S Anderson

A provisional database for the silicon content of foods in the United Kingdom

Si may play an important role in bone formation and connective tissue metabolism. Although biological interest in this element has recently increased, limited literature exists on the Si content of foods. To further our knowledge and understanding of the relationship between dietary Si and human health, a reliable food composition database, relevant for the UK population, is required. A total of 207 foods and beverages, commonly consumed in the UK, were analysed for Si content. Composite samples were analysed using inductively coupled plasma-optical emission spectrometry following microwave-assisted digestion with nitric acid and H(2)O(2). The highest concentrations of Si were found in cereals and cereal products, especially less refined cereals and oat-based products. Fruit and vegetables were highly variable sources of Si with substantial amounts present in Kenyan beans, French beans, runner beans, spinach, dried fruit, bananas and red lentils, but undetectable amounts in tomatoes, oranges and onions. Of the beverages, beer, a macerated whole-grain cereal product, contained the greatest level of Si, whilst drinking water was a variable source with some mineral waters relatively high in Si. The present study provides a provisional database for the Si content of UK foods, which will allow the estimation of dietary intakes of Si in the UK population and investigation into the role of dietary Si in human health.

The comparative absorption of silicon from different foods and food supplements.

Dietary Si (orthosilicic acid; OSA) appears important in connective tissue health, and although the sources and intakes of Si are well established, its absorption is not. Si absorption was measured from eight high-Si-containing sources: alcohol-free beer; OSA solution (positive control); bananas; green beans; supplemental choline-stabilised OSA (ChOSA); supplemental monomethyl silanetriol (MMST); supplemental colloidal silica (CS); magnesium trisilicate British Pharmacopoeia antacid (MTBP). Two of the supplements and the antacid were pre-selected following an in vitro dissolution assay. Fasting, healthy subjects (CS, n 3; others, n > or = 5) each ingested two of the sources separated by a 1-week wash-out period. Blood and urine were collected and measured for total Si concentrations by inductively coupled plasma optical emission spectrometry. Absorption, based on urinary Si excretion, was highest for MMST and alcohol-free beer (64% of dose), followed by green beans (44%), OSA (43%), ChOSA (17%), bananas and MTBP (4%) and CS (1%). Peak serum concentrations occurred by 0.5 h for MMST and green beans, 1.5 h for OSA and alcohol-free beer, 2 h for ChOSA and CS, and 4 h for MTBP. Area under the serum curves correlated positively with urinary Si output (r 0.82; P < 0.0001). Absorption of Si from supplements and antacids was consistent with their known chemical speciation and kinetics of dissolution under simulated gastrointestinal conditions. Monomeric silicates were readily absorbed, while particulate silicates were decreasingly well absorbed with increasing polymerisation. The present results highlight the need to allow for relative absorption of Si from different foods or supplements in subsequent epidemiological and intervention studies.

Optimising outcome on thiopurines in inflammatory bowel disease by co-prescription of allopurinol ☆

BACKGROUND AND AIMS Azathioprine and mercaptopurine remain first line immunomodulatory treatments for inflammatory bowel disease. Toxicity and non-response are significant issues. Co-prescription of allopurinol with reduced-dose (25-33%) azathioprine or mercaptopurine may overcome these problems. We present the outcome of co-prescription in a large single-centre cohort. METHOD Patients on thiopurine/allopurinol co-prescription were identified. Indication for and outcome on combination treatment were established. Blood parameters and metabolite results were compared on single agent and combination treatment. Toxicity associated with combination treatment was sought. RESULTS 110 patients on combination treatment were identified. Clinical remission was achieved in 60/79 (76%) of patients in whom the effect of thiopurine could be studied in isolation. 20/25 patients with hepatotoxicity tolerated combination treatment and normalised their liver function tests. 24/28 patients with atypical side effects tolerated co-therapy. 13/20 non-responders responded to combination treatment. In patients started on combination treatment as first line therapy, 15/23 achieved clinical remission. Thioguanine nucleotides were significantly higher and methylated metabolites significantly lower on combination therapy. Mean cell volume was higher and total white cell and neutrophil counts lower on combination treatment. 13 adverse events occurred, including 6 specific to co-therapy (3 rash, 2 abnormal liver function tests, 1 dosing error). All were minor and self-limiting. CONCLUSION This is the largest published experience of the use of allopurinol to optimise outcomes on thiopurine treatment. Combination therapy permitted successful treatment of a significant number of patients who would otherwise have been labelled as thiopurine failures. A few self-limiting side effects were encountered.

Increased longitudinal growth in rats on a silicon-depleted diet

Silicon-deficiency studies in growing animals in the early 1970s reported stunted growth and profound defects in bone and other connective tissues. However, more recent attempts to replicate these findings have found mild alterations in bone metabolism without any adverse health effects. Thus the biological role of silicon remains unknown. Using a specifically formulated silicon-depleted diet and modern methods for silicon analysis and assessment of skeletal development, we undertook, through international collaboration between silicon researchers, an extensive study of long-term silicon depletion on skeletal development in an animal. 21-day old female Sprague–Dawley rats (n = 20) were fed a silicon-depleted diet (3.2 µg Si/g feed) for 26 weeks and their growth and skeletal development were compared with identical rats (n = 10) on the same diet but with silicon added as Si(OH)4 to their drinking water (53.2 µg Si/g water); total silicon intakes were 24 times different. A third group of rats, receiving a standard rodent stock feed (322 µg Si/g feed) and tap water (5 µg Si/g water), served as a reference group for optimal growth. A series of anthropometric and bone quality measures were undertaken during and following the study. Fasting serum silicon concentrations and especially urinary silicon excretion were significantly lower in the silicon-deprived group compared to the supplemented group (P = 0.03 and 0.004, respectively). Tibia and soft-tissue silicon contents did not differ between the two groups, but tibia silicon levels were significantly lower compared to the reference group (P < 0.0001). Outward adverse health effects were not observed in the silicon-deprived group. However, body lengths from week 18 onwards (P < 0.05) and bone lengths at necropsy (P ≤ 0.002) were longer in this group. Moreover, these measures correlated inversely with serum silicon concentrations (P ≤ 0.02). A reduction in bone growth plate thickness and an apparent increase in chondrocyte density were also observed in the silicon-deprived animals. No other differences were observed between the two groups, except for tibia phosphorus concentrations, which were lower in the silicon-deprived animals (P = 0.0003). Thus in this study we were unable to reproduce the profound deficiency state reported in rats and chicks in the early 1970s. Indeed, although silicon intake and circulating fasting serum levels differed between the silicon-deprived and silicon-supplemented animals, tibia and soft-tissue levels did not and may explain the lack of difference in bone quality and bone markers (except serum CTx) between these two groups. Markedly higher tibia silicon levels in the reference group and nutritional differences between the formulated low-Si and reference diets suggest that one or more co-factors may be absent from the low-Si diet that affect silicon incorporation into bone. However, evidence for urinary silicon conservation (to maintain tissue levels), changes in bone/body lengths, bone calcium:phosphorus ratio and differences at the growth plate with silicon deprivation are all novel and deserve further study. These results suggest that rats actively maintain body silicon levels via urinary conservation, but the low circulating serum silicon levels during silicon deficiency result in inhibition of growth plate closure and increased longitudinal growth. Silicon-responsive genes and Si transporters are being investigated in the kidneys of these rats.

Small bowel MR enterography: problem solving in Crohn’s disease

AbstractMagnetic resonance enterography (MRE) is fast becoming the first-line radiological investigation to evaluate the small bowel in patients with Crohn’s disease. It can demonstrate both mural and extramural complications. The lack of ionizing radiation, together with high-contrast resolution, multiplanar capability and cine-imaging make it an attractive imaging modality in such patients who need prolonged follow-up. A key question in the management of such patients is the assessment of disease activity. Clinical indices, endoscopic and histological findings have traditionally been used as surrogate markers but all have limitations. MRE can help address this question. The purpose of this pictorial review is to (1) detail the MRE protocol used at our institution; (2) describe the rationale for the MR sequences used and their limitations; (3) compare MRE with other small bowel imaging techniques; (4) discuss how MRE can help distinguish between inflammatory, stricturing and penetrating disease, and thus facilitate management of this difficult condition. Main Messages • MR enterography (MRE) is the preferred imaging investigation to assess Crohn’s disease. T2-weighted, post-contrast and diffusion-weighted imaging (DWI) can be used.• MRE offers no radiation exposure, high-contrast resolution, multiplanar ability and cine imaging.• MRE can help define disease activity, a key question in the management of Crohn’s disease.• MRE can help distinguish between inflammatory, stricturing and penetrating disease.• MRE can demonstrate both mural and extramural complications.

Choline-stabilized orthosilicic acid supplementation as an adjunct to Calcium/Vitamin D3 stimulates markers of bone formation in osteopenic females: a randomized, placebo-controlled trial

BackgroundMounting evidence supports a physiological role for silicon (Si) as orthosilicic acid (OSA, Si(OH)4) in bone formation. The effect of oral choline-stabilized orthosilicic acid (ch-OSA) on markers of bone turnover and bone mineral density (BMD) was investigated in a double-blind placebo-controlled trial.MethodsOver 12-months, 136 women out of 184 randomized (T-score spine < -1.5) completed the study and received, daily, 1000 mg Ca and 20 μg cholecalciferol (Vit D3) and three different ch-OSA doses (3, 6 and 12 mg Si) or placebo. Bone formation markers in serum and urinary resorption markers were measured at baseline, and after 6 and 12 months. Femoral and lumbar BMD were measured at baseline and after 12 months by DEXA.ResultsOverall, there was a trend for ch-OSA to confer some additional benefit to Ca and Vit D3 treatment, especially for markers of bone formation, but only the marker for type I collagen formation (PINP) was significant at 12 months for the 6 and 12 mg Si dose (vs. placebo) without a clear dose response effect. A trend for a dose-corresponding increase was observed in the bone resorption marker, collagen type I C-terminal telopeptide (CTX-I).Lumbar spine BMD did not change significantly. Post-hoc subgroup analysis (baseline T-score femur < -1) however was significant for the 6 mg dose at the femoral neck (T-test). There were no ch-OSA related adverse events observed and biochemical safety parameters remained within the normal range.ConclusionCombined therapy of ch-OSA and Ca/Vit D3 had a potential beneficial effect on bone collagen compared to Ca/Vit D3 alone which suggests that this treatment is of potential use in osteoporosis. NTR 1029

Efficacy and safety of endoscopic dilation of esophageal strictures in epidermolysis bullosa

BACKGROUND Epidermolysis bullosa is a rare genetically determined disorder of the stratified squamous epithelium. Patients with the most severe forms develop scarring of the esophagus after ingestion of food. This results in dysphagia, which severely compromises the ability to eat. Maintenance of adequate nutritional intake is a central aim, but the most appropriate method is unknown. METHODS The results of endoscopic through-the-scope balloon dilation under propofol anesthesia in 53 patients with epidermolysis bullosa and esophageal strictures are reported. RESULTS Seventy-five percent of patients had a single stricture (range 1 to 6 strictures), most often in the proximal esophagus (median 20 cm from incisors). A total of 182 dilations were performed (median two per patient) over a median follow-up period of 3.5 years. For all but 3 patients, there was an improvement in the dysphagia score. There was a mean increase in weight after the procedure of 2.9 kg: 95% CI[2.0, 3.8]; p<0.001, over a median 29 days. There was no significant post-procedure morbidity. CONCLUSIONS Endoscopic balloon dilation is a safe and effective treatment for the esophageal strictures of epidermolysis bullosa. In the majority of patients, dilation relieves dysphagia and improves nutritional status.

The impact of introducing thioguanine nucleotide monitoring into an inflammatory bowel disease clinic

Background:  Thioguanine nucleotides (TGNs) are the active product of thiopurine metabolism. Levels have been correlated with effective clinical response. Nonetheless, the value of TGN monitoring in clinical practice is debated. We report the influence of introducing TGN monitoring into a large adult inflammatory bowel disease (IBD) clinic.

Clinical and pathological features of eosinophilic oesophagitis: a review

&NA; Eosinophilic oesophagitis (EOE) is a newly described clinicopathological entity that is being diagnosed with increasing frequency both in children and in adults. It is presumed to be an atopic disease involving both immediate and delayed‐type hypersensitivity to inhaled and ingested allergens. Because of the reflux‐type symptomatology, it is commonly misdiagnosed and treated as severe gastro‐oesophageal reflux disease (GORD) before an appropriate diagnosis is made. Pathologically, EOE is an inflammatory disorder with a predominantly eosinophilic infiltrate that is unresponsive to acid suppression therapy. The diagnosis of this disease requires histological confirmation with oesophageal biopsy specimens showing an intense eosinophilic infiltration. Although precise criteria or a specific cutoff point for the diagnosis of eosinophilic oesophagitis have not been established, many authors suggest that one high‐power field with >20 eosinophils or multiple high‐power fields with >15 eosinophils, together with clinical and endoscopic findings, should be sufficient for diagnosis. Recognition of EOE and differentiation from GORD are important, since allergen elimination or anti‐inflammatory therapy appears to be more effective than acid suppression in these patients. This review focuses on clinicopathological features and diagnosis of EOE in adults and children.

Hidradenitis suppurativa: MRI features in anogenital disease

BACKGROUND: Hidradenitis suppurativa is a rare chronic inflammatory disorder of apocrine gland-bearing skin, which commonly affects the anogenital region. There has been very little literature to date on the MRI appearances of anogenital hidradenitis suppurativa. OBJECTIVE: The aim of this study was to assess the MRI features of anogenital hidradenitis suppurativa in the largest cohort of patients to be published to date. DESIGN: After an institutional review board waiver, patients with hidradenitis suppurativa who were undergoing MRI for anogenital disease between 2005 and 2012 were identified from our institutional database. The MRI appearances were recorded by 2 radiologists in consensus, blinded to clinical details. Location of disease, number of tracts, presence of anal fistula, and supralevator involvement were recorded. Patient demographics were also noted. SETTINGS: This study was conducted at the Department of Radiology, Guy’s and St Thomas’ National Health Service Foundation Trust. PATIENTS: Patients included were those undergoing MRI for anogenital disease in hidradenitis suppurativa between 2005 and 2012. MAIN OUTCOME MEASURES: The distribution of sinus tracts in anogenital hidradenitis suppurativa on MRI was measured. RESULTS: Thirty-one MRIs were performed in 18 patients (15 men; mean age, 46 years). On the baseline MRI, multiple tracts were seen in the natal cleft (16/18; 83%), the perianal (12/18; 61%), the perineal (13/18; 56%), and the gluteal (8/18; 44%) regions. A communication with the anal canal was present in only 4 patients. Three patients had supralevator extension. Seven patients had follow-up MRIs with variable response to interval treatment: 3 of 7 showed responding disease, 3 of 7 showed stable disease, and 1 of 7 showed progressive disease. LIMITATIONS: This study was limited by its relatively small cohort of patients. CONCLUSIONS: In hidradenitis suppurativa, anogenital disease is usually subcutaneous but extensive, with only a minority of patients demonstrating deeper involvement. MRI may help define the extent of anogenital disease and assess response to treatment.