巨噬细胞铁代谢Hepcidin-Fpn1轴及其在动脉粥样硬化的作用

动脉粥样硬化(As)与铁代谢相关联,但斑块中聚集的铁是产生致病作用还是只是在As疾病发生发展过程中溶血等导致的一个单纯后果还存在争议。巨噬细胞在As斑块的形成和发展中发挥关键作用。本文总结巨噬细胞铁代谢与As的研究进展。首先介绍在巨噬细胞铁代谢中发挥重要作用的Hepcidin-Fpn1轴;接着从炎症、感染、斑块内出血3个方面介绍巨噬细胞铁代谢对As发生发展的影响;最后介绍与铁代谢相关的As治疗的新思路。     

Metabolic syndrome associates with left atrial dysfunction

Background and aims

Obesity and metabolic syndrome (MetS) are risk factors of atrial fibrillation (AF), but limited data exist on their effect on left atrial (LA) function. The aim of the study was to evaluate the effects of cardiac, hepatic and intra-abdominal ectopic fat depots and cardiometabolic risk factors on LA function in non-diabetic male subjects.

Electrocardiographic changes in Emphysema

Chronic obstructive lung disease(COPD), predominantly emphysema, causes several thoracic anatomical and hemodynamic changes which may cause changes in various electrocardiographic parameters. A 12-lead electrocardiogram(ECG), which is often a part of routine evaluation in most clinical settings, may serve as a useful screening modality for diagnosis of COPD or emphysema. Our current article aims to provide a comprehensive review of the electrocardiographic changes encountered in COPD/emphysema utilizing published PubMed and Medline literature database. Several important ECG changes are present in COPD/emphysema and may serve as a good diagnostic tool. Verticalization of Pvector, changes in QRS duration, pattern recognition of precordial R-wave progression and axial shifts can be considered some of the most valuable markers among other changes. In conclusion, 12-lead surface electrocardiogram can serve as a valuable tool for the diagnosis of COPD and/or emphysema. An appropriate knowledge of these ECG changes can not only help in the diagnosis but can also immensely help in an appropriate clinical management of these patients.     

Hypopituitarism following radiotherapy

Deficiencies in anterior pituitary hormones secretion ranging from subtle to complete occur following radiation damage to the hypothalamic-pituitary (h-p) axis, the severity and frequency of which correlate with the total radiation dose delivered to the h-p axis and the length of follow up. Selective radiosensitivity of the neuroendocrine axes, with the GH axis being the most vulnerable, accounts for the high frequency of GH deficiency, which usually occurs in isolation following irradiation of the h-p axis with doses less than 30 Gy. With higher radiation doses (30-50 Gy), however, the frequency of GH insufficiency substantially increases and can be as high as 50-100%. Compensatory hyperstimulation of a partially damaged h-p axis may restore normality of spontaneous GH secretion in the context of reduced but normal stimulated responses; at its extreme, endogenous hyperstimulation may limit further stimulation by insulin-induced hypoglycaemia resulting in subnormal GH responses despite normality of spontaneous GH secretion in adults. In children, failure of the hyperstimulated partially damaged h-p axis to meet the increased demands for GH during growth and puberty may explain what has previously been described as radiation-induced GH neurosecretory dysfunction and, unlike in adults, the ITT remains the gold standard for assessing h-p functional reserve. Thyroid-stimulating hormone (TSH) and ACTH deficiency occur after intensive irradiation only (>50 Gy) with a long-term cumulative frequency of 3-6%. Abnormalities in gonadotrophin secretion are dose-dependent; precocious puberty can occur after radiation dose less than 30 Gy in girls only, and in both sexes equally with a radiation dose of 30-50 Gy. Gonadotrophin deficiency occurs infrequently and is usually a long-term complication following a minimum radiation dose of 30 Gy. Hyperprolactinemia, due to hypothalamic damage leading to reduced dopamine release, has been described in both sexes and all ages but is mostly seen in young women after intensive irradiation and is usually subclinical. A much higher incidence of gonadotrophin, ACTH and TSH deficiencies (30-60% after 10 years) occur after more intensive irradiation (>60 Gy) used for nasopharyngeal carcinomas and tumors of the skull base, and following conventional irradiation (30-50 Gy) for pituitary tumors. The frequency of hypopituitarism following stereotactic radiotherapy for pituitary tumors is mostly seen after long-term follow up and is similar to that following conventional irradiation. Radiation-induced anterior pituitary hormone deficiencies are irreversible and progressive. Regular testing is mandatory to ensure timely diagnosis and early hormone replacement therapy.     

氟中毒对雄鼠垂体—性腺轴功能的影响

分别用腹腔注射氟化钠和喂饲含氟水的方法制造了雄鼠亚急性和慢性氟中毒模型,观察了对大鼠垂体—性腺轴功能的影响。得到如下结果:亚急性氟中毒大鼠前列腺、睾丸和垂体的相对重量均无显著变化,血清睾酮水平降低,LH 水平显著升高,但垂体 LH 含量无显著变化;慢性氟中毒大鼠睾丸和垂体的相对重量均无显著变化,但前列腺的相对重量有随饮水氟浓度的升高而降低的趋势,血清睾酮水平降低,且与饮水氟浓度呈剂量—效应关系,血清 LH 无明显变化,但垂体 LH 含量有所降低。     

Sonography of anencephaly: pitfalls in early diagnosis

A case in which the diagnosis of anencephaly was missed on a standard obstetrical sonogram performed at 12.5 menstrual weeks is described. Prompted by this case, we retrospectively reviewed the appearance of the cephalic pole of normal fetuses in 47 pregnancies ranging in menstrual age from 11 weeks to 16 weeks. Results indicate that the abnormal cephalic pole in the index case was similar to the appearance of many normal fetuses of similar menstrual age. We conclude that while anencephaly may be diagnosed as early as 11 menstrual weeks to 12 menstrual weeks, this defect may be difficult to diagnose on sonograms using standard sonographic techniques prior to 14 menstrual weeks.     

Effect of intraduodenal and intravenous triglyceride infusions on plasma gastric inhibitory polypeptide and insulin in fetal and neonatal pigs

Summary The responses of gastric inhibitory polypeptide (GIP) and insulin to intraduodenal and IV triglyceride infusions were measured in 11 late fetal and 10 neonatal pigs. Basal plasma glucose, insulin, and GIP concentrations were lower in fetal than in neonatal pigs. In the fetal pigs, plasma glucose increased slightly during intraduodenal and IV triglyceride infusions, whereas plasma insulin remained unchanged during the tests. No significant changes were observed in plasma GIP concentration following intraduodenal triglyceride infusion in the fetal pigs, but plasma GIP fell during the IV infusion of triglyceride in these pigs (p<0.01). In the neonatal pigs, plasma glucose and insulin remained unaffected by intraduodenal and triglyceride infusions. Plasma GIP did not change during the IV triglyceride infusion, but exhibited a paradoxical decline after the intraduodenal triglyceride infusion (p<0.05). It is concluded that the GIP-cell response to an oral triglyceride load is suppressed in late fetal and neonatal pigs. The abolished GIP response to oral triglycerides could play a causal role in the inactivity of the enteroinsular axis which is seen in both human and animal neonates.     

Gut microbes and metabolites as modulators of blood-brain barrier integrity and brain health

ABSTRACT

The human gastrointestinal (gut) microbiota comprises diverse and dynamic populations of bacteria, archaea, viruses, fungi, and protozoa, coexisting in a mutualistic relationship with the host. When intestinal homeostasis is perturbed, the function of the gastrointestinal tract and other organ systems, including the brain, can be compromised. The gut microbiota is proposed to contribute to blood-brain barrier disruption and the pathogenesis of neurodegenerative diseases. While progress is being made, a better understanding of interactions between gut microbes and host cells, and the impact these have on signaling from gut to brain is now required. In this review, we summarise current evidence of the impact gut microbes and their metabolites have on blood-brain barrier integrity and brain function, and the communication networks between the gastrointestinal tract and brain, which they may modulate. We also discuss the potential of microbiota modulation strategies as therapeutic tools for promoting and restoring brain health.     

Gut microbiota profiles of autism spectrum disorder and attention deficit/hyperactivity disorder: A systematic literature review.

ABSTRACT

Accumulating evidence has implicated an involvement of the gut-brain axis in autism spectrum disorder (ASD) and attention-deficit hyperactivity disorder (ADHD), however with highly diverse results. This systematic review aims to describe and evaluate studies investigating the gut microbiota composition in individuals with ASD or ADHD and to evaluate if variations in gut microbiota are associated with these disorders.

Twenty-four articles were identified in a systematic literature search of PubMed and Embase up to July 22, 2019. They consisted of 20 studies investigating ASD and four studies investigating ADHD. For ASD, several studies agreed on an overall difference in β-diversity, although no consistent bacterial variation between all studies was reported. For ADHD, the results were more diverse, with no clear differences observed.

Several common characteristics in gut microbiota function were identified for ASD compared to controls. In contrast, highly heterogeneous results were reported for ADHD, and thus the association between gut microbiota composition and ADHD remains unclear. For both disorders, methodological differences hampered the comparison of studies.     

Lactobacillus rhamnosus probiotic prevents airway function deterioration and promotes gut microbiome resilience in a murine asthma model

ABSTRACT

Allergic asthma is a highly prevalent inflammatory disease of the lower airways, clinically characterized by airway hyperreactivity and deterioration of airway function. Immunomodulatory probiotic bacteria are increasingly being explored to prevent asthma development, alone or in combination with other treatments.

In this study, wild-type and recombinant probiotic Lactobacillus rhamnosus GR-1 were tested as preventive treatment of experimental allergic asthma in mice. Recombinant L. rhamnosus GR-1 was designed to produce the major birch pollen allergen Bet v 1, to promote allergen-specific immunomodulation. Administration of wild-type and recombinant L. rhamnosus GR-1 prevented the development of airway hyperreactivity. Recombinant L. rhamnosus GR-1 also prevented elevation of airway total cell counts, lymphocyte counts and lung IL-1β levels, while wild-type L. rhamnosus GR-1 inhibited airway eosinophilia. Of note, a shift in gut microbiome composition was observed after asthma development, which correlated with the severity of airway inflammation and airway hyperreactivity. In the groups that received L. rhamnosus GR-1, this asthma-associated shift in gut microbiome composition was not observed, indicating microbiome-modulating effects of this probiotic.

These data demonstrate that L. rhamnosus GR-1 can prevent airway function deterioration in allergic asthma. Bet v 1 expression by L. rhamnosus GR-1 further contributed to lower airway inflammation, although not solely through the expected reduction in T helper 2-associated responses, suggesting involvement of additional mechanisms. The beneficial effects of L. rhamnosus GR-1 correlate with increased gut microbiome resilience, which in turn is linked to protection of airway function, and thus further adds support to the existence of a gut-lung axis.