The two synthetic cannabinoid compounds 4'-F-CBD and HU-910 efficiently restrain inflammatory responses of brain microglia and astrocytes.

To study the anti-inflammatory potential of the two synthetic cannabinoids 4'-F-CBD and HU-910, we used post-natal brain cultures of mouse microglial cells and astrocytes activated by reference inflammogens. We found that 4'-F-CBD and HU-910 efficiently curtailed the release of TNF-α, IL-6, and IL-1ß in microglia and astrocytes activated by the bacterial Toll-Like Receptor (TLR)4 ligand LPS. Upon LPS challenge, 4'-F-CBD and HU-910 also prevented the activation of phenotypic activation markers specific to microglia and astrocytes, that is, Iba-1 and GFAP, respectively. In microglial cells, the two test compounds also efficiently restrained LPS-stimulated release of glutamate, a non-cytokine inflammation marker for these cells. The immunosuppressive effects of the two cannabinoid compounds were concentration-dependent and observable between 1 and 10 µM. These effects were not dependent on cannabinoid or cannabinoid-like receptors. Both 4'-F-CBD and HU-910 were also capable of restraining the inflammogenic activity of Pam3CSK4, a lipopeptide that activates TLR2, and of BzATP, a prototypic agonist of P2X7 purinergic receptors, suggesting that these two cannabinoids could exert immunosuppressive effects against a variety of inflammatory stimuli. Using LPS-stimulated microglia and astrocytes, we established that the immunosuppressive action of 4'-F-CBD and HU-910 resulted from the inhibition of ROS produced by NADPH oxidase and subsequent repression of NF-κB-dependent signaling events. Our results suggest that 4'-F-CBD and HU-910 may have therapeutic utility in pathological conditions where neuroinflammatory processes are prominent.

Doxycycline attenuates l-DOPA-induced dyskinesia through an anti-inflammatory effect in a hemiparkinsonian mouse model.

The pharmacological manipulation of neuroinflammation appears to be a promising strategy to alleviate l-DOPA-induced dyskinesia (LID) in Parkinson's disease (PD). Doxycycline (Doxy), a semisynthetic brain-penetrant tetracycline antibiotic having interesting anti-inflammatory properties, we addressed the possibility that this compound could resolve LID in l-DOPA-treated C57BL/6 mice presenting either moderate or intermediate lesions of the mesostriatal dopaminergic pathway generated by intrastriatal injections of 6-OHDA. Doxy, when given subcutaneously before l-DOPA at doses of 20 mg kg-1 and 40 mg kg-1, led to significant LID reduction in mice with moderate and intermediate dopaminergic lesions, respectively. Importantly, Doxy did not reduce locomotor activity improved by l-DOPA. To address the molecular mechanism of Doxy, we sacrificed mice with mild lesions 1) to perform the immunodetection of tyrosine hydroxylase (TH) and Fos-B and 2) to evaluate a panel of inflammation markers in the striatum, such as cyclooxygenase-2 and its downstream product Prostaglandin E2 along with the cytokines TNF-α, IL-1ß and IL-6. TH-immunodetection revealed that vehicle and Doxy-treated mice had similar striatal lesions, excluding that LID improvement by Doxy could result from neurorestorative effects. Importantly, LID inhibition by Doxy was associated with decreased Fos-B and COX-2 expression and reduced levels of PGE2, TNF-α, and IL-1ß in the dorsolateral striatum of dyskinetic mice. We conclude 1) that Doxy has the potential to prevent LID regardless of the intensity of dopaminergic lesioning and 2) that the anti-inflammatory effects of Doxy probably account for LID attenuation. Overall, the present results further indicate that Doxy might represent an attractive and alternative treatment for LID in PD.

Neuroprotective Effects of a Novel Demeclocycline Derivative Lacking Antibiotic Activity: From a Hit to a Promising Lead Compound.

The antibiotic tetracycline demeclocycline (DMC) was recently reported to rescue α-synuclein (α-Syn) fibril-induced pathology. However, the antimicrobial activity of DMC precludes its potential use in long-term neuroprotective treatments. Here, we synthesized a doubly reduced DMC (DDMC) derivative with residual antibiotic activity and improved neuroprotective effects. The molecule was obtained by removal the dimethylamino substituent at position 4 and the reduction of the hydroxyl group at position 12a on ring A of DMC. The modifications strongly diminished its antibiotic activity against Gram-positive and Gram-negative bacteria. Moreover, this compound preserved the low toxicity of DMC in dopaminergic cell lines while improving its ability to interfere with α-Syn amyloid-like aggregation, showing the highest effectiveness of all tetracyclines tested. Likewise, DDMC demonstrated the ability to reduce seeding induced by the exogenous addition of α-Syn preformed fibrils (α-SynPFF) in biophysical assays and in a SH-SY5Y-α-Syn-tRFP cell model. In addition, DDMC rendered α-SynPFF less inflammogenic. Our results suggest that DDMC may be a promising drug candidate for hit-to-lead development and preclinical studies in Parkinson's disease and other synucleinopathies.

Doxycycline Interferes With Tau Aggregation and Reduces Its Neuronal Toxicity.

Tauopathies are neurodegenerative disorders with increasing incidence and still without cure. The extensive time required for development and approval of novel therapeutics highlights the need for testing and repurposing known safe molecules. Since doxycycline impacts α-synuclein aggregation and toxicity, herein we tested its effect on tau. We found that doxycycline reduces amyloid aggregation of the 2N4R and K18 isoforms of tau protein in a dose-dependent manner. Furthermore, in a cell free system doxycycline also prevents tau seeding and in cell culture reduces toxicity of tau aggregates. Overall, our results expand the spectrum of action of doxycycline against aggregation-prone proteins, opening novel perspectives for its repurposing as a disease-modifying drug for tauopathies.

CMT-3 targets different α-synuclein aggregates mitigating their toxic and inflammogenic effects.

Parkinson's disease (PD) is a neurodegenerative disorder for which only symptomatic treatments are available. Repurposing drugs that target α-synuclein aggregation, considered one of the main drivers of PD progression, could accelerate the development of disease-modifying therapies. In this work, we focused on chemically modified tetracycline 3 (CMT-3), a derivative with reduced antibiotic activity that crosses the blood-brain barrier and is pharmacologically safe. We found that CMT-3 inhibited α-synuclein amyloid aggregation and led to the formation of non-toxic molecular species, unlike minocycline. Furthermore, CMT-3 disassembled preformed α-synuclein amyloid fibrils into smaller fragments that were unable to seed in subsequent aggregation reactions. Most interestingly, disaggregated species were non-toxic and less inflammogenic on brain microglial cells. Finally, we modelled the interactions between CMT-3 and α-synuclein aggregates by molecular simulations. In this way, we propose a mechanism for fibril disassembly. Our results place CMT-3 as a potential disease modifier for PD and possibly other synucleinopathies.

Contributive Role of TNF-α to L-DOPA-Induced Dyskinesia in a Unilateral 6-OHDA Lesion Model of Parkinson's Disease.

Our present objective was to better characterize the mechanisms that regulate striatal neuroinflammation in mice developing L-DOPA-induced dyskinesia (LID). For that, we used 6-hydroxydopamine (6-OHDA)-lesioned mice rendered dyskinetic by repeated intraperitoneal injections of 3,4-dihydroxyphenyl-L-alanine (L-DOPA) and quantified ensuing neuroinflammatory changes in the dopamine-denervated dorsal striatum. LID development was associated with a prominent astrocytic response, and a more moderate microglial cell reaction restricted to this striatal area. The glial response was associated with elevations in two pro-inflammatory cytokines, tumor necrosis factor-α (TNF-α) and interleukin-1ß. Treatment with the phytocannabinoid cannabidiol and the transient receptor potential vanilloid-1 (TRPV-1) channel antagonist capsazepine diminished LID intensity and decreased TNF-α levels without impacting other inflammation markers. To possibly reproduce the neuroinflammatory component of LID, we exposed astrocyte and microglial cells in culture to candidate molecules that might operate as inflammatory cues during LID development, i.e., L-DOPA, dopamine, or glutamate. Neither L-DOPA nor dopamine produced an inflammatory response in glial cell cultures. However, glutamate enhanced TNF-α secretion and GFAP expression in astrocyte cultures and promoted Iba-1 expression in microglial cultures. Of interest, the antidyskinetic treatment with cannabidiol + capsazepine reduced TNF-α release in glutamate-activated astrocytes. TNF-α, on its own, promoted the synaptic release of glutamate in cortical neuronal cultures, whereas cannabidiol + capsazepine prevented this effect. Therefore, we may assume that the release of TNF-α by glutamate-activated astrocytes may contribute to LID by exacerbating corticostriatal glutamatergic inputs excitability and maintaining astrocytes in an activated state through a self-reinforcing mechanism.

Succinobucol, a Non-Statin Hypocholesterolemic Drug, Prevents Premotor Symptoms and Nigrostriatal Neurodegeneration in an Experimental Model of Parkinson's Disease.

Parkinson's disease (PD) is a neurodegenerative disorder characterized by non-motor and motor disabilities. This study investigated whether succinobucol (SUC) could mitigate nigrostriatal injury caused by intranasal 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) administration in mice. Moreover, the effects of SUC against MPTP-induced behavioral impairments and neurochemical changes were also evaluated. The quantification of tyrosine hydroxylase-positive (TH+) cells was also performed in primary mesencephalic cultures to evaluate the effects of SUC against 1-methyl-4-phenylpyridinium (MPP+) toxicity in vitro. C57BL/6 mice were treated with SUC (10 mg/kg/day, intragastric (i.g.)) for 30 days, and thereafter, animals received MPTP infusion (1 mg/nostril) and SUC treatment continued for additional 15 days. MPTP-infused animals displayed significant non-motor symptoms including olfactory and short-term memory deficits evaluated in the olfactory discrimination, social recognition, and water maze tasks. These behavioral impairments were accompanied by inhibition of mitochondrial NADH dehydrogenase activity (complex I), as well as significant decrease of TH and dopamine transporter (DAT) immunoreactivity in the substantia nigra pars compacta and striatum. Although SUC treatment did not rescue NADH dehydrogenase activity inhibition, it was able to blunt MPTP-induced behavioral impairments and prevented the decrease in TH and DAT immunoreactivities in substantia nigra (SN) and striatum. SUC also suppressed striatal astroglial activation and increased interleukin-6 levels in MPTP-intoxicated mice. Furthermore, SUC significantly prevented the loss of TH+ neurons induced by MPP+ in primary mesencephalic cultures. These results provide new evidence that SUC treatment counteracts early non-motor symptoms and neurodegeneration/neuroinflammation in the nigrostriatal pathway induced by intranasal MPTP administration in mice by modulating events downstream to the mitochondrial NADH dehydrogenase inhibition.

Estudo antropométrico das assimetrias craniofaciais na craniossinostose coronal unilateral / Anthropometric study of craniofacial asymmetry in unilateral coronal synostosis

INTRODUÇÃO: A craniossinostose coronal unilateral (CCU) é a ossificação prematura da sutura coronal unilateralmente e provoca uma deformidade em 3 dimensões, que pode afetar o crânio e as órbitas. O objetivo do presente trabalho foi aferir e comparar a assimetria do crânio e face dos pacientes portadores de CCU no período pré e pós-operatório. MÉTODO: Nove pacientes foram submetidos à correção da craniossinostose coronal unilateral, entre janeiro de 2007 a dezembro de 2010. Quatro pacientes foram do sexo feminino e cinco do sexo masculino. Foram aferidas medidas da região craniofacial para quantificar o índice de assimetria craniofacial no período pré-operatório e compará-lo com o período pós-operatório. O índice de assimetria craniofacial (IAC) foi determinado pela diferença entre as medidas craniofaciais diagonais obtidas com o goniômetro. RESULTADOS: A idade média dos pacientes submetidos à correção de CCU foi de 2 anos e 1 mês. O tempo médio de cirurgia foi de 2 horas e 46 minutos. O volume médio de sangue transfundido foi de 280 ml. A média das diferenças das medidas diagonais obtidas com o goniômetro no período pré-operatório (IAC) foi de 1,045 e do pós-operatório de 1,009 (p=0,0109), indicando forte tendência à simetria craniofacial após o ato cirúrgico. CONCLUSÃO: O tratamento proposto para as CCU foi eficiente na obtenção de simetria craniofacial. Foi necessária a sobrecorreção das estruturas ósseas para obtenção de simetria óssea no período pós-operatório.

INTRODUCTION: Unilateral coronal synostosis (UCS) is a premature fusion of the coronal suture and leads to a three-dimensional deformity that affects the cranium and orbits. The aim of this study was to compare craniofacial skeleton asymmetry preoperatively and postoperatively. METHODS: This is a retrospective study with nine patients who underwent treatment of unilateral coronal synostosis, between January 2007 and December 2010. Four patients were female and five male. The craniofacial measurements were done to quantify an index of craniofacial asymmetry preoperatively and compare to those obtained postoperatively. The craniofacial index (CI) was obtained by calculating the difference between the higher oblique measurement of the craniofacial skeleton and lower oblique measurement of the craniofacial skeleton. RESULTS: The average age of the patients who had undergone to unilateral coronal synostosis correction was 2 years and 1 month. The average time of surgery was 2 hours and 46 minutes. The blood volume transfused was 280 cc. The CI preoperatively was 1.045 and postoperatively was 1.009 (p=0.0109), indicating a tendency to craniofacial symmetry. CONCLUSION: The treatment of UCS was efficient. Bone over correction was necessary to achieve its goal of symmetry in the postoperative period.

Desvelando o cotidiano dos cuidadores informais de idosos / Revelando el cotidiano de los cuidadores informales de ancianos / Unveiling the routine of informal caregivers for the elderly

Este artigo objetivou descrever como os cuidadores informais de idosos interpretam e constroem o seu cotidiano. Estudo qualitativo, descritivo-exploratório, tendo como orientação teórico-metodológica, a dialética. O instrumento de coleta de dados foi a entrevista individual, com cinco cuidadores de idosos dependentes em domicílios de um Programa Saúde da Família, em Montes Claros Minas Gerais. Resultados evidenciaram situações adversas enfrentadas pelos cuidadores relacionadas ao sofrimento e sacrifícios na prestação dos cuidados e a falta de assistência para atender as necessidades do ser cuidado e do ser cuidador. Porém, exercem o cuidar com amor, carinho e dedicação, utilizando a fé e a espiritualidade como busca do equilíbrio biopsicossocial. Recomenda-se que esses profissionais tenham um olhar respeitoso e cooperativo ao trabalho desses cuidadores.

This article intends to describe how the informal caregivers interpret and build their daily routine. It is a qualitative study using dialectics as the theoretical-methodological framework. The instrument for data colection was individual interviews with five caregivers for elderly in homes in the Family Health Program, in Montes Claros, Minas Gerais State, Brazil. The results demonstrated adverse situations faced by caregivers in terms of suffering and sacrifice in providing care and a lack of support meeting the needs of the caregivers and those receiving care. However, they provided care with love and dedication using faith and spirituality in search of bio-psychosocial balance. It is recommended that health workers should have a respectful and cooperative approach to the work of these informal caregivers for the elderly.

El propósito del presente artículo ha sido describir cómo los cuidadores informales de ancianos interpretan y construyen su rutina. Se trata de un estudio cualitativo, descriptivo y exploratorio, con orientación teórico-metodológica. La recogida de datos se realizó mediante entrevistas individuales a cinco cuidadores de personas mayores dependientes que viven en domicilios incluidos en un Programa de Salud de la Familia de Montes Claros, Estado de Minas Gerais. Los resultados revelan que los cuidadores enfrentan situaciones hostiles que tienen que ver con sufrimiento y sacrificios en la prestación de los cuidados y con la falta de asistencia para atender a las necesidades del anciano y del cuidador. Pero, ejercen su tarea con amor, cariño y dedicación y, a través de la fe y de la espiritualidad, buscan su equilibrio biopsicosocial. Se aconseja que el trabajo de estos profesionales sea considerado com respecto y cooperación.

Atypical parkinsonism in the Caribbean island of Guadeloupe: etiological role of the mitochondrial complex I inhibitor annonacin.

On the French West Indian island of Guadeloupe, atypical parkinsonian patients represent two-thirds of all cases of parkinsonism, which is exceptionally frequent compared to epidemiological data from European countries where atypical parkinsonism accounts for only approximately 5% of all cases. The clinical entity was a unique combination of levodopa-resistant parkinsonism, tremor, myoclonus, hallucinations, REM sleep behavior disorder and fronto-subcortical dementia. Based on the presence or the absence of supranuclear gaze palsy, two subgroups of patients were distinguished. In patients with oculomotor signs that came to autopsy, neuronal loss was found to predominate in the substantia nigra and the striatum but other brain areas were also affected, including the frontal cortex. In addition, tau-containing lesions were detected throughout the brain. Epidemiological data suggested a close association of the disease with the regular consumption of soursop, a tropical annonaceous plant. Experimental studies performed in midbrain cell cultures identified annonacin, a selective mitochondrial complex I inhibitor contained in the fruit and leaves of soursop, as a probable etiological factor. Consistent with this view, chronic administration of annonacin to rats through Alzet osmotic minipumps showed that annonacin was able to reproduce the brain lesions characteristic of the human disease.

Classificação e resultado cirúrgico na deformidade labial secundária do paciente fissurado

Relatar a experiência na abordagem e no tratamento cirúrgico da deformidade secundária do lábio fissurado segundo classificação simplificada e avaliação de resultados após procedimento crúrgico. Cinqüenta pacientes foram submetidos a procedimento cirurgico para correção de deformidade sucndária do lábio fissurado. As deformidades labiais foram classificadas antes do procedimento cirúrgico em leve, moderada e grave, utilizando-se um sistema de pontuação baseado em alterações estéticas do lábio, o resultado estético da cirurgia foi avaliadopor meio de fotos antes e após o procedimento. Os resultados foram avaliados, os pacientes que tiveram melhora de pelo menos uma das alterações estéticas após procedimento foram classificados como resultado satisfatório e quando não houve melhora do resultado círúrgico foram classificados insatisfatórios. O seguimento dos pacientes variou de 4 meses a 16 meses e o trabalho foi enviado para apreciação de comissão de ética do hospital. A idade dos pacientes variou de 1 ano a 55 anos, com média de 15,12 anos. Vinte e quatro (48%) pacientes foram classificados como deformidade grave, 18 (36%) como deformidade moderada e 8 (16%) como deformidade leve. Trinta e oito (76%) pacientes tiveram resultado satisfatório segundo o critério de pontuação e 12 (24%), insatisfatório. Todos pacientes com deformidade leve segundo a classificação tiveram resultado satisfatório , 7 (58,3%) com deformidade moderada tiveram resultado insatisfatório e 5 (41,7) com deformidade grave operatório. Os melhores resultados foram obtidos com deformidades leves e em cirurgias onde houve retalhos com grande mobilização de tecidos.

Displasia craniofacial: um caso difícil

Objetivo: Relatar a conduta frente a um caso de displasia craniofacial de grande tamanho acometendo estruturas nobres da face e comprometendo visão e vias aéreas superiores. Relato de caso clínico de uma displasia craniofacial e revisão da literatura. Relato do caso: RSJ, 11 anos, natural e precedente de São Miguel Arcanjo - SP, paciente compareceu ao ambulatório de Cirurgia Plástica em 24/04/2006, devido à extensa massa tumoral na região malar esquerda com crescimento progressivo. Ele já havia realizado duas cirurgias para ressecção tumoral em outro serviço, no momento apresentava recidiva tumoral. Ao exame físico, havia presença de extensa massa tumoral de consistência endurecida, aderida a plano profundo, deformando toda maxila, osso zigomático, arcabouço nasal, palato anterior e assoalho da órbita esquerda, apresentava distopia orbitária e compressão do globo ocular. Realizou exames complementares: o laudo anatomopatológico possibilitou o diagnóstico de displasia óssea, a eletroneuromiografia com quadro sugestivo de processo neurológico periférico compremetendo o território do nervo facial esquerdo, principalmente o ramo temporal e zigomático a tomografia computadorizada e a angiografia evidenciaram extensa massa óssea com vascularização acentuada. Em procedimento cirúrgico no dia 10/01/2007, realizou-se a ressecção de massa óssea que comprometia maxila, arco zigomático, zigoma, nariz, palato anterior e todo assoalho orbitário; optou-se pela reconstrução do assoalho da órbita esquerda com enxerto ósseo de crista ilíaca e utilizou-se o retalho de pele excedente para reconstrução dos tecidos moles. No dia 21/05/2007, foi realizada suspensão do terço médio da hemifase esquerda e cantopexia medial esquerda e, em 15/08/2007, o paciente passou por novo procedimento cirúrgico para a correção de entropia...

Gordura centrifugada nas deformidades craniofaciais

Objetivo: Relatar experiência com gordura centrifugada para correção de deformidades craniofaciais por deformidade óssea ou defeitos de partes moles. Método: Trinta e dois pacientes com deformidades craniofaciais realizaram enxertia de gordura em face nos anos de 2006 e 2007, utilizando-se o método da centrifugação como coleta. Os resultados foram avaliados por meio de foto pré e pós-procedimento cirúrgico e os resultados classificados como satisfatório e insatisfatório. Os pacientes classificados como resultado satisfatório foram aqueles que não necessitaram de novo procedimento e insatisfatórios aqueles que necessitaram de novo procedimento. O seguimento dos pacientes variou de 6 meses a 30 meses e o trabalho foi enviado para apreciação de comissão de ética do hospital. Resultados: Trinta e dois pacientes submetidos a procedimento cirúrgico para correção de deformidades faciais, 8 (25%) pacientes com depressões em face pós-trauma, 6 (18,7%) pacientes com síndrome de Parry-Rombeg, 7 (21,9%) com fissura labial, 2 (6,2%) fissuras raras de face, 3 (9,4%) com síndrome de Treacher-Collins, 2 (6,2%) com assimetria facial congênita, 2 (6,2%) com esclerodermia e 2 (6,2%) com seqüela de tumor em face. Quatorze (43,75%) pacientes tiveram resultado satisfatório no primeiro procedimento cirúrgico e 18 (56,25%) necessitaram de novo procedimento...

Anquilose da articulação têmporo-mandibular (ATM): como tratamos no Instituto SOBRAPAR

Introdução: A anquilose da articulação têmpero-mandibular (ATM) é uma doença grave, que traz ao paciente dificuldades de alimentação, doenças ortodônticas e déficit do crescimento facial. Possui várias causas, desde congênitas até seqüelas de trauma. Seu diagnóstico e tratamentos são complexos, muitas vezes com recidivas e resultados não muito satisfatórios. O principal tratamento é o cirúrgico, apesar de ainda não existir consenso quanto ao procedimento e idade ideais. Método: Foram avaliados seis pacientes com anquilose de ATM submetidos a procedimento cirúrgico para correção da deformidade, sendo avaliados quanto a causas, tipo e número de procedimentos realizados e suas complicações. Resultados: Dos seis pacientes avaliados, quatro eram do sexo feminino e dois, do sexo masculino. Identificou-se causa congênita bilateral em dois pacientes com micrognatia associada. Dois pacientes tiveram infecção perinatal (otite e de mandíbula), um paciente relatou tocotrauma e uma paciente foi submetida a radioterapia por osteossarcoma na mandíbula. Um paciente havia sido submetido a nove cirurgias prévias e foi submetido a distração óssea de corpo de mandíbula bilateral com recidiva da anquilose. O procedimento cirúrgico realizado foi de artroplastia com interposição de músculo temporal. Um paciente que foi submetida a interposição de silastic apresentou rejeição, sendo necessária sua retirada. Foi realizada cirurgia complementar de distração óssea em quatro pacientes. As complicações encontradas foram infecção, fístula artério-venosa e parestesia transitória...

Retalho de abbé na queiloplastia secundária do paciente fissurado bilateral

Objetivo: Avaliar a possibilidade de uso do retalho de Abbé na queiloplastia secundária do paciente fissurado bilateral. Método: Foram avaliados 10 pacientes com seqüela de fissura lábio-palatina bilateral, de janeiro 2001 a janeiro 2007, com queixas diversas quanto ao encurtamento do pró-labio, sulco gengivo-labial curto, hipertrofia cicatricial, dificuldade para uso de aparelho ortodôntico, alteração da coluna filtral e do arco do cupido. Os pacientes apresentavam seguimento mínimo de 3 meses, sendo avaliados quanto a sexo, idade, tempo de autonomização do retalho, complicações, número de intervenções, comprimento e largura do retalho. A qualidade dos resultados foi avaliada conforme a presença ou não de complicações. Técnica cirúrgica: Marcação linha média do lábio inferior com limitação eqüilateral para largura de filtro de 8-10 mm e comprimento variável, relacionando com o defeito individual, tanto em "V", "W" ou "Lambda". Retalho baseado no pedículo vascular da artéria labial inferior, ramo da artéria facial, que se mostra constante, e um retalho composto (pele, musculatura e mucosa). A liberação do pedículo vascular é realizada após a autonomização do retalho entre 10-21 dias. Resultados: Foram realizados 10 retalhos de Abbé, em 9 pacientes do sexo masculino e 1 do feminino, sendo necessárias 28 cirurgias para correção final dos lábios, média de 2,8 procedimentos por paciente, todos com resultados secundária do lábio em pacientes fissurados bilaterais selecionados com bons resultados e poucas complicações.

[Unveiling the routine of informal caregivers for the elderly]. / Desvelando o cotidiano dos cuidadores informais de idosos.

This article intends to describe how the informal caregivers interpret and build their daily routine. It is a qualitative study using dialectics as the theoretical-methodological framework. The instrument for data colection was individual interviews with five caregivers for elderly in homes in the Family Health Program, in Montes Claros, Minas Gerais State, Brazil. The results demonstrated adverse situations faced by caregivers in terms of suffering and sacrifice in providing care and a lack of support meeting the needs of the caregivers and those receiving care. However, they provided care with love and dedication using faith and spirituality in search of bio-psychosocial balance. It is recommended that health workers should have a respectful and cooperative approach to the work of these informal caregivers for the elderly.

Annonacin, a lipophilic inhibitor of mitochondrial complex I, induces nigral and striatal neurodegeneration in rats: possible relevance for atypical parkinsonism in Guadeloupe.

In Guadeloupe, epidemiological data have linked atypical parkinsonism with fruit and herbal teas from plants of the Annonaceae family, particularly Annona muricata. These plants contain a class of powerful, lipophilic complex I inhibitors, the annonaceous acetogenins. To determine the neurotoxic potential of these substances, we administered annonacin, the major acetogenin of A. muricata, to rats intravenously with Azlet osmotic minipumps (3.8 and 7.6 mg per kg per day for 28 days). Annonacin inhibited complex I in brain homogenates in a concentration-dependent manner, and, when administered systemically, entered the brain parenchyma, where it was detected by matrix-associated laser desorption ionization-time of flight mass spectrometry, and decreased brain ATP levels by 44%. In the absence of evident systemic toxicity, we observed neuropathological abnormalities in the basal ganglia and brainstem nuclei. Stereological cell counts showed significant loss of dopaminergic neurones in the substantia nigra (-31.7%), and cholinergic (-37.9%) and dopamine and cyclic AMP-regulated phosphoprotein (DARPP-32)-immunoreactive GABAergic neurones (-39.3%) in the striatum, accompanied by a significant increase in the number of astrocytes (35.4%) and microglial cells (73.4%). The distribution of the lesions was similar to that in patients with atypical parkinsonism. These data are compatible with the theory that annonaceous acetogenins, such as annonacin, might be implicated in the aetiology of Guadeloupean parkinsonism and support the hypothesis that some forms of parkinsonism might be induced by environmental toxins.

Toxicity of Annonaceae for dopaminergic neurons: potential role in atypical parkinsonism in Guadeloupe.

In the French West Indies there is an abnormally high frequency of levodopa-resistant parkinsonism, suggested to be caused by consumption of fruit and infusions of tropical plants, especially Annona muricata (corossol, soursop). To determine whether toxic substances from this plant can cause the neuronal degeneration or dysfunction underlying the syndrome, we exposed mesencephalic dopaminergic neurons in culture to the total extract (totum) of alkaloids from Annona muricata root bark and to two of the most abundant subfractions, coreximine and reticuline. After 24 hours, 50% of dopaminergic neurons degenerated with 18 microg/ml totum, 4.3 microg/ml (13 microM) coreximine, or 100 microg/ml (304 microM) reticuline. The effects of the alkaloid totum were not restricted to the population of dopaminergic cells since GABAergic neurons were also affected by the treatment. Nuclei in dying neurons showed DNA condensation or fragmentation, suggesting that neuronal death occurred by apoptosis. Cell death was not excitotoxic and did not require toxin uptake by the dopamine transporter. Neurodegeneration was attenuated by increasing the concentration of glucose in the culture medium, which also reduced the effect of the dopaminergic neurotoxin MPP+, a mitochondrial respiratory chain inhibitor. Toxin withdrawal after short-term exposure arrested cell death. Acute treatment with totum, coreximine, or reticuline reversibly inhibited dopamine uptake by a mechanism that was distinct from that causing neuronal death. GABA uptake was not reduced under the same conditions. This study suggests that alkaloids from A. muricata can modulate the function and the survival of dopaminergic nerve cells in vitro. It is therefore conceivable that repeated consumption could cause the neuronal dysfunction and degeneration underlying the West Indian parkinsonian syndrome.

Programa de proteçäo respiratória em fundiçöes / Respiratory protective program for foundries

Relata-se a experiência na implantaçäo de um programa de saúde ocupacional, destacando-se a sistemática e a metodologia desenvolvidas no programa de proteçäo respiratória, em três fundiçöes de empresa multinacional automobilística. Através de um grupo de trabalho composto por médicos do trabalho, engenheiros de segurança e um higienista industrial, foram levantadas as condiçöes e ambientes de trabalho, estabelecendo-se um processo de vigilância médica, o qual permitiu açöes preventivas e corretivas, tanto no que se refere a local de trabalho como no tocante à saúde do trabalhador. Relatam-se os resultados das avaliaçöes médicas e ambientais, além de fato relevante a respeito do uso de máscaras descartáveis, utilizadas como proteçäo respiratória. As conclusöes do programa confirmaram a necessidade de se estabelecer controles sobre o trabalhador e seu ambiente de trabalho em fundiçöes e a validade da realizaçäo de censos espirométricos ao longo do tempo