Streptococcus pneumoniae: prevalence in nasopharyngeal carriers of more than 50-years-old,in a Mexican rural community

Introduction

Streptococcus pneumoniae (Sp) is the main cause of community-acquired pneumonia in the elderly, hence the importance to establish the prevalence of nasopharyngeal colonization by different Sp serotypes in adults.

p 53 gene rearrangements in chronic myelocytic leukemia

Summary We performed Southern-blot analysis of the p 53 gene in 41 consecutive patients with typical chronic myelocytic leukemia (CML). In two of them, we were able to study cells during both the chronic and the accelerated phases. Only one of the 29 chronic-phase samples had rearrangement of the p 53 gene, whereas three of the nine accelerated-phase samples and one of the five patients in blast crisis exhibited rearrangements. Gene deletion was observed in two patients, one in accelerated phase and the other in blast crisis. One patient with a nonrearranged p 53 gene in chronic phase showed rearrangement after progression to the accelerated phase. On the other hand, one patient in accelerated phase exhibited rearrangements which disappeared after reversion to chronic phase with successful treatment. Our findings support the opinion that alterations of the p 53 gene may play an important role in CML evolution.     

Exposure to Brominated Trihalomethanes in Water During Pregnancy and Micronuclei Frequency in Maternal and Cord Blood Lymphocytes

Background: Water disinfection by-products have been associated with an increased cancer risk. Micronuclei (MN) frequency in lymphocytes is a marker of genomic damage and can predict adult cancer risk.Objective: We evaluated maternal exposure to drinking water brominated trihalomethanes (BTHM) in relation to MN frequency in maternal and cord blood lymphocytes.Methods: MN frequency was examined in 214 mothers and 223 newborns from the Rhea mother–child cohort in Crete, Greece, in 2007–2008. Residential BTHM water concentrations were estimated during pregnancy using tap water analyses and modeling. Questionnaires on water related habits were used to estimate BTHM exposure from all routes. Associations between BTHM and MN frequency were estimated using negative binomial regression.Results: BTHM concentrations in residential tap water during pregnancy ranged from 0.06 to 7.1 μg/L. MN frequency in maternal binucleated lymphocytes was found to increase with BTHM concentrations in residential water for exposure during the first [rate ratio (RR) for 1 μg/L = 1.05; 95% CI: 1.00, 1.11] and second trimesters (RR for 1 μg/L = 1.03; 95% CI: 1.00, 1.06), and through all routes of BTHM exposure during the first trimester (RR for 1 μg/week = 3.14; 95% CI: 1.16, 8.50).Conclusions: These findings suggest that exposure to BTHM may increase the frequency of MN in maternal binucleated lymphocytes.Citation: Stayner LT, Pedersen M, Patelarou E, Decordier I, Vande Loock K, Chatzi L, Espinosa A, Fthenou E, Nieuwenhuijsen MJ, Gracia-Lavedan E, Stephanou EG, Kirsch-Volders M, Kogevinas M. 2014. Exposure to brominated trihalomethanes in water during pregnancy and micronuclei frequency in maternal and cord blood lymphocytes. Environ Health Perspect 122:100–106; http://dx.doi.org/10.1289/ehp.1206434     

Intranasal Dexamethasone Reduces Mortality and Brain Damage in a Mouse Experimental Ischemic Stroke Model

Neuroinflammation triggered by the expression of damaged-associated molecular patterns released from dying cells plays a critical role in the pathogenesis of ischemic stroke. However, the benefits from the control of neuroinflammation in the clinical outcome have not been established. In this study, the effectiveness of intranasal, a highly efficient route to reach the central nervous system, and intraperitoneal dexamethasone administration in the treatment of neuroinflammation was evaluated in a 60-min middle cerebral artery occlusion (MCAO) model in C57BL/6 male mice. We performed a side-by-side comparison using intranasal versus intraperitoneal dexamethasone, a timecourse including immediate (0 h) or 4 or 12 h poststroke intranasal administration, as well as 4 intranasal doses of dexamethasone beginning 12 h after the MCAO versus a single dose at 12 h to identify the most effective conditions to treat neuroinflammation in MCAO mice. The best results were obtained 12 h after MCAO and when mice received a single dose of dexamethasone (0.25 mg/kg) intranasally. This treatment significantly reduced mortality, neurological deficits, infarct volume size, blood–brain barrier permeability in the somatosensory cortex, inflammatory cell infiltration, and glial activation. Our results demonstrate that a single low dose of intranasal dexamethasone has neuroprotective therapeutic effects in the MCAO model, showing a better clinical outcome than the intraperitoneal administration. Based on these results, we propose a new therapeutic approach for the treatment of the damage process that accompanies ischemic stroke.Electronic supplementary materialThe online version of this article (10.1007/s13311-020-00884-9) contains supplementary material, which is available to authorized users.     

Sex differences in the performance of cognitive tasks in a murine model of metabolic syndrome

The metabolic syndrome includes changes in blood glucose levels, arterial hypertension, triglycerides, dyslipidemia and central obesity. Countless reports have described the correlation between the metabolic syndrome and cognitive impairment. However, only a few reports have assessed cognitive impairment associated with the metabolic syndrome in animals of both sexes. For this purpose, Sprague‐Dawley male and female rats were fed either with a hypercaloric diet as model of the metabolic syndrome or with a standard chow diet as controls. Subsequently, spatial learning and memory (Morris water maze) as well as short‐ and long‐term memory (passive avoidance task) were evaluated. Body weight, blood pressure, triglycerides, and total cholesterol significantly increased (F(1, 36) = 94.89, p < .001) in rats fed with hypercaloric diet compared to control rats. Furthermore, cognitive impairment was observed in spatial learning and spatial memory on male rats but not on female rats fed with hypercaloric diet. In addition, a long‐term memory impairment was observed in both groups fed with hypercaloric diet in comparison to their respective control group (F(1, 32) = 10.61, p = .0027). Immunohistochemistry results showed no changes in the number of positive cells for NeuN, GFAP and Ox‐42. In males fed with a hypercaloric diet, a decrease in testosterone levels was observed, whereas estradiol levels decreased in females when compared with their respective control group (p < .0001). In this MetS animal model, metabolic and cognitive differences were observed in males and females, which demonstrates that sex hormones play a significant role in metabolic regulation and neuroprotection related to the CA1 region of the hippocampus.     

Esophageal atresia and tracheoesophageal fistula in two infants born to hyperthyroid women receiving methimazole (tapazol®) during pregnancy

We report on 2 newborn infants with esophageal atresia and tracheoesophageal fistula (EA + TEF) born to hyperthyroid mothers receiving methimazole (Tapazol ®) before and during their entire pregnancies. Both mothers were euthyroid during gestation and developed hydramnios diagnosed during weeks 34 and 33 of gestation. Premature delivery (36.2 weeks of gestation) occurred in one case, and both newborn infants were small for date with palpable goiter; one of them had other associated malformations. Hypo-thyroidism was diagnosed by laboratory tests in both cases. Corrective surgery was undertaken, but both newborn infants developed septicemia and renal insufficiency and died in the first week of life. The EA + TEF and a normally placed enlarged thyroid gland were confirmed at necropsy. These cases represent a previously unreported example of the association of maternal ingestion of methimazole during pregnancy and EA + TEF. © 1992 Wiley-Liss, Inc.     

A missense mutation in the chloride/proton ClC-5 antiporter gene results in increased expression of an alternative mRNA form that lacks exons 10 and 11. Identification of seven new CLCN5 mutations in patients with Dent’s disease

Mutations in the voltage-gated chloride/proton antiporter ClC-5 gene, CLCN5, are associated with Dent’s disease, an X-linked renal tubulopathy. Our interest is to identify and characterize disease-causing CLCN5 mutations, especially those that alter the splicing of the pre-mRNA. We analyzed the CLCN5 gene from nine unrelated Spanish Dent’s disease patients and their relatives by DNA sequencing. Pre-mRNA splicing analysis was performed by RT-PCR. Seven new mutations were identified, consisting of three missense mutations (C219R, F273L, and W547G), one splice-site mutation (IVS-2A > G), one deletion (976delG), and two non-sense mutations (Y140X and W314X). We found that missense mutation W547G also led to increased expression of a new alternative isoform lacking exons 10 and 11 that was expressed in several human tissues. In addition, we describe another novel CLCN5 splicing variant lacking exon 11 alone, which was expressed only in human skeletal muscle. We conclude that missense mutation W547G can also alter the expression levels of a CLCN5 mRNA splicing variant. This type of mutation has not been previously described in the CLCN5 gene. Our results support the importance of a routine analysis at the pre-mRNA level of mutations that are commonly assumed to cause single amino acids alterations.     

Thin layer flows due to surface tension gradients over a membrane undergoing nonuniform, periodic strain

Measurements of surface tension in the lung have shown that a time-mean gradient exists with the potential to generate clearance flows toward the mouth in the thin liquid layer that lines the airways. A model is developed to explore this phenomenon in the simple case of a membrane with linear variation in strain along its length, coupled with the unique properties of pulmonary surfactant. The evolution equations are solved numerically for liquid layer thickness and surfactant concentration during a single oscillatory cycle, and the net volume exchanged is computed. The parameters governing the flow are shown to be time scales for viscous effects, {ie913-1}, surface diffusion, {ie913-2}, surfactant adsorption, {ie913-3}, surfactant desorption, {ie913-4}, oscillation, {ie913-5}, and the average membrane strain {ie913-6}. The volume pumped toward the less compliant end on the initial cycle is maximized when {ie913-7} and is relatively insensitive to {ie913-8}. Rapid adsorption generally augments liquid transport for {ie913-9}. Pumping drops precipitously if {ie913-10}. Effects of strain amplitude are reported as well. For parameter values approximating those in the lung, pumping rates are near optimal; the mean surface velocity is ∼0.05 mm/sec, compared with 0.2 mm/sec produced by the action of cilia on the mucus layer. This mechanism might therefore be important in assisting clearance from the lung or maintaining a liquid layer over alveolar facets.