Effects of 90 min of manual repetitive work on skin temperature and median and ulnar nerve conduction parameters: A pilot study in normal subjects

To test whether the influence of manual activity should be considered when interpreting the results of nerve conduction study (NCS) of the upper limbs performed during work shifts, we evaluated the short-term effect of 90-min repetitive manual work on NCS parameters. Twenty-eight healthy volunteers underwent NCS of the dominant limb at the end of an interview (T₀), after a 30-min rest in sitting position (T₁) and after performing a standardized 90-min manual task (T₂). The task was designed to simulate typical assembly and packing activities. No significant differences were observed for skin temperature (Ts) and NCS parameters between T₀ and T₁. Significantly (p < 0.001) higher Ts mean values were found at T₂ as compared to the previous tests for both females and males. The regression analysis showed an association between temperature variation and nerve conduction velocity values for the median and ulnar nerve at T₂ as compared to T₁. In females, a reduction of the mean sensory nerve action potential (SNAP) amplitude at T₂ was recorded, whereas an opposite trend was observed among males. Manual work is able to influence hand Ts and to modify NCS parameters. SNAP amplitudes changes suggest gender differences in peripheral nerve characteristics that deserve further investigation.     

N-acetylcysteine Protects Mice from Lethal Endotoxemia by Regulating the Redox State of Immune Cells

The excessive production of reactive oxygen species (ROS) associated with inflammation leads to oxidative stress, which is involved with the high mortality from several diseases such as endotoxic shock and can be controlled to a certain degree by antioxidants. The immune cells use ROS in order to support their functions and, therefore, need adequate levels of antioxidant defenses in order to avoid the harmful effect of an excessive ROS production. In the present work, the effect of the administration of the antioxidant N-acetylcysteine (NAC) on the redox state of peritoneal macrophages and lymphocytes from mice with lethal endotoxic shock (100 mg/kg i.p. of lipopolysaccharide, LPS), was studied. In both types of immune cells at 0, 2, 4, 12 and 24 h after LPS injection, an increase of ROS, of the proinflammatory cytokine tumor necrosis factor alpha (TNFα), the lipid peroxidation (malonaldehyde levels, MDA), inducible nitric oxide synthase (iNOS) expression and the oxidized/reduced glutathione (GSSG/GSH) ratio, as well as a decrease of enzymatic antioxidant defenses, such as superoxide dismutase (SOD) and catalase (CAT) activity, was observed. The injection of NAC (150 mg/kg i.p. at 30 min after LPS injection) decreased the ROS, the TNFα the MDA levels, iNOS expression and the GSSG/GSH ratio, and increased the antioxidant defenses in both macrophages and lymphocytes. Moreover, the NAC treatment prevented the activation of nuclear translocation of the nuclear factor κB (NF-κB), which regulates ROS, inflammatory cytokines and antioxidant levels. Our present results provide evidence that both cell types have a relevant role in the pathogenesis of endotoxic shock, and that NAC, by improving the redox state of these immune cells, could increase mouse survival. Thus, antioxidants could offer an alternative treatment of human endotoxic shock.     

A potential role of alkaloid extracts from Salsola species (Chenopodiaceae) in the treatment of Alzheimer's disease

From the aerial parts of Salsola oppositofolia, S. soda and S. tragus an alkaloid extract was obtained and tested to evaluate antioxidant and anti-cholinesterase activities. The in vitro study of the antioxidant activity by the DPPH method revealed a significant activity of Salsola alkaloid extracts with IC₅₀ values ranging from 16.30 μg/mL for S. oppositifolia to 26.17 μg/mL for S. tragus. Acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) inhibitory activities were evaluated. S. tragus alkaloid extract exerted the highest inhibitory activity against AChE (IC₅₀ of 30.2 μg/mL) and BChE (IC₅₀ of 26.5 μg/mL). Interestingly, S. soda and S. oppositifolia exhibited a selective inhibitory activity against BChE with IC₅₀ values of 34.3 μg/mL and 32.7 μg/mL, respectively. Tetrahydroisoquinoline alkaloids were identified and quantified by GC/MS analysis.     

Ambiguous Base Pairing of 1-(2-Deoxy-β-D-Ribofuranosyl)imidazole-4-carboxamide During PCR

Abstract

The use of 5′-triphosphate of 1-(2-deoxy-β-D-ribofuranosyl)imidazole-4-carboxamide (dYTP) in DNA amplification reaction in place of dATP or dGTP yielded mutations frequencies of 3–4×10^?2 per base per amplification. A reasonable proportion of transversions (11–15%) was observed in the absence of deletions and insertions.     

Purine Nucleoside Phosphorylase Deficiency: A Mutation Update

Purine nucleoside phosphorylase (PNPase) deficiency is an autosomal recessive disorder affecting purine degradation and salvage pathways. Clinically, patients typically present with severe immunodeficiency, neurological dysfunction, and autoimmunity. Biochemically, PNPase deficiency may be suspected in the presence of hypouricemia. We report biochemical and genetic data on a cohort of seven patients from six families identified as PNPase deficient. In all patients, inosine, deoxyinosine, guanosine, and deoxyguanosine were elevated in urine, and mutation analysis revealed seven different mutations of which three were novel. The mutation c.770A>G resulted in the substitution p.His257Arg. A second novel mutation c.257A>G (p.His86Arg) was identified in two siblings and a third novel mutation, c.199C>T (p.Arg67X), was found in a 2-year-old female with delayed motor milestones and recurrent respiratory infections. A review of the literature identified 67 cases of PNPase deficiency from 49 families, including the cases from our own laboratory. PNPase deficiency was confirmed in 30 patients by genotyping and 24 disease causing mutations, including the three novel mutations described in this paper, have been reported to date. In five of the seven patients, plasma uric acid was found to be within the pediatric normal range, suggesting that PNPase deficiency should not be ruled out in the absence of hypouricemia.     

High Frequency Ultrasound for In Vivo Pregnancy Diagnosis and Staging of Placental and Fetal Development in Mice

Background

Ultrasound is a valuable non-invasive tool used in obstetrics and gynecology to monitor the growth and well being of the human fetus. The laboratory mouse has recently emerged as an appropriate model for fetal and perinatal studies because morphogenetic processes in mice exhibit adequate homology to those in humans, and genetic manipulations are relatively simple to perform in mice. High-frequency ultrasound (HFUS) has recently become available for small animal preclinical imaging and can be used to study pregnancy and development in the mouse. The objective of the current study was to assess the main applications of HFUS in the evaluation of fetal growth and placental function and to better understand human congenital diseases.

Methodology/Principal Findings

On each gestational day, at least 5 dams were monitored with HFUS; a total of ∼200 embryos were examined. Because it is not possible to measure each variable for the entire duration of the pregnancy, the parameters were divided into three groups as a function of the time at which they were measured. Univariate analysis of the relationship between each measurement and the embryonic day was performed using Spearman’s rank correlation (Rs). Continuous linear regression was adopted for multivariate analysis of significant parameters. All statistical tests were two-sided, and a p value of 0.05 was considered statistically significant.

Conclusions/Significance

The study describes the main applications of HFUS to assess changes in phenotypic parameters in the developing CD1 mouse embryo and fetus during pregnancy and to evaluating physiological fetal and placental growth and the development of principal organs such as the heart, kidney, liver, brain and eyes in the embryonic mouse. A database of normal structural and functional parameters of mouse development will provide a useful tool for the better understanding of morphogenetic and cardiovascular anomalies in transgenic and mutant mouse models.