Ortho-silicic acid enhances osteogenesis of osteoblasts through the upregulation of miR-130b which directly targets PTEN.

AIMS: Osteoporosis is considered a common skeletal disease. Ortho-silicic acid has been found to enhance the osteogenic differentiation of osteoblasts. However, the molecular mechanism of osteogenesis induced by ortho-silicic acid is still undefined totally. MicroRNAs (miRs) play a key role in osteogenesis of osteoblasts. This study investigated the role of miR-130b in promoting osteogenesis induced by ortho-silicic acid. MAIN METHODS AND KEY FINDINGS: In this study, we found ortho-silicic acid enhanced osteogenesis of osteoblasts in vitro and promoted preventing and treating osteoporosis in vivo. Furthermore, the expression of miR-130b increased under application of ortho-silicic acid. In vitro, experiments demonstrated miR-130b overexpression or inhibition significantly promoted or suppressed osteogenic differentiation of osteoblasts under application of ortho-silicic acid, respectively. Consistently, downregulation of miR-130b in ovariectomy (OVX) rats dropped off the beneficial effect of ortho-silicic acid against bone loss. Mechanistically, we identified phosphatase and tensin homologue deleted on human chromosome 10 (PTEN) as the direct target of miR-130b during osteogenesis induced by ortho-silicic acid. SIGNIFICANCE: In conclusion, our findings reveal that ortho-silicic acid promotes the osteogenesis of osteoblasts mediated by the miR-130b/PTEN signaling axis, which identifies a new target to prevent and treat osteoporosis.

A Histologic Perspective on Electrical and Thermal Burn-Injured Human Skin.

OBJECTIVE: To analyze specific spectroscopic (FT-Raman) and thermal (limiting oxygen index) aspects of skin samples exposed to electrical injury compared with thermal injury. METHODS: An observational case-control study was conducted at the Dr Stanislaw Sakiel Center for Burns Treatment in Siemianowice, Silesia, Poland. A scanning electron microscope was used to diagnose and illustrate the topography of skin samples from electrical and thermal burns and the morphologic effects on damaged versus undamaged skin surfaces. In particular, researchers attempted to detect spectroscopic and thermal changes at the molecular level, namely, specific biomarkers of tissue degeneration and their regeneration under the influence of the applied modifiers (antioxidants and orthosilicic acid solutions). RESULTS: Modification with L-ascorbic acid and hydrogel of orthosilicic acid caused an increase in the intensity of the amide I Raman peaks, whereas modification with sodium ascorbate and orthosilicic acid resulted in the separation of the band protein side chains (1,440-1,448 cm), which is a part of tissue regeneration. The best result was obtained when the skin was treated with 7% orthosilicic acid (limiting oxygen index, 26%). CONCLUSIONS: Antioxidant treatment may be advantageous in minimizing injury in patients with thermal burns but not always in electrical burns.

Use of silicon for skin and hair care: an approach of chemical forms available and efficacy

Abstract Silicon is the second most abundant element on Earth, and the third most abundant trace element in human body. It is present in water, plant and animal sources. On the skin, it is suggested that silicon is important for optimal collagen synthesis and activation of hydroxylating enzymes, improving skin strength and elasticity. Regarding hair benefits, it was suggested that a higher silicon content in the hair results in a lower rate of hair loss and increased brightness. For these beneficial effects, there is growing interest in scientific studies evaluating the efficacy and safety of using dietary supplements containing silicon. Its use aims at increasing blood levels of this element and improving the skin and its annexes appearance. There are different forms of silicon supplements available and the most important consideration to be made in order to select the best option is related to safety and bioavailability. Silicon supplements are widely used, though there is wide variation in silicon bioavailability, ranging from values below 1% up to values close to 50%, depending on the chemical form. Therefore, the aim of this study was to evaluate the scientific literature related to the different chemical forms of silicon supplements available and the limitations and recent progress in this field. According to reported studies, among the different chemical forms available, the orthosilicic acid (OSA) presents the higher bioavailability, whereas the others forms have absorption inversely proportional to the degree of polymerization. However, clinical studies evaluating safety and efficacy are still lacking.

Randomised clinical trial: alginate (Gaviscon Advance) vs. placebo as add-on therapy in reflux patients with inadequate response to a once daily proton pump inhibitor.

BACKGROUND: Many reflux patients remain symptomatic on a standard dose of proton pump inhibitor (PPI). Alginates decrease the number of reflux events by forming a raft on top of the stomach content and thus offer a supplemental mechanism of action to acid suppression. AIM: To assess the efficacy of an alginate (Gaviscon Advance, Reckitt Benckiser, Slough, UK) on reflux symptoms in patients with persistent symptoms despite once daily PPI. METHODS: This was a multicentre, randomised, placebo-controlled, 7-day double-blind trial preceded by a 7-day run-in period. Reflux symptoms were assessed using the Heartburn Reflux Dyspepsia Questionnaire (HRDQ). Based on symptom score during run-in, eligible patients were randomised to Gaviscon Advance 10 mL four times a day or placebo in addition to a once daily PPI. The primary endpoint was change in HRDQ score post-treatment compared to baseline. RESULTS: One hundred and thirty-six patients were randomised. Change in HRDQ reflux score was significantly greater for Gaviscon Advance (mean: -5.0, s.d.: 4.7) than for placebo (mean: -3.5, s.d.: 5.5) with an LS mean difference of 1.6 [95% CI -3.1 to -0.1], P = 0.03. A decrease in the mean (s.d.) number of nights with symptoms was observed from 3.6 (2.8) to 3.0 (3.0) in the placebo group and from 3.9 (2.8) to 2.2 (2.7) for the Gaviscon Advance group. This reduction was significantly greater in the Gaviscon Advance group than in the placebo group [LS mean difference = -0.9, 95% CI (-1.6 to -0.2), P < 0.01]. CONCLUSION: In patients with residual reflux symptoms despite PPI treatment, adding an alginate offers additional decrease in the burden of reflux symptoms (EudraCT/IND Number: 2011-005486-21).

Acceleration of bone-defect repair by using A-W MGC loaded with BMP2 and triple point-mutant HIF1α-expressing BMSCs.

BACKGROUND: The goal of this study is to explore the effects of A-W MGC (apatite-wollastonite magnetic bioactive glass-ceramic) loaded with BMP2 (bone morphogenetic protein 2)- and HIF1α(mu) (hypoxia-inducible factor 1 mutation)-expressing BMSCs (bone marrow mesenchymal stem cells) on the bone defect repair. METHODS: (1) BMSCs were infected with viral solution containing BMP2 and HIF1α(mu) with the best MOI (multiplicity of infection). The efficiency was observed via hrGFP (human renilla reniformis green fluorescent protein). (2) The cells were divided into five groups (A-E), and ALP (alkaline phosphatase) activity was measured. (3) BMP2 and HIF1α (hypoxia-inducible factor 1α) protein were measured. (4) A-W MGC was loaded with BMSCs that contain the genes and implanted into the bone defect model. The animals were sacrificed 8 and 12 weeks later. (5) The healing was measured with X-ray, histology, and biomechanics. RESULTS: (1) BMSCs in A-D showed high transfection efficiency. (2) ALP in A and B was higher than the others (p = 0.041 or 0.038); A was higher than B (p = 0.038); (3) BMP2 in A and B was higher than the others (p = 0.014). HIF1α in A and C was higher than the others (p = 0.020). (4) 8 and 12 weeks after, an X-ray indicated that bone defect was nearly fully repaired in A and C. (5) 12 weeks after, the bone remodeling was complete in A and C. (6) The flexural strength in A and C was stronger than the others (p = 0.043). CONCLUSION: Engineered A-W MGC with BMP2 and HIF1α(mu)-expressing BMSCs exhibits comparable therapeutic effects of bone-defect repair as an autologous bone graft.

Biocompatibility and in vivo osteogenic capability of novel bone tissue engineering scaffold A-W-MGC/CS.

BACKGROUND: This study aims to investigate the biocompatibility and in vivo osteogenic capability of the novel bone tissue engineering scaffold apatite-wollastonite-magnetic glass ceramic/chitosan (A-W-MGC/CS). METHODS: Rabbit bone marrow stromal cells (BMSCs) were transfected with adenovirus-human bone morphogenetic protein-2-green fluorescent protein (Ad-hBMP2-GFP). The transfected BMSCs were then inoculated onto the scaffold material A-W-MGC/CS to construct tissue-engineered bone. The attachment and proliferation of BMSCs were observed by scanning electron microscopy (SEM) and 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) detection, respectively. Rabbit models of bone defects were established and divided into three groups. Experimental group 1 was implanted with prepared tissue-engineered bone. Experimental group 2 was implanted with A-W-MGC/CS without transfected BMSCs. The blank group was injected with transfected BMSCs, without implantation of any scaffold. In the 12th week after surgery, the repair of bone defect was observed by X-ray examination, and histological observations of the area of bone defect were performed. RESULTS: A-W-MGC/CS resulted in good BMSC attachment and had no obvious effects on cell proliferation. In experimental group 1, good repair of bone defect was observed, and the scaffold material degraded completely. In experimental group 2, new bone was formed, but its quality was poor. In the blank group, there was mainly filling of fibrous connective tissues with no observable bone defect repair. CONCLUSION: A-W-MGC/CS possesses good biocompatibility and in vivo osteogenic capability for bone defect repair.

[Update on gastroesophageal reflux disease]. / Puesta al día en el reflujo gastroesofágico.

Gastroesophageal reflux disease is a highly frequent disorder classically characterized by the presence of heartburn and/or acid regurgitation that improves with drug therapy that reduces acid content in the stomach. However, especially in patients with non-erosive disease, response to proton pump inhibitors is unsatisfactory in approximately 1 out of 3 patients, and consequently, in these patients, it is important to establish a definitive diagnosis and an alternative therapeutic strategy. In the last few years, advances have been made in knowledge of the physiopathology of reflux, such as identification of the role of the acid pocket in producing reflux, technological advances that allow differentiation among acid reflux, non-acid reflux and slightly acid reflux, and advances in the treatment of reflux with drugs that attempt to act on the barrier function of the esophagogastric junction.

Abrasion, polishing, and stain removal characteristics of various commercial dentifrices in vitro.

OBJECTIVE: To evaluate, using conventional in vitro procedures, the abrasivity, enamel polishing properties, and stain removal effectiveness of various commercial dentifrices that have a variety of compositions and are marketed for cleaning, whitening, and/or polishing capabilities, and to examine their relationships between stain removal and abrasivity. METHODS: The Relative Dentin Abrasivity (RDA) method was used to measure abrasivity, and the Pellicle Cleaning Ratio (PCR) procedure was used to evaluate stain removal performance. A Cleaning Efficiency Index (CEI) was calculated using the RDA and PCR values. Enamel polish was determined on bovine enamel specimens using a reflectometer. All treatments were performed on a V-8 cross-brushing machine using aqueous dentifrice slurries and standard nylon-bristle toothbrushes. A total of 26 dentifrices, purchased at retail, were tested against the American Dental Association (ADA) calcium pyrophosphate reference standard. RESULTS: All dentifrices removed extrinsic stain and produced some dentin abrasion, but scores ranged widely between products (from 36 to 269 for RDA and from 25 to 138 for PCR). The majority of dentifrices contained hydrated silicas, and those with high PCR scores often, but not always, had higher RDA values. Products containing other abrasives (e.g., dicalcium phosphate, sodium bicarbonate, and calcium carbonate) generally had lower RDA values and usually lower PCR scores. There were exceptions (e.g., refined kaolin clay) that had high PCR scores and low RDA values, resulting in higher CEI values. Similarly, brushing with all dentifrices significantly increased reflectance readings of acid-dulled teeth, but polish scores also were highly variable among products (ranging from 38 to 97). The polish scores of dentifrices containing hydrated silica varied extensively (ranging from 38 to 80), and the scores of products containing other abrasives fell within this same range, except for dentifrices containing either Fuller's earth (86) or kaolin (97). CONCLUSION: With only a few exceptions, dentifrices marketed as "whitening" products were generally more abrasive to dentin, especially for those containing silicas. Similarly, aside from two non-silica products, those dentifrices advertised for polishing ability generally were no more effective than other products. The relationship between stain-removal ability and abrasivity of dentifrices was not necessarily direct.

Submental fat reduction by mesotherapy using phosphatidylcholine alone vs. phosphatidylcholine and organic silicium: a pilot study.

BACKGROUND: Excess skin and fatty tissues beneath the jaw lead to a double chin deformity. Localized fat deposits in this area are a cause of discomfort and anguish, leading patients to undergo surgical procedures such as liposuction and dermolipectomy to improve the cosmetic effect. Both procedures require anesthesia and an operating room setting and are quite expensive. Fearful of extensive surgery and its complications, patients and physicians seek less invasive methods. Mesotherapy with phosphatidylcholine and other cocktails have been used to treat localized fat deposits. However, there are few published articles regarding its effectiveness and some are even anecdotal. OBJECTIVE: This study aims to determine the efficacy of phosphatidylcholine alone vs. phosphatidylcholine and organic silicium in submental fat reduction. METHODS: Twelve patients with submental fat deposit with no coexisting morbidity and with informed consent were included in the study. They were submitted to one to five treatment sessions with an average interval of 2 weeks between each session. The medication administered was injected, either pure phosphatidylcholine or a combination of phosphatidylcholine and organic silicium. Baseline measurements of submental fat using vernier caliper and digital photographs of the patients were taken during each treatment session. The occurrence of adverse effects was likewise noted. Results Among the 12 patients, 11 completed the treatment course, and 1 was excluded from the study because of failure to follow up. Both phosphatidylcholine and a combination of phosphatidylcholine and organic silicium were equally effective in reducing submental fat deposits. There was no significant difference as to the rate and degree of reduction. Significant reduction in the thickness of submental fat was achieved after three treatment sessions. Adverse reactions in both groups were mild and transitory ranging from heavy sensation, localized heat, nodulations, and slight bruising that abated 3 to 5 days after treatment. Limitations As of this writing, information on the use of both phosphatidylcholine and organic silicium for mesotherapy of localized fat such as the submental area is scarce. The exact mechanisms of action of both treatments are likewise unknown. Ultrasound and histopathological changes were not documented. The study did not involve a double-blind, placebo-controlled design, and the sample size was small. CONCLUSION: Mesotherapy using phosphatidylcholine vs. phosphatidylcholine plus organic silicium was similarly effective in reducing submental fat. There was no significant difference between them in terms of rate and degree of reduction. Optimal reduction of submental fat was achieved after three treatment sessions. Adverse reactions were few, mild, and transitory. Therefore, both regimens are safe, efficacious, cost-effective, and can be used as alternatives to invasive surgical procedures.

Failures in a proton pump inhibitor therapeutic substitution program: lessons learned.

The pathogenesis of patient dissatisfaction following involuntary therapeutic substitutions involving proton pump inhibitors (PPIs) is poorly understood. The aim of this study was to describe the patient population experiencing therapeutic failure and investigate whether failure was related to individual differences in response to the different PPIs. Treatment failures in a lansoprazole-rabeprazole therapeutic substitution program were compared to switch successes. A subgroup was randomized in a double-blind, double-dummy, crossover study to four 2-week periods of lansoprazole-rabeprazole-lansoprazole-rabeprazole or vice versa. Measures included overall rating of gastrointestinal reflux disease (GERD) symptoms for the past week as well as the frequency and distress scales of the GERD Symptom Assessment Scale. One hundred fifteen nonresponders were compared with 54 successful responders. Nonresponders consisted primarily of patients with GERD (74%, vs. 44% of responders; P = 0.005) who had undergone upper gastrointestinal endoscopy (50%, vs. 31% of responders; P = 0.02). Twelve patients completed the randomized treatment study. The interrater kappa coefficient for responder status was estimated to be 0.80 for lansoprazole and 0.21 for rabeprazole. The majority of PPI nonresponders had a clinical diagnosis of GERD and were receiving >/=40 mg of rabeprazole daily. This pilot study provides new insights into the design of subsequent studies of nonresponders in PPI therapeutic substitution programs.

[Efficacy and perspective of application of preparation based on hydrogel and xerogel of methyl-silicic acid in patients with the intestinal malignancy]. / Efektivnist' ta perspektyvy zastosuvannia preparativ na osnovi hidroheliu ta kseroheliu metylkremniievoï kysloty u khvorykh iz zloiakisnym novoutvorenniam travnoho kanalu.

There was studied the influence of medicinal preparations, created on the base of methylsiliconorganic matrix, on immediate and late follow-up result of treatment of more than 2000 patients with the digestive channel malignancy. High efficacy of application in complex of preoperative preparation of immobilized antibiotics and cytostatics, enterosorpent enterosgel for the purulent-inflammatory complications prophylaxis, lowering of bilirubin level in tumoral obturative jaundice, and in intraoperative usage for the tumor and metastases recurrences prophylaxis.

Eradicating Helicobacter pylori reduces hypergastrinaemia during long-term omeprazole treatment.

BACKGROUND: Both proton pump inhibitor drug treatment and Helicobacter pylori infection cause hypergastrinaemia in man. AIMS: To determine whether eradicating H pylori is a means of reducing hypergastrinaemia during subsequent proton pump inhibitor treatment. METHODS: Patients with H pylori were randomised to treatment with either anti-H pylori or symptomatic treatment. One month later, all received four weeks treatment with omeprazole 40 mg/day for one month followed by 20 mg/day for six months. Serum gastrin concentrations were measured before and following each treatment. RESULTS: In the patients randomised to anti-H pylori treatment, eradication of the infection lowered median fasting gastrin by 48% and meal stimulated gastrin by 46%. When gastrin concentrations one month following anti-H pylori/symptomatic treatment were used as baseline, omeprazole treatment produced a similar percentage increase in serum gastrin in the H pylori infected and H pylori eradicated patients. Consequently, in the patients in which H pylori was not eradicated, median fasting gastrin concentration was 38 ng/l (range 26-86) at initial presentation and increased to 64 ng/l (range 29-271) after seven months omeprazole, representing a median increase of 68% (p < 0.005). In contrast, in the patients randomised to H pylori eradication, median fasting gastrin at initial presentation was 54 ng/l (range 17-226) and was unchanged after seven months omeprazole at 38 ng/l (range 17-95). CONCLUSION: Eradicating H pylori is a means of reducing the rise in gastrin during subsequent long term omeprazole treatment. In view of the potential deleterious effects of hypergastrinaemia it may be appropriate to render patients H pylori negative prior to commencing long-term proton pump inhibitor treatment.

The effect of silicol gel compared with placebo on papulopustular acne and sebum production. A double-blind study.

Altogether 30 patients (19 females and 11 males), mean age 19 years, were divided randomly into two groups. All patients had chronic papulopustular acne of the face. A total of 15 patients were treated topically with Silicol gel for 20 min twice daily for 6 weeks and the remaining 15 patients were treated with a placebo gel in a similar fashion. A clinical evaluation was carried out at baseline, and after 2, 4 and 6 weeks of treatment. The clinical variables evaluated were as follows: number of comedones, papules, pustules and cysts on a standard area of the left cheek (area 5 x 5 cm) and measurement of sebum production on the same area by the use of Sebumeter SM 810 PC (Courage and Khazaka, Ltd, Germany). No concomitant treatment was allowed during the study period. One patient using Silicol gel withdrew after 2 weeks of treatment because of severe irritation of the facial skin, leaving 29 patients who could be evaluated. In the active group, the number of comedones decreased from a mean of 48.5 to 15.1 after 6 weeks of treatment. The corresponding figures for papules were 10.7 and 1.0, for pustules 6.8 and 0, and for cysts 0.6 and 0. In the placebo group no improvement could be observed. There was a highly significant difference in efficacy between the two groups (P < 0.001) in favour of the actively treated group. The mean sebum index was 193 at baseline and 88 after 6 weeks. Correspondingly in the placebo group the mean sebum index at baseline was 187 and after 6 weeks 179. This difference between the two groups was also statistically significant (P < 0.001). After a short follow-up period (3 months) no deterioration was observed in the 14 'active' patients, showing either complete cure or improvement.

Long term follow up of radiosynovectomy with yttrium-90 silicate in haemophilic haemarthrosis.

OBJECTIVES: The aim of this study was to evaluate the long term effect of radiation synovectomy with yttrium-90 silicate in haemophiliac patients with recurrent haemarthrosis. METHODS: The bleeding frequency and the mobility of the joint were recorded in 16 joints of 14 patients 1 year before radiosynovectomy and during follow up, which ranged from 3 to 6 years. Patients evaluated the effect of their own treatment by completing a questionnaire. Radiographs of the joints were scored by an independent radiologist before treatment. RESULTS: A satisfactory reduction of the frequency of haemorrhage was achieved in 94% of joints during the first year after treatment and was maintained in 63% until the end of the follow up period. In general there was no decrease in mobility attributable to radiosynovectomy, and the patients' own evaluations agreed with the evaluations based on the frequencies of haemarthrosis in 75%. Patients who had only minor, or no, radiological abnormalities of the joints before treatment showed the best results. One patient developed synovitis as a complication of the radiosynovectomy. CONCLUSION: Radiosynovectomy is an effective and safe treatment for recurrent haemarthrosis in haemophiliac patients, especially in those who have joints with no or minor radiological damage.

Induction of micronuclei in peripheral blood lymphocytes of patients treated for rheumatoid or osteo-arthritis of the knee with dysprosium-165 hydroxide macroaggregates or yttrium-90 silicate.

The advantages of radiation synovectomy, using preparations containing dysprosium-165 (Dy-165), over conventional materials based on yttrium-90 (Y-90) include a more ideal spectrum of decay energies, and a much shorter half-life permitting quicker and more efficient treatment. A new therapeutic agent, Dy-165 hydroxide macroaggregates, has been developed for the treatment of arthritis making use of these advantages. As part of a clinical trial of this material 42 patients were examined for micronucleus frequency in their peripheral blood lymphocytes prior to, and 2 weeks after, radiation synovectomy using Dy-165 hydroxide macroaggregates or Y-90 silicate. In the majority of patients from each treatment group no significant increase in micronucleus frequency was observed. This indicates that in these cases leakage of material from the site of treatment was not resulting in detectable irradiation of circulating cells irrespective of the choice of radiopharmaceutical. The maximum increase in micronucleus frequency observed corresponded to a radiation dose to circulating cells of approximately 0.3 Gray.

[Multicenter study of sodium alginate in the treatment of regurgitation in infants]. / Etude clinique multicentrique de l'alginate de sodium dans le traitement des régurgitations du nourrisson.

An open multicenter study was performed to assess the efficacy and safety of alginic acid in two different dosages in 76 pediatric patients with gastroesophageal reflux confirmed by pH monitoring. Among the 69 patients in whom endoscopy was carried out before treatment, 18 had erythematous esophagitis and 5 had erosive esophagitis. Irrespective of the dosage used, the frequency of regurgitation and vomiting decreased significantly (p < 0.00001 and p = 0.01, respectively). Clinical and biochemical tolerance were outstanding and no adverse effects were recorded. On the basis of these data, the recommended dosage is 1 to 2 ml/kg/day in divided doses after meals.

Barrett's oesophagus: effect of antireflux surgery on symptom control and development of complications.

Forty-five patients with histologically proven Barrett's columnar-lined oesophagus (CLO) were treated in one unit over a 9-year period. Patients were studied prospectively as part of a surveillance programme; all initially received standard conservative treatment including high-dose H2-receptor antagonists. A satisfactory initial response was seen in 21 patients, but in 24 the symptoms were unchanged or progressed; 19 patients in the latter group were considered suitable for antireflux surgery and underwent fundoplication. Symptoms of heartburn or dysphagia persisted or recurred in 88 per cent of patients receiving medical treatment alone and complications developed in 38 per cent, including nine strictures and one adenocarcinoma. In patients undergoing antireflux surgery, symptoms persisted or recurred in 21 per cent and complications developed in 16 per cent (P < 0.01). Complete regression of Barrett's CLO occurred in two patients (11 per cent) after antireflux surgery. The results of this study suggest the superiority of antireflux surgery over pharmacological acid suppression in the control of symptoms and prevention of complications in patients with Barrett's CLO.