Assessment of day-to-day functioning in prodromal and early Huntington disease

The Functional Rating Scale Taskforce for pre-Huntington Disease (FuRST-pHD) is a multinational, multidisciplinary initiative with the goal of developing a data-driven, comprehensive, psychometrically sound, rating scale for assessing symptoms and functional ability in prodromal and early Huntington disease (HD) gene expansion carriers. The process involves input from numerous sources to identify relevant symptom domains, including HD individuals, caregivers, and experts from a variety of fields, as well as knowledge gained from the analysis of data from ongoing large-scale studies in HD using existing clinical scales. This is an iterative process in which an ongoing series of field tests in prodromal (prHD) and early HD individuals provides the team with data on which to make decisions regarding which questions should undergo further development or testing and which should be excluded. We report here the development and assessment of the first iteration of interview questions aimed to assess functional impact in day-to-day activities in prHD and early HD individuals.

Assessing behavioural manifestations prior to clinical diagnosis of Huntington disease: "anger and irritability" and "obsessions and compulsions"

The Functional Rating Scale Taskforce for pre-Huntington Disease (FuRST-pHD) is a multinational, multidisciplinary initiative with the goal of developing a data-driven, comprehensive, psychometrically sound, rating scale for assessing symptoms and functional ability in prodromal and early Huntington disease (HD) gene expansion carriers. The process involves input from numerous sources to identify relevant symptom domains, including HD individuals, caregivers, and experts from a variety of fields, as well as knowledge gained from the analysis of data from ongoing large-scale studies in HD using existing clinical scales. This is an iterative process in which an ongoing series of field tests in prodromal (prHD) and early HD individuals provides the team with data on which to make decisions regarding which questions should undergo further development or testing and which should be excluded. We report here the development and assessment of the first iteration of interview questions aimed to assess "Anger and Irritability" and "Obsessions and Compulsions" in prHD individuals.

Assessment of depression, anxiety and apathy in prodromal and early Huntington disease

The Functional Rating Scale Taskforce for pre-Huntington Disease (FuRST-pHD) is a multinational, multidisciplinary initiative with the goal of developing a data-driven, comprehensive, psychometrically sound, rating scale for assessing symptoms and functional ability in prodromal and early Huntington disease (HD) gene expansion carriers. The process involves input from numerous sources to identify relevant symptom domains, including HD individuals, caregivers, and experts from a variety of fields, as well as knowledge gained from the analysis of data from ongoing large-scale studies in HD using existing clinical scales. This is an iterative process in which an ongoing series of field tests in prodromal (prHD) and early HD individuals provides the team with data on which to make decisions regarding which questions should undergo further development or testing and which should be excluded. We report here the development and assessment of the first iteration of interview questions aimed to assess Depression, Anxiety and Apathy in prHD and early HD individuals.

Assessment of motor symptoms and functional impact in prodromal and early Huntington disease.

The Functional Rating Scale Taskforce for pre-Huntington Disease (FuRST-pHD) is a multinational, multidisciplinary initiative with the goal of developing a data-driven, comprehensive, psychometrically sound, rating scale for assessing symptoms and functional ability in prodromal and early Huntington disease (HD) gene expansion carriers. The process involves input from numerous sources to identify relevant symptom domains, including HD individuals, caregivers, and experts from a variety of fields, as well as knowledge gained from the analysis of data from ongoing large-scale studies in HD using existing clinical scales. This is an iterative process in which an ongoing series of field tests in prodromal (prHD) and early HD individuals provides the team with data on which to make decisions regarding which questions should undergo further development or testing and which should be excluded. We report here the development and assessment of the first iteration of interview questions aimed to assess functional impact of motor manifestations in prHD and early HD individuals.

An item response analysis of the motor and behavioral subscales of the unified Huntington's disease rating scale in huntington disease gene expansion carriers

Although the Unified Huntington's Disease Rating Scale (UHDRS) is widely used in the assessment of Huntington disease (HD), the ability of individual items to discriminate individual differences in motor or behavioral manifestations has not been extensively studied in HD gene expansion carriers without a motor-defined clinical diagnosis (ie, prodromal-HD or prHD). To elucidate the relationship between scores on individual motor and behavioral UHDRS items and total score for each subscale, a nonparametric item response analysis was performed on retrospective data from 2 multicenter longitudinal studies. Motor and behavioral assessments were supplied for 737 prHD individuals with data from 2114 visits (PREDICT-HD) and 686 HD individuals with data from 1482 visits (REGISTRY). Option characteristic curves were generated for UHDRS subscale items in relation to their subscale score. In prHD, overall severity of motor signs was low, and participants had scores of 2 or above on very few items. In HD, motor items that assessed ocular pursuit, saccade initiation, finger tapping, tandem walking, and to a lesser extent, saccade velocity, dysarthria, tongue protrusion, pronation/supination, Luria, bradykinesia, choreas, gait, and balance on the retropulsion test were found to discriminate individual differences across a broad range of motor severity. In prHD, depressed mood, anxiety, and irritable behavior demonstrated good discriminative properties. In HD, depressed mood demonstrated a good relationship with the overall behavioral score. These data suggest that at least some UHDRS items appear to have utility across a broad range of severity, although many items demonstrate problematic features.

Peripheral Oxidative Stress Biomarkers in Mild Cognitive Impairment and Alzheimer`s Disease

Oxidative stress has been associated with normal aging and Alzheimer`s disease (AD). However, little is known about oxidative stress in mild cognitive impairment (MCI) patients who present a high risk for developing AD. The aim of this study was to investigate plasma production of the lipid peroxidation marker, malonaldehyde (MDA) and to determine, in erythrocytes, the enzymatic antioxidant activity of catalase, glutathione peroxidase (GPx), glutathione reductase (GR), and glutathione S-transferase (GST) in 33 individuals with MCI, 29 with mild probable AD and 26 healthy aged subjects. GR/GPx activity ratio was calculated to better assess antioxidant defenses. The relationship between oxidative stress and cognitive performance was also evaluated by the Mini Mental State Examination (MMSE). AD patients showed higher MDA levels than both MCI and healthy elderly subjects. MCI subjects also exhibited higher MDA levels compared to controls. Catalase and GPx activity were similar in MCI and healthy individuals but higher in AD. GR activity was lower in MCI and AD patients than in healthy aged subjects. Additionally, GR/GPx ratio was higher in healthy aged subjects, intermediate in MCI and lower in AD patients. No differences in GST activity were detected among the groups. MMSE was negatively associated with MDA levels (r = -0.31, p = 0.028) and positively correlated with GR/GPx ratio in AD patients (r = 0.68, p < 0.001). MDA levels were also negatively correlated to GR/GPx ratio (r = -0.31, p = 0.029) in the AD group. These results suggest that high lipid peroxidation and decreased antioxidant defenses may be present early in cognitive disorders.

Novel ruthenium complexes as potential drugs for Chagas`s disease: enzyme inhibition and in vitro/in vivo trypanocidal activity

Background and purpose: The discovery of the pharmacological functions of nitric oxide has led to the development of NO donor compounds as therapeutic agents. A new generation of ruthenium NO donors, cis-[Ru(NO)(bpy)(2)L]X(n) , has been developed, and our aim was to show that these complexes are able to lyse Trypanosoma cruzi in vitro and in vivo. Experimental approach: NO donors were incubated with T. cruzi and their anti-T. cruzi activities evaluated as the percentage of lysed parasites compared to the negative control. In vivo, trypanocidal activity was evaluated by observing the levels of parasitaemia, survival rate and elimination of amastigotes in mouse myocardial tissue. The inhibition of GAPDH was monitored by the biochemical reduction of NAD+ to NADH. Key results: The NO donors cis-[Ru(NO)(bpy)(2)L]X(n) presented inhibitory effects on T. cruzi GAPDH (IC(50) ranging from 89 to 153 mu M). The crystal structure of the enzyme shows that the inhibitory mechanism is compatible with S-nitrosylation of the active cysteine (cys166) site. Compounds cis-[Ru(NO)(bpy)(2)imN](PF(6))(3) and cis-[Ru(NO)(bpy)(2)SO(3)]PF(6), at a dose of 385 nmol center dot kg-1, yielded survival rates of 80 and 60%, respectively, in infected mice, and eradicated any amastigotes from their myocardial tissue. Conclusions and implications: The ruthenium compounds exhibited potent in vitro and in vivo trypanocidal activities at doses up to 1000-fold lower than the clinical dose for benznidazole. Furthermore, one mechanism of action of these compounds is via the S-nitrosylation of Cys166 of T. cruzi GAPDH. Thus, these compounds show huge potential as candidates for the development of new drugs for the treatment of Chagas`s disease. This article is commented on by Machado et al., pp. 258-259 of this issue. To view this commentary visit http://dx.doi.org/10.1111/j.1476-5381.2010.00662.x and to view a related paper in this issue by Guedes et al. visit http://dx.doi.org/10.1111/j.1476-5381.2010.00576.x.

PREVALENCE of SALMONELLA SPP. ANTIBODIES TO TOXOPLASMA GONDII, and NEWCASTLE DISEASE VIRUS IN FERAL PIGEONS (COLUMBA LIVIA) IN THE CITY of JABOTICABAL, BRAZIL

The rock pigeon (Columba livia) may serve as a reservoir for several pathogenic agents that can be transmitted to poultry, wildlife, domesticated pets, and/or humans via excreta, secretions, or dust from feathers. In addition, ingestion of infected pigeons by wild and domestic animals can also transmit these pathogenic agents. The health status of 126 free-living pigeons in an urban area was evaluated by microbiologic culture for Salmonella and serologic testing for the presence of antibodies for Toxoplasma gondii and for Newcastle disease virus (NDV) from 120 and 109 pigeons, respectively. After drawing blood, the birds were euthanized, and fragments of the liver, spleen, lungs, and gonads, and feces were cultured for Salmonella spp. Salmonella spp. was isolated from 10 birds (7.94%), of which 8 were Salmonella typhimurium, one was Salmonella enterica subsp. enterica serotype 4,12 and one was Salmonella enterica subsp. enterica serotype 4,12,i. Six of 109 pigeons (5.50%) were positive for NDV antibodies when using the hemagglutination inhibition test. Toxoplasma gondii antibodies were detected by immunofluorescence in one of 120 sera tested (0.83%). The results indicate that feral rock pigeons were exposed to NDV and T gondii, although the exposure was low. In addition, these birds had Salmonella spp. and could disseminate this pathogen in the environment.

Pulmonary tuberculosis: Hematology, serum biochemistry and the relation with the disease duration

The aim of the present study was to analyze the relationship between hematological and biochemical parameters and tuberculosis process activity time according to clinical complaint duration. It was a retrospective study analyzing medical records from 80 pulmonary tuberculosis patients at Botucatu Medical School University Hospital ( Botucatu, São Paulo State, Brazil), who were divided into 2 groups according to clinical complaint duration: Group 1 ( G1) - up to three months; Group 2 ( G2) - over three months. Parameters included: age, gender, bacilloscopy, erythrocyte sedimentation rate ( ESR), platelet count, alpha1-globulin, alpha2-globulin, gamma globulin, mucoprotein, alpha1-acid glycoprotein values, and the presence of risk factors such as smoking, alcoholism, drug addiction, sexual promiscuity, contact with tuberculosis carriers, and previous treatment. Groups were compared by calculating t and p, and Chi-square (X-2) and p. Comparisons revealed a tendency towards smoking with a higher frequency of smokers in G1 ( 0.05< p< 0.10). G1 also tended to present greater platelet values than G2 ( 0.05< p< 0.10) and presented significantly higher ESR values than G2 ( p< 0.05). Other factors did not show any significantly different behavior between groups ( p> 0.05). A correlation was found between ESR, platelet count, smoking and less than three months clinical duration.

Definition of a diagnostic routine in individuals with inconclusive serology for chagas disease

Despite the existence of highly sensitive tests, inconclusive serological results are frequent in chronic chagasic infection. This study aimed to define a diagnostic conduct for 30 individuals with inconclusive serology (G3) for chagasic infection assisted at the Outpatient Unit for Infectious and Parasitic Diseases of the Botucatu School of Medicine. Twenty-one individuals with negative serology (G1) and 33 with positive serology (G2) were also studied. Serological methods ELISA, HAI, IFI and immunoblotting TESA-cruzi were used for G1, G2 and G3, and parasitological methods xenodiagnosis, hemoculture and PCR-LIT were used for G2 and G3 individuals. ELISA, HAI and IFI were performed in 5 different blood samples in G2 and G3. TESA-cruzi was carried out only once in G1, G2 and G3 and, since it is the most sensitive, it was utilized as standard. In G3, positivity for ELISA reached 86% in the fifth blood sample; the ELISA+HAI+IFI combination showed a maximum of 44.8% in the second sample; and TESA-cruzi, 76% in one single sample. Xenodiagnosis positivity was 9.4%; hemoculture showed 15.2%; and PCR-LIT exhibited 22% positivity in G2. Nevertheless, in G3, positivity percentage was 3.4% for xenodiagnosis, 6.7% for PCR-LIT, and no positive result was found for hemoculture. In G3, PCR-LIT resolved one case which was still inconclusive according to serology tests. In order to define inconclusive diagnoses, the results suggest the combined use of ELISA+HAI+IFI in 2 blood samples, decreasing the occurrence of false positive/negative results. If results remain inconclusive, the performance of TESA-cruzi and PCR-LIT, if necessary, is recommended.

Surveillance of canine visceral leishmaniasis in a disease-free area

A leishmaniose é uma importante parasitose re-emergente observada no mundo, particularmente em países tropicais. Não há ainda relatos de casos autóctones no estado do Paraná. Não há até o momento referência de vigilância no reservatório canino, tais como Curitiba e região metropolitana do estado. O objetivo do estudo foi determinar a soroprevalência da leishmaniose visceral em cães entregues ao Centro de Controle de Zoonoses de São José dos Pinhais, Paraná para eutanásia. A detecção sorológica da presença de anticorpos contra Leishmania sp. foi realizada por (ELISA) indireto e pela Reação de Imunofluorescência Indireta (RIFI). Além disso, impressão de linfonodo poplíteo coletadas ao acaso de 50 cães com sinais clínicos suspeitos para leishmaniose visceral e analisados sob microscopia óptica para detecção de formas amastigotas, foram negativas. Amostras de soro de 364 animais foram testadas, e os resultados mostraram somente uma amostra positiva (0,0027%), reagente ao ELISA e negativa à RIFI, entretanto, o cão não apresentava sinais clínicos. A vigilância ao acaso em uma população de vários locais de uma área metropolitana pode ser uma forma de prevenção da disseminação da doença. Com base nos resultados observados, Curitiba e região metropolitana foram consideradas de baixo risco para a leishmaniose visceral.

Periodontal Disease Decreases Insulin Sensitivity and Insulin Signaling

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Differential regulation of MMP-13 expression in two models of experimentally induced periodontal disease in rats

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Sequential IL-23 and IL-17 and increased Mmp8 and Mmp14 expression characterize the progression of an experimental model of periodontal disease in type 1 diabetes

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)