Impasses do diagnóstico precoce da doença celíaca e suas repercussões clínicas e sociais / Impasses in the early diagnosis of celiac disease and its clinical and social repercussions / Impasos del diagnóstico temprano de la enfermedad celámica y su impacto clínico y social

A turva Doença Celíaca (DC) demonstra sua opacidade através dos aspectos clínicos de difícil detecção precoce. Essa delonga em identificar o enfermo e orientá-lo acerca dos hábitos de vida indispensáveis à saúde do portador de DC, acarreta desdobramentos prognósticos negativos, visto que o consumo crônico dos agentes irritantes gera lesões inflamatórias insistentes que, paulatinamente agridem o tecido gastrintestinal em diferentes níveis. Para além das lesões epiteliomucosas, as dores enfrentadas por esses pacientes permeiam a exclusão e a fobia social, as patologias psiquiátricas e as síndromes de humor deprimido. Além da demora diagnóstica que compromete de curto a extenso prazo os doentes, nota-se evidente falha nos dados epidemiológicos, que parecem se relacionar com o subdiagnóstico. Assim, reunimos estudos de epidemiologia de diferentes regiões e, em progressão de tempo, que demonstram aumento nos índices diagnósticos, além de teorias fisiopatológicas que parecem contribuir para o aumento de diagnósticos precoces. Para isso, extensas revisões literárias em livros referência dentre a prática médica e pesquisas complementares, tanto em artigos de aprofundamento e atualização literária, quanto diretrizes nacionais de manejo, constroem o presente estudo. Enfim, demonstra-se as importantes lacunas de conhecimento acerca dessa patologia cada vez mais prevalente.

The blurred celiac disease demonstrates its opacity through clinical aspects that are difficult to detect early. This delay in identifying the patient and guiding him about the life habits essential to the health of the CD patient, leads to negative prognostic consequences, since the chronic consumption of irritating agents generates persistent inflammatory lesions that, gradually attack the gastrointestinal tissue at different levels . In addition to epitheliomucosal lesions, the pain faced by these patients permeates exclusion and social phobia, psychiatric pathologies and depressed mood syndromes. In addition to the diagnostic delay that compromises patients in the short to long term, there is an evident failure in the epidemiological data, which seems to be related to underdiagnosis. Thus, we gathered epidemiology studies from different regions and, over time, that demonstrate an increase in diagnostic rates, in addition to pathophysiological theories that seem to contribute to the increase in early diagnoses. For this, extensive literary reviews in reference books within medical practice and complementary research, both in deepening articles and literary updating, as well as national management guidelines, build the present study. Finally, it demonstrates the important gaps in knowledge about this increasingly prevalent pathology.

La Enfermedad Celular Nublada (DC) demuestra su opacidad a través de los aspectos clínicos de difícil detección en una etapa temprana. Este retraso en la identificación del enfermo y en el asesoramiento sobre los hábitos de vida indispensables para la salud del portador de DC, trae consigo un desarrollo pronóstico negativo, ya que el consumo crónico de agentes irritantes genera lesiones inflamatorias insistente que, gradualmente, dañan el tejido gastrointestinal a diferentes niveles. Además de las lesiones epiteliomucosiales, el dolor que enfrentan estos pacientes permea la exclusión social y la fobia, los trastornos psiquiátricos y los síndromes deprimidos. Además del retraso en el diagnóstico que pone en peligro a los pacientes en el corto y largo plazo, es evidente que los datos epidemiológicos, que parecen estar relacionados con el subdiagnóstico, han fracasado. Por lo tanto, reunimos estudios epidemiológicos de diferentes regiones y, en una progresión del tiempo, que demuestran un incremento en los índices diagnósticos, además de teorías fisiopatológicas que parecen contribuir a un aumento en los diagnósticos precoces. Para ello, se construyen en este estudio amplias revisiones literarias en libros de referencia entre la práctica médica y las investigaciones complementarias, tanto en artículos de profundización y actualización literaria como en directrices nacionales para su manejo. En resumen, se están demostrando las importantes lagunas de conocimiento sobre esta patología cada vez más prevalente.

Resistance exercise training induces subcutaneous and visceral adipose tissue browning in Swiss mice.

Aerobic exercise training (AER) may promote several adaptations in white adipose tissue (WAT), including a phenotypic change known as browning. The present study aimed at assessing if resistance exercise training (RES) would be as efficient as AER in inducing a brown-like adipocyte reprogramming in WAT. Thirty Swiss male mice were randomly divided into 3 groups with 10 animals each: 1) sedentary (SED), 2) AER, and 3) RES. After the adaptation training, an incremental test was performed at the beginning of each week to adjust training load. Mice were submitted to 8 wk of AER or RES. After the experimental period, inguinal and retroperitoneal WAT (iWAT and rpWAT) and brown adipose tissue (BAT) were collected. The prescription of AER and RES was effective in increasing the performance of both groups. Also, RES presented a lower body weight than AER/SED. AER and RES reduced the area of iWAT and rpWAT adipocytes and the lipid area of BAT, induced an increase of vascular endothelial growth factor (VEGF) and cluster of differentiation 31 (CD31) and uncoupling protein 1 (UCP-1), and increased the expression of selective genes of brown and beige phenotype in adipocytes after 8 wk. In general, we demonstrated here that AER and RES training similarly induced the browning of iWAT and rpWAT.NEW & NOTEWORTHY Aerobic exercise training (AER) induces the browning of white adipose tissue, turning adipocytes multilocular, highly vascularized and expressing uncoupling protein 1 (UCP-1). The current study compared the efficiency of resistance to aerobic exercise training to promote a brown-like phenotype. Our results suggest that both types of training similarly induce subcutaneous and visceral adipose tissue browning.

Methyl jasmonate: a phytohormone with potential for the treatment of inflammatory bowel diseases.

OBJECTIVES: The phytohormone methyl jasmonate (MeJA) has been identified as a vital cell regulator in plants. This substance is analogous to eicosanoids and similar to that of anti-inflammatory prostaglandins. In animals and in animal cells, it displayed an efficient neuroprotective, anti-inflammatory and antioxidant action; while in tumoral strains, it demonstrates a potentially highly attractive mechanism of apoptosis induction through various cellular and molecular mechanisms. The aim of the present review was to explore two new hypotheses that explain the action of MeJA, a lipid phytohormone and its potentially anti-apoptotic mechanism for use as a therapeutic target for future treatment of Inflammatory bowel diseases (IBDs). KEY FINDINGS: Methyl jasmonate is a new candidate for the treatment of IBDs, modulating the expression of the major classes of caspase-type protease families that selectively act on the extrinsic and intrinsic pathways of the apoptotic process. Its action is based on the reduction of the expression in tumour necrosis factor tissue levels and the modulating action of reactive oxygen species production, acting only on the destruction of cells that express the diseased phenotype, and preserving cells that are not transformed. CONCLUSIONS: Methyl jasmonate may represent an alternative for the transduction processes of important signals in the cellular renewal of the intestinal mucosa.

Insulin complexed with cyclodextrins stimulates epithelialization and neovascularization of skin wound healing in rats.

INTRODUCTION: Skin lesions are a significant public health problem, above all that wounds fail to heal properly and become chronic. Due to its reepithelization action, insulin has the potential to heal skin lesions, by stimulating the proliferation and migration of keratinocytes, angiogenic stimulus, and increasing collagen deposition. In the present study insulin was complexed with 2-hydroxypropyl-ß-cyclodextrin (HPßCD) and its wound healing effect and inclusion complex (HPßCD-I) were evaluated in excisional wounds in the skin of rats. MATERIAL AND METHODS: Three different gel based pharmaceutical forms were created: carbopol 940® base gel, an insulin gel comprising the base gel plus 50 IU of insulin and a gel complex comprising the base gel plus (HPßCD) complexed with insulin (HPßCD-I) were used to verify wound healing in vitro and in vivo assays. RESULTS: The wounds in the skin of rats were treated with gel containing HPßCD-I not cytoxically irritating and cytotoxic. Analysis of cell proliferation and measurement of the length and thickness of the epidermis showed that HPßCD-I prolonged the proliferation and migration of keratinocytes. Revascularization analysis of lesions treated with HPßCD-I compared to those treated with insulin found that angiogenic stimulus was less intense, but more constant and prolonged in the modified release process. There was increased deposition of type I and III collagen fibers in accordance with the treatment time. CONCLUSION: Therefore, the slow release of complexed insulin modulated the reepithelialization process by stimulating cell proliferation and migration of keratinocytes, favoring greater concentration of serum insulin, modulating inflammatory response, matrix remodeling and promoting neovascularization. Angiogenesis extended by the steady release of insulin can be effective in the treatment of chronic wounds.

Chronic Glibenclamide Treatment Attenuates Walker-256 Tumour Growth in Prediabetic Obese Rats.

BACKGROUND/AIMS: The sulphonylurea glibenclamide (Gli) is widely used in the treatment of type 2 diabetes. In addition to its antidiabetic effects, low incidences of certain types of cancer have been observed in Gli-treated diabetic patients. However, the mechanisms underlying this observation remain unclear. The aim of the present work was to evaluate whether obese adult rats that were chronically treated with an antidiabetic drug, glibenclamide, exhibit resistance to rodent breast carcinoma growth. METHODS: Neonatal rats were treated with monosodium L-glutamate (MSG) to induce prediabetes. Control and MSG groups were treated with Gli (2 mg/kg body weight/day) from weaning to 100 days old. After Gli treatment, the control and MSG rats were grafted with Walker-256 tumour cells. After 14 days, grafted rats were euthanized, and tumour weight as well as glucose homeostasis were evaluated. RESULTS: Treatment with Gli normalized tissue insulin sensitivity and glucose tolerance, suppressed fasting hyperinsulinaemia, reduced fat tissue accretion in MSG rats, and attenuated tumour growth by 27% in control and MSG rats. CONCLUSIONS: Gli treatment also resulted in a large reduction in the number of PCNA-positive tumour cells. Although treatment did improve the metabolism of pre-diabetic MSG-rats, tumour growth inhibition may be a more direct effect of glibenclamide.

Involvement of cytokines in the modulation and progression of renal fibrosis induced by unilateral ureteral obstruction in C57BL/6 mice: effects of thalidomide and dexamethasone.

This study investigated the kinetics of cytokines that are involved in the development of interstitial fibrosis in mice that were subjected to UUO, the interstitial type I and III collagen deposition, and the effects of Thalido and Dexa treatment on these parameters. Inbred C57BL/6 mice were divided into the groups: Normal (not submitted surgery), Sham (sham surgery), Control (UUO treated with 0.5% carboxymethyl cellulose), Thalido (UUO treated with 5 mg/kg thalidomide), and Dexa (UUO treated with 1 mg/kg dexamethasone). The treatments began the day before surgery and were administered once daily by gavage for 1, 7, or 14 days. At the end of each treatment period, blood samples were collected for the determination of creatinine, urea, cytokines. The Control group exhibited a increase in creatinine concentration compared with the Normal and Sham groups within the first 24 h after UUO, which remained high until days 7 and 14. The urea concentration was higher on days 7 and 14 in the Control group compared with the Sham group. In the Thalido and Dexa groups, a reduction of serum creatinine concentration was seen on day 14. Treatment with Dexa reduced the serum concentration of urea on day 7. The serum concentrations of cytokines (TNF-α, IL-1ß, IL-6, IL-10 and IL-17) and chemokines (KC, MIG, bFGF) increased in UUO mice at all of the sampling times. The Dexa and Thalido groups exhibited alterations in the concentrations of these cytokines, suggesting the involvement of anti-inflammatory and immunomodulatory mechanisms that may have modified the fibrosis framework.