Quantitative Proteomic Analysis Reveals Metabolic Alterations, Calcium Dysregulation, And Increased Expression Of Extracellular Matrix Proteins In Laminin α2 Chain-deficient Muscle.

Congenital muscular dystrophy with laminin α2 chain deficiency (MDC1A) is one of the most severe forms of muscular disease and is characterized by severe muscle weakness and delayed motor milestones. The genetic basis of MDC1A is well known, yet the secondary mechanisms ultimately leading to muscle degeneration and subsequent connective tissue infiltration are not fully understood. In order to obtain new insights into the molecular mechanisms underlying MDC1A, we performed a comparative proteomic analysis of affected muscles (diaphragm and gastrocnemius) from laminin α2 chain-deficient dy(3K)/dy(3K) mice, using multidimensional protein identification technology combined with tandem mass tags. Out of the approximately 700 identified proteins, 113 and 101 proteins, respectively, were differentially expressed in the diseased gastrocnemius and diaphragm muscles compared with normal muscles. A large portion of these proteins are involved in different metabolic processes, bind calcium, or are expressed in the extracellular matrix. Our findings suggest that metabolic alterations and calcium dysregulation could be novel mechanisms that underlie MDC1A and might be targets that should be explored for therapy. Also, detailed knowledge of the composition of fibrotic tissue, rich in extracellular matrix proteins, in laminin α2 chain-deficient muscle might help in the design of future anti-fibrotic treatments. All MS data have been deposited in the ProteomeXchange with identifier PXD000978 (http://proteomecentral.proteomexchange.org/dataset/PXD000978).

Growth Factor Stimulation Improves The Structure And Properties Of Scaffold-free Engineered Auricular Cartilage Constructs.

The reconstruction of the external ear to correct congenital deformities or repair following trauma remains a significant challenge in reconstructive surgery. Previously, we have developed a novel approach to create scaffold-free, tissue engineering elastic cartilage constructs directly from a small population of donor cells. Although the developed constructs appeared to adopt the structural appearance of native auricular cartilage, the constructs displayed limited expression and poor localization of elastin. In the present study, the effect of growth factor supplementation (insulin, IGF-1, or TGF-β1) was investigated to stimulate elastogenesis as well as to improve overall tissue formation. Using rabbit auricular chondrocytes, bioreactor-cultivated constructs supplemented with either insulin or IGF-1 displayed increased deposition of cartilaginous ECM, improved mechanical properties, and thicknesses comparable to native auricular cartilage after 4 weeks of growth. Similarly, growth factor supplementation resulted in increased expression and improved localization of elastin, primarily restricted within the cartilaginous region of the tissue construct. Additional studies were conducted to determine whether scaffold-free engineered auricular cartilage constructs could be developed in the 3D shape of the external ear. Isolated auricular chondrocytes were grown in rapid-prototyped tissue culture molds with additional insulin or IGF-1 supplementation during bioreactor cultivation. Using this approach, the developed tissue constructs were flexible and had a 3D shape in very good agreement to the culture mold (average error <400 µm). While scaffold-free, engineered auricular cartilage constructs can be created with both the appropriate tissue structure and 3D shape of the external ear, future studies will be aimed assessing potential changes in construct shape and properties after subcutaneous implantation.

Omentum For Mammary Disorders: A 30-year Systematic Review.

Although the safety of applying omentum to the female breast for total breast reconstruction is controversial, it has recently been used to treat certain mammary disorders as well. A systematic review was therefore conducted to analyze and establish the suitability and safety of applying omentum to the breast. Covereing the interval from January 1984 to December 2013, we performed searches in MEDLINE, Embase, SciELO, and Google-Scholar for original articles describing the applicability of greater omentum to the breast and its clinical complications. Sixty observational articles with 985 women were chosen. The main clinical indications were total breast reconstruction after mastectomy due to breast cancer (45 studies), radiation damage (23 studies), and congenital Poland syndrome (4 studies). Altogether, 273 complications were identified among the 985 women treated. The most frequent was flap necrosis (26.74 %). The most serious was injury to the digestive system (1.10 %). There was a 35.48 % incidence of local breast cancer recurrence in eight observational studies on oncological risk. Seven of the eight included only women with advanced cancer. One of these studies reported the incidence and relapse time predominantly according to the primary tumor size. Although the oncological risk remains unclear, there was a high volume of complications that affected the digestive system. These findings suggest that omentum has well established applicability, but only for total breast reconstruction of huge defects, where muscular/myocutaneous or perforator flaps may be unsuitable.

Fibrodysplasia ossificans progressiva: case report

Fibrodysplasia ossificans progressiva is a rare genetic disease characterized by widespread soft tissue ossification and congenital stigmata of the extremities. We report on a male child followed for ten years since the age of 3 years and 9 months, when the diagnosis was made. He was born with bilateral hypoplasic hallux valgus and ventricular septal defect, corrected by transsternal approach when 32 months old. Restriction of neck mobility followed and foci of ectopic ossification appeared. Four crises of disease exacerbation were treated with oral prednisone and/or other antiinflammatory drugs. Sodium etidronate 5 to 10 mg/kg/day was prescribed intermittently during about six years but was discontinued due to osteopenia. The disease course has been relentless, with severe movement restriction including the chest wall. A review showed few similar case reports in the Brazilian literature. We revisit the criteria for diagnosis and the essentials of management and treatment.

Síndrome de Rett: estudo retrospectivo e prospectivo de 28 pacientes

From November 1982 to May 1999, 28 children with Rett syndrome were followed-up for a medium period of 6 years and 2 months. Regression of developmental milestones started at the age between 5 and 20 months. Nineteen cases of typical Rett syndrome had uneventful pre and perinatal periods, loss of previously acquired purposeful hand skills, mental and motor regression and developed hand stereotypies; sixteen had head growth deceleration and 12 gait apraxia. Nine patients were atypical cases, 2 formes frustres, 2 congenital, 3 with early seizure onset, 1 preserved speech and 1 male. Epilepsy was present in 21 patients, predominantly partial seizures and the drug of choise was carbamazepine (15 patients). In the initial evaluation most patients were distributed on Stages II and III and on follow-up on Stages III and IV. Three children died.

46,XX DSD and Antley-Bixler syndrome due to novel mutations in the cytochrome P450 oxidoreductase gene

Deficiency of the enzyme P450 oxidoreductase is a rare form of congenital adrenal hyperplasia with characteristics of combined and partial impairments in steroidogenic enzyme activities, as P450 oxidoreductase transfers electrons to CYP21A2, CYP17A1, and CYP19A1. It results in disorders of sex development and skeletal malformations similar to Antley-Bixley syndrome. We report the case of a 9-year-old girl who was born with virilized genitalia (Prader stage V), absence of palpable gonads, 46,XX karyotype, and hypergonadotropic hypogonadism. During the first year of life, ovarian cyst, partial adrenal insufficiency, and osteoarticular changes, such as mild craniosynostosis, carpal and tarsal synostosis, and limited forearm pronosupination were observed. Her mother presented severe virilization during pregnancy. The molecular analysis of P450 oxidoreductase gene revealed compound heterozygosis for the nonsense p.Arg223*, and the novel missense p.Met408Lys, inherited from the father and the mother, respectively. Arq Bras Endocrinol Metab. 2012;56(8):578-85

Fibrose congênita de reto inferior atípica com hipotonia muscular generalizada: relato de um caso

A case report of an atipical inferior rectus congenital fibrosis associated with a generalized muscular hypotonia is presented. It shows mild hipotropia with a normal visual acuity and binocularity in infraversion position contrasting with the severe hipotropia and ambliopy found. The surgical procedure took these facts into consideration, so we performed a small retrocess of the muscle with the objective to correct the head position without changes in the reading position. The postoperative results were satisfactory.

Utilização de recursos ópticos e equipamentos por escolares com deficiência visual

PURPOSE: To verify perceptions and conduct of students with visual impairment regarding devices and equipment utilized in schooling process. METHODS: A transversal descriptive study on a population of 12-year-old or older students in schooling process, affected by congenital or acquired visual impairment, inserted in the government teaching system of Campinas during the year 2000. An interview quiz, created based on an exploratory study was applied. RESULTS: A group of 26 students, 46% of them with low vision and 53.8% affected by blindness was obtained. Most of the students were from fundamental teaching courses (65.4%), studying in schools with classrooms provided with devices (73.1%). Among the resources used in reading and writing activities, 94.1% of the students reported they used the Braille system and 81.8% reported that the reading subject was dictated by a colleague. Most of the students with low vision wore glasses (91.7%), and 33.3% utilized a magnifying glass as optical devices. Among the non-optical devices, the most common were the environmental ones, getting closer to the blackboard (75.0%) and to the window (66.7%) for better lighting. CONCLUSIONS: It became evident that students with low vision eye-sight made use of devices meant for bearers of blindness, such as applying the Braille system. A reduced number of low vision students making use of optical and non-optical devices applicable to their problems were observed, indicating a probable unawareness of their visual potential and the appropriate devices to improve efficiency.

Avaliação dos tipos de glaucoma no serviço de oftalmologia da UNICAMP

PURPOSE: To evaluate the frequency of different types of glaucoma at the Hospital das Clínicas of Campinas State University. METHODS: Cross-sectional study of 329 patients followed at the Glaucoma Service of Campinas State University from October 1 to December 20, 2000. The frequency of each type of glaucoma and the treatment were analyzed. RESULTS: There were 329 patients examined at the Glaucoma Service: 132 (40.1%) were referred to the service as glaucoma suspects and 197 (59.9%) as glaucoma patients. Ninety of the 132 glaucoma suspects had glaucoma (68.2%) and 42 are still under investigation (31.8%). Among the 329 patients, 283 (86%) had glaucoma, 42 (12.8%) were glaucoma suspects, 2 (0.6%) had ocular hypertension and 2 (0.6%) did not have glaucoma. There were 530 eyes with glaucoma: 298 (56.2%) with primary open angle glaucoma, 108 (20.4%) with chronic angle closure glaucoma, 21 (4%) with glaucoma following cataract surgery, 19 (3.6%) congenital glaucoma and 16 (3%) with low-tension glaucoma. All patients received initial clinical treatment with IOP-lowering medication. After a mean follow up of 10.5 months, 89 (16.8%) underwent laser therapy: 72 (13.6%) iridotomy, 7 (1.3%) trabeculoplasty and 10 (1.9%) panphotocoagulation. A hundred and seventy nine (33%) eyes required surgical treatment. CONCLUSION: The most frequent types of glaucoma were primary open angle and angle closure glaucoma. Low tension glaucoma and glaucoma associated with exfoliation syndrome were uncommon in this population.

Hemiparesia congênita avaliação neuropsicológica complementar utilizando computador

We present the neuropsychological assessment with computer aid of six cerebral palsy children. Three children had right hemiparesis and three, left hemiparesis. The tomographic examination showed parietal cavities (porencephalic cyst in 4 children, ischemic injury in 1 case and subarachnoid cyst in 1 case). We have proposed to assess the visuo-spatial function since we suspected the children could have disturbance of this function. We did not detect this disturbance. On the other hand, the children had astereognosia and the right hemiparetic children preferred to execute signs on the right part of the computer visor. We discuss and propose explanations for both findings.

Crianças com fissura labiopalatina e baixo peso ao nascimento em testes auditivos centrais

INTRODUÇÃO: Alterações neurológicas ou sensoriais, entre elas as alterações auditivas periféricas e/ou centrais, são enfatizadas na população com baixo peso ao nascimento (BP), assim como, na presença de malformação craniofacial, tal como a fissura labiopalatina (FLP). OBJETIVO: Verificar e comparar o resultado de testes de processamento auditivo, Teste Dicótico de Dígitos (TDD) e Teste de Fusão Auditiva-Revisado (AFT-R), de crianças com FLP com e BP ao nascimento, com o de crianças sem FLP e nascida com peso normal. MÉTODO: Estudo retrospectivo e comparativo de 73 prontuários, dos quais foram verificados o sexo, peso ao nascimento, presença/ausência de FLP e o resultado de TDD e AFT-R. Foram constituídos três grupos de acordo com a análise do peso ao nascimento e presença ou ausência de FLP. RESULTADOS: Para o TDD a Análise de Covariância não mostrou diferença entre os grupos e sexos, porém a co-variável idade mostrou relação estatisticamente significante. Para o AFT-R não mostrou diferença entre os grupos, sexos e idades. CONCLUSÃO: Crianças com FLP e BP, embora sem significância estatística, apresentam maiores alterações nos testes de processamento auditivo utilizados ao comparar com crianças com FLP isolada e com crianças sem esta malformação craniofacial e sem BP. Ressalta-se ainda que o aumento da idade melhorou o desempenho no TDD.

Importância do fonoaudiólogo no acompanhamento de indivíduos com hipotireoidismo congênito

TEMA: o hipotireoidismo congênito é uma alteração metabólica que traz conseqüência graves para indivíduos não tratados e mesmo as crianças que realizam o tratamento podem apresentar distúrbios do desenvolvimento. O Programa Nacional de Triagem Neonatal, instituído pelo Ministério da Saúde, prevê o acompanhamento longitudinal de indivíduos com equipe multidisciplinar. Entretanto, a Fonoaudiologia não é incluída nesta equipe. Deste modo, considerando a ocorrência de distúrbios da comunicação nestes indivíduos, realizou-se levantamento bibliográfico nas bases de dados Lilacs, MedLine e PubMed, no período de 1987 a 2007, referente às alterações em habilidades do desenvolvimento decorrentes do hipotireoidismo congênito. OBJETIVO: verificar, na literatura científica, presença de alterações do desenvolvimento em indivíduos com hipotireoidismo congênito e refletir sobre a importância da atuação fonoaudiológica, em conjunto com equipe multidisciplinar especializada, no acompanhamento dos mesmos. CONCLUSÃO: a literatura relata alterações nas habilidades do desenvolvimento (motoras, cognitivas, lingüísticas e de autocuidados) e destaca que crianças com hipotireoidismo congênito são de risco para alterações no desenvolvimento lingüístico e, portanto, necessitam do acompanhamento longitudinal do desenvolvimento comunicativo. Torna-se evidente a importância da atuação do fonoaudiólogo nos Programas de Triagem Neonatal credenciados pelo Ministério da Saúde. Ressalta-se ainda a necessidade de investigações referentes às outras alterações metabólicas contempladas nestes programas, nas quais o fonoaudiólogo pode atuar de modo a prevenir, habilitar e reabilitar os distúrbios da comunicação, contribuindo para o trabalho em equipe, promovendo saúde nesta população.

Motor and functional evaluation of patients with spastic paraplegia, optic atrophy, and neuropathy (SPOAN)

Spastic paraplegia, optic atrophy, and neuropathy (SPOAN) is an autosomal recessive complicated form of hereditary spastic paraplegia, which is clinically defined by congenital optic atrophy, infancy-onset progressive spastic paraplegia and peripheral neuropathy. In this study, which included 61 individuals (age 5-72 years, 42 females) affected by SPOAN, a comprehensive motor and functional evaluation was performed, using modified Barthel index, modified Ashworth scale, hand grip strength measured with a hydraulic dynamometer and two hereditary spastic paraplegia scales. Modified Barthel index, which evaluate several functional aspects, was more sensitive to disclose disease progression than the spastic paraplegia scales. Spasticity showed a bimodal distribution, with both grades 1 (minimum) and 4 (maximum). Hand grip strength showed a moderate inverse correlation with age. Combination of early onset spastic paraplegia and progressive polyneuropathy make SPOAN disability overwhelming.

The Na+/glucose cotransporters: from genes to therapy

Glucose enters eukaryotic cells via two types of membrane-associated carrier proteins, the Na+/glucose cotransporters (SGLT) and the facilitative glucose transporters (GLUT). The SGLT family consists of six members. Among them, the SGLT1 and SGLT2 proteins, encoded by the solute carrier genes SLC5A1 and SLC5A2, respectively, are believed to be the most important ones and have been extensively explored in studies focusing on glucose fluxes under both physiological and pathological conditions. This review considers the regulation of the expression of the SGLT promoted by protein kinases and transcription factors, as well as the alterations determined by diets of different compositions and by pathologies such as diabetes. It also considers congenital defects of sugar metabolism caused by aberrant expression of the SGLT1 in glucose-galactose malabsorption and the SGLT2 in familial renal glycosuria. Finally, it covers some pharmacological compounds that are being currently studied focusing on the interest of controlling glycemia by antagonizing SGLT in renal and intestinal tissues.

Desenvolvimento de conceitos em cegos congênitos: caminhos de aquisição do conhecimento

O objetivo deste trabalho foi estudar o desenvolvimento de conceitos por cegos congênitos. Participaram sete cegos congênitos, de ambos os sexos, com idades entre 8 e 13 anos. Foi solicitado aos participantes que definissem 15 conceitos, subdivididos em concretos e abstratos. As respostas foram agrupadas em 13 categorias. Verificou-se que cada tipo de conceito envolve formas diferenciadas de definição e de utilização de recursos perceptivos. Foram identificados alguns meios utilizados pelo cego congênito na aquisição do conhecimento, evidenciando a multiplicidade de possibilidades de aquisição e expressão de conceitos. As implicações deste trabalho para o processo de ensino/aprendizagem de cegos foram consideradas.