Contribution of in vitro NMR spectroscopy to metabolic and neurodegenerative disorders

In vitro Nuclear Magnetic Resonance (NMR) spectroscopy is a validated biochemical tool for metabolic analyses of human body fluids and diagnosis of inborn errors of metabolism in children and adults. The technique is of special interest because it requires minimal sample preparation, it can detect simultaneously compounds of different nature and it offers structural information on the metabolites present in body fluids. In the last decade, in vitro NMR spectroscopy contributed to the identification of new inborn errors of metabolism, some of which are amenable to therapeutic intervention. Standardized analyses of body fluids, especially cerebrospinal fluid, are therefore indicated in patients affected with neurodegenerative disorders of unknown etiologies, for which extensive metabolic and genetic screening failed to identify the primary defect. In addition, the use of multivariate statistical analyses allows the comparison of the whole metabolic profile between patients with a given neurodegenerative disorder and controls. This so-called metabonomic approach yields promises for the discovery of biomarkers that can help detecting disease onset and progression, as well as evaluating therapeutic efficacy. Finally, the combination of in vitro NMR spectroscopy with genetic analytical tools may constitute a successful pathophysiological approach to investigate neurological disorders of unknown etiology.     

Hepatitis C awareness among adolescents in the Alpes-Maritimes area of France

OBJECTIVES: Certain practices with a potential risk of hepatitis C virus (HCV) transmission begin early, during adolescence. In 2004, primary prevention interventions targeting adolescents aged 13-17 years attending school in the Alpes-Maritimes region of France were conducted by the "Réseau Hépatite C Ville H?pital C?te d'Azur". The aim of this study was to assess the adolescents' knowledge about HCV and to evaluate the impact of such interventions.METHODS: A random sample of secondary state schools in the Alpes-Maritimes was invited to participate in the study. Before and after presenting a slide show about HCV in the selected classrooms, the investigators asked the students to complete an anonymous self-administered questionnaire designed to assess their knowledge about HCV infection.RESULTS: The intervention concerned a study population of 2,946 students, mean age 14.4 +/- 2.5 years. Before the interventions, 21% had good knowledge of HCV infection and 24% had good know-ledge of disease contagion. These percentages increased significantly after the interventions to 95% and 84% respectively. Knowledge improvement was more significant among high school students and among students whose parents had an employment.CONCLUSIONS: Adolescents are poorly informed about HCV infection. The present intervention enabled significant improvement in their knowledge about the infection and disease contagion, independently of gender, age and geographical area.     

Identification and Treatment of Osteoporosis among Elderly Patients with Hip Fractures

OBJECTIVE:

To evaluate the profile of osteoporosis treatment among patients hospitalized due to hip fractures at a tertiary-level university hospital. To compare the impact of hospitalization on approaches toward treating bone mass losses.

METHOD:

The medical records of 123 hip fracture patients aged 60 years and over at the Institute of Orthopedics, Hospital das Clínicas, University of São Paulo School of Medicine, between 2004 and 2006 were reviewed and analyzed with respect to approaches towards investigating osteoporosis and treatments before and after fracture.

RESULTS:

The patients’ mean age was 78 ± 8.3 years, and the majority were women (71.54%). The patients had a mean of 2.72 comorbidities and used 3.26 medications on average. Among these patients, 12.3% reported a previous diagnosis of osteoporosis, and 5.83% were on medication for this. The mean waiting time for surgery was 6.3 ± 7.54 days, and seven patients (5.7%) died during the hospitalization. There were no investigations using bone densitometry, no changes in osteoporosis therapy between admission and discharge (p = 0.375), and no reports of referrals for the patient to have access to treatment.

CONCLUSIONS:

Investigations and treatments of osteoporosis and strategies for preventing new fractures were not implemented during the hospitalization of these elderly patients with hip fractures, even though this is the most feared complication of osteoporosis. These data need to be disseminated so that professionals dealing with elderly patients are attentive to the need for primary and secondary prevention of osteoporosis because of the impact of fractures on these patients’ quality of life, independence, morbidities, and mortality.     

Does gender matter in glioblastoma?

Background  

The clinical outcome of glioblastoma (GBM) patients who receive radiotherapy alone or with chemotherapy is well established. However, little is known about how many patients do not receive this treatment. We consider it is important to investigate why a proportion of operated patients do not receive further treatment after surgery.     

The Lys234Arg substitution in the enzyme SHV-72 is a determinant for resistance to clavulanic acid inhibition

The new beta-lactamase SHV-72 was isolated from clinical Klebsiella pneumoniae INSRA1229, which exhibited the unusual association of resistance to the amoxicillin-clavulanic acid combination (MIC, 64 microg/ml) and susceptibility to cephalosporins, aztreonam, and imipenem. SHV-72 (pI 7.6) harbored the three amino acid substitutions Ile8Phe, Ala146Val, and Lys234Arg. SHV-72 had high catalytic efficiency against penicillins (k(cat)/K(m), 35 to 287 microM(-1) x s(-1)) and no activity against oxyimino beta-lactams. The concentration of clavulanic acid necessary to inhibit the enzyme activity by 50% was 10-fold higher for SHV-72 than for SHV-1. Molecular-dynamics simulation suggested that the Lys234Arg substitution in SHV-72 stabilized an atypical conformation of the Ser130 side chain, which moved the O gamma atom of Ser130 around 3.5 A away from the key O gamma atom of the reactive serine (Ser70). This movement may therefore decrease the susceptibility to clavulanic acid by preventing cross-linking between Ser130 and Ser70.