs were immersed in artificial saliva changed daily. The control group (G4) consisted of slabs (n=10) that did not receive any varnish treatment and were maintained in artificial saliva for 14 days. Microhardness tests were performed with Knoop indentation with a load of 25 grams for 5 seconds at the beginning of the treatment (baseline values) and after 7 and 14 days. Cylinders were made with microhybrid resin composite and one-bottle adhesive system for shear bond strength tests. Using a universal testing machine with a speed of 0.5 mm/minute to obtain the values in MPa. RESULTS: The Kruskal-Wallis test showed no changes in microhardness values among groups after 7-day varnish application, although there was a decrease in microhardness values when using an 18% carbamide peroxide varnish twice a day with a time-interval of 5 hours between applications (P < 0.05). For enamel shear bond strength, ANOVA test (P > 0.05) did not show significant differences among the groups (G1=15.8; G2=15.2; G3=19.0; G4=15.1).