Association of volatile methylsiloxanes exposure with non-alcoholic fatty liver disease among Chinese adults.

Owing to the wide use of volatile methylsiloxanes (VMSs) in various industries and consumer products, both cyclic VMSs (cVMS) and linear VMSs (lVMS) have been detected in human plasma. Experimental studies suggest that exposure to cVMSs may induce liver disease. Whereas, there is no human evidence of the potential health effects of VMSs yet. In this cross-sectional study, we evaluated the association of plasma VMSs concentrations with liver enzymes and Nonalcoholic fatty liver disease (NAFLD) among adults located in southwestern China. We used the fibrosis 4 calculator (FIB-4) as the NAFLD index and defined FIB-4≥1.45 as the NAFLD case. Among 372 participants, 45 (12.1%) of them were classified as NAFLD. Positive associations of plasma cVMSs concentrations with liver enzymes and NAFLD were observed among all participants. With per doubling increase in the total cVMSs, we observed a 1.40 (95%CI: 0.31, 2.48) increase in Alanine aminotransferase (ALT), a 1.56 (95%CI: 0.52, 2.61) increase in aspartate aminotransferase (AST) and a 0.04 (0.00, 0.09) increase in NAFLD index. A 19% increased risk of NAFLD was also found to be associated with per doubling increase in total cVMSs. In addition, positive associations of total lVMSs with ALT, AST and NAFLD were also detected when restricting our analyses to 230 participants living in industrial areas. Our study first provides epidemiological evidence on the association between VMSs and liver health, indicating more careful usage of VMSs may potentially reduce the burden of NAFLD, though more well-designed cohort studies are needed to confirm these findings.

Efficacy and tolerability of an investigational nitric oxide-releasing topical gel in patients with molluscum contagiosum: A randomized clinical trial.

BACKGROUND: Although a variety of ablative, topical, and systemic therapies are used for molluscum contagiosum (MC), none has been well studied or approved by the US Food and Drug Administration. OBJECTIVES: To compare the efficacy and tolerability of topical SB206 (berdazimer sodium gel coadministered with hydrogel) with vehicle. METHODS: A 12-week, phase 2, multicenter, randomized, double-blind, vehicle-controlled clinical trial of topical SB206. RESULTS: A total of 256 patients (mean age, approximately 7 years) participated. Of patients who completed 12 weeks of treatment (n = 217), all MC lesions cleared in 20.0% of patients who received vehicle compared with 13.2%, 41.0%, and 35.1% of patients treated with twice daily SB206 4%, 8%, and 12%, respectively, and 41.9% of patients treated with once daily SB206 12%. Application-site erythema occurred in 10.6% of patients treated with SB206. Application-site reactions were the most common adverse events leading to treatment discontinuation, affecting 2 patients (approximately 4%) in each of the SB206 4%, 8%, and 12% twice daily groups and 0 patients in the vehicle or SB206 12% once daily groups. LIMITATIONS: A larger study is needed to confirm the efficacy of SB206 12% once daily and provide additional safety assessments. CONCLUSION: Of the doses studied, SB206 12% applied once daily provided the best balance between MC lesion clearance and tolerability for evaluation in a larger study.

Induction of the Estrogenic Marker Calbindn-D9k by Octamethylcyclotetrasiloxane.

Interrupting the hormonal balance of an organism by interfering with hormones and their target receptors gives rise to various problems such as developmental disorders. Collectively, these reagents are known as endocrine disruptors (EDs). Cyclic volatile methyl siloxanes (cVMSs) are a group of silicone polymers that including octamethylcyclotetrasiloxane (D4). In the present study, we examined the estrogenicity of D4 through in vitro and in vivo assays that employed calcium-binding protein 9K (calbindin-D9k; CaBP-9K) as a biomarker. For in vitro investigation, GH3 rat pituitary cells were exposed to vehicle, 17ß-estradiol (E2), or D4 with/without ICI 182 780 (ICI). CaBP-9K and progesterone receptor (PR) both were up-regulated by E2 and D4 which were completely blocked by ICI. Transcription of estrogen receptor α (ER α) was decreased by E2 and D4 but increased by ICI. D4 was also administered to immature female rats for an uterotrophic (UT) assay and detection of CaBP-9K. Ethinyl estradiol (EE) or D4 was administered subcutaneously with or without ICI. Although uterine weight was not significant altered by D4, an effect thought to be due to cytochrome P450 (CYP), it induced CaBP-9K and PR gene expression. Based on these results we reveal that D4 has estrogenic potential proven under in vitro and in vivo experimental conditions.

Cytokine release from human leukocytes exposed to silorane- and methacrylate-based dental materials.

OBJECTIVES: Silorane-based dental monomers contain an epoxy functional group. Less is known about the toxicological and inflammatory potential of silorane-based composites. Therefore we compared the release of 24 cytokines from human leukocytes after incubation with silorane-based Filtek™ Silorane (Silo) and methacrylate-based TetricEvo Flow® (TC). METHODS: Leukocytes from nine healthy test persons (P) were incubated with Silo or TC for up to 72h. All 24h cytokines were quantified with a magnetic bead assay. RESULTS: Silo stimulates the leukocytes to higher release of cytokines when compared to TC. 72h after beginning the experiment, leukocytes from P6 incubated with Silo secreted more than an 18-fold amount of interleukin (IL)-6 when compared with leukocytes incubated with TC (771.8 vs 42.1pg/ml). Only leukocytes from P8 incubated with Silo release up to 14.4pg/ml IL-2 after 72h. SIGNIFICANCE: The significantly higher induction of cytokines with Silo in comparison to TC is test person independent. This indicates a higher sensitization potential for Silo. Because of the cytokine release pattern (especially the release of T-cell dependent IL-2) from leukocytes from P8 after incubation with Silo it is likely that P8 can develop an allergic Type IV sensitization to Silo. Therefore the cytokine release assay is a helpful tool for providing information about possible immunological reactions to dental resins in individual cases as well as for a general risk assessment and comparison between different dental materials.

Organically modified silica nanoparticles are biocompatible and can be targeted to neurons in vivo.

The application of nanotechnology in biological research is beginning to have a major impact leading to the development of new types of tools for human health. One focus of nanobiotechnology is the development of nanoparticle-based formulations for use in drug or gene delivery systems. However most of the nano probes currently in use have varying levels of toxicity in cells or whole organisms and therefore are not suitable for in vivo application or long-term use. Here we test the potential of a novel silica based nanoparticle (organically modified silica, ORMOSIL) in living neurons within a whole organism. We show that feeding ORMOSIL nanoparticles to Drosophila has no effect on viability. ORMOSIL nanoparticles penetrate into living brains, neuronal cell bodies and axonal projections. In the neuronal cell body, nanoparticles are present in the cytoplasm, but not in the nucleus. Strikingly, incorporation of ORMOSIL nanoparticles into the brain did not induce aberrant neuronal death or interfered with normal neuronal processes. Our results in Drosophila indicate that these novel silica based nanoparticles are biocompatible and not toxic to whole organisms, and has potential for the development of long-term applications.

A clinical study on the effects of cordless and conventional retraction techniques on the gingival and periodontal health.

AIM: To investigate the influence of two cordless techniques on the periodontium in comparison with conventional cords. MATERIAL AND METHODS: Dental students (n=60) with healthy gingival conditions were recruited - an expanding poly vinyl siloxane material (Magic Foam Cord), a paste-like material (Expasyl), and a conventional retraction cord (Ultrapak) were applied on the buccal aspects of three premolars of each subject. Probing depth, clinical attachment level, gingival index (GI), plaque index, mobility, bleeding, and sensitivity were assessed at baseline, and at 1 and 7 days after application. Data were analysed using Kruskal-Wallis and Mann-Whittney tests (alpha=0.05). RESULTS: The periodontal parameters were not statistically significant among the groups at all time intervals except for the GI, which was increased for all groups after 1 day. The highest was in Expasyl (p=0.011). After 7 days, the GI returned to a non-significant level compared with baseline except for Expasyl, which was still significant (p=0.044). Expasyl induced sensitivity in four subjects. Bleeding was only induced by Ultrapak in 28.3% and 26.7% during and after retraction, respectively. CONCLUSIONS: All techniques caused a temporary gingival inflammation; the greatest was in Expasyl, which also showed slower recovery. Cordless techniques did not induce bleeding during or after retraction.

Invasive micropapillary carcinomas arising 42 years after augmentation mammoplasty: a case report and literature review.

BACKGROUND: There has been no definitive consensus regarding the causal relationships between foreign bodies in the breast and carcinogenesis. This report describes the first case of invasive micropapillary carcinomas after augmentation mammoplasty. Multiple tumors located in immediate contact with the siliconomas suggested a causal link between the siliconomas and carcinomas. CASE PRESENTATION: This report presents the case of a 64-year-old female who underwent liquid silicone injections for augmentation mammoplasty 42 years previously. Eight years before admission, siliconomas of the left breast were removed due to pain and discomfort. The patient visited the hospital for further treatment of newly diagnosed carcinoma of the left breast. Images showed multiple tumors located in various areas of the left breast. The pathological findings of the left breast showed each tumor to be solitary and not continuous with the others. The tumors were diagnosed to be invasive micropapillary carcinomas, and they all came into immediate contact with the residual siliconomas. The siliconomas were therefore suspected to have played a causative role in the development of the breast cancer. CONCLUSION: This rare case of multiple invasive micropapillary carcinomas following augmentation mammoplasty provides evidence that siliconomas may lead to carcinomas. Although a causal relationship was not established unequivocally, we review evidence that suggest silicone gel may cause cell damage responsible for carcinoma development.

Silsesquioxane nanocomposites as tissue implants.

BACKGROUND: Silicone implants are being used increasingly worldwide, especially in breast augmentation procedures. The most common morbidity observed is capsular contracture, which occurs in 15 percent of cases. To overcome this problem, the authors have developed a novel nanocomposite based on polyhedral oligomeric silsesquioxane-poly(carbonate-urea)urethane (POSS-PCU) for use as tissue implants. METHODS: These polymers were implanted in six healthy sheep (n = 6) for 36 months and a siloxane served as the positive control. After explantation, these polymers were extracted, as was the surrounding capsule, if any. Attenuated total reflectance Fourier transform infrared spectroscopy analysis was performed to look for signs of surface degradation on the polymers and histopathologic and electron microscopic examinations were performed to study the interaction between the biomaterial and the host environment in greater detail. RESULTS: After implantation, the authors observed minimal inflammation of the nanocomposite within the sheep model as compared with the siloxane control. Contact angle measurements and fibrinogen enzyme-linked immunosorbent assay tests were then conducted on the POSS-PCU nanocomposite to determine the reason for this behavior. The increased fibrinogen adsorption on POSS-PCU, its amphilicity, and large contact-angle hysteresis indicated that POSS-PCU inhibits inflammation by adsorbing and inactivating fibrinogen on its surface. In complete contrast, the control siloxane in the same setting demonstrated very significant inflammation and degradation, resulting in capsular formation. Naturally, there was no evidence of degradation of the nanocomposite compared with the siloxane control. CONCLUSIONS: POSS-PCU nanocomposites have enhanced interfacial biocompatibility and better biological stability as compared with conventional silicone biomaterials, thus making them safer as tissue implants.

Environmental oestrogens, cosmetics and breast cancer.

The established role of oestrogen in the development and progression of breast cancer raises questions concerning a potential contribution from the many chemicals in the environment which can enter the human breast and which have oestrogenic activity. A range of organochlorine pesticides and polychlorinated biphenyls possess oestrogen-mimicking properties and have been measured in human breast adipose tissue and in human milk. These enter the breast from varied environmental contamination of food, water and air, and due to their lipophilic properties can accumulate in breast fat. However, it is emerging that the breast is also exposed to a range of oestrogenic chemicals applied as cosmetics to the underarm and breast area. These cosmetics are left on the skin in the appropriate area, allowing a more direct dermal absorption route for breast exposure to oestrogenic chemicals and allowing absorbed chemicals to escape systemic metabolism. This review considers evidence in support of a functional role for the combined interactions of cosmetic chemicals with environmental oestrogens, pharmacological oestrogens, phyto-oestrogens and physiological oestrogens in the rising incidence of breast cancer.

Pathogenetic and diagnostic aspects of siliconosis.

Silicones have an adverse effect on human health well beyond that suggested by the recent superficial public controversy. The evidence for immune responses to injected/implanted silicones is extensive, detailed, often very specific, and not at all new. Comprehending the immunopathogenicity, realized and potential, of silicone has grown as our general understanding of the immune system has developed. Several major issues in furthering this comprehension pertain to the nature of the essential epitope, special risk of silicones to women, and definition of the chronic disease complex so evident clinically, one defying classification within currently traditional disease categories and states. The commentary presented here emphasizes the immunopathic evidence, explores the question of the essential epitope, estimates the minimal threshold of silicone load for immune reactivity, presents a profile of autoantibodies for siliconosis, and calls attention to specific silicone-based female contraceptive modalities. The silicone content of personal care products, not always revealed by retail package labeling, is explored as a potential sensitizing factor in the environment.

In vivo measurement of colour changes in natural teeth.

It has been observed that teeth become lighter when they are dried. The present study was designed to quantify these changes and the time taken for tooth colour to return to normal. The colour of an upper central incisor in each of seven subjects was measured using a reflectance spectrophotometer before and after application of a rubber dam and, in another seven subjects before and after taking a polyvinylsiloxane impression. There were statistically significant changes in the L*, a* and b* values following rubber dam application and in the L* value following impression taking. The results demonstrate that teeth become brighter and less colour saturated after rubber dam application and brighter after impression taking. The original values were regained after 30 min.

Environmental immunogens and T-cell-mediated responses in fibromyalgia: evidence for immune dysregulation and determinants of granuloma formation.

Thirty-nine patients with fibromyalgia syndrome (FMS) according to American College of Rheumatology criteria were studied for cell-mediated sensitivity to environmental chemicals. Lymphocytes were tested by standard [(3)H]thymidine incorporation in vitro for T cell memory to 11 chemical substances. Concanavalin A (Con A) was used to demonstrate T cell proliferation. Controls were 25 contemporaneous healthy adults and 252 other concurrent standard controls without any aspect of FMS. Significantly higher (P < 0.01) stimulation indexes (SI) were found in FMS for aluminum, lead, and platinum; borderline higher (0.05 > P > 0.02) SI were found for cadmium and silicon. FMS patients showed sporadic responses to the specific substances tested, with no high-frequency result (>50%) and no obvious pattern. Mitogenic responses to Con A indicated some suppression of T cell functionality in FMS. Possible links between mitogenicity and immunogenic T cell proliferation, certain electrochemical specifics of granuloma formation, maintenance of connective tissue, and the fundamental nature of FMS are considered.

[Value of negative oral contrast media in MR cholangiopancreatography (MRCP)]. / Der Stellenwert negativer oraler Kontrastmittel in der MR-Cholangiopancreatographie (MRCP).

PURPOSE: Evaluation of the use of a negative oral contrast material in MR cholangiopancreatography (MRCP). MATERIAL AND METHODS: We performed MRCP in single-shot technique (TSE, TR = 2800 ms, TE = 1100 ms, ETL = 64) in 38 patients before and 20-30 min after oral administration of 300-600 ml of a negative oral contrast material. The visualization ducts and details important for the diagnosis was evaluated in a blinded manner. Ductal diameters were measured. Both sets of images were evaluated qualitatively. RESULTS: The ductal diameters did not change after administration of oral contrast material. In 1/3 of all cases the ductal structures were superimposed by a high signal intensity of fluid in the gastrointestinal tract, especially in the tail of the pancreas. After administration of oral contrast material only in 3 patients could a complete visualization of the ducts not be achieved. In 5 cases, details relevant for the diagnostic decision could be seen only on post-contrast images. The anatomic orientation was not compromised by the absence of signal in the gastrointestinal tract. CONCLUSION: Negative oral contrast material should be given before performing a MRCP to provide non-superimposed visualization of the bile and pancreatic ducts. There is no negative influence of the oral contrast material on the diameter of the ducts.