Characterization of the autoimmune response against the nerve tissue S100ß in patients with type 1 diabetes.

Type 1 diabetes results from destruction of insulin-producing beta cells in pancreatic islets and is characterized by islet cell autoimmunity. Autoreactivity against non-beta cell-specific antigens has also been reported, including targeting of the calcium-binding protein S100ß. In preclinical models, reactivity of this type is a key component of the early development of insulitis. To examine the nature of this response in type 1 diabetes, we identified naturally processed and presented peptide epitopes derived from S100ß, determined their affinity for the human leucocyte antigen (HLA)-DRB1*04:01 molecule and studied T cell responses in patients, together with healthy donors. We found that S100ß reactivity, characterized by interferon (IFN)-γ secretion, is a characteristic of type 1 diabetes of varying duration. Our results confirm S100ß as a target of the cellular autoimmune response in type 1 diabetes with the identification of new peptide epitopes targeted during the development of the disease, and support the preclinical findings that autoreactivity against non-beta cell-specific autoantigens may have a role in type 1 diabetes pathogenesis.

[Total knee replacement in patients under 60 years with high functional demand: functional outcomes and return to sports after an average 2-year follow-up]. / Reemplazo total de rodilla en pacientes menores de 60 años con demanda funcional elevada: resultados funcionales y retorno al deporte después de un promedio de dos años de seguimiento.

INTRODUCTION: a common concern in presurgical medical appointment of total knee replacement medical appointment is return to exercise. The purpose of this study was to analyze functional results and return to sport in patients under 60 years of age after this surgery. MATERIAL AND METHODS: we retrospectively analyzed 41 total knee replacements in 36 athletic patients (average age: 53 years [46-60]). Average follow-up of two years (6 months-5 years). Diagnoses: 37 osteoarthritis, three sequelae of Rheumatoid Arthritis, 1 extra-articular deformity. Functional and radiographic outcomes assessed using modified Knee Society and High Activity Arthroplasty Scores. RESULTS: average improvement from 31.95 to 91.61 in KSS and average from 7.95 to 13.73 in HAAS. Return to sport in 3.5 months average (range 2-6 months). Three patients did not return to sport. CONCLUSIONS: we consider that delaying surgery in these patients will cause progression in their osteoarthritis pathology and cessation of their sports activities. This makes the surgical technique difficult in addition to reducing the patient's physical performance. Analyzing the survival rate of implants in young patients, more than 80% is reported in a 25-year follow-up.

INTRODUCCIÓN: una inquietud frecuente en consultas prequirúrgicas de reemplazo total de rodilla es el regreso al ejercicio. El propósito de este estudio fue analizar resultados funcionales y retorno al deporte en pacientes menores de 60 años posterior a esta cirugía. MATERIAL Y MÉTODOS: analizamos retrospectivamente 41 reemplazos totales de rodilla en 36 pacientes deportistas (edad promedio: 53 años [46-60]). Seguimiento promedio de dos años (6 meses-5 años). Diagnósticos: 37 gonartrosis, tres secuelas de artritis reumatoidea, una deformidad extraarticular. Resultados funcionales y radiográficos evaluados mediante Knee Society modificado y High Activity Arthroplasty Score. RESULTADOS: mejoría promedio de 31.95 a 91.61 en KSS y promedio de 7.95 a 13.73 en HAAS. Retorno al deporte en 3.5 meses promedio (rango: 2-6 meses). Tres pacientes no retornaron al deporte. CONCLUSIONES: consideramos que el retraso de la cirugía en estos pacientes producirá progresión en su patología artrósica y cese de sus actividades deportivas. Esto dificulta la técnica quirúrgica además de disminuir el rendimiento físico del paciente. Analizando la tasa de supervivencia de implantes en pacientes jóvenes, se reporta más de 80% en seguimientos de 25 años.

Efficacy and safety of Cerebrolysin in moderate to moderately severe Alzheimer's disease: results of a randomized, double-blind, controlled trial investigating three dosages of Cerebrolysin.

BACKGROUND: cerebrolysin is a neuropeptide preparation mimicking the effects of neurotrophic factors. This subgroup analysis assessed safety and efficacy of Cerebrolysin in patients with moderate to moderately severe Alzheimer's disease (AD) (ITT data set: N = 133; MMSE: 14-20) included in a dose-finding study (ITT data set: N = 51; MMSE: 14-25). Results of the mild AD subgroup (ITT data set: N = 118; MMSE: 21-25) are also presented. METHODS: patients with AD received 100 ml IV infusions of Cerebrolysin (10, 30 or 60 ml diluted in saline; N = 32, 34 and 35, respectively) or placebo (saline; N = 32) over twelve weeks (5 days per week for 4 weeks and 2 days per week for another 8 weeks). Primary efficacy criteria ADAS-cog+ (Alzheimer's Disease Assessment Scale Cognitive Subpart Modified) and CIBIC+ (Clinical Interview-based Impression of Change with Caregiver Input) were assessed 24 weeks after baseline. RESULTS: at week 24, Cerebrolysin improved the global clinical function significantly with all three dosages and induced significant improvements in cognition, initiation of activities of daily living (ADL) and neuropsychiatric symptoms at 10-, 30- and 60-ml doses, respectively. Treatment effects on total ADL and other secondary parameters (MMSE, Trail-making test) were not significant. Cerebrolysin was safe and well tolerated. CONCLUSIONS: these results demonstrate the efficacy of Cerebrolysin in moderate to moderately severe AD, showing dose-specific effects similar to those reported for patients with mild to moderate AD. The benefits of Cerebrolysin in advanced AD need to be confirmed in larger trials.

Neuropeptide dietary supplement N-PEP-12 enhances cognitive function and activates brain bioelectrical activity in healthy elderly subjects.

N-PEP-12 is a dietary supplement consisting of neuropeptides and amino acids. In animal experiments, the compound has been shown to enhance cognitive function and reduce neurodegenerative events associated with aging. In this study, we investigated the effects of a single oral dose of N-PEP-12 (180 mg) on brain bioelectrical activity and cognitive performance in healthy elderly subjects. N-PEP-12 induced a significant (p < 0.05) increase in relative alpha-activity power 6 h after administration. This enhancement was accompanied by a generalized decrease in slow Delta-activity. Significant improvement in memory performance subtests was also seen 6 h after N-PEP-12 administration in some but not in all tests. Taken together, these data suggest that N-PEP-12 might be a reliable dietary supplement to be investigated for improving and, perhaps, maintaining brain function among healthy older adults.

Immunocytochemical localization of calretinin in the olfactory system of the adult lamprey, Lampetra fluviatilis.

The distribution of calretinin immunoreactive (CR-ir) structures in the adult lamprey (Lampetra fluviatilis) olfactory system was studied by using immunocytochemical techniques. In the olfactory epithelium, a subpopulation of olfactory receptor cells was CR-ir. In the olfactory bulbs, three different cell populations were observed. Large CR-ir cells (mitral cells) were located medially to the olfactory glomeruli and occasionally between them. In the inner cellular layer, two types of CR-ir perikarya were found: numerous small CR-ir cells (granule cells) and some medium-sized CR-ir cells (putative displaced periglomerular cells). In addition, different intensities of CR-ir fibers were present in particular rootlets of the olfactory nerves, as well as in particular glomeruli. The presence of CR-ir cells and fibers in all layers of the lamprey olfactory bulbs supports the idea that this protein is present in pathways underlying the processing of sensory information throughout evolution.

Cerebrolysin reduces microglial activation in vivo and in vitro: a potential mechanism of neuroprotection.

Neurotrophins, such as NGF, BDNF and NT-3 play a regulatory role on the function of microglial cells in vivo and in vitro, and the identification of new compounds with neurotrophic properties is becoming a new strategy for the prevention and/or treatment of neurodegenerative disorders. In this study we describe the use of two different models to demonstrate the ability of Cerebrolysin to reduce microglial activation. The results of these in vitro and in vivo studies indicate that Cerebrolysin might exert a neuroimmunotrophic activity reducing the extent of inflammation and accelerated neuronal death under pathological conditions such as those observed in neurodegenerative diseases.

Oral Cerebrolysin enhances brain alpha activity and improves cognitive performance in elderly control subjects.

Cerebrolysin is a porcine brain derived peptide preparation with potential neurotrophic activity. The effects of a single oral dose of the Cerebrolysin solution (30 ml) on brain bioelectrical activity and on cognitive performance were investigated in healthy elderly people. A single oral dose of Cerebrolysin induced a progressive increase in relative alpha activity power from 1 to 6 hours after treatment in almost all the brain electrodes in elderly control subjects. As compared with baseline alpha power (45.8+/-9.5%), the increase in relative alpha activity in the left occipital electrode (O1) reached significant values at 1 hour (57.2+/-8.5%; p < 0.05), 3 hours (59.4+/-7.6%; p < 0.05) and 6 hours (63.4+/-9.8%; p < 0.05) after Cerebrolysin administration. Enhancement in relative alpha power was accompanied by a generalized decrease in slow delta activity that was maximum at 6 hours after Cerebrolysin intake. A significant improvement in memory performance, evaluated with items of the ADAS cog, was also found in elderly people taken a single dose of oral Cerebrolysin (6.9+/-1.0 errors at baseline versus 4.9+/-1.0 errors after treatment; p < 0.01). This memory improvement was more evident in recognition (2.8+/-0.6 errors vs. 1.5+/-0.7 errors; p < 0.05) than in recall tasks (4.1+/-0.5 errors versus 3.4+/-0.5 errors; ns). These data indicate that Cerebrolysin potentiates brain alpha activity, reduces slow EEG delta frequencies and improves memory performance in healthy elderly humans, suggesting that this compound activates cerebral mechanisms related to attention and memory processes. According to the present results, it seems that oral Cerebrolysin might be useful for the treatment of memory impairment and brain damage in eldely subjects with or without neurodegenerative disorders.

The disodium salt of EDTA inhibits the binding of vasoactive intestinal peptide to macrophage membranes: endodontic implications.

The purpose of this study was to investigate the effect of the disodium salt of ethylenediamine tetraacetate (EDTA), a calcium ion chelator used in the root canal therapy, on vasoactive intestinal peptide (VIP) binding to macrophage membranes (MM's). Binding assays were conducted at 15 degrees C in 0.5 ml of 50 mM Tris-HCl buffer (pH 7.5) containing 1.6% (w/v) bovine serum albumin, 1.2 mg/ml of bacitracin, and different EDTA concentrations, using 45 pM of [125I]VIP as tracer. Results showed that EDTA inhibits VIP binding to MM's in a dose-dependent manner, with an IC50 value of 5.4 mM (p < 0.01). EDTA concentrations equal or higher than 100 mM of abolished VIP-MM interaction. Taking into account that the macrophage plays an essential role in inflammatory reactions and the immune response, we conclude that the apical extrusion of EDTA during root canal therapy could modify VIP-macrophage interaction modulating the inflammatory mechanisms involved in periapical lesions.

EDTA inhibits in vitro substrate adherence capacity of macrophages: endodontic implications.

The disodium salt of ethylenediamine tetraacetate (EDTA) is a calcium ion chelator used in endodontics to enlarge root canals. This study investigated the effect of EDTA on substrate adherence capacity of rat inflammatory macrophages to determine if EDTA leakage to periapical tissues during root canal therapy can alter macrophage function. Inflammatory macrophages were obtained from Wistar rats and resuspended in RPMI-1640 medium. Substrate adherence capacity assays were carried out in Eppendorf tubes for 15 min of incubation at 37 degrees C in a humidified atmosphere of 5% CO2. The adherence index (AI) was calculated. Results showed that EDTA decreased substrate adherence capacity of inflammatory macrophages in a time and dose-dependent manner. The lowest EDTA concentration that caused a significant inhibition of AI was 50 mM (p < 0.05), and the EDTA concentration that caused half-maximal inhibition (IC50) was 194 +/- 20 mM (p < 0.01). Calcium chloride (10 mM) increased the adherence index of macrophages by 17.1% (p < 0.05) and decreased the EDTA inhibitory effect on AI by 49.5% (p < 0.05). We conclude that an EDTA concentration lower than that used in endodontics decreased the substrate adherence capacity of macrophages significantly. Adhesion is the first step in the phagocytic process and in antigen presentation, but leakage of EDTA to periapical tissues during root canals preparation may inhibit macrophage function and reduce periapical inflammatory reactions.

Citicoline protects hippocampal neurons against apoptosis induced by brain beta-amyloid deposits plus cerebral hypoperfusion in rats.

Citicoline is an endogenous intermediate involved in the biosynthesis of brain phospholipids and acetylcholine which has been extensively used for the treatment of several neurodegenerative conditions. The effects of citicoline on neurodegeneration, apoptosis and learning were investigated in male Sprague Dawley rats subjected to implants of the beta-amyloid fragment 1-40 (A beta 4: 3 Mmol) into the right hippocampus and to permanent unilateral occlusion of the carotid artery. Citicoline (CDP; 0, 62.5, 125 and 250 mg/kg/day i.p.) was given during 2 days before and for 5 days after surgery, and the extension of the degeneration and the number of apoptotic figures (TUNEL technique) were evaluated in the dentate gyrus (DG) and the CA1 area of the hippocampus. Citicoline, at 125 and 250 mg/kg, reduced the number of apoptotic neurons in the hippocampus of rats with A beta 4/hypoperfusion-induced neurodegeneration (CDP0 = 105.3 +/- 32.8 apoptotic figures; CDP125 = 39.2 +/- 7.4** apoptotic figures; CDP250 = 34.5 +/- 14.4** apoptotic figures; **p < 0.01 vs. CDP0). CDP also reduced neuronal degeneration in the CA1 area in a dose-dependent manner (CDP0 = 450.5 +/- 130.1 microns; CDP62.5 = 280.6 +/- 76.3 microns; CDP125 = 86.6 +/- 37.3* microns; CDP250 = 121.7 +/- 85.3* microns; p < 0.05 vs. CDP0). Variability of results was very high in the DG, where a significant reduction in the extent of neurodegeneration was only observed in the group of rats receiving 62.5 mg/kg of citicoline. Finally, citicoline improved retention of a passive avoidance learning task, increasing the number of avoidances (Av) (CDP0 = 4.2 +/- 0.7 Av; CDP62.5 = 6.9 +/- 1.0 Av; CDP125 = 7.9 +/- 0.7** Av; CDP250 = 8.5 +/- 0.6** Av; **p < 0.01 vs. CDP0) in a dose-related manner. Based on these results, it was concluded that citicoline exerts antiapoptotic, neuroprotective and antiamnesic effects in conditions of neurodegeneration induced by A beta 4 plus hypoperfusion.

[Changes in HIV-related attitudes and knowledge of teenagers following the Aulasida intervention in 1996-1997]. / Cambios en las actitudes y conocimientos de los adolescentes sobre la infección por VIH tras la intervención escolar Aulasida, 1996-1997.

BACKGROUND: Schools being the ideal setting for carrying out Health Education activities, the aim of this study was that of pinpointing and quantifying the changes in attitudes and knowledge on the part of teenagers enrolled in school in Algemesí (Valencia) following an educational intervention regarding HIV infection. METHOD: Eleven schools at which a total of 2,599 teenagers (ages 12-19) were enrolled in eleven different years of study (Secondary Education, Secondary Ed. and School Leaving Certificate, College Preparation Course and Vocational Training) were invited to take part. The Aulasida intervention carried out during the 1996-1997 school year consisted of an informative lecture-panel discussion and student involvement activities in small groups using educational materials. The gauging instrument was a questionnaire. This questionnaire was designed in a before-and-after cross-sectional study. An analysis was made divided into age and educational level strata. The averages were compared with the Student "t" test and the percentages of change with ji square. RESULTS: A total of nine schools accepted taking part. 1575 students answered the "before" test (47.4% males and 52.1% females), the average age being 15.2 (1.96) years old. The average number of correct answers to the "before" test was 13.5 (2.8). The "after" test showed an overall increase of up to 14.7 (3.0) correct answers (p < 0.01). By educational levels, this increase was highly appreciable in the younger age group. The most common sources of information on HIV were: television (80.8%); Aulasida (76.8%), teachers (60.9%), pamphlets (58.4%) and films (53.7%9. CONCLUSIONS: Educational interventions are useful tools for increasing knowledge and improving attitudes regarding HIV infection. Secondary schools are the best environment for this purpose, it being necessary to carry out interventions among younger groups, as a greater impact is thus achieved.

Combination treatment in Alzheimer's disease: results of a randomized, controlled trial with cerebrolysin and donepezil.

Treatment with neurotrophic agents might enhance and/or prolong the effects of cholinesterase inhibitors (ChEIs) in Alzheimer's disease (AD). We compared the safety and efficacy of the neurotrophic compound Cerebrolysin (10 ml; n=64), donepezil (10 mg; n=66) and a combination of both treatments (n=67) in mild-to-moderate (mini-mental state examination-MMSE score 12-25) probable AD patients enrolled in a randomized, double-blind trial. Primary endpoints were global outcome (Clinician's Interview-Based Impression of Change plus caregiver input; CIBIC+) and cognition (change from baseline in AD Assessment Scale-cognitive subscale+; ADAS-cog+) at week 28. Changes in functioning (AD Cooperative Study-Activities of Daily Living scale, ADCS-ADL) and behaviour (Neuropsychiatric Inventory, NPI) were secondary endpoints. Treatment effects in cognitive, functional and behavioral domains showed no significant group differences; whereas improvements in global outcome favored Cerebrolysin and the combination therapy. Cognitive performance improved in all treatment groups (mean±SD for Cerebrolysin: -1.7±7.5; donepezil: -1.2±6.1; combination: -2.3±6.0) with best scores in the combined therapy group at all study visits. Cerebrolysin was as effective as donepezil, and the combination of neurotrophic (Cerebrolysin) and cholinergic (donepezil) treatment was safe in mild-to-moderate AD. The convenience of exploring long-term synergistic effects of this combined therapy is suggested.

Neuroimagen del linfoma primario del sistema nervioso central en pacientes inmunodeprimidos / Neuroimaging in immunodeficient patients with primary CNS lymphoma of the brain

Objetivos: El linfoma primario del sistema nervioso central (LPSNC) es una entidad rara con un pronóstico fatal. Dado el aumento en el número de casos con inmunosupresión adquirida, nuestros objetivos son estudiar las características epidemiológicas y neurorradiológicas de aquellos pacientes inmunodeprimidos con diagnóstico de LPSNC con afectación cerebral e investigar si existen diferencias entre los pacientes con el virus de la inmunodeficiencia humana (VIH) positivo y negativo.Materiales y métodos: Se realizó un estudio descriptivo y retrospectivo de los pacientes inmunodeprimidos con afectación cerebral por LPSNC, diagnosticados durante los últimos 13 años en 2 hospitales de referencia. Se evaluaron múltiples variables. El nivel de significación estadística utilizado fue p < 0,05.Resultados: El grupo VIH-positivo tenía una media de edad de 36,82 ± 5,4 años, frente a los55,60 ± 21,43 años de los pacientes VIH-negativo (p < 0,022). Los pacientes VIH-positivo tuvieron una media de 1,27 ± 0,65 lesiones por paciente, mientras que en el grupo VIH-negativo fue de 2,60 ± 1,78 (p < 0,039). El 18,2% (n = 2) del grupo VIH-positivo y el 80% (n = 8) del grupo VIH-negativo presentaron lesiones homogéneas (p < 0,005). Ningún paciente VIH-positivo tuvo afectación del cuerpo calloso, pero el grupo VIH-negativo presentó un 50% (n = 5) de afectación(p < 0,012).Conclusiones: El LPSNC en pacientes inmunodeprimidos puede presentar múltiples características en las imágenes. Existen diferencias entre los pacientes VIH positivo y negativo, por lo que es importante reconocerlas para establecer un manejo y tratamiento diferente entre ambos grupos.

Purposes: Primary central nervous system lymphoma (PCNSL) is a rare tumour with poor prognosis. Due to the increased number of patients with acquired immunodeficiency, our purposes are to describe epidemiological and imaging findings in immunodeficient patients with PCNSL of the brain and to study the differences between HIV-positive and HIV-negative patients with PCNSL.Materials and methods: A retrospective, descriptive study was performed with immunodeficient patients diagnosed of PCNSL of the brain during the last 13 years in two reference hospitals. Twenty-one patients fulfilled the inclusion criteria. Multiple variables were evaluated. Significance was defined as p<0.05.Results: HIV-positive group was a mean age of 36,82±5,4 years and the mean age in HIV-negative group was 55,60±21,43 years (p<0,022). The mean number of lesions was 1,27±0,65 in HIV-positive group and 2,60±1,78 in HIV-negative group (p<0,039). The lesions were homogeneous in 18,2% (n=2) HIV-positive group and 80% (n=8) in HIV-negative group (p<0,005). No HIV-positive patient and 50% (n=5) of HIV-negative patients showed corpus callosum involvement (p<0,012).Conclusions: PCNSL in immunodeficient patients is associated with a large spectrum of radiological findings. There were differences between HIV-positive and HIV-negative patients, is important recognize these differences as the therapeutic management of these two groups vary.

Neuroimagen del linfoma primario del sistema nervioso central en pacientes inmunodeprimidos

Objetivos: El linfoma primario del sistema nervioso central (LPSNC) es una entidad rara con un pronóstico fatal. Dado el aumento en el número de casos con inmunosupresión adquirida, nuestros objetivos son estudiar las características epidemiológicas y neurorradiológicas de aquellos pacientes inmunodeprimidos con diagnóstico de LPSNC con afectación cerebral e investigar si existen diferencias entre los pacientes con el virus de la inmunodefi ciencia humana (VIH) positivo y negativo. Materiales y métodos: Se realizó un estudio descriptivo y retrospectivo de los pacientes inmunodeprimidos con afectación cerebral por LPSNC, diagnosticados durante los últimos 13 años en 2 hospitales de referencia. Se evaluaron múltiples variables. El nivel de significación estadística utilizado fue p < 0,05. Resultados: El grupo VIH-positivo tenía una media de edad de 36,82 ± 5,4 años, frente a los 55,60 ± 21,43 años de los pacientes VIH-negativo (p < 0,022). Los pacientes VIH-positivo tuvieron una media de 1,27 ± 0,65 lesiones por paciente, mientras que en el grupo VIH-negativo fue de 2,60 ± 1,78 (p < 0,039). El 18,2% (n = 2) del grupo VIH-positivo y el 80% (n = 8) del grupo VIH-negativo presentaron lesiones homogéneas (p < 0,005). Ningún paciente VIH-positivo tuvo afectación del cuerpo calloso, pero el grupo VIH-negativo presentó un 50% (n = 5) de afectación (p < 0,012). Conclusiones: El LPSNC en pacientes inmunodeprimidos puede presentar múltiples características en las imágenes. Existen diferencias entre los pacientes VIH positivo y negativo, por lo que es importante reconocerlas para establecer un manejo y tratamiento diferente entre ambos grupos.(AU)

Purposes: Primary central nervous system lymphoma (PCNSL) is a rare tumour with poor prognosis. Due to the increased number of patients with acquired immunodeficiency, our purposes are to describe epidemiological and imaging findings in immunodeficient patients with PCNSL of the brain and to study the differences between HIV-positive and HIV-negative patients with PCNSL. Materials and methods: A retrospective, descriptive study was performed with immunodeficient patients diagnosed of PCNSL of the brain during the last 13 years in two reference hospitals. Twenty-one patients fulfilled the inclusion criteria. Multiple variables were evaluated. Significance was defined as p<0.05. Results: HIV-positive group was a mean age of 36,82±5,4 years and the mean age in HIV-negative group was 55,60±21,43 years (p<0,022). The mean number of lesions was 1,27±0,65 in HIV-positive group and 2,60±1,78 in HIV-negative group (p<0,039). The lesions were homogeneous in 18,2% (n=2) HIV-positive group and 80% (n=8) in HIV-negative group (p<0,005). No HIV-positive patient and 50% (n=5) of HIV-negative patients showed corpus callosum involvement (p<0,012). Conclusions: PCNSL in immunodeficient patients is associated with a large spectrum of radiological findings. There were differences between HIV-positive and HIV-negative patients, is important recognize these differences as the therapeutic management of these two groups vary.(AU)

A 24-week, double-blind, placebo-controlled study of three dosages of Cerebrolysin in patients with mild to moderate Alzheimer's disease.

Cerebrolysin (Cere) is a compound with neurotrophic activity shown to be effective in Alzheimer's disease in earlier trials. The efficacy and safety of three dosages of Cere were investigated in this randomized, double-blind, placebo-controlled, study. Two hundred and seventy-nine patients were enrolled (69 Cere 10 ml; 70 Cere 30 ml; 71 Cere 60 ml and 69 placebo). Patients received iv infusions of 10, 30, 60 ml Cere or placebo 5 days/week for the first 4 weeks and thereafter, two iv infusions per week for 8 weeks. Effects on cognition and clinical global impressions were evaluated 4, 12 and 24 weeks after the beginning of the infusions using the CIBIC+ and the modified Alzheimer's Disease Assessment Scale (ADAS)-cog. At week 24, significant improvement of cognitive performance on the ADAS-cog (P=0.038) and global function (CIBIC+; P>0.001) was observed for the 10 ml dose. The 30 and 60 ml doses showed significant improvement of the global outcome but failed to show significant improvement of cognition. The results are consistent with a reversed U-shaped dose-response relationship for Cere. The percentage of patients reporting adverse events was similar across all study groups. Cere treatment was well tolerated and led to significant, dose-dependent improvement of cognition and global clinical impression.

Speciation of volatile aromatic and chlorinated hydrocarbons in an urban atmosphere using TCT-GC/MS.

Several aromatic and chlorinated volatile hydrocarbons (VOCs) were measured in Vitoria-Gasteiz City (Spain) throughout the years 1999 and 2002 in order to find out the concentration of these pollutants in urban air. These VOCs were retained in Tenax TA, subsequently desorpted by using a thermal desorption cold trap injector (TCT), and thereafter analyzed by gas chromatography/mass spectrometry (GC/MS). This analytical methodology permits the determination of 42 VOCs at very low concentrations, although only 32 of them were found in the urban air of the city (ranging from 205.51 to 0.01 microg m(-3)), with high reproducibility (%RSD lower than 10%). Twenty-four-hour samples were taken each sampling day to ascertain their total daily concentration, and rigorous quality controls were carried out to check the representativeness of sampling. Results of this exhaustive study show that toluene (T), xylenes (X), ethylbenzene (E), and benzene (B) were, respectively, the most abundant of these VOCs in the urban area during that period. The total concentration of BTEX represented, on average, more than 72.6% of the VOC total concentration, with the highest concentrations being reached in autumn, except for benzene and derived compounds (in winter). Benzene was the minority BTEX pollutant, its yearly mean concentration being less than the maximum established by the European Directive 2000/69/CE (5 microg m(-3)).

Persistence of the insecticide Dimilin 45 ODC on conifer forest foliage in an Atlantic-climate ecosystem.

The oil formulation of diflubenzuron (Dimilin 45 ODC) persisted for 10-12 weeks on the foliage of a conifer forest in an Atlantic-climate ecosystem. Within 22-30 days following treatment, 55-80% of the insecticide had been removed from the foliage. During this period, the concentration of diflubenzuron was higher than 370 ng g(-1). Aerial application at 56.3 g of Al ha(-1) resulted in deposition levels of the insecticide ranging from 867.5 to 1824.4 ng g(-1), depending upon forest characteristics. The results showed that aerial application is only a suitable technique for the treatment of forest areas with dense foliage and/or high tree density and no more than 15% of tree-free area. The only metabolite detected was 2,6-difluorobenzamide, and this persisted on foliage until the first rainfalls occurred. An empirical mathematical correlation was found to express the influence of meteorological variables--rainfall, solar radiation and temperature--on the persistence of the insecticide. These results suggested that degradation of diflubenzuron on foliage could be due to photodegradation. Some recommendations were made to optimize the deposition of the insecticide on foliage and to minimize its persistence and the off-site spray drift.

Correlation between gender and spontaneous C-cell tumors in the thyroid gland of the Wistar rat.

In many rat strains, C-cell hyperplasia occurs in an age-dependent manner and is often associated with multifocal C-cell carcinoma. The purpose of this study was to investigate the spectrum of spontaneous, proliferative C-cell disorders by gender in Wistar rats throughout their lifespan. The incidence of C-cell hyperplasia shows a significant increase with age (P<0.001) and is much higher in female rats than in male rats (P<0.05). From 3 to 24 months of life, 27.5% of female rats showed a normal C-cell pattern, 55.0% showed C-cell hyperplasia, and 17.5% showed C-cell tumors; while 57.5% of male rats showed a normal C-cell pattern, 32.5% showed C-cell hyperplasia, and 10% showed C-cell tumors. Although the overall frequency of C-cell neoplasms in females was nearly double that in males, these data are not statistically significant. However, the number of C-cell tumors showed a significant increase with age (P<0.05). Therefore, we can conclude that there were significant differences in the incidence of the total spectrum of C-cell proliferative abnormalities in the thyroid gland of Wistar rats that were both age-dependent and gender-dependent.