Multi-generational exposure of Daphnia magna to pharmaceuticals: Effects on colonization, reproduction, and habitat selection behavior.

The presence of pharmaceuticals in the aquatic environment is increasing due to their growing use for human health. Although most studies are based on short exposures to these contaminants, the present study has emerged from the need to study pharmaceuticals in aquatic organisms over a long-term exposure to understand any multi-generational chronic effects and alterations regarding habitat selection. Therefore, this study shows: (1) the ability of Daphnia magna to colonize environments contaminated with caffeine, ibuprofen and fluoxetine, and (2) the effect of these pharmaceuticals on reproduction and habitat selection (under two scenarios: with and without food) after a long-term exposure period of three generations.

Eating disorders in young patients with neurofibromatosis type 1.

Aim: We describe the association of neurofibromatosis type 1 (NF1) and feeding and eating disorders (FED) in five patients admitted to our third level centre for both FED and NF1.

Methods: Case series of five adolescent females with NF1 treated for FED.

Results: We collected data from five patients with NF1 aged between 14 and 22 years, all females.

Quadriceps muscle strength in Duchenne muscular dystrophy and effect of corticosteroid treatment.

Objectives: In Duchenne muscular dystrophy, quadriceps weakness is recognized as a key factor in gait deterioration. The objective of this work was three-fold: first, to document the strength of the quadriceps in corticosteroid-naïve DMD boys; second, to measure the effect of corticosteroids on quadriceps strength; and third, to evaluate the correlation between baseline quadriceps strength and the age when starting corticosteroids with the loss of ambulation.

Methods: Quadriceps muscle strength using hand-held dynamometry was measured in 12 ambulant DMD boys who had never taken corticosteroids and during corticosteroid treatment until the loss of ambulation.

Neuropsychological profile in Italian children with neurofibromatosis type 1 (NF1) and their relationships with neuroradiological data: Preliminary results.

Background: Neurofibromatosis type 1 is a genetic disorder associated with cognitive deficits, learning disabilities and behavioral problems. These domains appear to have a still controversial debated association with local areas of T2-hyperintensities on MRI images, called unidentified bright objects (UBOs).

Methods: A cohort of 36 children (aged 7-11 years) included consecutively, underwent neuropsychological and behavioral assessment to determine their cognitive and neuropsychological profile, and the frequency of specific learning disabilities.

Subcutaneous immunoglobulin in CIDP and MMN: a short-term nationwide study.

This multi-center Italian prospective observational study reports the 4 months follow-up data of 87 patients affected by chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) and multifocal motor neuropathy (MMN) shifted from intravenous to subcutaneous immunoglobulin treatment. A therapeutic shift from intravenous to subcutaneous immunoglobulin was performed in 87 patients (66 CIDP; 21 MMN) affected by immune-mediated peripheral neuropathies with evidence of a sustained clinical response to intravenous immunoglobulin. Patients were evaluated by means of the Overall Neuropathy Limitation Scale, Medical Research Council Scale and Life Quality Index questionnaire, both at the time of therapeutic shift and after 4 months of subcutaneous immunoglobulin treatment.

Epilepsy in Mowat-Wilson syndrome: delineation of the electroclinical phenotype.

Mowat-Wilson syndrome (MWS) is a genetic disease caused by heterozygous mutations or deletions of the ZEB2 gene and is characterized by distinctive facial features, epilepsy, moderate to severe intellectual disability, corpus callosum abnormalities and other congenital malformations. Epilepsy is considered a main manifestation of the syndrome, with a prevalence of about 70-75%. In order to delineate the electroclinical phenotype of epilepsy in MWS, we investigated epilepsy onset and evolution, including seizure types, EEG features, and response to anti-epileptic therapies in 22 patients with genetically confirmed MWS.

Early corticosteroid treatment in 4 Duchenne muscular dystrophy patients: 14-year follow-up.

Introduction: Corticosteroid treatment is the standard of care in Duchenne muscular dystrophy (DMD), but the optimal age to initiate treatment and dosage pattern remain a matter of discussion.

Methods: We performed a long-term study of alternate-day corticosteroids in five 2- to 4-year-old DMD patients. The primary outcome measure was prolongation of the ability to walk.

Case report of pyruvate dehydrogenase deficiency with unusual increase of fats during ketogenic diet treatment.

This article describes a case of pyruvate dehydrogenase deficiency in a 3-year-old boy who presented generalized hypotonia, severe psychomotor development delay, and generalized and partial seizures and was refractory to antiepileptic drugs. After the diagnosis, the patient was put on a ketogenic diet. Six months later, seizure frequency was reduced and psychomotor development had improved.

VNS in drug resistant epilepsy: preliminary report on a small group of patients.

Background: In 1997 Vagus Nerve Stimulation (VNS) received approval from the US Food and Drug Administration (FDA) as an adjunctive therapy in the treatment of medically intractable partial epilepsy in people aged 12 years and older who are ineligible for resective epilepsy surgery. Although the exact mechanisms of action are unknown, the use of VNS with children has increased, including those younger than 12 years of age, or those with generalized epilepsy.

Methods: We describe the outcome for the first group of nine patients, aged 8-28 years, who had pharmaco-resistant epilepsy and were treated with VNS.

Prospective study on long-term treatment with oxcarbazepine in pediatric epilepsy.

Following a previous preliminary report on a group of children suffering from partial epilepsies, we present the final considerations on the same group in order to evaluate the long-term efficacy, tolerability and safety of oxcarbazepine (OXC). We enrolled 36 patients (mean age 8.5), between January 2003 and December 2004, with new diagnosis of partial epilepsy: 25 patients were affected by idiopathic partial epilepsy, eight by symptomatic epilepsy and three by cryptogenic epilepsy.

SAFA: A new measure to evaluate psychiatric symptoms detected in a sample of children and adolescents affected by eating disorders. Correlations with risk factors.

In order to evaluate the psychiatric symptoms associated with a diagnosis of eating disorders (ED) we have administered a new psychometric instument: the Self Administrated Psychiatric Scales for Children and Adolescents (SAFA) test. SAFA was administered to a cohort of 97 patients, aged from 8.8 to 18, with an ED diagnosis.

Preliminary report on effects of oxcarbazepine-treatment on serum lipid levels in children.

The aim of the present study was to assess serum lipid levels before and after treatment with oxcarbazepine (OXC) in children with epilepsy. We measured total cholesterol (TC), triglycerides (TGs) and high-density lipoprotein cholesterol (HDL-C) in 28 patients whereas only TC levels in 11 patients, during baseline period and at 3 months after the beginning of therapy with OXC. During baseline period, median values were: 4.

Open prospective study on oxcarbazepine in epilepsy in children: a preliminary report.

Purpose: To evaluate the long-term efficacy, tolerability, and safety of oxcarbazepine (OXC) in children with epilepsy.

Methods: We enrolled 36 patients (median age 7.75) with new diagnosis of partial epilepsy in an open prospective study.

Clinical features of benign infantile convulsions: familial and sporadic cases.

The authors describe the so-called benign convulsions of infancy and confirm the existence of benign nonfamilial infantile convulsions during the first 2 years of life and their benign course. The authors evaluated 58 patients: 17 subjects had a family history of benign epilepsy, and 41 did not. No clinical differences were observed between the two groups.

Familial severe myoclonic epilepsy of infancy: truncation of Nav1.1 and genetic heterogeneity.

Background: Severe myoclonic epilepsy of infancy (SMEI) or Dravet syndrome has been long suspected of having a genetic origin. Recently, mutations in SCN1A and GABRG2 have been described in SMEI patients. The sporadic nature of the SMEI syndrome and the occurrence of SCN1A and GABRG2 mutations in a mild familial phenotype, termed generalized epilepsy with febrile seizure plus complicates genotype-phenotype correlations.

Oxidative modification of aldose reductase induced by copper ion. Definition of the metal-protein interaction mechanism.

Aldose reductase (ALR2) is susceptible to oxidative inactivation by copper ion. The mechanism underlying the reversible modification of ALR2 was studied by mass spectrometry, circular dichroism, and molecular modeling approaches on the enzyme purified from bovine lens and on wild type and mutant recombinant forms of the human placental and rat lens ALR2. Two equivalents of copper ion were required to inactivate ALR2: one remained weakly bound to the oxidized protein whereas the other was strongly retained by the inactive enzyme.

Physiological thiols as promoters of glutathione oxidation and modifying agents in protein S-thiolation.

Glutathione is one of the most relevant antioxidants present in cells. It exerts its scavenging action through the involvement of efficient and ubiquitous enzymes. GSH on the other hand, because of its chemical features, can scavenge reactive oxygen species without the involvement of enzymatic systems.

Thiol/disulfide interconversion in bovine lens aldose reductase induced by intermediates of glutathione turnover.

The effectiveness of cysteine and cysteinylglycine to act as protein thiolating agents was investigated using bovine lens aldose reductase (ALR2) as the protein target. Disulfides of both thiol compounds appear to be very effective as ALR2 thiolating agents. Cysteine- and CysGly-modified ALR2 forms (Cys-ALR2 and CysGly-ALR2, respectively) are characterized by the presence of a mixed disulfide bond involving Cys298, as demonstrated by a combined electrospray mass spectrometry and Edman degradation approach.

Modulation of aldose reductase activity through S-thiolation by physiological thiols.

The glutathionyl-modified aldose reductase (GS-ALR2) is unique, among different S-thiolated enzyme forms, in that it displays a lower specific activity than the native enzyme (ALR2). Specific interactions of the bound glutathionyl moiety (GS) with the ALR2 active site, were predicted by a low perturbative molecular modelling approach. The outcoming GS allocation, involving interactions with residues relevant for catalysis and substrate allocation, explains the rationale behind the observed differences in the activity between GS-ALR2 and other thiol-modified enzyme forms.

A new approach against sugar cataract through aldose reductase inhibitors.

Aldose reductase inhibition is one of the therapeutic strategies that has been proposed to prevent or ameliorate long term diabetic complications including retinopathy and sugar cataract. Rats were fed with a galactose rich diet and the aldose reductase inhibitor Tolrestat was topically delivered by ocular instillation. The levels of lens aldose reductase activity, galactitol and the onset of cataract were evaluated during and after treatment with the inhibitor.

Oxidative modification of aldose reductase induced by copper ion. Factors and conditions affecting the process.

Bovine lens aldose reductase (ALR2) is inactivated by copper ion [Cu(II)] through an oxygen-independent oxidative modification process. A stoichiometry of 2 equiv of Cu(II)/enzyme mol is required to induce inactivation. While metal chelators such as EDTA or o-phenantroline prevent but do not reverse the ALR2 inactivation, DTT allows the enzyme activity to be rescued by inducing the recovery of the native enzyme form.

Thioltransferase activity of bovine lens glutathione S-transferase.

A Mu-class glutathione S-transferase purified to electrophoretic homogeneity from bovine lens displayed thioltransferase activity, catalysing the transthiolation reaction between GSH and hydroxyethyldisulphide. The thiol-transfer reaction is composed of two steps, the formation of GSSG occurring through the generation of an intermediate mixed disulphide between GSH and the target disulphide. Unlike glutaredoxin, which is only able to catalyse the second step of the transthiolation process, glutathioneS-transferase catalyses both steps of the reaction.

Site-specific inactivation of aldose reductase by 4-hydroxynonenal.

Bovine lens aldose reductase (ALR2), which catalyzes the NADPH-dependent reduction of 4-hydroxy-2-nonenal (HNE), is readily inactivated by its own substrate in a time- and concentration-dependent manner. Both DTT and NADP+ can prevent enzyme inactivation but neither extensive dialysis nor thiol-reducing treatment were able to restore enzyme activity once inactivation had occurred. Unlike the native enzyme, S-glutathionyl-modified ALR2 is unaffected by HNE, and can be easily reverted to the native form under thiol-reducing conditions.