OBJETIVO: Elucidar o efeito da fisioterapia na Amplitude de Movimento Articular (ADM) e na fibrose muscular em animais GRMD. MÉTODOS: Estudo não randomizado, com grupo controle, cego, seis meses de intervenção, avaliação antes e depois da intervenção. Seis animais da raça Golden Retriever, distróficos, machos, média de idade 10,16±3,46 meses e peso de 17,75±6,01 kg foram separados em grupo tratado (n=3) e não tratado. Esses grupos de animais foram nomeados: G1=grupo tratado antes do tratamento; G2=grupo tratado após tratamento; G3=grupo não tratado antes do tratamento; G4=grupo não tratado após tratamento. O G1 participou do programa de fisioterapia que consistiu em um circuito de 300 metros com obstáculos. As ADMs do joelho, tarso, cotovelo e carpo foram avaliadas com goniômetro antes e após o tratamento. A área de colágeno do músculo vastus lateralis foi mensurada por histomorfometria, e a localização dos tipos de colágeno I, III e IV foi estudada por Imuno-histoquímica (IHC). RESULTADOS: Os valores da ADM do tarso do G2 apresentaram uma tendência a aumentar. A área de colágeno muscular foi diferente entre os grupos após o tratamento, e uma tendência ao aumento desses valores no G4 foi observada. Os colágenos dos tipos I e III foram os mais observados, constituindo feixes largos no perimísio nos dois grupos (G2 e G4). O colágeno do tipo I foi mais observado no endomísio do que o colágeno do tipo III. O colágeno do tipo IV foi observado apenas na lâmina basal. CONCLUSÃO: A Fisioterapia parece aumentar a ADM do tarso dos animais do grupo tratado sem aumentar a fibrose muscular.

OBJECTIVE: To elucidate the effect of physical therapy on joint range of motion (ROM) and muscle fibrosis in GRMD animals. METHODS: This was a nonrandomized blinded study with a control group, with six months of intervention evaluated beforehand and afterwards. Six dystrophic male Golden Retrievers of mean age 10.16±3.46 months and weight 17.75±6.01 kg were divided into a treated group (n=3) and an untreated group. These groups of dogs were named: G1=treated group before treatment; G2=treated group after treatment; G3=untreated group before treatment; and G4=untreated group after treatment. G1 underwent a physical therapy program that consisted of a 300-meter circuit with obstacles. Stifle, tarsal, elbow and carpal ROM were assessed using a goniometer before and after treatment. The area of collagen in the vastus lateralis muscle was measured using histomorphometry. The locations of collagen types I, III and IV were studied using immunohistochemistry. RESULTS: The tarsal ROM values in G2 presented an increasing trend. The area of muscle collagen differed between the groups after treatment and an increasing trend in these values was observed in G4. Collagen types I and III were the ones most frequently observed, forming broad bands in the perimysium of both G2 and G4. Type I collagen was observed in the endomysium more than type III collagen. Type IV collagen was observed only in the basal layer. CONCLUSION: Physical Therapy seemed to improve tarsal ROM in the treated group without increasing muscular fibrosis.

Muscular dystrophies are a heterogeneous group of genetically determined progressive disorders of the muscle with a primary or predominant involvement of the pelvic or shoulder girdle musculature. The clinical course is highly variable, ranging from severe congenital forms with rapid progression to milder forms with later onset and a slower course. In recent years, several proteins from the sarcolemmal muscle membrane (dystrophin, sarcoglycans, dysferlin, caveolin-3), from the extracellular matrix (alpha2-laminin, collagen VI), from the sarcomere (telethonin, myotilin, titin, nebulin), from the muscle cytosol (calpain 3, TRIM32), from the nucleus (emerin, lamin A/C, survival motor neuron protein), and from the glycosylation pathway (fukutin, fukutin-related protein) have been identified. Mutations in their respective genes are responsible for different forms of neuromuscular diseases. Protein analysis using Western blotting or immunohistochemistry with specific antibodies is of the utmost importance for the differential diagnosis and elucidation of the physiopathology of each genetic disorder involved. Recent molecular studies have shown clinical inter- and intra-familial variability in several genetic disorders highlighting the importance of other factors in determining phenotypic expression and the role of possible modifying genes and protein interactions. Developmental studies can help elucidate the mechanism of normal muscle formation and thus muscle regeneration. In the last fifteen years, our research has focused on muscle protein expression, localization and possible interactions in patients affected by different forms of muscular dystrophies. The main objective of this review is to summarize the most recent findings in the field and our own contribution.

As amiotrofias espinhais progressivas (SMAs) constituem as doenças degenerativas de origem genética letais mais comuns do sistema nervoso central e mais freqüentes dentre as doenças autossômicas recessivas após a mucoviscidose. A incidência estimada das SMAs é de aproximadamente 1:10.000 nativivos. Clinicamente, as SMAs são classificadas em mais grave (doença de Werdnig-Hoffmann, tipo I), intermediária (tipo II) e tardia e benigna (doença de Kugelberg-Welander, tipo III). O gene para os três tipos de SMAs foi mapeado no cromossomo 5 q11.2-13.3. Foram identificados dois genes candidatos na mesma região: SMN (sobrevida do neurônio motor) e NAIP (proteína inibidora de apoptose neuronal). Estudamos ambos genes em 87 pacientes brasileiros (20 tipo I,14 tipo II e 53 tipo III) pertencentes a 74 famílias, utilizando as técnicas de PCR e SSCP. Foi encontrada deleção nos exons 7 e/ou 8 do gene SMN em 69% das famílias: 16/20 na tipo I, 9/12 na tipo II e 26/42 na tipo III. Dentre as 51 famílias com deleção, 44 tiveram deleção nos exons 7 e 8 enquanto 7 tiveram deleção somente no exon 7. Deleção no exon 5 do gene NAIP foi encontrada em 7/20 na tipo I, 2/12 na tipo II e 1/42 na tipo III. Não foi encontrada deleção nos genes SMN e NAIP nos 112 progenitores, 26 irmandades assintomáticas e 104 controles normais. Não houve correlação entre deleção de um ou ambos genes com a gravidade do quadro clínico.

Spinal muscular atrophy (SMA), the second most common lethal autosomal recessive disorder, has an incidence of 1:10,000 newborns. SMA is divided into acute (Werdnig-Hoffmann disease, type I), intermediate (type II) and juvenile forms (Kugelberg-Welander disease, type III). The gene of all three forms of SMA maps to chromosome 5q 11.2-13.3. Two candidate genes, the survival motor neuron (SMN) gene and the neuronal apoptosis inhibitory protein (NAIP) gene, have been identified; SMN is deleted in most SMA patients. We studied both genes in 87 Brazilian SMA patients (20 type I, 14 type II and 53 type III) from 74 unrelated families, by using PCR and single strand conformation polymorphism (SSCP). Deletions of exons 7 and/or 8 of the SMN gene were found in 69% of the families: 16/20 in type I, 9/12 in type II and 26/42 in type III. Among 51 families with deletions, 44 had both exons deleted while seven had deletions only of exon 7. Deletions of exon 5 of the NAIP gene were found in 7/20 of type I, 2/12 of type II and 1/42 of type III patients. No deletion of SMN and NAIP genes was found in 112 parents, 26 unaffected sibs and 104 normal controls. No correlation between deletions of one or both genes and phenotype severity was found.

Genetic and environmental factors have been implicated in the development of Alzheimer's disease (AD), the most common form of dementia in the elderly. Mutations in 3 genes mapped on chromosomes 21, 14 and 1 are related to the rare early onset forms of AD while the <FONT FACE="Symbol">e</font>4 allele of the apolipoprotein E (APOE) gene (on chromosome 19) is the major susceptibility locus for the most common late onset AD (LOAD). Serotonin (5-hydroxytryptamine or 5-HT) is a key neurotransmitter implicated in the control of mood, sleep, appetite and a variety of traits and behaviors. Recently, a polymorphism in the transcriptional control region upstream of the 5-HT transporter (5-HTT) gene has been studied in several psychiatric diseases and personality traits. It has been demonstrated that the short variant(s) of this 5-HTT gene-linked polymorphic region (5-HTTLPR) is associated with a different transcriptional efficiency of the 5-HTT gene promoter resulting in decreased 5-HTT expression and 5-HT uptake in lymphocytes. An increased frequency of this 5-HTTLPR short variant polymorphism in LOAD was recently reported. In addition, another common polymorphic variation in the 5-HT2A and 5-HT2C serotonin receptor genes previously analyzed in schizophrenic patients was associated with auditory and visual hallucinations in AD. These observations suggest that the involvement of the serotonin pathway might provide an explanation for some aspects of the affective symptoms commonly observed in AD patients. In summary, research on genetic polymorphisms related to AD and involved in receptors, transporter proteins and the enzymatic machinery of serotonin might enhance our understanding of this devastating neurodegenerative disorder.