SWI versus GRE-T2*: Assessing cortical superficial siderosis in advanced cerebral amyloid angiopathy.

BACKGROUND AND PURPOSE: Cortical superficial siderosis (cSS) is a key neuroimaging marker of cerebral amyloid angiopathy (CAA) detected on blood-sensitive magnetic resonance imaging (MRI). We aimed to assess cSS in advanced CAA patients and explore differences in its evaluation between susceptibility weighted imaging (SWI) and gradient recalled echo-T2* (GRE-T2*). MATERIALS AND METHODS: Neuroimaging data gathered from a prospective cohort of CAA patients with probable or definite CAA were retrospectively analyzed by two independent raters. SWI and GRE-T2* were used to assess presence and severity (absent, focal [≤3 sulci] or disseminated [>3 sulci]) of cSS and number of foci. Ratings were compared between sequences and inter-rater agreement was determined. Post hoc analysis explored differences in cSS multifocality scores. RESULTS: We detected cSS in 38 patients with SWI and in 36 with GRE-T2* (70.4% versus 66.7%; P=0.5). The two raters agreed in detecting more disseminated cSS when using SWI: 16 focal (29.63%) and 20 disseminated (37.04%) cases of cSS seen on GRE-T2* and 11 (20.37%) focal and 27 (50%) disseminated cSS cases seen using SWI (P=0.008). Inter-rater agreement was equivalent for the two sequences (κpresence 0.7 versus 0.69; κseverity 0.74 versus 0.66) for assessing both presence and severity of cSS. Post hoc analysis showed higher multifocality scores from both raters' SWI evaluations, with agreement equivalent to that for T2* evaluations. CONCLUSIONS: Our findings suggest that SWI ratings could show more disseminated cSS and higher multifocality scores in advanced CAA patients with inter-rater reliability equivalent to that obtained using GRE-T2*, regardless of level of experience.

Different clinical outcomes between cerebral amyloid angiopathy-related inflammation and non-inflammatory form.

OBJECTIVE: Cerebral amyloid angiopathy-related inflammation (CAA-ri) is a rare manifestation related to CAA, thought to be more severe. We aimed to compare the clinical and radiological outcomes of CAA-ri and non-inflammatory CAA. MATERIALS AND METHODS: We retrospectively included all patients with CAA-ri from 13 French centers. We constituted a sex- and age-matched control cohort with non-inflammatory CAA and similar disease duration. Survival, autonomy and cognitive evolution were compared after logistic regression. Cerebral microbleeds (CMB), intracerebral hemorrhage, cortical superficial siderosis and hippocampal atrophy were analyzed as well as CSF biomarker profile and APOE genotype when available. Outcomes were compared using Kaplan-Meier curves and log-rank tests. RESULTS: Data from 48 CAA-ri patients including 28 already reported and 20 new patients were analyzed. Over a mean of 3.1 years, 11 patients died (22.9%) and 18 (37.5%) relapsed. CAA-ri patients were more frequently institutionalized than non-inflammatory CAA patients (30% vs 8.3%, p < 0.001); mortality rates remained similar. MMSE and modified Rankin scale scores showed greater severity in CAA-ri at last follow-up. MRI showed a higher number of CMB at baseline and last follow-up in CAA-ri (p < 0.001 and p = 0.004, respectively). CSF showed lower baseline levels of Aß42 in CAA-ri than non-inflammatory CAA (373.3 pg/ml vs 490.8 pg/ml, p = 0.05). CAA-ri patients more likely carried at least one APOE ε4 allele (76% vs 37.5%, adjusted p = 0.05) particularly as homozygous status (56% vs 6.2%, p < 0.001). INTERPRETATION: CAA-ri appears to be more severe than non-inflammatory CAA with a significant loss of autonomy and global higher amyloid burden, shown by more CMB and a distinct CSF profile. This burden may be partially promoted by ε4 allele.

Peak Width of Skeletonized Mean Diffusivity as Neuroimaging Biomarker in Cerebral Amyloid Angiopathy.

BACKGROUND AND PURPOSE: Whole-brain network connectivity has been shown to be a useful biomarker of cerebral amyloid angiopathy and related cognitive impairment. We evaluated an automated DTI-based method, peak width of skeletonized mean diffusivity, in cerebral amyloid angiopathy, together with its association with conventional MRI markers and cognitive functions. MATERIALS AND METHODS: We included 24 subjects (mean age, 74.7 [SD, 6.0] years) with probable cerebral amyloid angiopathy and mild cognitive impairment and 62 patients with MCI not attributable to cerebral amyloid angiopathy (non-cerebral amyloid angiopathy-mild cognitive impairment). We compared peak width of skeletonized mean diffusivity between subjects with cerebral amyloid angiopathy-mild cognitive impairment and non-cerebral amyloid angiopathy-mild cognitive impairment and explored its associations with cognitive functions and conventional markers of cerebral small-vessel disease, using linear regression models. RESULTS: Subjects with Cerebral amyloid angiopathy-mild cognitive impairment showed increased peak width of skeletonized mean diffusivity in comparison to those with non-cerebral amyloid angiopathy-mild cognitive impairment (P < .001). Peak width of skeletonized mean diffusivity values were correlated with the volume of white matter hyperintensities in both groups. Higher peak width of skeletonized mean diffusivity was associated with worse performance in processing speed among patients with cerebral amyloid angiopathy, after adjusting for other MRI markers of cerebral small vessel disease. The peak width of skeletonized mean diffusivity did not correlate with cognitive functions among those with non-cerebral amyloid angiopathy-mild cognitive impairment. CONCLUSIONS: Peak width of skeletonized mean diffusivity is altered in cerebral amyloid angiopathy and is associated with performance in processing speed. This DTI-based method may reflect the degree of white matter structural disruption in cerebral amyloid angiopathy and could be a useful biomarker for cognition in this population.

Role of neuroimaging before reperfusion therapy. Part 1 - IV thrombolysis - Review.

This review paper summarises the yield of the different imaging modalities in the evaluation of patients for IV thrombolysis. Non-contrast CT and CTA or brain MRI combined with MRA are the recommended sequences for the evaluation of patients within the 4.5 hours time window. Multimodal MRI (DWI/PWI), and more recently, CT perfusion, offer reliable surrogate of salvageable penumbra, the target mismatch, which is now currently used as selection criteria for revascularisation treatment in an extended time window. Those sequences may also help the physician for the management of other limited cases when the diagnosis of acute ischemic stroke is difficult. Another approach the DWI/FLAIR mismatch has been proposed to identify among wake-up stroke patients those who have been experiencing an acute ischemic stroke evolving from less than 4.5hrs. Other biomarkers, such as the clot imaging on MRI and CT, help to predict the recanalisation rate after IVT, while the impact of the presence microbleeds on MRI remains to be determined.

Interhemispheric distribution of amyloid and small vessel disease burden in cerebral amyloid angiopathy-related intracerebral hemorrhage.

BACKGROUND AND PURPOSE: Intracerebral hemorrhage (ICH) is a devastating presentation of cerebral amyloid angiopathy (CAA), but the mechanisms leading from vascular amyloid deposition to ICH are not well known. Whether amyloid burden and magnetic resonance imaging (MRI) markers of small vessel disease (SVD) are increased in the ICH-affected hemisphere compared to the ICH-free hemisphere in patients with a symptomatic CAA-related ICH was investigated. METHODS: Eighteen patients with CAA-related ICH and 18 controls with deep ICH who underwent brain MRI and amyloid positron emission tomography using 18 F-florbetapir were prospectively enrolled. In each hemisphere amyloid uptake using the standardized uptake value ratio and the burden of MRI markers of SVD including cerebral microbleeds, chronic ICH, cortical superficial siderosis, white matter hyperintensities and lacunes were evaluated. Interhemispheric comparisons were assessed by non-parametric matched-pair tests within each patient group. RESULTS: Amyloid burden was similarly distributed across the brain hemispheres in patients with CAA-related ICH (standardized uptake value ratio 1.11 vs. 1.12; P = 0.74). Cortical superficial siderosis tended to be more common in the ICH-affected hemisphere compared to the ICH-free hemisphere (61% vs. 33%; P = 0.063). Other MRI markers of SVD did not differ across brain hemispheres. In controls with deep ICH, no interhemispheric difference was observed either for amyloid burden or for MRI markers of SVD. CONCLUSIONS: Brain hemorrhage does not appear to be directly linked to amyloid burden in patients with CAA-related ICH. These findings provide new insights into the mechanisms leading to hemorrhage in CAA.

Topical monomethylsilanetriol can deliver silicon to the viable skin.

OBJECTIVE: Organic silicon has been linked to positive effects on the skin rejuvenation, mainly by the oral route. Thus, the main objective of the present study was to assess whether monomethylsilanetriol (MMST, a source of organic silicon) can deliver silicon to the epidermis and dermis, when applied topically in a cream. Once the hypothesis was confirmed, the present study also evaluated whether the product was toxic to keratinocytes; additionally, its possible antioxidant activity was assessed. METHODS: The ex vivo skin permeation profile was determined using human skin in Franz-cells equipment; cytotoxicity was assessed using HaCaT keratinocytes. Antioxidant capacity was determined as scavenging activity, measured according to the 1,1-diphenyl-2-picrylhydrazil free radical method. RESULTS: The permeation percentage was almost 60% of the applied MMST, with a large quantity of drug found in the viable epidermis and dermis. The cell viability assay showed no significant difference in the percentage of viable keratinocytes among the treated groups at the doses used. In terms of antioxidant activity, the IC50 value obtained was 2400 µg mL-1 . Low antioxidant activity, negligible toxicity for keratinocytes and a significant percentage of permeation were observed. CONCLUSION: We provide evidence that MMST applied topically can deliver silicon to the skin in biorelevant levels for cosmetic purposes.

OBJECTIF: Le silicium organique a été associé à des effets positifs sur le rajeunissement de la peau, principalement par voie orale. Ainsi, l'objectif principal de la présente étude était d'évaluer si le monométhylsilanetriol (MMST, une source de silicium organique) pouvait livrer du silicium à l'épiderme et au derme, lorsqu'il était appliqué localement dans une crème. Une fois l'hypothèse confirmée, la présente étude a également évalué si le produit était toxique pour les kératinocytes; de plus, son éventuelle activité antioxydante a été évaluée. MÉTHODES: Le profil de permeation cutanée ex vivo a été déterminé en utilisant de la peau humaine dans un équipement à cellules Franz; la cytotoxicité a été évaluée à l'aide de kératinocytes HaCaT. La capacité d'antioxydant a été déterminée en tant qu'activité de piégeage, mesurée selon la méthode des radicaux libres au 1,1-diphényl-2-picrylhydrazil. RÉSULTATS: Le pourcentage de perméation était proche de 60% du MMST appliqué, une grande quantité de médicament se trouvant dans l'épiderme et le derme viables. Le test de viabilité cellulaire n'a montré aucune différence significative dans le pourcentage de kératinocytes viables parmi les groupes traités aux doses utilisées. En termes d'activité antioxydante, la valeur de la CI50 obtenue était de 2400 µg mL−1 . Une faible activité antioxydante, une toxicité négligeable pour les kératinocytes et un pourcentage important de perméation ont été observés. CONCLUSION: Nous apportons la preuve que le MMST appliqué localement peut délivrer du silicium sur la peau à des niveaux biologiquement pertinents à des fins esthétiques.

Acute ischaemic lesions are associated with cortical superficial siderosis in spontaneous intracerebral hemorrhage.

BACKGROUND AND PURPOSE: Diffusion-weighted imaging (DWI) commonly detects acute ischaemic lesions in patients with acute intracerebral hemorrhage (ICH), especially with cerebral amyloid angiopathy (CAA). We investigated the relationship between cortical superficial siderosis (cSS), a neuroimaging marker of CAA, and DWI lesions in patients with acute ICH. METHODS: We conducted a retrospective analysis of prospectively collected data from consecutive patients with acute supratentorial ICH who underwent brain magnetic resonance imaging within 10 days after symptom onset. Magnetic resonance imaging scans were analyzed for DWI lesions, cSS and other markers for small-vessel disease. Univariate and multivariate analyses were performed to assess the association between cSS and DWI lesions. RESULTS: Among 246 ICH survivors (mean age 71.4 ± 12.6 years) who were enrolled, 126 had lobar ICH and 120 had deep ICH. Overall, DWI lesions were observed in 38 (15.4%) patients and were more common in patients with lobar ICH than deep ICH (22.2% vs. 8.3%; P = 0.003). In multivariate logistic regression analysis, the extent of white matter hyperintensities [odds ratio (OR), 1.29; 95% confidence interval (CI), 1.05-1.58; P = 0.02] and cSS severity (focal cSS: OR, 3.54; 95% CI, 1.28-9.84; disseminated cSS: OR, 4.41; 95% CI, 1.78-10.97; P = 0.001) were independently associated with the presence of DWI lesions. CONCLUSIONS: Diffusion-weighted imaging lesions are more frequently observed in patients with acute lobar ICH than in those with deep ICH. cSS severity and white matter hyperintensity extent are independent predictors for the presence of DWI lesions, suggesting that CAA may be involved in the pathogenesis of DWI lesions associated with acute ICH.

Serotonin Selective Reuptake Inhibitors (SSRIs) and Stroke.

PURPOSE OF REVIEW: The interest in SSRIs after stroke has increased in the past few years, with better knowledge of post-stroke depression and with the demonstrated capacity of some SSRIs to act on the functional recovery of non-depressed subjects. RECENT FINDINGS: Arguments for the action of SSRIs in favour of post-stroke neurological function recovery have improved through new elements: basic science and preclinical data, positive clinical trials and repeated series of stroke patient meta-analysis, and confirmation of favourable safety conditions in post-stroke patients. Global coherence is appearing, showing that SSRIs improve stroke recovery in non-depressed patients when given for 3 months after the stroke, with highly favourable safety conditions and a favourable benefit/risk ratio. Large series are still needed.

Cortical superficial siderosis and acute convexity subarachnoid hemorrhage in cerebral amyloid angiopathy.

BACKGROUND AND PURPOSE: Acute convexity subarachnoid hemorrhage (cSAH) and cortical superficial siderosis (cSS) are neuroimaging markers of cerebral amyloid angiopathy (CAA) that may arise through similar mechanisms. The prevalence of cSS in patients with CAA presenting with acute cSAH versus lobar intracerebral hemorrhage (ICH) was compared and the physiopathology of cSS was explored by examining neuroimaging associations. METHODS: Data from 116 consecutive patients with probable CAA (mean age, 77.4 ± 7.3 years) presenting with acute cSAH (n = 45) or acute lobar ICH (n = 71) were retrospectively analyzed. Magnetic resonance imaging scans were analyzed for cSS and other imaging markers. The two groups' clinical and imaging data were compared and the associations between cSAH and cSS were explored. RESULTS: Patients with cSAH presented mostly with transient focal neurological episodes. The prevalence of cSS was higher amongst cSAH patients than amongst ICH patients (88.9% vs. 57.7%; P < 0.001). In multivariable logistic regression analysis, focal [odds ratio (OR) 6.73; 95% confidence interval (CI) 1.75-25.81; P = 0.005] and disseminated (OR 11.68; 95% CI 3.55-38.35; P < 0.001) cSS were independently associated with acute cSAH, whereas older age (OR 0.93; 95% CI 0.87-0.99; P = 0.025) and chronic lobar ICH count (OR 0.45; 95% CI 0.25-0.80; P = 0.007) were associated with acute lobar ICH. CONCLUSIONS: Amongst patients with CAA, cSS is independently associated with acute cSAH. These findings suggest that cSAH may be involved in the pathogenesis of the cSS observed in CAA. Longitudinal studies are warranted to assess this potential causal relationship.

Cerebral amyloid angiopathy-related cognitive impairment: The search for a specific neuropsychological pattern.

Cerebral amyloid angiopathy is diagnosed in stroke units after lobar intracerebral hemorrhage. CAA can also be diagnosed in memory clinics when patients are referred for cognitive impairment assessment, and may be a reason for admission to emergency or neurology departments because of rapidly progressive cognitive or neurological decline, or a transient focal neurological episode. CAA may even be observed in older community-dwelling individuals. Neuropsychological impairment in CAA has been described over the past 20 years. The symptoms most commonly reported are perceptual speed, episodic memory, semantic memory, attention and executive function, and global cognitive impairments. Psychiatric symptoms, such as personality changes, behavioral disturbances and depression, have been more recently described. CAA is also a risk factor for the development of dementia, and its relationship with Alzheimer's disease has been demonstrated in post-mortem studies. Yet, despite the increase in literature on CAA-related cognitive and psychiatric symptoms, the specific characteristics of symptoms in CAA are difficult to assess because of the substantial prevalence of comorbidities such as small vessel disease due to high blood pressure, Lewy body disease and, of course, AD, all of which act as important confounding factors. Also, within the entity of CAA itself, the additive and perhaps synergistic effects of each lesion on cognition remain to be assessed. In the present paper, the focus is on the latest evidence of neuropsychological impairment observed in CAA patients, and the emergence of a possible specific neuropsychological profile due to CAA is also discussed.

Impact of spontaneous intracerebral hemorrhage on cognitive functioning: An update.

Intracerebral hemorrhage (ICH) accounts for 15% of all strokes and approximately 50% of stroke-related mortality and disability worldwide. Patients who have experienced ICH are at high risk of negative outcome, including stroke and cognitive disorders. Vascular cognitive impairment are frequently seen after brain hemorrhage, yet little is known about them, as most studies have focused on neuropsychological outcome in ischemic stroke survivors, using well-documented acute and chronic cognitive scores. However, recent evidence supports the notion that ICH and dementia are closely related and each increases the risk of the other. The location of the lesion also plays a significant role as regards the neuropsychological profile, while the pathophysiology of ICH can indicate a specific pattern of dysfunction. Several cognitive domains may be affected, such as language, memory, executive function, processing speed and gnosis.

Screening antimycobacterial activity of Baccharis dracunculifolia, Centella asiatica, Lantana camara and Pterodon emarginatus / Atividade anti-micobacteriana de Baccharis dracunculifolia, Centella asiatica, Lantana camara e Pterodon emarginatus

ABSTRACT The permanent investigation of new antimycobacterial drugs is necessary for the eradication programs of tuberculosis and other mycobacterium-related diseases. The aim of the present study is to search for new sources of antimycobacterial drugs using plant materials. In this study, 11 plant materials (extracts, essential oils and some fractions) obtained from 4 species of medicinal plants traditionally used as general therapeutics for different illnesses and specifically as treatment of tuberculosis, were evaluated using the microplate resazurin assay against 2 species of the Mycobacterium tuberculosis Complex and 3 nontuberculous mycobacteria. The results showed the hexane extract and the essential oil from fruits of Pterodonemarginatus (Vogel) as potential sources of antimycobacterial drugs against 4 species of tested mycobacteria. The hexane fraction of methanol extract from leaves of Centella asiatica also presented significant mycobacterial growth inhibition, but against M. chelonae only. In conclusion, it was possible to contribute to the antimycobacterial investigations by presenting three new samples of plants with significant antimicrobial activity against four Mycobacteriumspp and suggest future studies about the antimycobacterial properties of fruits from P. emarginatus.

RESUMO A investigação permanente de novas drogas antimicobacterianas é necessária no programa de erradicação da tuberculose e de outras doenças relacionadas com micobactérias. O objetivo deste estudo foi buscar novas fontes de drogas antimicobacterianas usando material vegetal. Neste estudo, 11 materiais de base vegetal (extratos, óleos essenciais e algumas frações) foram avaliados contra 5 espécies de micobactérias. Estes materiais foram obtidos a partir de 4 espécies de plantas medicinais tradicionalmente utilizadas como terapêutica geral para diferentes doenças e, especificamente, no tratamento de tuberculose (Baccharis dracunculifolia, Centella asiatica, Lantana camara, Pterodon emarginatus). Os ensaios foram realizados em microplacas com resazurina contra duas espécies do Complexo Mycobacteriumtuberculosis e 3 espécies de micobactérias não tuberculosas. Os resultados mostraram o extrato hexânico e o óleo essencial de frutos de P.emarginatus como potenciais fontes para drogas antimicobacterianas contra quatro espécies de micobactérias testadas. A fração hexânica do extrato metanólico das folhas de C. asiatica também apresentou significativa inibição do crescimento de micobactérias apenas contra M.chelonae. Em conclusão, foi possível contribuir para as investigações de antimicobacterianos por apresentar três novas amostras de plantas com atividade antimicrobiana significativa contra quatro Mycobacterium spp e sugerir a realização de estudos futuros sobre as propriedades antimicobacterianas de frutos de P. emarginatus.

Monoaminergic drugs for motor recovery after ischemic stroke.

Today, administering rTPA thrombolytic therapy within the first hours of a stroke is the only validated drug therapy for improving the spontaneous--and most of the time incomplete--recovery of neurological functions post-stroke. However in the past decade, thanks in part to the considerable advances of neuroimaging techniques, we have learned that spontaneous recovery of neurological functions was associated with a wide intracerebral reorganization of the damaged human brain. The question of whether lesioned-brain plasticity can be modulated by external factors like pharmacological agents is now addressed in the hope of improving recovery and reducing the chronic impairments of stroke patients. In this paper, we review the preclinical and clinical evidence for a direct action of SSRIs in promoting recovery in ischemic stroke patients.

Cytotoxicity and expression of genes involved in the cellular stress response and apoptosis in mammalian fibroblast exposed to cotton cellulose nanofibers.

Cellulose nanofibers (CNF) have mechanical properties that make them very attractive for applications in the construction of polymeric matrices, drug delivery and tissue engineering. However, little is known about their impact on mammalian cells. The objective of this study was to evaluate the cytotoxicity of CNF and their effect on gene expression of fibroblasts cultured in vitro. The morphology of CNF was analyzed by transmission electron microscopy and the surface charge by Zeta potential. Cell viability was analyzed by flow cytometry assay and gene expression of biomarkers focused on cell stress response such as Heat shock protein 70.1 (HSP70.1) and Peroxiredoxin 1 (PRDX1) and apoptosis as B-cell leukemia (BCL-2) and BCL-2 associated X protein (BAX) by RT-PCR assay. Low concentrations of CNF (0.02-100 µg ml(-1)) did not cause cell death; however, at concentrations above 200 µg ml(-1), the nanofibers significantly decreased cell viability (86.41 ± 5.37%). The exposure to high concentrations of CNF (2000 and 5000 µg ml(-1)) resulted in increased HSP70.1, PRDX1 and BAX gene expression. The current study concludes that, under the conditions tested, high concentrations (2000 and 5000 µg ml(-1)) of CNF cause decreased cell viability and affect the expression of stress- and apoptosis-associated molecular markers.

Use of antidepressant medications to improve outcomes after stroke.

Interest in the use of antidepressants after stroke has been renewed by better knowledge of poststroke depression, but mainly by the capacity of some of them to promote functional recovery of nondepressed subjects. Recombinant tissue plasminogen activator thrombolysis within the first few hours after the stroke is currently the only validated treatment able to improve the spontaneous--and most of the time incomplete--recovery of neurological functions after stroke. However, we have learned from research over the last decade, in part based on the considerable improvement of neuroimaging techniques, that spontaneous recovery of neurological functions is associated with a large intracerebral reorganization of the damaged human brain. The question of whether lesioned-brain plasticity can be modulated by external factors such as pharmacological antidepressant agents is now being addressed with the aim of improving recovery and reducing the final disability of patients. Poststroke depression is known to be frequent and deleterious for patient outcome. We review the interest in the use of antidepressants after stroke in classic but often neglected poststroke depression and we strongly underline the action of some antidepressants in promoting functional recovery of nondepressed patients after stroke.

Altered neurotrophin, neuropeptide, cytokines and nitric oxide levels in autism.

INTRODUCTION: Modifications in neurotrophins, neuropeptides, cytokines and nitric oxide (NO) levels in autism may represent different biological aspects of the disease. In the present study we investigate simultaneously all these variables as an attempt to clarify their interrelationships in autism. METHODS: Plasma levels of vasoactive intestinal peptide (VIP), neurotrophin-3 (NT-3), cytokines and nitric oxide (NO) were determined in children with DSM-IV autistic disorder (n = 24) and in age- and gender-matched healthy controls (n = 24). VIP, NT-3, IFN-γ and IL-1ß levels were measured by ELISA, TNF-α, IL-10, IL-6, IL-4, IL-2 were evaluated by fl ow cytometry, and NO by Griess reaction. RESULTS: Plasma levels of VIP, IFN-γ and NO were significantly higher and NT-3 plasma levels were significantly lower in children with autism, compared to the healthy subjects. In children with autism there was a positive correlation between plasma levels of NO and IFN-γ. DISCUSSION: Our results indicate the presence of altered levels of neurotrophin and neuropeptide in infantile autism and provide additional evidence that higher levels of IFN-γ may be associated with increased oxidative stress in autism.

Eficácia e toxicidade do pó comercial de Hoodia gordonii (Masson) swet ex decne utilizado no tratamento da obesidade / Efficacy and toxicity of Hoodia gordonii commercial powder used to combat obesity

A obesidade é atualmente o principal problema de saúde em países desenvolvidos e em desenvolvimento. Diversos recursos terapêuticos têm sido empregados para o tratamento da obesidade destacando-se os fitoterápicos, consagrados pelo conhecimento popular. Nesse contexto, a planta Hoodia gordonii tem despertado atualmente grande interesse mundial, principalmente pelas recentes descobertas e comprovações científicas da inibição do apetite e da sede pelo glicosídeo ativo P57 isolado de espécies da planta. Apesar disso, tais efeitos ainda não foram avaliados e comprovados em amostras comerciais do pó de H. gordonii (PHG), não existindo evidências científicas que garantam a sua eficácia e segurança. Portanto, o objetivo deste trabalho foi realizar ensaios biológicos com ratos para avaliar a atividade farmacológica e a toxicidade de amostras comerciais do pó de H. gordonii. As amostras foram administradas por gavagem em doses equivalentes a 20 vezes as recomendadas para humanos em ratas Wistar durante 4 semanas sendo avaliados os parâmetros indicadores do efeito terapêutico. Após as 4 semanas, os animais foram sacrificados, e amostras de sangue e órgãos foram coletados e submetidos à avaliação dos indicadores metabólicos, endócrinos, hematológicos e histopatológicos. Os resultados demonstraram que para todos os parâmetros avaliados não houve diferenças significativas entre o grupo controle que recebeu somente solução salina estéril e os grupos tratados com PHG indicando que os mesmos, apesar de não apresentarem quaisquer indícios de toxicidade, são incapazes de produzir os supostos efeitos de inibição de apetite e consequente tratamento da obesidade.

Obesity is currently the main health problem in developed and developing countries. Several therapeutic methods have been employed for the treatment of obesity, especially herbal medicines, highlighted by popular knowledge. In this context, the plant Hoodia gordonii has currently aroused great interest worldwide, especially for recent discoveries and scientific proof of inhibition of appetite and thirst by the active glycoside P57 isolated from plant species. Nevertheless, such effects have not been evaluated and proven for commercial samples of H. gordonii powder (PHG), with no scientific evidence to ensure its effectiveness and safety. Therefore, the aim of this study was to conduct biological tests with rats to evaluate the pharmacological activity and toxicity of commercial samples of H. gordonii powder. The samples were administered through gavage, at doses equivalent to 20 times those recommended for humans, in female Wistar rats during 4 weeks for evaluation of the parameters indicative of therapeutic efficacy. After 4 weeks, the animals were sacrificed and blood and organ samples were collected and subjected to the evaluation of metabolic, endocrine, hematological and histopathological indicators. Results showed that for all evaluated parameters, there were no significant differences between the control group that only received sterile saline solution and the groups treated with PHG, indicating that the latter, although presenting no evidence of toxicity, are unable to produce the alleged effects of appetite inhibition and subsequent obesity treatment.

Body mass index increase, serum leptin, adiponectin, neuropeptide Y and lipid levels during treatment with olanzapine and haloperidol.

INTRODUCTION: Body mass index (BMI) increase is an undesired effect associated with antipsychotics, and crucial for patients' global health and treatment compliance. We aimed to investigate the relation between BMI during olanzapine or haloperidol treatments and leptin, neuropeptide Y (NPY), adiponectin and lipid serum levels. METHODS: In this 9-month, randomized and naturalist study, 34 male patients, 18 on olanzapine and 16 on haloperidol group were enrolled, all were under monotherapy. Patient outcome was evaluated with positive and negative syndrome scale (PANSS) at every 3-month period. In each visit, BMI, leptin, NPY, lipid, olanzapine or haloperidol levels were also monitored. RESULTS AND DISCUSSION: Leptin levels positively correlated with BMI in olanzapine (r=0.64, p<0.001) and haloperidol (r=0.73, p<0.001) groups; only in olanzapine patients, the former also correlated with PANSS score (r=0.54, p<0.05). NPY levels negatively correlated with olanzapine levels (r=− 0.65, p<0.01). Adiponectin levels had not significantly varied. CONCLUSION: Antipsychotics probably interfere on leptin and NPY signalling ways and disturb these hormones in eating behaviour control.

Etiologic investigation of ischemic stroke in young adults.

OBJECTIVES: We attempted to classify causes of ischemic stroke in young adults using a progressive diagnostic algorithm and the ASCO (atherosclerosis, small-vessel disease, cardiac source, other cause) classification system. METHODS: Patients aged 16-54 years consecutively treated for acute ischemic stroke in a tertiary stroke unit were included in this retrospective analysis. Causes of stroke were classified using the ASCO system, which assigns a graded level of likelihood to each potential cause in individual patients. The initial etiologic workup included brain imaging, magnetic resonance or CT angiography of cerebral and cervical vessels, EKG, and routine blood studies. Patients without a definite cause of ischemic stroke after initial evaluation underwent transesophageal echocardiography. RESULTS: We included 318 patients (195 men and 123 women); 131 patients were aged 16-44 years, and 187 were aged 45-54 years. A definite cause of stroke (ASCO grade 1) could be identified in 145 patients (45.5%). An uncertain cause of stroke (ASCO grade 2) was found in 59 (18.5%) further patients. Most (130 of 145) definite causes were identified by initial evaluation. The 2 major definite or uncertain causes of stroke were patent foramen ovale associated with atrial septal aneurysm (PFO-ASA) (20 of 131 [15.3%]) and dissection of the cervical or cerebral artery (19 of 131 [14.5%]) in patients aged 16-44 years and large-vessel atherosclerosis (37 of 187 [19.8%]) and PFO-ASA (23 of 187 [12.3%]) in patients aged 45-54 years. CONCLUSIONS: Our findings suggest that PFO-ASA may be a major cause of ischemic stroke in young adults.