Betaine eliminates CFA-induced depressive-like behaviour in mice may be through inhibition of microglia and astrocyte activation and polarization.

Chronic pain can induce not only nociceptive but also depressive emotions. A previous study demonstrated that betaine, a commonly used nutrient supplement, has an anti-nociceptive effect, but whether betaine can alleviate chronic pain-induced depressive emotion is elusive. Our current study found that betaine administration significantly eliminated complete Freund's adjuvant (CFA)-induced pain-related depressive-like behaviour. Mechanistically, betaine treatment inhibited microglia and astrocyte activation. Furthermore, betaine significantly promoted the transition of microglia from the M1 to the M2 phenotype, as well as the transition of astrocytes from the A1 to the A2 phenotype. Additionally, the release of pro-inflammatory factors such as IL-18, IL-1ß and IL-6 and anti-inflammatory factors such as IL-10 in the hippocampus induced by CFA were also reversed by betaine administration. Overall, betaine has therapeutic effects on pain-related depressive-like phenotypes caused by CFA, possibly through altering the polarization of microglia and astrocytes to reduce neuroinflammation.

Betaine prevents cognitive dysfunction by suppressing hippocampal microglial activation in chronic social isolated male mice.

Chronic social isolation (SI) stress, which became more prevalent during the COVID-19 pandemic, contributes to abnormal behavior, including mood changes and cognitive impairment. Known as a functional nutrient, betaine has potent antioxidant and anti-inflammatory properties in vivo. However, whether betaine can alleviate the abnormal behavior induced by chronic SI in mice remains unknown. In this study, we investigated the efficacy of betaine in the treatment of behavioral changes and its underlying mechanism. Three-week-old male mice were randomly housed for 8 weeks in either group housing (GH) or SI. The animals were divided into normal saline-treated GH, normal saline-treated SI, and betaine-treated SI groups in the sixth week. The cognitive and depression-like behavior was determined in the eighth week. We found that long-term betaine administration improved cognitive behavior in SI mice but failed to prevent depression-like behavior. Moreover, long-term betaine administration inhibited hippocampal microglia over-activation and polarized microglia toward the M2 phenotype, which effectively inhibited the expression of inflammatory factors in SI mice. Finally, the protective effect of betaine treatment in SI mice might not be due to altered activity of the hypothalamic-pituitary-adrenal axis. Collectively, our findings reveal that betaine can improve SI-induced cognitive impairment, thus providing an alternative natural source for the prevention of memory loss caused by SI or loneliness.

[ANALYSIS OF PATCH TEST RESULTS USING COCAMIDOPROPYL BETAINE-RELATED SURFACTANTS].

BACKGROUND: A few previous studies have compared the patch test (PT) results obtained using different types of PT units. OBJECTIVES: This study aimed to compare PT results between the Patch Tester 'Torii' and Finn Chamber. METHODS: Thirty-four patients with intractable scalp dermatitis were enrolled in this study. PT were performed with three kinds of amphoteric surfactants, cocamidopropyl betaine (CAPB), high-concentration CAPB (h-CAPB), and lauramidopropyl betaine (LAPB), using both the Patch Tester 'Torii' and Finn Chamber, and the changes in the subjects' symptoms after they stopped using these surfactants were examined. RESULTS: Regarding the PT results for CAPB, h-CAPB, and LAPB, the results obtained with the Finn Chamber included a significantly lower frequency of irritant reactions (CAPB; p=0.003, h-CAPB; p=0.046, LAPB; p=0.002) than those obtained with the Patch Tester 'Torii'. However, there were no significant differences in the frequencies of positive reactions between the Patch Tester 'Torii' and Finn Chamber in each surfactant. The same tendency was seen in PT with LAPB (p=0.041) in 17 selected patients, who showed positive or doubtful reactions in PT performed with the surfactant-containing products they had used and whose symptoms 'markedly improved' or 'improved' after they stopped using these products. Among these surfactants, CAPB exhibited the highest positivity rate; however, the differences were not significant. CONCLUSION: In patients with intractable scalp dermatitis, PT of the abovementioned surfactants performed using the Finn Chamber were superior to those conducted using the Patch Tester 'Torii' because they resulted in fewer irritant reactions.

Analysis of patch testing with cocamidopropyl betaine and its impurities in patients with intractable scalp dermatitis in a single clinic in Japan.

BACKGROUND: The allergen responsible for cocamidopropyl betaine (CAPB) allergies has been debated. OBJECTIVES: To investigate the sensitizing agents of CAPB, the patch test positivity rates of impurities were examined in Japanese patients with CAPB-related allergic contact dermatitis. MATERIALS AND METHODS: Thirty patients with scalp dermatitis and positive patch tests for CAPB and/or lauramidopropyl betaine (LAPB) were enrolled in this study. They were patch tested with the detergents that they had been using at the time of their first visit and with the impurities dimethylaminopropylamine (DMAPA) and lauramidopropyl dimethylamine (LAPDMA). RESULTS: The positivity rate in patch tests of the 37 detergents that the patients had been using was 78.4% (29/37). The positivity rates of DMAPA 1% pet., 1% aq. and 0.2% aq. were 32.1% (9/28), 14.3% (4/28) and 13.3% (4/30), respectively, whereas those of LAPDMA 0.1% and 0.05% were 30.0% (9/30) and 16.7% (5/30), respectively. Among the 30 patients, 6 exhibited positive results for both DMAPA and LAPDMA, 3 showed positive results for DMAPA alone and 6 produced positive results for LAPDMA alone. CONCLUSION: Patch tests produced an overall positivity rate for DMAPA, LAPDMA or both of 50.0% (15/30) in patients with scalp dermatitis and positive patch test results for CAPB and/or LAPB.

[A CASE OF ALLERGIC CONTACT DERMATITIS CAUSED BY DETERGENTS CONTAINING COCAMIDOPROPYL BETAINE IN WHICH AN IMPURITY WAS THE POSSIBLE CAUSATIVE AGENT].

Cocamidopropyl betaine (CAPB) is an amphoteric surfactant. It has several functions, including producing effervescence and washing effects, and thus, it is used in many cleansing products, such as shampoo and liquid body cleansers. Recently, it has become clear that some impurities that arise during the manufacturing process can have sensitizing effects. Herein, we report a case of allergic contact dermatitis caused by detergents containing CAPB, in which an impurity was determined to be the possible causative agent by patch testing and chemical analysis.A 64-year-old Japanese female developed a skin rash on the hairlines of her forehead and nuchal region one month before her first visit to our clinic. Later, the rashes, which were composed of desquamative erythema, expanded to her face, neck, upper back, and chest. Patch tests produced positive results for a shampoo and liquid body cleanser (1% aq.) that she had used as well as for CAPB (1% aq.); lauramidopropyl betaine (LAPB) (1% aq.); and lauramidopropyl dimethylamine (LAPDMA) (0.05% aq.), which is an impurity of CAPB. The rashes resolved completely after we instructed her to use products without CAPB and LAPB. When issuing such instructions, clinicians should have correct knowledge about surfactants, such as the differences between cosmetic ingredient names and quasi-drug ingredient names.

Postauthorization safety study of betaine anhydrous.

Patient registries for rare diseases enable systematic data collection and can also be used to facilitate postauthorization safety studies (PASS) for orphan drugs. This study evaluates the PASS for betaine anhydrous (Cystadane), conducted as public private partnership (PPP) between the European network and registry for homocystinurias and methylation defects and the marketing authorization holder (MAH). Data were prospectively collected, 2013-2016, in a noninterventional, international, multicenter, registry study. Putative adverse and severe adverse events were reported to the MAH's pharmacovigilance. In total, 130 individuals with vitamin B6 nonresponsive (N = 54) and partially responsive (N = 7) cystathionine beta-synthase (CBS) deficiency, as well as 5,10-methylenetetrahydrofolate reductase (MTHFR; N = 21) deficiency and cobalamin C (N = 48) disease were included. Median (range) duration of treatment with betaine anhydrous was 6.8 (0-9.8) years. The prescribed betaine dose exceeded the recommended maximum (6 g/day) in 49% of individuals older than 10 years because of continued dose adaptation to weight; however, with disease-specific differences (minimum: 31% in B6 nonresponsive CBS deficiency, maximum: 67% in MTHFR deficiency). Despite dose escalation no new or potential risk was identified. Combined disease-specific treatment decreased mean ± SD total plasma homocysteine concentrations from 203 ± 116 to 81 ± 51 µmol/L (p < 0.0001), except in MTHFR deficiency. Recommendations for betaine anhydrous dosage were revised for individuals ≥ 10 years. PPPs between MAH and international scientific consortia can be considered a reliable model for implementing a PASS, reutilizing well-established structures and avoiding data duplication and fragmentation.

Pathogenic Mechanisms of Trimethylamine N-Oxide-induced Atherosclerosis and Cardiomyopathy.

Trimethylamine N-oxide (TMAO) is a gut microbiota metabolite derived from trimethylamine- containing nutrient precursors such as choline, L-carnitine, and betaine, which are rich in many vegetables, fruits, nuts, dairy products, and meats. An increasing number of clinical studies have demonstrated a strong relationship between elevated plasma TMAO levels and adverse cardiovascular events. It is commonly agreed that TMAO acts as an independent risk factor and a prognostic index for patients with cardiovascular disease. Although most animal (mainly rodent) data support the clinical findings, the mechanisms by which TMAO modulates the cardiovascular system are still not well understood. In this context, we provide an overview of the potential mechanisms underlying TMAO-induced cardiovascular diseases at the cellular and molecular levels, with a focus on atherosclerosis. We also address the direct effects of TMAO on cardiomyocytes (a new and under-researched area) and finally propose TMAO as a potential biomarker and/or therapeutic target for diagnosis and treatment of patients with cardiovascular disease.

Betaine Supplementation Moderately Increases Total Cholesterol Levels: A Systematic Review and Meta-Analysis.

Betaine is used to lower elevated plasma homocysteine levels, which are a risk factor for cardiovascular diseases (CVD). However, some studies have shown that betaine may have a negative effect on blood lipids. Betaine supplementation is becoming more and more common, but the relationship between betaine supplementation and blood lipoprotein levels are unclear. The purpose of the study described here was thus to perform a meta-analysis of randomized placebo-controlled trials on the effects of betaine supplementation at a daily dose of at least 4 g on blood lipids in adults. Six randomized controlled trials published between 2002 and 2018 were identified. All six studies used adult participants supplemented with at least 4 g/d of betaine for six to twenty-four weeks. A meta-analysis was carried out using a random-effects model, and the overall effect size was calculated for changes in plasma total cholesterol (TC), HDL cholesterol, LDL cholesterol, and triglycerides (TG). The pooled estimate of the effects of betaine supplementation compared to placebo on TC was 0.34 mmol/L (95% CI: 0.02, 0.65), p = 0.0352. No significant effect was observed for LDL, HDL, or TG. Supplementation with at least 4 g/d of betaine for a minimum of six weeks may moderately increase plasma TC, which might be important in the context of cardiovascular health.

Prevalence of Surfactant in the Contact Allergen Management Program.

BACKGROUND: Surfactants are common ingredients in topical products, which can cause both irritant and allergic contact dermatitis. OBJECTIVE: The aim of this study was to determine the prevalence of 12 common groups of surfactants and 12 common individual surfactants among products in each category in the American Contact Dermatitis Society Contact Allergen Management Program (CAMP). METHODS: The American Contact Dermatitis Society CAMP was queried for the 12 surfactant groups and the 12 individual surfactants. RESULTS: The laureth/pareth sulfate group was the most prevalent surfactant group in CAMP products (17.9%). Laureth/pareth sulfates were the most common surfactant group in all product categories, except household and eye care products. The betaine/sultaine group (13.5%) and glucosides (10.0%) were also found in a significant proportion of CAMP products. Oleamidopropyl dimethylamine has the highest positive reaction rate (3.5%) but was tied for the lowest prevalence (0.20%) of the 12 individual surfactants studied. In contrast, cocamidopropyl betaine has a lower positive reaction rate (1.6%) with a higher prevalence (10.4%). CONCLUSIONS: Surfactants were commonly found across all product types in CAMP. This study provides important information on allergen and irritant exposures in care products.

Effect of Betaine on Reducing Body Fat-A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

Animal studies have shown the beneficial effect of betaine supplementation on reducing body fat, while the data from human studies are controversial and inconsistent. The objective of the present systematic review was to investigate the effects of betaine intervention on treating obesity in humans and quantitatively evaluate the pooled effects based on randomized controlled trials with a meta-analysis. The PubMed and Scopus databases, and the Cochrane Library, were searched up to September 2019. Weighted mean differences were calculated for net changes in obesity-related indices by using a random-effects model. Publication bias was estimated using Begg's test. Six studies with 195 participants were identified. Betaine supplementation significantly reduced the total body fat mass (-2.53 kg; 95% CI: -3.93, -0.54 kg; I2 = 6.6%, P = 0.36) and body fat percentage (-2.44%; 95% CI: -4.20, -0.68%; I2 = 0.0%, P = 0.44). No changes were observed regarding body weight (-0.29 kg; 95% CI: -1.48, 0.89 kg; I2 = 0.00%, P = 0.99) and body mass index (-0.10 kg/m2; 95% CI: -5.13, 0.31 kg/m2; I2 = 0.00%, P = 0.84). The results suggested that dietary betaine supplementation might be an effective approach for reducing body fat.

Betaine anhydrous in homocystinuria: results from the RoCH registry.

BACKGROUND: The Registry of Adult and Paediatric Patients Treated with Cystadane® - Homocystinuria (RoCH) is a non-interventional, observational, multi-centre, post-authorization safety study that aimed to identify safety of betaine anhydrous (Cystadane®) in the treatment of patients with inborn errors of homocysteine metabolism (homocystinuria) in order to minimise the treatment associated risks and establish better knowledge on its clinical use. The registry included patients of all ages with homocystinuria who were treated with betaine anhydrous in conjunction with other therapies. Clinical data were collected retrospectively from 2007 to 2013, then prospectively up to February 2014. All adverse events (AEs) reported during the study were recorded. The clinical and biological status of patients was monitored at least once a year. RESULTS: A total of 125 patients with homocystinuria (adults [> 18 years]: 50; paediatric [≤18 years]: 75) were enrolled at 29 centres in France and Spain. Patients were treated with betaine anhydrous for a mean duration of 7.4 ± 4.3 years. The median total daily dose of betaine anhydrous at the first and last study visits was 6 g/day for cystathionine ß-synthase (CBS)-deficient vitamin B6 responders and 9 g/day for methylenetetrahydrofolate reductase-deficient patients, while the median daily dose increased in CBS-deficient B6 non-responders (from 6 to 9 g/day) and cobalamin metabolism-defective patients (from 3 to 6 g/day) between the first and last visits. Treatment caused a mean overall reduction of 29% in plasma homocysteine levels in the study population. A total of 277 AEs were reported during the study, of which two non-serious AEs (bad taste and headache) and one serious AE (interstitial lung disease) were considered to be drug related. Overall, betaine anhydrous was well tolerated with no major safety concerns. CONCLUSIONS: Data from the RoCH registry provided real-world evidence on the clinical safety and efficacy of betaine anhydrous in the management of homocystinuria in paediatric and adult patients.

Safety Assessment of Alkyl Betaines as Used in Cosmetics.

The Cosmetic Ingredient Review Expert Panel (Panel) reviewed the safety of 11 alkyl betaines as used in cosmetics. These ingredients are reported to function as hair and skin conditioning agents, antistatic agents, surfactants-cleansing agents, and viscosity-increasing agents in cosmetic products. Although there are data gaps, the shared chemical core structure, similar functions and concentrations of use in cosmetics, and the expected similarities in physicochemical properties enabled grouping these ingredients and reading across the available toxicological data to support the safety assessment of each individual compound in the entire group. The Panel concluded alkyl betaines were safe as cosmetic ingredients in the present practices of use and concentration, when formulated to be nonirritating.

Analytic Approaches for the Treatment of Hyperhomocysteinemia and Its Impact on Vascular Disease.

Homocysteine is an intermediary metabolite in the methionine cycle. Accumulation of homocysteine is caused either by mutation of relevant genes or by nutritional depletion of related vitamin(s). This review covers the historical background of hyperhomocysteinemia in which indispensable subjects in relation to underlying pathophysiological processes are discussed with the view of metabolism and genetics of folate and methionine cycles. This review emphasizes the unique role of homocysteine that is clearly distinct from other risk factors, particularly cholesterol in the development of vascular disease. The critical issue in understanding the role of homocysteine is the relation with plasma folic acid. The majority of subjects with homocysteine > 15 µmol/L exhibit plasma folate < 9 nmol/ L, indicating that depletion of folate is the main cause of hyperhomocysteinemia irrespective of the presence or absence of vascular disease. Furthermore, only the group of subjects with homocysteine levels > 15 µmol/L demonstrated a higher prevalence of vascular disease. Analytic approaches to treat hyperhomocysteinemia are discussed in which stepwise administration with nutritional doses of folic acid, 5-methyitetrahydrofolate (5-MTHF), and betaine is provided singly or by combined manner based on clinical and laboratory evaluations. Whether correction of hyperhomocysteinemia is able to prevent the development of homocysteine-associated vascular disease remains an unresolved issue. The review discussed a biochemical and mechanistic approach to resolve questions involved in the relation between homocysteine and the development of atherosclerotic vascular disease.

Prevalence of Contact Allergens in Personal Care Products for Babies and Children.

BACKGROUND: Personal care products marketed for babies and children are often regarded as "safe" or "gentle." However, little is known about the prevalence of contact allergens in these types of products. OBJECTIVE: This study assessed the prevalence of important sensitizers in personal care products marketed for babies and children. A secondary objective of this study was to determine whether a product's cost correlates with content of sensitizing ingredients. METHODS: The ingredient lists of 533 unique personal care products were analyzed for presence of fragrance, betaines, propylene glycol, methylchloroisothiazolinone, methylisothiazolinone, formaldehyde, lanolin, and neomycin. Price per ounce was determined for each product as well. CONCLUSIONS: Most personal care products for babies and children contain 1 or more sensitizers. Products containing more sensitizers tend to cost less than those without any sensitizing ingredients.

Betaine Supplementation Enhances Lipid Metabolism and Improves Insulin Resistance in Mice Fed a High-Fat Diet.

Obesity is a major driver of metabolic diseases such as nonalcoholic fatty liver disease, certain cancers, and insulin resistance. However, there are no effective drugs to treat obesity. Betaine is a nontoxic, chemically stable and naturally occurring molecule. This study shows that dietary betaine supplementation significantly inhibits the white fat production in a high-fat diet (HFD)-induced obese mice. This might be due to betaine preventing the formation of new white fat (WAT), and guiding the original WAT to burn through stimulated mitochondrial biogenesis and promoting browning of WAT. Furthermore, dietary betaine supplementation decreases intramyocellular lipid accumulation in HFD-induced obese mice. Further analysis shows that betaine supplementation reduced intramyocellular lipid accumulation might be associated with increasing polyunsaturated fatty acids (PUFA), fatty acid oxidation, and the inhibition of fatty acid synthesis in muscle. Notably, by performing insulin-tolerance tests (ITTs) and glucose-tolerance tests (GTTs), dietary betaine supplementation could be observed for improvement of obesity and non-obesity induced insulin resistance. Together, these findings could suggest that inhibiting WAT production, intramyocellular lipid accumulation and inflammation, betaine supplementation limits HFD-induced obesity and improves insulin resistance.

Dietary Choline and Betaine and Risk of CVD: A Systematic Review and Meta-Analysis of Prospective Studies.

Studies implicate choline and betaine metabolite trimethylamine N-oxide (TMAO) in cardiovascular disease (CVD). We conducted a systematic review and random-effects meta-analysis to quantify a summary estimated effect of dietary choline and betaine on hard CVD outcomes (incidence and mortality). Eligible studies were prospective studies in adults with comprehensive diet assessment and follow-up for hard CVD endpoints. We identified six studies that met our criteria, comprising 18,076 incident CVD events, 5343 CVD deaths, and 184,010 total participants. In random effects meta-analysis, incident CVD was not associated with choline (relative risk (RR): 1.00; 95% CI: 0.98, 1.02) or betaine (RR: 0.99; 95% CI: 0.98, 1.01) intake. Results did not vary by study outcome (incident coronary heart disease, stroke, total CVD) and there was no evidence for heterogeneity among studies. Only two studies provided data on phosphatidylcholine and CVD mortality. Random effects meta-analysis did not support an association between choline and CVD mortality (RR: 1.09, 95% CI: 0.89, 1.35), but one study supported a positive association and there was significant heterogeneity (I² = 84%, p-value < 0.001). Our findings do not support an association between dietary choline/betaine with incident CVD, but call for further research into choline and CVD mortality.

Pediatric Contact Dermatitis Registry Inaugural Case Data.

BACKGROUND: Little is known about the epidemiology of allergic contact dermatitis (ACD) in US children. More widespread diagnostic confirmation through epicutaneous patch testing is needed. OBJECTIVE: The aim was to quantify patch test results from providers evaluating US children. METHODS: The study is a retrospective analysis of deidentified patch test results of children aged 18 years or younger, entered by participating providers in the Pediatric Contact Dermatitis Registry, during the first year of data collection (2015-2016). RESULTS: One thousand one hundred forty-two cases from 34 US states, entered by 84 providers, were analyzed. Sixty-five percent of cases had one or more positive patch test (PPT), with 48% of cases having 1 or more relevant positive patch test (RPPT). The most common PPT allergens were nickel (22%), fragrance mix I (11%), cobalt (9.1%), balsam of Peru (8.4%), neomycin (7.2%), propylene glycol (6.8%), cocamidopropyl betaine (6.4%), bacitracin (6.2%), formaldehyde (5.7%), and gold (5.7%). CONCLUSIONS: This US database provides multidisciplinary information on pediatric ACD, rates of PPT, and relevant RPPT reactions, validating the high rates of pediatric ACD previously reported in the literature. The registry database is the largest comprehensive collection of US-only pediatric patch test cases on which future research can be built. Continued collaboration between patients, health care providers, manufacturers, and policy makers is needed to decrease the most common allergens in pediatric consumer products.

A Proposed Computed Tomography Contrast Agent Using Carboxybetaine Zwitterionic Tantalum Oxide Nanoparticles: Imaging, Biological, and Physicochemical Performance.

OBJECTIVES: The aim of this study was to produce and evaluate a proposed computed tomography (CT) contrast agent based on carboxybetaine zwitterionic (CZ)-coated soluble tantalum oxide (TaO) nanoparticles (NPs). We chose tantalum to provide superior imaging performance compared with current iodine-based clinical CT contrast agents. We developed the CZ coating to provide biological and physical performance similar to that of current iodinated contrast agents. In addition, the aim of this study was to evaluate the imaging, biological, and physicochemical performance of this proposed contrast agent compared with clinically used iodinated agents. MATERIALS AND METHODS: We evaluated CT imaging performance of our CZ-TaO NPs compared with that of an iodinated agent in live rats, imaged centrally located within a tissue-equivalent plastic phantom that simulated a large patient. To evaluate vascular contrast enhancement, we scanned the rats' great vessels at high temporal resolution during and after contrast agent injection. We performed several in vivo CZ-TaO NP studies in healthy rats to evaluate tolerability. These studies included injecting the agent at the anticipated clinical dose (ACD) and at 3 times and 6 times the ACD, followed by longitudinal hematology to assess impact to blood cells and organ function (from 4 hours to 1 week). Kidney histological analysis was performed 48 hours after injection at 3 times the ACD. We measured the elimination half-life of CZ-TaO NPs from blood, and we monitored acute kidney injury biomarkers with a kidney injury assay using urine collected from 4 hours to 1 week. We measured tantalum retention in individual organs and in the whole carcass 48 hours after injection at ACD. Carboxybetaine zwitterionic TaO NPs were synthesized and analyzed in detail. We used multidimensional nuclear magnetic resonance to determine surface functionality of the NPs. We measured NP size and solution properties (osmolality and viscosity) of the agent over a range of tantalum concentrations, including the high concentrations required for standard clinical CT imaging. RESULTS: Computed tomography imaging studies demonstrated image contrast improvement of approximately 40% to 50% using CZ-TaO NPs compared with an iodinated agent injected at the same mass concentration. Blood and organ analyses showed no adverse effects after injection in healthy naive rats at 3 times the ACD. Retention of tantalum at 48 hours after injection was less than 2% of the injected dose in the whole carcass, which very closely matched the reported retention of existing commercial iodine-based contrast agents. Urine analysis of sensitive markers for acute kidney injury showed no responses at 1 week after injection at 3 times the ACD; however, a moderate response in the neutrophil gelatinase-associated lipocalin biomarker was measured at 24 and 48 hours. Compared with other TaO NPs reported in the literature, CZ-TaO NPs had relatively low osmolality and viscosity at concentrations greater than 200 mg Ta/mL and were similar in these physical properties to dimeric iodine-based contrast agents. CONCLUSIONS: We found that a CZ-TaO NP-based contrast agent is potentially viable for general-purpose clinical CT imaging. Our results suggest that such an agent can be formulated with clinically viable physicochemical properties, can be biologically safe and cleared rapidly in urine, and can provide substantially improved image contrast at CT compared with current iodinated agents.

Cutaneous Delayed-Type Hypersensitivity to Surfactants.

BACKGROUND: Repeated and prolonged use of surfactants can cause irritant as well as allergic contact dermatitis. OBJECTIVE: This study reports the frequency of positive patch test results to surfactants tested on the North American Contact Dermatitis Group screening series including cocamidopropyl betaine (CAPB), amidoamine (AA), dimethylaminopropylamine (DMAPA), oleamidopropyl dimethylamine (OPD), and cocamide diethanolamide (CDEA), and correlations of positive reactions between CAPB and the other surfactants. METHODS: This was a retrospective analysis of 10 877 patients patch tested between 2009 and 2014 to the surfactants CAPB, AA, DMAPA, OPD, and CDEA. Frequencies of positive reactions to these surfactants were calculated, and trends of reactivity between the surfactants analyzed. CONCLUSIONS: The OPD had the highest rate of positive patch reactions (2.3%) followed by DMAPA (1.7%), and CAPB (1.4%). The AA and CDEA had the lowest rate of positive reactions (0.8%). There was a high degree of overlap in positive patch tests between the surfactants. The CDEA was the least likely to coreact with another surfactant.