Comparison of exposure assessment methods in occupational exposure to benzene in gasoline filling-station attendants

The aim of this study was to assess gasoline filling-station attendants' exposure to benzene and to determine which biological exposure index (BEI), trans,trans-muconic acid (t,t-MA) or S-phenylmercapturic acid (S-PMA), shows better correlation with environmental exposure. Exposure to benzene was measured using passive samplers (Radiello) attached to the collar of the overalls of subjects (n=33) just before the work-shift (approximately 8h); analysis was performed by GC-FID. S-PMA and t,t-MA were determined, respectively, by an immunochemiluminescent assay based on specific monoclonal antibodies and by HPLC-UV at 264 nm. Both methods of biological monitoring were performed on beginning and end-shift urine samples, and expected t,t-MA and S-PMA values were calculated. Smoking habits and life-style were ascertained by means of a questionnaire. Both environmental and biological monitoring data showed that benzene exposure for gasoline filling-station attendants was low when compared with the respective ACGIH limit values (means-benzene: 0.044 mg/m(3); t,t-MA: 171 microg/g creatinine; S-PMA: 2.7 microg/g creatinine). No significant correlation was found between exposure to benzene and t,t-MA or S-PMA excretion data. The use of expected values was also experimented for S-PMA and t,t-MA. This consists of calculating, on the basis of the known half-life of the benzene metabolite, the concentration of that metabolite that a worker should present at the end of the work-shift, the difference between this value and the value actually found is a measure of benzene exposure during work. The use of expected values in biological monitoring did not improve correlations. At these low benzene levels, environmental monitoring seems to be the best method of evaluating individual exposure. However, biological monitoring remains useful, as a mean of assessing group exposure.     

NK cells and their receptors during viral infections

Increasing evidence indicates the importance of human natural killer (NK) cells in the immune response against certain viral infections. In the present article, we summarize information on NK cell responses against several viruses and on the nature of NK cell receptor-ligand interactions involved in these responses. Recent studies indicate that NK cells display functional features that are normally attributed exclusively to cells of the adaptive immune system. In this context, experiments both in mice and humans suggest the existence of long-lived NK cells that expand during viral infections and retain a 'memory' of previous exposure to a specific antigen. However, further studies are necessary to better define the characteristics of these long-lived NK cell populations and their role in viral infections.     

Rectal obstruction after a vaginal posterior compartment polypropylene mesh fixed to the sacrospinous ligaments

We present a case in which a polypropylene mesh was placed over the posterior vaginal wall and was fixed to the sacrospinous ligaments on both sides. Postoperative a rectal obstruction developed which was only resolved after splitting the entire mesh in the midline. It is hypothesised that the obstruction was due to the fixation of the mesh with irresolvable suture material to the sacrospinous ligaments acting as a hinge on which the bowel folded.     

Between hope and fear: patient��s expectations prior to pelvic organ prolapse surgery

Introduction and hypothesis  

The aim of our study was to analyse the patient’s expectations (fears and goals (hopes)) in women who are scheduled for pelvic organ prolapse (POP) surgery.     

NMDA receptor antagonist felbamate reduces behavioral deficits and blood-brain barrier permeability changes after experimental subarachnoid hemorrhage in the rat

Increased levels of glutamate and aspartate have been detected after subarachnoid hemorrhage (SAH) that correlate with neurological status. The NMDA receptor antagonist felbamate (FBM; 2-phenyl-1,3-propanediol dicarbamate) is an anti-epileptic drug that elicits neuroprotective effects in different experimental models of hypoxia-ischemia. The aim of this dose-response study was to evaluate the effect of FBM after experimental SAH in rats on (1) behavioral deficits (employing a battery of assessment tasks days 1-5 post-injury) and (2) blood-brain barrier (BBB) permeability changes (quantifying microvascular alterations according to the extravasation of protein-bound Evans Blue by a spectrophotofluorimetric technique 2 days post-injury). Animals were injected with 400 muL of autologous blood into the cisterna magna. Within 5 min, rats received daily oral administration of FBM (15, 30, or 45 mg/kg) for 2 or 5 days. Results were compared with sham-injured controls treated with oral saline or FBM (15, 30, or 45 mg/kg). FBM administration significantly ameliorated SAH-related changes in Beam Balance scores on days 1 and 2 and Beam Balance time on days 1-3, Beam Walking performance on days 1 and 2, and Body Weight on days 3-5. FBM also decreased BBB permeability changes in frontal, temporal, parietal, occipital, and cerebellar cortices; subcortical and cerebellar gray matter; and brainstem. This study demonstrates that, in terms of behavioral and microvascular effects, FBM is beneficial in a dose-dependent manner after experimental SAH in rats. These results reinforce the concept that NMDA excitotoxicity is involved in the cerebral dysfunction that follows SAH.     

Menarcheal timing in intensively treated girls with type 1 diabetes mellitus

Background and aimPrevious studies on menarcheal age (MA) in type 1 diabetes mellitus (T1DM) have shown conflicting results about the effects of DM, but most lack a control group. The present study design is peculiar in that it covers a study population of 73 intensively treated menarcheal adolescents with premenarcheal onset of T1DM (Group A), whose MA was compared with that recorded in three control populations: the first one consisting of 280 healthy adolescents, the second one consisting of 20 T1DM adolescents with postmenarcheal DM onset (Group B) and the third one represented by the respective mothers.Methods and resultsMA of Group A patients was significantly delayed when compared with the respective mothers, healthy controls and Group B patients. By contrast MA of Group B girls was superimposable to the one of both their respective mothers and healthy controls. In Group A MA was strongly related (p < 0.0005) to HbA1c at the time of menarche and to average HbA1c concentrations during the last years before menarche. In Group A no relationship between patients' and mothers' MAs was found, whilst such a correlation was significant in Group B.Conclusions(a) MA is significantly delayed in girls with premenarcheal presentation of T1DM, even if intensively treated; (b) menarcheal retardation is more severe in the patients with suboptimal metabolic control at the time of menarche; and (c) MA in premenarcheal presenting T1DM is irrespective of maternal MA, age and HbA1c concentrations at DM presentation, body mass index and daily insulin dose at menarche.     

Molecular analysis of ANT1, TWINKLE and POLG in patients with multiple deletions or depletion of mitochondrial DNA by a dHPLC-based assay

ANT1, TWINKLE and POLG genes affect mtDNA stability and are involved in autosomal dominant PEO, while mutations in POLG are responsible for numerous clinical presentations, including autosomal recessive PEO, sensory ataxic neuropathy, dysarthria and ophthalmoparesis (SANDO), spino-cerebellar ataxia and epilepsy (SCAE) or Alpers syndrome. In this study, we report on the mutational analysis of ANT1, TWINKLE and POLG genes in 15 unrelated patients, using a dHPLC-based protocol. This series of patients illustrates the large array of clinical presentations associated with mtDNA stability defects, ranging from isolated benign PEO to fatal Alpers syndrome. A total of seven different mutations were identified in six of 15 patients (40%). Six different recessive mutations were found in POLG, one in TWINKLE while no mutation was identified in ANT1. Among the POLG mutations, three are novel and include two missense and one frameshift changes. Seventeen neutral changes and polymorphisms were also identified, including four novel neutral polymorphisms. Overall, this study illustrates the variability of phenotypes associated with mtDNA stability defects, increases the mutational spectrum of POLG variants and provides an efficient and reliable detection protocol for ANT1, TWINKLE and POLG mutational screening.     

Activating PTPN11 mutations play a minor role in pediatric and adult solid tumors

The PTPN11 gene encodes SHP-2, a widely expressed cytoplasmic protein tyrosine phosphatase functioning as a signaling transducer. Germ-line PTPN11 mutations cause Noonan syndrome (NS), a developmental disorder characterized by an increased risk of malignancies. Recently, a novel class of activating mutations in PTPN11 has been documented as a somatic event in a heterogeneous group of leukemias. Because of the relatively higher prevalence of certain solid tumors in children with NS and the positive modulatory function of SHP-2 in RAS signaling, a wider role for activating PTPN11 mutations in cancer has been hypothesized. Here, we screened a number of solid tumors, including those documented in NS or in which deregulated RAS signaling occurs at significant frequency, for PTPN11 mutations. No disease-associated mutation was identified in rhabdomyosarcoma (n = 13), neuroblastoma (n = 32), melanoma (n = 50), thyroid (n = 85), and colon (n = 48) tumors; a novel missense change, promoting an increased basal phosphatase activity of SHP-2, was observed in one glioma specimen. Our data document that deregulated SHP-2 function does not represent a major molecular event in pediatric and adult tumors, further supporting our previous evidence indicating that the oncogenic role of PTPN11 mutations is cell-context specific.