COVID-19 vaccine confidence in the post-vaccination era: Perceptions among adults with immune-mediated inflammatory diseases.

Objective: Assess the perceived protection afforded by a range of COVID-19 vaccines in immune-mediated inflammatory diseases patients previously vaccinated against SARS-CoV-2. Study design: Survey. Methods: On-line cross-sectional survey aimed at evaluating the perceived protection (and its determinants) afforded by a range of COVID-19 vaccines among immune-mediated inflammatory diseases previously vaccinated for COVID-19. Results: Out of 493 eligible respondents who lived in Brazil, 397 (80.5%) were confident that their primary vaccination series would protect them against severe COVID-19. In multivariate analysis, only overlapping immune-mediated inflammatory diseases remained (negatively) associated with the perception of protection. Conclusions: No influence was found between COVID-19 vaccine types and the perception of protection after initial vaccinations.

Incidence and risk factors for osteoporotic non-vertebral fracture in low-income community-dwelling elderly: a population-based prospective cohort study in Brazil. The São Paulo Ageing and Health (SPAH) study.

We ascertained the incidence of non-vertebral fracture in a low-income Brazilian elderly cohort. To the best of our knowledge, this is the first population-based study to demonstrate the frequency of non-vertebral fracture in elderly Latin Americans. Age, prior fracture, and bone mineral density (BMD) at hip were predictors of fracture. INTRODUCTION: No data on incidence of osteoporotic non-vertebral fracture have been reported in low-income countries where the population's aging has been faster. Even in developed countries, currently available prospective data on major fracture rates beyond hip are scarce. The aim of this study is to describe the incidence and risk factors for non-vertebral fracture in a longitudinal prospective Brazilian population-based elderly cohort. METHODS: Seven hundred seven older adults (449 women, 258 men) were evaluated at baseline and after a mean follow-up of 4.3 ± 0.8 years. Clinical questionnaire, bone mineral density (BMD), and laboratory tests were performed at baseline. New non-vertebral fracture (hip, proximal humerus, rib, forearm) was determined during the follow-up. Multivariate Poisson regression models were used to identify independent predictors of fracture. RESULTS: The age-standardized incidence of non-vertebral fracture was 1562.3/100,000 (1085.7-2248.1/100,000) person-years (pyr) in women and 632.8/100,000 (301.7-1327.3/100,000) in men. Concerning to hip fractures, the incidence was 421.2/100,000 (210.7-842.3/100,000) pyr in women and 89.9/100,000 (12.7-638.5/100,000) in men. In a multivariate analysis, age (RR 2.07, 95% CI 1.13-3.82, p = 0.019, each 10-year increase), prior non-vertebral fracture (RR 3.08, 95% CI 1.36-6.95, p = 0.007), and total hip BMD (RR 1.68, 95% CI 1.11-2.56, p = 0.015, each 1 SD decrease) were predictors of new non-vertebral fracture. In men, fitting a model of risk factors for fracture was prevented by the limited number of events in male sample. CONCLUSION: This is the first population-based study to ascertain the incidence of major non-vertebral fractures in elderly Latin Americans, confirming the high frequency of the disorder. Age, prior fracture, and hip BMD were predictors of the short-term incidence of fracture.

Visceral fat measured by DXA is associated with increased risk of non-spine fractures in nonobese elderly women: a population-based prospective cohort analysis from the São Paulo Ageing & Health (SPAH) Study.

The present study investigates the relationship between visceral fat measured by dual-energy X-ray absorptiometry (DXA) and the incidence of non-spine fractures in community-dwelling elderly women. We demonstrated a potential negative effect of visceral fat on bone health in nonobese women. INTRODUCTION: The protective effect of obesity on bone health has been questioned because visceral fat has been demonstrated to have a deleterious effect on bone. The aim of this study was to investigate the association of visceral fat measured by DXA with the incidence of non-spine fractures in community-dwelling elderly women. METHODS: This longitudinal prospective population-based cohort study evaluated 433 community-dwelling women aged 65 years or older. A specific clinical questionnaire, including personal history of a fragility fracture in non-spine osteoporotic sites, was administered at baseline and after an average of 4.3 years. All incidences of fragility fractures during the study period were confirmed by affected-site radiography. Visceral adipose tissue (VAT) was measured in the android region of a whole-body DXA scan. RESULTS: The mean age was 72.8 ± 4.7 years, and 28 incident non-spine osteoporotic fractures were identified after a mean follow-up time of 4.3 ± 0.8 years. According to the Lipschitz classification for nutritional status in the elderly, 38.6 % of women were nonobese (BMI ≤ 27 kg/m2) and 61.4 % were obese/overweight. Logistic regression models were used to estimate the relationship between VAT and non-spine fractures in elderly women. After adjusting for age, race, previous fractures, and BMD, VAT (mass, area, volume) had a significant association with the incidence of non-spine fractures only in nonobese elderly women (VAT mass: OR, 1.42 [95 % CI, 1.09-1.85; p = 0.010]; VAT area: OR, 1.19 [95 % CI, 1.05-1.36; p = 0.008]; VAT volume: OR, 1.40 [95 % CI, 1.09-1.80; p = 0.009]). CONCLUSION: This study suggests a potential negative effect of visceral adiposity on bone health in nonobese women.

Associations between OPG and RANKL polymorphisms, vertebral fractures, and abdominal aortic calcification in community-dwelling older subjects: the Sao Paulo Ageing & Health Study (SPAH).

This is the first study analyzing concomitantly osteoprotegerin (OPG)/receptor activator of nuclear factor kappa B ligand (RANKL) polymorphisms and OPG/RANKL serum levels and their association with bone mineral density (BMD), vertebral fractures, and vascular aortic calcification in a cohort of 800 subjects in community-dwelling older individuals. INTRODUCTION: Osteoprotegerin (OPG) and RANKL play an important role in osteoclast activation and differentiation as well as in vascular calcification. At present, there are no studies of OPG or RANKL gene polymorphisms in Brazilian older populations. The aim of this study was to evaluate OPG/RANKL polymorphism and their association with vertebral fractures (VFs) and aortic calcification. METHODS: Eight hundred subjects (497 women/303 men) were genotyped for the OPG 1181G>C (rs2073618), 163C>T (rs3102735), 245T>G (rs3134069), and 209G>A (rs3134070) and RANKL A>G (rs2277438) single-nucleotide polymorphisms (SNPs). VFs were evaluated by spine radiography (Genant's method). Aortic calcification was quantified using Kauppila's method. RESULTS: The isolated genotype analyses and single-allele frequency data showed association of OPG 163C, 245G, and 209A alleles with presence of VFs (P < 0.05). Multiple logistic regression of subjects with absence of VFs vs. those with VFs (grades II/III) revealed only OPG 209A homozygosity as a risk factor for higher-grade VFs (odds ratio (OR) = 4.17, 95 % CI 1.03-16.93, P = 0.046). Regarding aortic calcification, the isolated genotype analysis frequency data revealed a significant association of OPG 1181G, 163C, 245G, and 209A alleles with absent aortic calcification (P < 0.05). Multiple logistic regression data confirmed that the OPG 209A allele was protective for aortic calcification (OR = 0.63, 95 % CI 0.45-0.88, P = 0.007) and the OPG 1181C allele was a risk factor for aortic calcification (OR = 1.26, 95 % CI 1.00-1.58, P = 0.046). CONCLUSION: This study showed that the OPG 209AA genotype was a risk factor for higher-grade VFs, the OPG 209A allele was protective for aortic calcification, and the OPG 1181C was a risk factor for aortic calcification, supporting the involvement of OPG polymorphisms in the analyzed phenotypes and the concept that the related pathogenesis is multifactorial.

Persistent hypovitaminosis D and loss of hip bone mineral density over time as additional risk factors for recurrent falls in a population-based prospective cohort of elderly persons living in the community. The São Paulo Ageing & Health (SPAH) Study.

UNLABELLED: We performed concomitant evaluation of clinical, laboratory, and bone mineral density (BMD) parameters as potential risk factors for falls in a population-based prospective cohort of older adults, since previous studies have focused mostly in clinical risk factors. Loss of hip BMD and persistent hypovitaminosis D were associated with recurrent falls in community-dwelling elderly. INTRODUCTION: Few studies have performed a concomitant evaluation of clinical data, laboratory bone parameters, and bone mineral density (BMD) to determine more accurately the contribution of each of these variables to risk of falls in elderly persons. We investigated the association between bone parameters and recurrent falls in a population-based prospective cohort of community-dwelling older adults. METHODS: A total of 705 elderly individuals (448 women, 257 men) were evaluated with clinical data, BMD, and laboratory bone tests at baseline and after a mean follow-up of 4.3 ± 0.8 years. Individuals with recurrent falls (≥2 falls in the previous year from the date of the second evaluation) were considered chronic fallers. Logistic regression models were used to identify independent risk factors for recurrent falls. RESULTS: The frequency of chronic fallers was 16.5%. In multivariate analyses, risk factors for recurrent falls were visual impairment (odds ratio (OR) = 2.49, 95% confidence interval (CI) 1.30-4.74, p = 0.006), use of psychotropic drugs (OR = 2.47, 95% CI 1.37-4.49, p = 0.003), clinical fracture (OR = 2.78, 95% CI 1.48-5.20, p = 0.001), persistently low 25-hydroxyvitamin D (25OHD) (<20 ng/mL) (OR = 1.71, 95% CI 1.10-2.64, p = 0.016), and loss of total hip BMD during the study (OR = 1.21, 95% CI 1.17-1.25, p = 0.035 for each 4% decrease). CONCLUSIONS: In addition to traditional clinical risk factors for falls, loss of hip BMD and hypovitaminosis D were associated with recurrent falls in community-dwelling elderly persons. Thus, recognizing these factors is essential to preventing falls and improving the outcomes of this population.

B2 receptor blockage prevents Aß-induced cognitive impairment by neuroinflammation inhibition.

BACKGROUND AND PURPOSE: Aß-induced neuronal toxicity and memory loss is thought to be dependent on neuroinflammation, an important event in Alzheimer's disease (AD). Previously, we demonstrated that the blockage of the kinin B2 receptor (B2R) protects against the memory deficits induced by amyloid ß (Aß) peptide in mice. In this study, we aimed to investigate the role of B2R on Aß-induced neuroinflammation in mice and the beneficial effects of B2R blockage in synapses alterations. EXPERIMENTAL APPROACH: The selective kinin B2R antagonist HOE 140 (50 pmol/site) was given by intracerebroventricular (i.c.v.) route to male Swiss mice 2 h prior the i.c.v. injection of Aß(1-40) (400 pmol/site) peptide. Animals were sacrificed, at specific time points after Aß(1-40) injection (6 h, 1 day or 8 days), and the brain was collected in order to perform immunohistochemical analysis. Different groups of animals were submitted to behavioral cognition tests on day 14 after Aß(1-40) administration. KEY RESULTS: In this study, we report that the pre-treatment with the selective kinin B2R antagonist HOE 140 significantly inhibited Aß-induced neuroinflammation in mice. B2R antagonism reduced microglial activation and the levels of pro-inflammatory proteins, including COX-2, iNOS and nNOS. Notably, these phenomena were accompanied by an inhibition of MAPKs (JNK and p38) and transcription factors (c-Jun and p65/NF-κB) activation. Finally, the anti-inflammatory effects of B2R antagonism provided significant protection against Aß(1-40)-induced synaptic loss and cognitive impairment in mice. CONCLUSIONS AND IMPLICATIONS: Collectively, these results suggest that B2R activation may play a critical role in Aß-induced neuroinflammation, one of the most important contributors to AD progression, and its blockage can provide synapses protection.

Incidence and risk factors for osteoporotic vertebral fracture in low-income community-dwelling elderly: a population-based prospective cohort study in Brazil. The São Paulo Ageing & Health (SPAH) Study.

UNLABELLED: We ascertained the incidence and predictors of radiographic vertebral fracture in a Brazilian elderly cohort, since no data in this field have been reported in low-income countries. This is the first population-based study to demonstrate the high frequency of vertebral fracture in elderly Latin Americans. Age, prior fracture, BMD, and bone turnover were predictors of fracture. INTRODUCTION: Vertebral fractures are associated with increased future fracture risk and mortality. No data on incidence of osteoporotic vertebral fracture have been reported in low-income countries where the population's aging has been faster. Thus, we sought to describe the incidence and risk factors for radiographic vertebral fracture in a longitudinal prospective Brazilian population-based elderly cohort. METHODS: 707 older adults (449 women and 258 men) were evaluated with spinal radiographs obtained at baseline and after a mean follow-up of 4.3 ± 0.8 years. New vertebral fracture was defined as distinct alteration in the morphology of vertebrae resulting in higher grade of deformity on the second radiograph when compared to the baseline radiograph. Clinical questionnaire, bone mineral density (BMD), and laboratory tests were performed at baseline. Multivariate Poisson regression models were used to identify independent predictors of fracture. RESULTS: The age-standardized incidence of vertebral fracture was 40.3/1,000 person-years in women and 30.6/1,000 in men. In women, three models of risk factors for fracture were fitted: (1) age (relative risks (RR) 2.46, 95 % confidence interval (CI) 1.66-3.65), previous osteoporotic fracture (RR 1.65, 95 % CI 1.00-2.71), and lumbar spine BMD (RR 1.21, 95 % CI 1.03-1.41); (2) age (RR 2.25, 95 % CI 1.52-3.34) and femoral neck BMD (RR 1.42, 95 % CI 1.11-1.81); (3) age (RR 2.11, 95 % CI 1.41-3.15) and total hip BMD (RR 1.56, 95 % CI 1.21-2.0). In men, the highest quartile of cross-linked C-telopeptide (CTx) (RR 1.96, 95 % CI 0.98-3.91) and prior fracture (RR 2.10, 95 % CI 1.00-4.39) were predictors of new vertebral fracture. CONCLUSIONS: This is the first population-based study to ascertain the incidence of vertebral fracture in elderly Latin Americans, confirming the high frequency of the disorder. Age, prior fracture, BMD, and bone turnover were predictors of the short-term incidence of vertebral fracture.

Prevalence of sarcopenia and associated risk factors by two diagnostic criteria in community-dwelling older men: the São Paulo Ageing & Health Study (SPAH).

UNLABELLED: Sarcopenia is an aging syndrome that can be characterized by many criteria adjusted or not by fat mass. This study suggested that the optimal criteria should be selected according to body mass index (BMI) in older men and identified age, BMI, race, smoking, physical activity, hip bone mineral density (BMD) as risk factors for this syndrome. INTRODUCTION: This study aims to analyze the prevalence of sarcopenia and associated risk factors using appendicular skeletal mass (ASM)/height(2) and ASM adjusted for total fat mass criteria in older men from community. METHODS: Three hundred ninety-nine men were included and answered a questionnaire about lifestyle and medical history. Individuals were classified by their BMI using the classification adjusted by age. Body composition and bone mineral density were measured by dual X-ray absorptiometry. Sarcopenia was classified according to both criteria. Logistic regression models were used to analyze risk factors associated with sarcopenia. RESULTS: The mean BMI was 26.46 kg/m(2): 12.5 % underweight, 43.6 % normal, and 43.9 % overweight/obese. Fifty-four (13.5 %) were considered sarcopenic by ASM/height(2) and 79 (19.8 %) by ASM adjusted for fat (p = 0.001). Fifty-one (12.8 %) individuals had discordant sarcopenia classification: 13 were classified only by ASM/height(2) and 38 only by ASM adjusted for fat. Of the 13 subjects classified as sarcopenic only by ASM/height(2), 84.6 % (11/13) were underweight and solely one (7.7 %) was considered overweight/obese. In contrast, of those 38 older men classified as sarcopenic only by ASM adjusted for fat, none were underweight and 53 % (20/38) were overweight/obese. Subjects classified as sarcopenic according to both criteria had the same risk factors in the final model analyses (age, BMI, race, smoking, physical activity, hip BMD; p < 0.05). CONCLUSION: This study suggested that the optimal criteria for sarcopenia should be selected according to BMI in community-dwelling older men.

Discriminating sarcopenia in community-dwelling older women with high frequency of overweight/obesity: the São Paulo Ageing & Health Study (SPAH).

SUMMARY: The criteria most used for the definition of sarcopenia, those based on the ratio between the appendicular skeletal muscle mass (ASM) and the square of the height (h(2)) underestimate prevalence in overweight/obese people whereas another criteria consider ASM adjusted for total fat mass. We have shown that ASM adjusted for fat seems to be more appropriate for sarcopenia diagnosis. INTRODUCTION: Since the prevalence of overweight and obesity is a growing public health issue, the aim of this study was to evaluate the prevalence and risk factors associated with sarcopenia, based on these two criteria, among older women. METHODS: Six hundred eleven community-dwelling women were evaluated by specific questionnaire including clinical data. Body composition and bone mineral density were evaluated by dual X-ray absorptiometry. Logistic regression models were used to identify factors independently related to sarcopenia by ASM/h(2) and ASM adjusted for total fat mass criteria. RESULTS: The prevalence of overweight/obesity was high (74.3 %). The frequency of sarcopenia was lower using the criteria of ASM/h(2) (3.7 %) than ASM adjusted for fat (19.9 %) (P < 0.0001). We also note that less than 5 %(1/23) of sarcopenic women, according to ASM/h(2), had overweight/obesity, whereas 60 % (74/122) of sarcopenic women by ASM adjusted for fat had this complication. Using ASM/h(2), the associated factors observed in regression models were femoral neck T-score (OR = 1.90; 95 % CI 1.06-3.41; P = 0.03) and current alcohol intake (OR = 4.13, 95 % CI 1.18-14.45, P = 0.03). In contrast, we have identified that creatinine (OR = 0.21; 95 % CI 0.07-0.63; P = 0.005) and the White race (OR = 1.81; 95 % CI 1.15-2.84; P = 0.01) showed a significant association with sarcopenia using ASM adjusted for fat. CONCLUSIONS: In women with overweight/obesity, ASM adjusted for fat seems to be the more appropriate criteria for sarcopenia diagnosis. This finding has relevant public health implications, considering the high prevalence of overweight/obesity in older women.

The selective and competitive N-methyl-D-aspartate receptor antagonist, (-)-6-phosphonomethyl-deca-hydroisoquinoline-3-carboxylic acid, prevents synaptic toxicity induced by amyloid-ß in mice.

The toxicity of amyloid ß (Aß) is highly associated with Alzheimer's disease (AD), which has a high incidence in elderly people worldwide. While the current treatment for moderate and severe AD includes blockage of the N-methyl-d-aspartate receptor (NMDAR), the molecular mechanisms of its effect are still poorly understood. Herein, we report that a single i.p. administration of the selective and competitive (NMDAR) antagonist LY235959 reduced Aß neurotoxicity by preventing the down-regulation of glial glutamate transporters (glutamate-aspartate transporter (GLAST) and glutamate transporter-1 (GLT-1)), the decrease in glutamate uptake, and the production of reactive oxygen species (ROS) induced by Aß(1-40). Importantly, the blockage of NMDAR restored the Aß(1-40)-induced synaptic dysfunction and cognitive impairment. However, LY235959 failed to prevent the inflammatory response associated with Aß(1-40) treatment. Altogether, our data indicate that the acute administration of Aß promotes oxidative stress, a decrease in glutamate transporter expression, and neurotoxicity. Our results reinforce the idea that NMDAR plays a critical regulatory action in Aß toxicity and they provide further pre-clinical evidence for the potential role of the selective and competitive NMDAR antagonists in the treatment of AD.

Design and realization of a wireless sensor gateway for health monitoring.

This paper describes the design and realization of a wireless sensor gateway (WSG) within a wireless sensor network (WSN) for health monitoring. The WSN allows recording and wireless transmission of biosignals, namely the electrocardiogram, pulse wave and body weight, which are important parameters for cardiovascular monitoring. These can be displayed, analysed, and saved on the WSG through a user interface based on a touch screen. The proposed WSG has the distinctive feature of using two different radio transceivers, exploiting the advantages of each device. Currently, most personal computers and handhelds have standardized Bluetooth interfaces (IEEE 802.15.1) but not ZigBee interfaces (IEEE 802.15.4). Hence, the proposed gateway is designed to receive data from wireless sensors through its ZigBee interface and to forward them to a personal computer via its Bluetooth interface. This feature, combined with simple touch screen menu navigation will reach increased patient compliance and consequently increased benefit for patient in terms of healthcare and safety.

Low power wireless acquisition module for wearable health monitoring systems.

This paper presents a low power wireless acquisition module for use within wearable health monitoring systems and Ambient Assisted Living applications. The acquisition module provides continuous monitoring of the user's electrocardiogram (ECG) and activity, as well as the local temperature at the module. The module is placed on the chest of the user, and its wearability is achieved due to its fabrication based on a flexible PCB, and by the complete absence of connecting wires, as a result of the integration of flexible and dry ECG monitoring electrodes on the acquisition module, which do not require preparation with electrolyte gel. The design of the acquisition module also aimed for the minimization of power consumption to enable long-term continuous monitoring, namely concerning the wireless link, for which a proprietary low power solution was adopted. A low power analog frontend was custom designed for single-lead ECG monitoring, achieving a current consumption of 220 εA. The wireless acquisition module has a current consumption down to 1.3 mA while processing the acquisition of sensor data, and 4 mA when the wireless transceiver is active.

D-dimer as a possible prognostic marker of operable hormone receptor-negative breast cancer.

BACKGROUND: Breast cancer is the most common cause of death in women by neoplasia. The mechanisms related to recurrence are unclear, specially the hemostatic alterations that occur during the development of the disease. Plasma D-dimer is a hypercoagulability and fibrinolytic system marker and is increased in patients with various solid tumors. The purpose of this study was to evaluate the hemostatic status assessed by plasma D-dimer in operable breast cancer patients and to investigate its value as a prognostic marker. MATERIALS AND METHODS: The study comprised 32 patients with operable hormone receptor-negative breast cancer and a control group with 43 healthy women. Variables included presence and absence of breast cancer, clinical and histopathology findings, and overall survival. RESULTS: Plasma D-dimer level was normal in the control group and significantly higher in breast cancer patients (P = 0.001), as well as in nonsurvivors compared with survivors (P = 0.025). The results showed that plasma D-dimer levels were not correlated with clinical and histopathology findings (P > 0.213). CONCLUSIONS: The results taken together indicate the presence of a hypercoagulability state in women with operable hormone receptor-negative breast cancer given the increased levels of D-dimer in this group. Therefore, considering higher levels of D-dimer in patients with a poor outcome, its evaluation may be a promising tool for prognosis in women with operable hormone receptor-negative breast cancer.

Cellular prion protein modulates age-related behavioral and neurochemical alterations in mice.

The cellular prion protein (PrP(C)) is a neuronal-anchored glycoprotein that has been associated with various functions in the CNS such as synaptic plasticity, cognitive processes and neuroprotection. Here we investigated age-related behavioral and neurochemical alterations in wild-type (Prnp(+/+)), PrP(C) knockout (Prnp(0/0)) and the PrP(C) overexpressing Tg-20 mice. Three- or 11 month-old animals were submitted to a battery of behavioral tasks including open field, activity cages, elevated plus-maze, social recognition and inhibitory avoidance tasks. The 11 month-old Prnp(+/+) and Prnp(0/0) mice exhibited significant impairments in their locomotor activity and social recognition memory and increased anxiety-related responses. Remarkably, Tg-20 mice did not present these age-related impairments. The i.c.v. infusion of STI1 peptide 230-245, which includes the PrP(C) binding site, improved the age-related social recognition deficits in Prnp(+/+). In comparison with the two other age-matched genotypes, the 11 month-old Tg-20 mice also exhibited reduced activity of seric acetylcholinesterase, increased expression of the protein synaptophysin and decreased caspase-3 positive-cells in the hippocampus. The present findings obtained with genetic and pharmacological approaches provide convincing evidence that PrP(C) exerts a critical role in the age-related behavioral deficits in mice probably through adaptive mechanisms including apoptotic pathways and synaptic plasticity.

Therapeutic action and underlying mechanisms of a combination of two pentacyclic triterpenes, alpha- and beta-amyrin, in a mouse model of colitis.

BACKGROUND AND PURPOSE: alpha- and beta-amyrin are pentacyclic triterpenes found in plants and are known to exhibit pronounced anti-inflammatory effects. Here, we evaluated the effects of a 1:1 mixture of alpha- and beta-amyrin (alpha,beta-amyrin) on an experimental model of colitis in mice. EXPERIMENTAL APPROACH: Colitis was induced in Swiss male mice by trinitrobenzene sulphonic acid (TNBS) and followed up to 72 h; animals were treated systemically with alpha,beta-amyrin, dexamethasone or vehicle. Macro- and microscopic damage, myeloperoxidase activity and cytokine levels were assessed in colons. Histological sections were immunostained for cyclooxygenase-2 (COX-2), vascular endothelial growth factor, phospho-p65 nuclear factor-kappaB (NF-kappaB) and phospho-cyclic AMP response element-binding protein (CREB). KEY RESULTS: TNBS-induced colitis was associated with tissue damage, neutrophil infiltration and time-dependent increase of inflammatory mediators. Treatment with alpha,beta-amyrin (3 mg x kg(-1), i.p.) or dexamethasone (1 mg x kg(-1), s.c.) consistently improved tissue damage scores and abolished polymorphonuclear cell infiltration. alpha,beta-Amyrin, like dexamethasone, significantly diminished interleukin (IL)-1beta levels and partially restored IL-10 levels in colon tissues 72 h after colitis induction, but only alpha,beta-amyrin reduced vascular endothelial growth factor expression by immunohistochemistry. The colonic expression of COX-2 at 24 h and that of phospho-NF-kappaB and phospho-CREB (peaking at 6 h) after colitis induction were consistently inhibited by both alpha,beta-amyrin and dexamethasone. CONCLUSIONS AND IMPLICATIONS: Systemic administration of alpha,beta-amyrin exerted a marked and rapid inhibition of TNBS-induced colitis, related to the local suppression of inflammatory cytokines and COX-2 levels, possibly via inhibition of NF-kappaB and CREB-signalling pathways. Taken together, our data suggest a potential use of alpha,beta-amyrin to control inflammatory responses in bowel disease.

Emotional, cognitive and neurochemical alterations in a premotor stage model of Parkinson's disease.

In addition to classic motor symptoms, Parkinson's disease (PD) is characterized by cognitive and emotional deficits, which have been demonstrated to precede motor impairments. The present study addresses the question of whether a partial degeneration of dopaminergic neurons using 6-hydroxydopamine (6-OHDA) in rats is able to induce premotor behavioral signs. The time-course of nigrostriatal damage was evaluated by tyrosine hydroxylase immunohistochemistry and the levels of dopamine, noradrenaline, and 5-HT in various brain regions were analyzed by high performance liquid chromatography (HPLC). Behavioral tests that assessed a variety of psychological functions, including locomotor activity, emotional reactivity and depression, anxiety and memory were conducted on 6-OHDA lesioned rats. Bilateral infusion of 6-OHDA in the striatum of rats caused early (1 week) damage of dopaminergic terminals in striatum and in cell bodies in substantia nigra pars compacta. The nigrostriatal lesion was accompanied by early loss of dopamine in the striatum, which remained stable through a 3-week period of observation. In addition, a late (3 weeks) loss of dopamine in the prefrontal cortex, but not in the hippocampus, was seen. Additional noradrenergic and serotonergic alterations were observed after 6-OHDA administration. The results indicated that 6-OHDA lesioned rats show decreased sucrose consumption and an increased immobility time in the forced swimming test, an anhedonic-depressive-like effect. In addition, an anxiogenic-like activity in the elevated plus maze test and cognitive impairments were observed on the cued version of the Morris water maze and social recognition tests. These findings suggest that partial striatal dopaminergic degeneration and parallel dopaminergic, noradrenergic and serotonergic alterations in striatum and prefrontal cortex may have caused the emotional and cognitive deficits observed in this rat model of early phase PD.