Early transplantation of human immature dental pulp stem cells from baby teeth to golden retriever muscular dystrophy (GRMD) dogs: Local or systemic?

<p>Abstract</p> <p>Background</p> <p>The golden retriever muscular dystrophy (GRMD) dogs represent the best available animal model for therapeutic trials aiming at the future treatment of human Duchenne muscular dystrophy (DMD). We have obtained a rare litter of six GRMD dogs (3 males and 3 females) born from an affected male and a carrier female which were submitted to a therapeutic trial with adult human stem cells to investigate their capacity to engraft into dogs muscles by local as compared to systemic injection without any immunosuppression.</p> <p>Methods</p> <p>Human Immature Dental Pulp Stem Cells (hIDPSC) were transplanted into 4 littermate dogs aged 28 to 40 days by either arterial or muscular injections. Two non-injected dogs were kept as controls. Clinical translation effects were analyzed since immune reactions by blood exams and physical scores capacity of each dog. Samples from biopsies were checked by immunohistochemistry (dystrophin markers) and FISH for human probes.</p> <p>Results and Discussion</p> <p>We analyzed the cells' ability in respect to migrate, engraftment, and myogenic potential, and the expression of human dystrophin in affected muscles. Additionally, the efficiency of single and consecutive early transplantation was compared. Chimeric muscle fibers were detected by immunofluorescence and fluorescent <it>in situ </it>hybridisation (FISH) using human antibodies and X and Y DNA probes. No signs of immune rejection were observed and these results suggested that hIDPSC cell transplantation may be done without immunosuppression. We showed that hIDPSC presented significant engraftment in GRMD dog muscles, although human dystrophin expression was modest and limited to several muscle fibers. Better clinical condition was also observed in the dog, which received monthly arterial injections and is still clinically stable at 25 months of age.</p> <p>Conclusion</p> <p>Our data suggested that systemic multiple deliveries seemed more effective than local injections. These findings open important avenues for further researches.</p

Mitochondrial physiology

As the knowledge base and importance of mitochondrial physiology to evolution, health and disease expands, the necessity for harmonizing the terminology concerning mitochondrial respiratory states and rates has become increasingly apparent. The chemiosmotic theory establishes the mechanism of energy transformation and coupling in oxidative phosphorylation. The unifying concept of the protonmotive force provides the framework for developing a consistent theoretical foundation of mitochondrial physiology and bioenergetics. We follow the latest SI guidelines and those of the International Union of Pure and Applied Chemistry (IUPAC) on terminology in physical chemistry, extended by considerations of open systems and thermodynamics of irreversible processes. The concept-driven constructive terminology incorporates the meaning of each quantity and aligns concepts and symbols with the nomenclature of classical bioenergetics. We endeavour to provide a balanced view of mitochondrial respiratory control and a critical discussion on reporting data of mitochondrial respiration in terms of metabolic flows and fluxes. Uniform standards for evaluation of respiratory states and rates will ultimately contribute to reproducibility between laboratories and thus support the development of data repositories of mitochondrial respiratory function in species, tissues, and cells. Clarity of concept and consistency of nomenclature facilitate effective transdisciplinary communication, education, and ultimately further discovery

Serum levels of brain-derived neurotrophic factor in acute and posttraumatic stress disorder: a case report study Nível sérico do fator neurotrófico derivado do cérebro no transtorno de estresse agudo e no transtorno de estresse pós-traumático: relato de casos

OBJECTIVE: The aim of this study was to evaluate brain-derived neurotrophic factor levels in two patients, one with posttraumatic stress disorder and one with acute stress disorder, before and after treatment, and to compare those levels to those of healthy controls. METHOD: Brain-derived neurotrophic factor level, Davidson Trauma Scale, Beck Depression Inventory, Global Assessment of Functioning, and Clinical Global Impression were assessed before and after 6 weeks of treatment. RESULTS: Brain-derived neurotrophic factor levels were higher in patients than in matched controls before treatment. After 6 weeks, there was a reduction in symptoms and an improvement in functioning in both cases. At the same time, brain-derived neurotrophic factor levels decreased after treatment, even in case 2, treated with psychotherapy only. CONCLUSIONS: These results suggest that serum levels of brain-derived neurotrophic factor, as opposed to what has been described in mood disorders, are increased in posttraumatic stress disorder as well as in acute stress disorder.<br>OBJETIVO: O objetivo do estudo foi avaliar os níveis séricos do fator neurotrófico derivado do cérebro em um paciente com transtorno de estresse pós-traumático e em um paciente com transtorno de estresse agudo antes e após o tratamento, comparando esses níveis aos de controles saudáveis. MÉTODO: Os níveis do fator neurotrófico derivado do cérebro, a Escala Davidson de Trauma, o Inventário de Depressão de Beck, a Avaliação do Funcionamento Global e a Impressão Clínica Global foram medidos antes e após seis semanas de tratamento. RESULTADOS: Os níveis de fator neurotrófico derivado do cérebro foram maiores nos pacientes, quando comparados aos controles, antes do tratamento. Depois de seis semanas houve redução dos sintomas e melhora do funcionamento nos dois casos. Ao mesmo tempo, houve redução dos níveis de fator neurotrófico derivado do cérebro, mesmo no caso 2, tratado exclusivamente com psicoterapia. CONCLUSÕES: Esses resultados sugerem que o fator neurotrófico derivado do cérebro está aumentado tanto no transtorno de estresse pós-traumático quanto no transtorno de estresse agudo, de forma oposta às alterações até então descritas nos transtornos do humor

Spatial distribution of tuberculosis in a municipality in the interior of São Paulo, 2008-2013

Objective: to describe the epidemiological clinical profile of tuberculosis and analyze the spatial distribution of cases in a municipality in the state of São Paulo. Method: descriptive and ecological study of cases of tuberculosis through the records in an information system. Descriptive statistics were used to calculate central tendency (mean) and chi-square test, with Yates correction or Fisher exact test, when necessary. The Kernel technique was also used to calculate the occurrence densities of tuberculosis cases, using a radius of 1000 meters. Type I error was set at 5%. Results: 299 cases of tuberculosis were identified, with 290 (96.98%) being geocoded. The majority of these were male (n = 212; 70.91%), median age 40 years, and the pulmonary clinical form was predominant (n = 244, 81.60%). The distribution occurred in a non-random manner, observing important areas of the municipality with a higher density of cases of the disease. Conclusion: the study evidenced an epidemiological profile of tuberculosis cases similar to those in the literature; however, their distribution does not occur in a random manner, pointing to specific population groups that require greater management and planning of health services for the control of tuberculosis.Objetivo: caracterizar el perfil epidemiológico clínico de tuberculosis y analizar la distribución espacial de casos en un municipio paulista. Métodos: Estudio descriptivo y ecológico de casos de tuberculosis registrados en un sistema de información. Se utilizó estadística descriptiva con medidas de tendencia central (media) y aplicación de chi-cuadrado, con correlación de Yates o prueba exacta de Fisher según necesidad. Para el calcular la densidad en la ocurrencia de casos de tuberculosis, se aplicó la técnica uniforme Kernel utilizando una distancia de 1000 metros. El error de tipo I fue fijado en 5%. Resultados: Se identificaron 299 casos de tuberculosis, siendo geocodificados 290 (96.98%). La mayoría de los casos fueron de sexo masculino (n=212; 70,91%), con edad mediana de 40 años, siendo la forma pulmonar la más predominante (n=244; 81,60%). La distribución de casos fue forma no aleatoria, identificando áreas del municipio con mayor densidad de casos con esta patología. Conclusión: el perfil epidemiológico de casos de tuberculosis observado fue similar a lo observado en la literatura, aunque la distribución de estos no ocurre de manera aleatoria, identificando grupos específicos de la población los cuales requieren de mayores gestión y planificación en los servicios de salud para el control de la tuberculosis.Objetivo: caracterizar o perfil clínico epidemiológico da tuberculose (TB) e analisar a distribuição espacial dos casos em município paulista. Método: estudo descritivo e ecológico dos casos de tuberculose registrados em um sistema de informação. Recorreu-se à estatística descritiva com cálculo de medidas de tendência central (média) e aplicação do teste qui-quadrado, com correção de Yates ou teste exato de Fisher, quando necessários. Aplicou-se ainda a técnica de Kernel para o cálculo das densidades de ocorrência dos casos da TB, utilizando um raio de 1000 metros. Fixou-se o erro tipo I em 5%. Resultados: identificou-se 299 casos de TB, sendo geocodificados 290 (96,98%). A maioria destes foi do sexo masculino (n=212; 70,91%), idade mediana 40 anos, sendo a forma clínica pulmonar predominante (n=244; 81,60%). A distribuição ocorreu de forma não aleatória, observando-se áreas importantes do município com maior densidade de casos da doença. Conclusão: o estudo evidenciou perfil epidemiológico dos casos de tuberculose semelhante ao da literatura, no entanto, a distribuição dos mesmos não ocorre de forma aleatória, apontando grupos específicos da população que necessitam de maior gestão e planejamento dos serviços de saúde para o controle da tuberculose

(A) Positive control: expression of Mandys106 2C6 antibody in normal human muscles

(B) Negative control: lack of expression of same antibody in the muscles of normal dog. (C, D) MT1-S shows positive staining with Mandys106 2C6 in large dystrophic fibers (white arrows). (E) Positive control: expression of C-terminal in normal human muscles. (F) C-terminal antibody in the muscles of normal dog presents weak labeling. (G) Negative control: lack of its expression in the muscles of affected dog. (H-J) MT1-S shows positive staining with C-terminal antibody in some large dystrophic fibers (arrow). K) Toluidine blue and L) HE staining shows very large fibers with multiple centrally located nuclei and splitting. A, C, E-H = Fcm + DIC, B = DIC, D,I,= EF, J,K = Light microscopy, Scale bars = 50 μm<p><b>Copyright information:</b></p><p>Taken from "Early transplantation of human immature dental pulp stem cells from baby teeth to golden retriever muscular dystrophy (GRMD) dogs: Local or systemic?"</p><p>http://www.translational-medicine.com/content/6/1/35</p><p>Journal of Translational Medicine 2008;6():35-35.</p><p>Published online 3 Jul 2008</p><p>PMCID:PMC2529267.</p><p></p

GRMD puppies from a colony of dogs with X-linked muscular dystrophy were genotyped within 48 hs after birth

The genomic PCR product digested with Sau96I produces the wild type band (310 pb) and the mutant band (150 pb) labelled with arrows. ■ = Affected male. ● = Affected female. ◉ = Carrier female.<p><b>Copyright information:</b></p><p>Taken from "Early transplantation of human immature dental pulp stem cells from baby teeth to golden retriever muscular dystrophy (GRMD) dogs: Local or systemic?"</p><p>http://www.translational-medicine.com/content/6/1/35</p><p>Journal of Translational Medicine 2008;6():35-35.</p><p>Published online 3 Jul 2008</p><p>PMCID:PMC2529267.</p><p></p