Influence of a high-fat diet on gut microbiota, intestinal permeability and metabolic endotoxaemia

Lipopolysaccharide (LPS) may play an important role in chronic diseases through the activation of inflammatory responses. The type of diet consumed is of major concern for the prevention and treatment of these diseases. Evidence from animal and human studies has shown that LPS can diffuse from the gut to the circulatory system in response to the intake of high amounts of fat. The method by which LPS move into the circulatory system is either through direct diffusion due to intestinal paracellular permeability or through absorption by enterocytes during chylomicron secretion. Considering the impact of metabolic diseases on public health and the association between these diseases and the levels of LPS in the circulatory system, this review will mainly discuss the current knowledge about high-fat diets and subclinical inflammation. It will also describe the new evidence that correlates gut microbiota, intestinal permeability and alkaline phosphatase activity with increased blood LPS levels and the biological effects of this increase, such as insulin resistance. Although the majority of the studies published so far have assessed the effects of dietary fat, additional studies are necessary to deepen the understanding of how the amount, the quality and the structure of the fat may affect endotoxaemia. The potential of food combinations to reduce the negative effects of fat intake should also be considered in future studies. In these studies, the effects of flavonoids, prebiotics and probiotics on endotoxaemia should be investigated. Thus, it is essential to identify dietetic strategies capable of minimising endotoxaemia and its postprandial inflammatory effects.     

Prevalence of Delirium in End-of-Life Palliative Care Patients: An Observational Study

ObjectivesThe aim of this study was to assess the prevalence of delirium, using the Assessment Test for Delirium and Cognitive Impairment (4AT) in end-of-life palliative care patients.Subjects and MethodsThis retrospective cross-sectional study was conducted on end-of-life patients in a hospice or at home. All patients were evaluated with the 4AT for the presence of delirium.ResultsOf the 461 patients analyzed, 76 (16.5%) were inpatients and 83.5% (385) outpatients. The median age was 79.5 (72–86) years, and 51.0% were female. According to the 4AT score, 126 patients (27.3%) had delirium (A4T ≥4) at admission, 28 (36.8%) were inpatients, and 98 (25.5%) outpatients. Around 33.8% of the cancer inpatients had delirium, while 20.6% of the cancer outpatients had delirium. The prevalence of delirium varied according to the setting, clinical condition, and life expectancy. In addition, 55.0% (11) actively dying inpatients, within 3 days, had delirium, and 56.7% (17) outpatients had delirium; while among those with life expectancy longer than 4 days, 30.4% (17) inpatients and 22.8% (81) outpatients were with delirium.ConclusionsOur study confirms that delirium is common in cancer and noncancer palliative care patients. Further research on delirium in end-of-life palliative care patients should consider the complexity of palliative care of this population as well as of the characteristics of the settings.     

A new familial sclerosing bone dysplasia

Osteoscleroses are a heterogeneous group of bone remodeling disorders characterized by an increase in bone density. Here we report on a consanguineous Lebanese family in which two sisters, aged 39 and 36 years, exhibit a severe genu varum, a square‐face appearance, high forehead, slight proptosis of the eyes, symmetric enlargement of the jaw, protruding chin, and short stature. Bone X‐rays showed the presence of hyperostosis of the cranial base and vault with increased density of the orbits, hyperostosis of the bones, thickening of the cortices, diaphyseal modeling defects, cortical thickening of the medullary cavity, mild enlargement of the medullary cavity of the short long bones, short femoral necks, increased width of the ribs, and narrow interpedicular distances of the lower lumbar spine. Osteodensitometry showed values 200% to 300% above values for age. A cervical MRI revealed the presence of a diffuse osteosclerosis with calcification of the posterior vertebral ligament and a narrow canal between C2 and T2. Blood test results were unremarkable. Serum osteocalcin levels were in the normal range, whereas high values of serum C ‐ telopeptide were noted. A bone biopsy showed only the presence of compact bone and did not allow for histomorphometric analysis. Molecular studies excluded genes known to be involved in sclerosing bone dysplasias as the cause of this condition. In vitro analysis of osteoclast function indicated that contrary to most cases of autosomal recessive osteopetrosis, osteoclasts both formed and resorbed but exhibited a small decrease in resorptive activity compared with osteoclasts generated from normal control individuals. Differential diagnoses are discussed, and the possibility that this may be a novel clinical entity is raised. © 2010 American Society for Bone and Mineral Research.     

Antimetastatic activity and low systemic toxicity of tetradecyl gallate in a preclinical melanoma mouse model

Gallates with eight or more carbon atoms in the lateral chain show potent anticancer activity against various cell lines. However, studies regarding the in vivo antimelanoma activity of tetradecyl gallate (C₁₄) have not yet been reported. In this study an evaluation of the ability of C₁₄ to inhibit metastasis, using lung metastases as a model, was carried out. The experimental mouse melanoma model was established by intravenous injection of metastatic B16F10 melanoma cells. The systemic toxicity of C₁₄ was evaluated in vivo by monitoring the weight, survival, biochemical and hematological parameters, and through histological analysis. It was observed that C₁₄ decreased lung metastasis in vivo by 80% and increased the survival rate of the animals without toxic effects. Additionally, C₁₄ induced cytotoxic effects on B16F10 cells, inhibited the inter-cellular adhesion molecule 1 (ICAM-1) and vascular cell adhesion molecule 1 (VCAM-1) expression, and significantly decreased cell adhesion. These results reveal that C₁₄ has potent antimetastatic ability and is a good candidate for further study as a potential therapeutic agent for tumor metastases.     

Effects of radial shock waves therapy on osteoblasts activities

Radial shock waves therapy (RSWT) differs from extracorporeal shock waves therapy (ESWT) in that it produces a non-focused wave that is dissipated radially at the skin. Few studies have yet explored the effects of RSWT on bone tissue. Osteoblasts in culture flasks were studied by polymerase chain reaction after treatment with RSW (500 impulses, 0.05?mJ/mm²). An inhibited osteoblastogenesis was observed, with a statistically significant reduction in type 1 collagen, osterix, bone sialoprotein and receptor activator NF kappa ligand expression at 24 and 48?h, of osteocalcin at 24, 48 and 72?h, and osteopontin at 48 and 72?h. These findings show that RSWT is not indicated for treatment of delayed fracture union, pseudoarthrosis, and complex regional pain syndrome. The observed reduction in the receptor activator of nuclear factor-kB ligand/osteoprotegerin ratio suggests that it has an inhibiting effect on osteoclastogenesis, which could make it a useful tool for applications in proliferative diseases.