Application of live biotherapeutic products and perspective in the treatment of inherited metabolic disease / 生物工程学报

Live biotherapeutic products (LBPs) refer to the living bacteria derived from human body intestinal gut or in nature that can be used to treat the human disease. However, the naturally screened living bacteria have some disadvantages, such as deficient therapeutic effect and great divergence, which fall short of the personalized diagnosis and treatment needs. In recent years, with the development of synthetic biology, researchers have designed and constructed several engineered strains that can respond to external complex environmental signals, which speeded up the process of development and application of LBPs. Recombinant LBPs modified by gene editing can have therapeutic effect on specific diseases. Inherited metabolic disease is a type of disease that causes a series of clinical symptoms due to the genetic defect of some enzymes in the body, which may cause abnormal metabolism the corresponding metabolites. Therefore, the use of synthetic biology to design LBPs targeting specific defective enzymes will be promising for the treatment of inherited metabolic defects in the future. This review summarizes the clinic applications of LBPs and its potential for the treatment of inherited metabolic defects.

Recent research on inherited metabolic diseases in children / 中国当代儿科杂志

With the improvement in the research level and the diagnosis and treatment technology of inherited metabolic diseases (IMD), the research on pediatric IMD in China has made great progress, but there is still some distance from the international level. Due to the vast territory of China and the uneven distribution of medical resources, the regional characteristics of IMD remain unclear in China, and there are many problems and difficulties in early diagnosis and treatment. Therefore, it is necessary to improve the understanding of pediatric IMD among pediatricians, so as to improve the diagnosis and treatment level, achieve an early identification, diagnosis, and treatment of pediatric IMD, and effectively reduce the fatality and disability rates of children with IMD. This article reviews the research progress of IMD in children in China, and analyzes the features of representative IMDs. Citation:Chinese Journal of Contemporary Pediatrics, 2022, 24(3): 326-331.

Research progress of the role of IGF-1 in metabolic diseases and the effect of exercise intervention / 生理学报

Insulin-like growth factor-1 (IGF-1) is a peptide with a similar molecular structure to insulin. IGF-1 plays a key role in tissue growth and development, as well as cell metabolism, proliferation, differentiation and apoptosis. Liver is the main source of IGF-1, with the production of IGF-1 up to 75% of the total in the whole body, while the remaining 25% are secreted by skeletal muscles, heart, kidney, spleen and other organs. Target organs of IGF-1 include heart, blood vessels, liver, bone and skeletal muscles. It has been well documented that IGF-1 plays an important role in the prevention and treatment of metabolic diseases. Different types of exercise have different effects on IGF-1 expression with organ differences. In this article, we reviewed the preventive and therapeutic effects of IGF-1 on metabolic diseases and IGF-1-mediated exercise-induced benefits.

Application of continuous renal replacement therapy in the treatment of neonates with inherited metabolic diseases / 中国当代儿科杂志

OBJECTIVE@#To study the efficacy and safety of continuous renal replacement therapy (CRRT) in the treatment of neonates with inherited metabolic diseases and hyperammonemia.@*METHODS@#A retrospective analysis was performed on the medical records of neonates with inherited metabolic diseases and hyperammonemia who were hospitalized and underwent CRRT in the Department of Neonatology, Hunan Children's Hospital, from September 2016 to March 2020, including general conditions, clinical indices, laboratory markers, and adverse reactions.@*RESULTS@#A total of 11 neonates were enrolled, with 7 boys (64%) and 4 girls (36%). The neonates had a mean gestational age of (38.9±0.8) weeks, a mean body weight of (3 091±266) g on admission, and an age of (5.7±2.0) days at the time of CRRT. The main clinical manifestations were vomiting (100%), convulsions (100%), and coma (55%), and the main primary disease was urea cycle disorder (55%). The mean duration of CRRT was (44±14) hours, the medium duration of coma before CRRT was 2 hours, and the total duration of coma was 10 hours. The patients had a mean hospital stay of (18±10) days and a survival rate of 73%, and 2 survivors had epilepsy. After treatment, all patients had significant reductions in blood ammonia, lactic acid, and K@*CONCLUSIONS@#CRRT is safe and effective in the treatment of neonates with inherited metabolic diseases and hyperammonemia.

Rol de la osteocalcina más allá del hueso / Role of osteocalcin beyond bone

Los hallazgos osteológicos se intensi!caron en los últimos años. Se demostró que el esqueleto se comporta, además de sus funciones clásicas, como un órgano de secreción endocrina que sintetiza al menos dos hormonas: el factor de crecimiento de !broblastos 23 (FGF-23) y la osteocalcina (Ocn). La Ocn es un péptido pequeño que contiene 3 residuos de ácido glutámico. Estos residuos se carboxilan postraduccionalmente, quedando retenida en la matriz ósea. La forma decarboxilada en el primer residuo de ácido glutámico (GluOcn) fue reportada por poseer efectos biológicos; la resorción ósea es el mecanismo clave para su bioactivación. La presente revisión se centra en los conocimientos actuales sobre la función hormonal de la Ocn. A la fecha se reporta que la Ocn regularía el metabolismo energético aumentando la proliferación de células ` pancreáticas, y la secreción de insulina y de adiponectina. Sobre el músculo esquelético actuaría favoreciendo la absorción y el catabolismo de nutrientes. La función reproductiva masculina estaría regulada mediante el estímulo a las células de Leydig para sintetizar testosterona; en el desarrollo cerebral y la cognición, la Ocn aumentaría la síntesis de neurotransmisores monoaminados y disminuiría el neurotransmisor inhibidor GABA. Si bien son indispensables mayores evidencias para dilucidar los mecanismos reguladores por medio de los cuales actuaría la Ocn, los resultados enumerados en los distintos estudios experimentales establecen la importancia de este novedoso integrante molecular. Dilucidar su rol dentro de estos procesos interrelacionados en seres humanos abriría la posibilidad de utilizar a la Ocn en el tratamiento de enfermedades endocrino-metabólicas. (AU)

Osteological !ndings have intensi!ed in recent years. The skeleton behaves as an endocrine secretion organ that synthesizes at least two hormones: osteocalcin (Ocn) and !broblast growth factor 23 (FGF-23). Ocn is a small peptide that contains 3 glutamic acid residues. After translation, these residues are carboxylated to make possible its retention into the bone matrix. Decarboxylation on the !rst glutamic acid residue (GluOcn) has been reported to have biological effects. Bone resorption is the key mechanism for its bioactivation. This review focuses on current knowledge on Ocn hormonal function. It has been reported that Ocn regulates energy metabolism by increasing the proliferation of pancreatic ` cells, and the secretion of insulin and adiponectin. On the skeletal muscle, it may act by favoring the absorption and catabolism of nutrients. Male reproductive function might be regulated by stimulating Leydig cells to synthesize testosterone. Regarding brain development and cognition, Ocn would increase monoamine neurotransmitters synthesis and decrease inhibitory neurotransmitter GABA. Although more evidence is needed to elucidate the regulatory mechanisms of Ocn, different experimental studies establish the importance of this novel molecular mediator. Clarifying its role within interrelated processes in humans, might open the possibility of using Ocn in different treatments of endocrine-metabolic diseases. (AU)

Role of exosome-associated microRNA in diagnostic and therapeutic applications to metabolic disorders / 浙江大学学报（英文版）（B辑：生物医学和生物技术）

Metabolic disorders are classified clinically as a complex and varied group of diseases including metabolic syndrome, obesity, and diabetes mellitus. Fat toxicity, chronic inflammation, and oxidative stress, which may change cellular functions, are considered to play an essential role in the pathogenetic progress of metabolic disorders. Recent studies have found that cells secrete nanoscale vesicles containing proteins, lipids, nucleic acids, and membrane receptors, which mediate signal transduction and material transport to neighboring and distant cells. Exosomes, one type of such vesicles, are reported to participate in multiple pathological processes including tumor metastasis, atherosclerosis, chronic inflammation, and insulin resistance. Research on exosomes has focused mainly on the proteins they contain, but recently the function of exosome-associated microRNA has drawn a lot of attention. Exosome-associated microRNAs regulate the physiological function and pathological processes of metabolic disorders. They may also be useful as novel diagnostics and therapeutics given their special features of non-immunogenicity and quick extraction. In this paper, we summarize the structure, content, and functions of exosomes and the potential diagnostic and therapeutic applications of exosome-associated microRNAs in the treatment of metabolic disorders.

Adherence to medication before and after the use of a Drug-Dispensing System with usage control / Adesão à medicação antes e após o uso de um sistema de dispensação de drogas com controle de uso

The aim of the present work was to assess the adherence to medication from polymedicated patients before and after the use of a Drug-dispensing System with Usage Control (DDSUC) and compare the levels of the clinical parameters - blood pressure, postprandial glycemia, glycated hemoglobin, triglycerides and cholesterol. DDSUC consisted of a monthly drug-dispensing package, in the shape of a blister with a calendar. This quasi-experimental study was performed in a Basic Health Unit. Twenty four patients were selected to use DDSUC for 4 months. Medication adherence was assessed through Morisky-Green test. Among the participants of the study, 62.5% were women and the average age was 67 years old. Before the use of DDSUC, 83.3% of the patients were considered as "less adherent". After the use of the system, 100% were considered as "more adherent" (p < 0.01), the means of the systolic blood pressure decreased 23.7 mmHg (p=0.000), the diastolic blood pressure decreased 12.1 mmHg (p=0.004) and glycemia diminished 79.3 mg/dl (p=0.000). The use of DDSUC improved the adherence to medication and decreased the values of the clinical parameters, making patients safer when it comes to respecting the correct use of their medication...

O objetivo deste estudo foi avaliar a adesão ao tratamento medicamentoso de pacientes polimedicados antes e após o uso de um Sistema de Dispensação de Medicamentos e Controle de Uso (SDMCU) e comparar os níveis dos parâmetros clínicos - pressão arterial, glicemia pós-prandial, hemoglobina glicada, triglicérides e colesterol. O SDMCU foi constituído por uma embalagem mensal de dispensação de medicamentos, em forma de blister com calendário. Este estudo, do tipo quase-experimental, foi realizado em uma Unidade Básica de Saúde. Selecionaram-se 24 pacientes para utilizar o SDMCU por 4 meses. A adesão medicamentosa foi avaliada através do Teste de Morisky e Green. Entre os participantes do estudo, 62,5% eram mulheres e a idade média foi de 67 anos. Antes do uso do SDMCU, 83,3% dos pacientes foram considerados "menos aderentes". Após o uso do sistema, 100% foram considerados "mais aderentes" (p<0,01), a média da pressão arterial sistólica diminuiu 23,7 mmHg (p=0,000), a diastólica diminuiu 12,1 mmHg (p=0,004) e a glicemia diminuiu 79,3 mg/dL (p=0,000). O uso do SDMCU melhorou a adesão medicamentosa e diminuiu os valores dos parâmetros clínicos, proporcionando aos pacientes uma segurança no que diz respeito à utilização correta de seus medicamentos...

Genetic and Biochemical Consequences of Adenosine Deaminase Deficiency in Humans.

Adenosine deaminase deficiency accounts for ~15-20% of severe combined immunodeficiency in humans. The gene for adenosine deaminase is located on chromosome 20q12-q13.11 and codes for an aminohydrolase that catalyzes the deamination of adenosine and deoxyadenosine to inosine and deoxyinosine, respectively. Absence of the enzyme causes a build-up of the substrates in addition to excess deoxyadenosine triphosphate, thereby compromising the regenerative capacity of the immune system. Due to underlying allelic heterogeneity, the disorder manifests as a spectrum, ranging from neonatal onset severe combined immunodeficiency to apparently normal partial adenosine deaminase deficiency. Tandem mass spectrometry coupled with high efficiency separation systems enables postnatal diagnosis of the disorder, while prenatal diagnosis relies on assaying enzyme activity in cultured amniotic fibroblasts or chorionic villi sampling. Screening of adenosine deaminase deficiency for relatives-at-risk may reduce costs of treatment and ensure timely medical intervention as applicable. This article reviews the genetic, biochemical and clinical aspects of adenosine deaminase deficiency.

Significados da dieta e mudanças de hábitos para portadores de doenças metabólicas crônicas: uma revisão / The significance of dietary and behavioral changes in patients with chronic metabolic disorders: a review

Eating behavior and the psycho-cultural significance of food for patients with chronic metabolic disorders have been a focus of interest due to the difficulty in ensuring the compliance of these patients in terms of changing their habits and in fostering self-care. A review of the literature was condusted using the LILACS and MEDLINE databases and the PUBMED search engine to identify qualitative studies in which the opinion of patients with respect to diet and lifestyle was analyzed. Key words used were: metabolic syndrome; eating behavior; diet; obesity; psychological factors; qualitative study; and dietary habits. Inclusion criteria consisted of: articles in English, Spanish or Portuguese, published between 2000 and 2008; studies carried out in adult populations; containing one or more of the key words in the title. Based on the 15 papers analyzed, it was concluded that compliance with a change of habit is a dynamic process that depends on various individual factors and requires greater interaction between professionals and patients in clinical practice. Promoting self-care depends on respecting the decisions and feelings resulting from personal experience.

Comportamento alimentar e significados psicoculturais da alimentação para portadores de distúrbios metabólicos crônicos têm sido foco de interesse em virtude da dificuldade de adesão às mudanças de hábitos e à promoção do autocuidado. Revisão bibliográfica foi realizada a partir das bases de dados Lilacs e Medline® e no sistema de busca Pubmed, visando estudos qualitativos que analisam a visão dos pacientes sobre dieta e estilo de vida. Palavras chaves: metabolic syndrome, eating behavior, diet, obesity, psychological factors, qualitative study e dietary habits. Critérios de inclusão: idioma inglês, espanhol ou português; período 2000 a 2008; população adulta; contendo um ou mais descritores no título. A partir de 15 artigos analisados foi concluído que a adesão às mudanças de hábitos é um processo dinâmico, dependente de vários fatores individuais para seu estabelecimento e requer maior interação entre profissionais e pacientes na prática clínica. A promoção do autocuidado depende do respeito às decisões e aos sentimentos decorrentes da vivência pessoal.

La medicación dopaminérgica podría ser útil para mejorar el síndrome metabólico en la enfermedad de Parkinson / Dopaminergic medication could be of use in improving metabolic syndrome in Parkinson’s disease

Realizamos un estudio de casos y controles con 483 pacientes consecutivos con enfermedad de Parkinson idiopática (EP) y 533 controles apareados por edad y sexo con el fin de investigar la relación entre la EP y los factores de riesgo de enfermedades cardiovasculares. Mediante análisis multivariado, la diabetes, la hipertensión, los antecedentes de tabaquismo, colesterol elevado y altos niveles de triglicéridos fueron significativamente menos frecuentes en la EP que en los controles. Además, estas asociaciones resultaban más evidentes para los pacientes tratados con levodopa. Interpretamos esta asociación entre EP y reducción de los factores de riesgo vascular como debidos a insuficiencia en el eje hipotálamo-hipófisosuprarrenal, desnervación simpática generalizada en la EP y estimulación central o periférica de los receptores dopamínicos D1 y D2 por la levodopa. Estos efectos cardiovasculares y metabólicos favorables sugieren que la medicación dopaminérgica puede resultar útil en el tratamiento de los trastornos cardiovasculares.

Repercussão das medidas de correção das comorbidades no resultado da reabilitação vestibular de idosos / The treatment of diseases related to balance disorders in the elderly and the effectiveness of vestibular rehabilitation

OBJETIVO: Considerando o aumento da população idosa e conseqüentemente as alterações de equilíbrio a ela relacionadas, realizamos um estudo para avaliar o impacto do tratamento adequado das doenças coexistentes ao desequilíbrio corporal no resultado da Reabilitação Vestibular (RV). MATERIAL E MÉTODOS: 52 idosos com queixa de tontura e/ou desequilíbrio com indicação RV participaram deste ensaio clínico aberto e prospectivo realizado no Ambulatório de Otoneurologia Geriátrica da Instituição, entre 2003 e 2005. Os pacientes do grupo de estudo foram previamente tratados das doenças clínicas diagnosticadas e posteriormente submetidos à RV. Foram então comparados com o grupo total de idosos tratados pela RV no mesmo período. RESULTADOS: Os pacientes do grupo de estudo apresentaram 65 comorbidades diagnosticadas, com média de 1,25 por paciente. A efetividade total foi de 84,5 por cento neste grupo contra 81,8 por cento no grupo controle, sem diferença significante. No entanto, a completa remissão dos sintomas ocorreu em 69,2 por cento dos casos contra 43,18 por cento dos controles, significante para p<0,02. CONCLUSÃO: A diferença na efetividade da RV entre os grupos demonstra a importância do tratamento etiológico das afecções clínicas coexistentes aos problemas de equilíbrio corporal.

The aim of this study was to assess the impact of adequate treatment of concomitant diseases in the elderly undergoing Vestibular Rehabilitation (VR). METHOD: 52 elderly patients with complaints of vertigo and/or imbalance requiring VR participated in this prospective study. The trial was designed as an open clinical assay at the Ear Nose and Throat Department Geriatric Otoneurology Clinic, and was done between 2003 and 2005. Patients were compared with the total group of elderly individuals treated with VR during the same period. RESULTS: 65 diseases were diagnosed in the study group, an average 1.25 diseases per patient. After the treatment of these diseases, patients underwent VR. The effectiveness of VR (remission and partial improvement rates) was 84.5 percent in the study group against 81.8 percent in the control group, which was not significant. Remission of symptoms, however, was present in 69.2 percent of the study group against 43.18 percent of the control group, which was statistically significant. CONCLUSION:The difference in the effectiveness of VR in both groups highlights the importance of the etiological treatment of concomitant diseases in patients with vestibular disorders.

Haematopoietic stem cell transplantation: current status.

Haematopoietic stem cell transplantation (HSCT) is now an established treatment fora number of non-malignant and malignant conditions. Bone marrow- or peripheral blood-derived allogeneic SCT from an HLA-identical sibling or matched unrelated donor cures more than half the patients with severe aplastic anaemia, thalassaemia major, congenital immunodeficiency diseases and genetic metabolic disorders. Among the malignant conditions, acute and chronic leukaemia, multiple myeloma, Hodgkin and non-Hodgkin lymphoma, and high risk neuroblastoma are important conditions that can be treated by HSCT. The major morbidities associated with HSCT are regimen-related toxicities, development of acute or chronic graft-versus-host disease (GVHD), failure of engraftment of the bone marrow and complications related to the immunodeficiency that occurs in the post-transplant period. Peripheral blood stem cells are now being used as an alternative to bone marrow stem cells for allogeneic HSCT and exclusively for autologous HSCT. Reduced intensity conditioning for allogeneic HSCT has resulted in a lower frequency and severity of GVHD and risk of infections. This has resulted in allogeneic HSCT being done in older patients and for those with co-morbid conditions. Patients with low grade Hodgkin and non-Hodgkin lymphoma, chronic lymphocytic leukaemia and multiple myeloma appear to benefit more with this approach. Prevention of acute GVHD while maintainingthe graft-versus-tumour effect and close monitoring of the kinetics of chimerism hold promise for improving the outcome of those receiving reduced intensity allogeneic HSCT. In recipients ofautologous HSCT, identification of patients at increased risk for relapse and use of agents (interferon, interleukin-2) post-transplant to augment the graft-versus-tumour effect are possible areas of further research.

Nutrición y SIDA: alteraciones metabólicas nutricionales en el Síndrome de Inmunodeficiencia Adquirida / Nutrition and aids: nutritional metabolic alterations in the acquired inmunodeficiencia syndrome

El diagnóstico de posibles carencias calórico-proteicas, de vitaminas y/o minerales, en este tipo de pacientes, puede ayudar a prevenir riesgos nutricionales de distinta gravedad. La valoración nutricional debe incluir esencialmente anamnesis alimentaria, examen físico y de los tiempos de la nutrición, estudio de la composición corporal, y análisis bioquímicos. También se analiza el cuadro de lipodistrofia, la conducta terapéutica, parámetos a tener en cuenta en la valoración nutricional, efectos de nutrientes específicos sobre la función inmune, suplementos vitamínicos, terapia hormonal, y alimentación enteral y parenteral

Prevención y tratamiento de la obesidad desde la niñez: la estrategia para disminuir las enfermedades crónicas no transmisibles del adulto / Prevention and treatment of obesity since childhood: a strategy to decrease the prevalence of non transmissible chronic diseases in the adult

The prevalence of obesity among children and teenagers is increasing by 1.5 percent per year, probably due to a higher consumption of highly caloric foods and to physical inactivity. Hypercholesterolemia, increased insulin levels and high blood pressure of childhood obesity, precede atherosclerosis, coronary artery disease, diabetes and hypertension in adulthood. The prevention of childhood obesity is an efficient strategy to decrease the prevalence of non transmissible chronic diseases in the adult. The recommendations of experts committees for the prevention, diagnosis and treatment of childhood obesity are reviewed. They aim at a change in dietary habits and increasing physical activity. A well balanced healthy diet and a decrease in physical inactivity time will result in a successful treatment approach for obesity

Nutrição enteral em Pediatria / Enteral nutrition in Pediatrics

O autor conceitua o que se entende por nutriçäo enteral, apresenta os diferentes tipos de dietas, fórmulas completas, modulares, artesanais e comerciais, analisa as condiçöes que requerem o uso de fórmulas lácteas especiais (prematuridade, imaturidade e inflamaçäo intestinal, alergia ao leite de vaca), as vias e a técnica de administraçäo e de passagem de sonda, cuidados com a dieta enteral e sua monitorizaçäo, particularidades do RN e complicaçöes, finalizando com estudo da interaçäo entre drogas e nutrientes

Síndrome metabólica / Metabolic syndrome

Parece que a dislipidemia, hipertensão, obesidade, intolerância à glicose e a hiperinsulinemia fazem parte de uma única síndrome. É importante que os clínicos saibam como diagnosticar e tratar todos os componentes como um processo interrelacionado. A Síndrome Metabólica se desenvolve a partir da resistencia à insulina, aumentando o risco de doença aterosclerótica e de diabetes tipo 2, sendo a hiperinsulinemia a característica primária...