Exogenous lipoid pneumonia in children: A systematic review.

OBJECTIVES: To describe the clinical-radiological-pathological characteristics and treatment outcomes of children with suspected exogenous lipoid pneumonia (ELP). DESIGN: Systematic review. We searched electronic databases and reference lists published between 1967 and 2018, restricted to non-accidental cases. RESULTS: Forty-four studies including 489 participants aged 1 day to 17 years from 13 countries were included. Cultural, medical, and behavioural rationale for oil-use was described. The clinical-radiological presentation varied widely. Diagnostic certainty was deemed highest if ELP was confirmed on bronchoalveolar lavage/frozen section lung biopsy with documented extracellular lipid on cytological staining and/or fat analysis. Non-tuberculous mycobacteria infection was identified in six studies: Mycobacterium fortuitum/chelonei, Mycobacterium smegmatis and Mycobacterium abscessus. Treatment comprised supportive therapy, corticosteroids, stopping oil, therapeutic lung-lavage and surgical resection. Outcomes were reported inconsistently. CONCLUSION: Paediatric ELP resulting from cultural and medical practices continues to be described globally. Preventive interventions, standardized reporting, and treatment efficacy studies for cases not averted, are lacking. Protocol registration: PROSPERO CRD42017068313.

[Paraffin oil injecions due to bigorexia may cause hypercalcaemia].

Paraffin oil injections may cause severe hypercalcaemia, likely due to development of granulomas at injection sites, activating 1,25 dihydroxyvitamin D and increasing calcium uptake from gut, kidney and bone. This is a case report of a 39-year-old male with severe hypercalcaemia and renal failure due to paraffin oil injections. He was treated with prednisolone (25-50 mg daily), but the disease recurred the next two summers probably due to erroneous vitamin D supplement and sun exposure. The disease course and prognosis are unknown. Treatment options are discussed, and paraffin oil injections should be avoided.

[Safety evaluation for medical ozone oil on skin].

OBJECTIVE: To evaluate skin irritation, acute toxicity, and allergy of medical ozone oil for clinical application.
 Methods: In contrast to their left and right side irritation, one or more skin irritation tests were performed on the intact and damaged skins of guinea pigs. With the maximum concentration, acute skin toxicity test was applied on the intact and damaged skins of rats.Active cutaneous anaphylaxis was applied to the guinea pigs.
 Results: High concentration (ozone consumption: 150 g/L) of medical ozone oil showed a slight irritation on the broken skin of guinea pigs, while low concentrations did not show skin irritation.Medical ozone oil had no obvious acute toxicity to rats. The medical ozone oil and base oil showed mildallergy for the skin of guinea pig.
 Conclusion: The irritation of medical ozone oil is related to its concentration. With appropriateconcentration and duration of treatment, medical ozone oil is safe.

Type III hypersensitivity reactions to a B cell epitope antigen are abrogated using a depot forming vaccine platform.

Peptide antigens are combined with an adjuvant in order to increase immunogenicity in vivo. The immunogenicity and safety of a RSV vaccine formulated in a novel oil-based platform, DepoVax™ (DPX), was compared to an alum formulation. A peptide B cell epitope derived from RSV small hydrophobic ectodomain (SHe) served as the antigen. Both vaccines induced SHe-specific antibodies after immunization of mice. A single dose of the DPX-based formulation resulted in anti-SHe titres for up to 20 weeks. Boosting with Alum-SHe, but not with DPX-SHe, led to unexpected clinical signs such as decreased activity, cyanosis and drop in body temperature in mice but not in rabbits. The severity of adverse reactions correlated with magnitude of SHe-specific IgG immune responses and decreased complement component 3 plasma levels, indicating a type III hypersensitivity reaction. By RP-HPLC analysis, we found that only 8-20% of the antigen was found to be adsorbed to alum in vitro, indicating that this antigen is likely released systemically upon injection in vivo. Clinical signs were not observed in rabbits, indicating the response correlates with peptide dose relative to size of animal. These results suggest that peptide antigens targeted to produce B cell mediated response may result in increased incidence of type III hypersensitivity reactions when delivered in non-depot forming vaccines. The DPX formulation induced strong antibody titres to the antigen without causing adverse events, likely due to the strength of the depot in vivo, and demonstrates the potential safety and immunogenicity of this platform for B cell peptide antigens.

Acute and subchronic toxicity studies of seabuckthorn (Hippophae rhamnoides L.) oil in rodents.

Seabuckthorn (Hippophae rhamnoides L.) has been traditionally used as medicine and nutritional supplement for a long period of time. However, information on the systemic toxicity and safety evaluation of seabuckthorn and its extracts is still scarce. The purpose of this study was to evaluate the potential toxicity of seabuckthorn oil by an acute oral toxicity study in mice and a 90-day repeated oral toxicity study in rats. No mortality or signs of toxicity was observed in mice treated with 20 mL/kg body weight seabuckthorn oil in the acute toxicity study. In the subchronic toxicity study, 80 Sprague-Dawley rats (10 animals per sex per treatment group) were administrated with 10, 5, 2.5 and 0 (control) mL/kg body weight of seabuckthorn oil daily for 90 days by gavage. There were no signs of toxicity and treatment-related changes in rats treated with seabuckthorn oil on mortality, body and organ weights, food consumption, blood biochemistry and hematology, gross necropsy and histopathological examinations. Based on the finding of this study, the maximum tolerated dose of seabuckthorn oil was >20 mL/kg for mice for acute toxicity study, and the no-observed-adverse-effect level was 10 mL/kg body weight for both male and female rats for 90-day toxicity study.

A Review of Indigo Naturalis as an Alternative Treatment for Nail Psoriasis.

INTRODUCTION: Nail psoriasis is challenging to treat. The few currently available therapies are limited in efficacy, and often produce unfavorable side effects. A plant extract widely used in Traditional Chinese Medicine, indigo naturalis (Qing Dai), is presented in this review as an alternative topical treatment for skin and nail psoriasis. The purpose of this article is to present information on a viable alternative treatment with a favorable side effect profile for a difficult disease to treat. METHODS: A PubMed search for the term "indigo naturalis" was performed, and literature from 2006 to the present relevant to indigo naturalis and treatment of psoriasis and nail psoriasis was reviewed. RESULTS: Indigo naturalis shares several therapeutic mechanisms with current psoriasis treatments, such as regulation of keratinocyte proliferation and differentiation, restoration of epidermal barrier function, and reduction of inflammatory processes. Clinically, it is well tolerated. CONCLUSION: Recent research of indigo naturalis suggests that it is a safe, inexpensive, and effective alternative topical treatment for skin and nail psoriasis.

Double-Blind, Placebo-Controlled Pilot Study of Processed Ultra Emu Oil Versus Placebo in the Prevention of Radiation Dermatitis.

PURPOSE: The purpose of this single-institution pilot study was to evaluate the feasibility and safety of an oil-based skin agent, Ultra Emu Oil, on skin-related toxicity in patients undergoing radiation therapy to the breast or chest wall. METHODS AND MATERIALS: Patients were randomized 2:1 in a double-blind fashion and were instructed to apply processed Ultra Emu Oil or placebo (cottonseed oil) twice daily during the course of radiation therapy. The oils were applied before the third fraction and continued for 6 weeks after completion of treatment. The primary endpoint was the area under the curve (AUC) of Skindex-16 scale scores over time. Secondary outcomes included maximum grade of radiation dermatitis using the Common Terminology Criteria (CTC) for Adverse Events (CTCAE 3.0), the Skin Toxicity Assessment Tool, quality of life (QOL) measured by Linear Analogue Self-Assessment, and a symptom experience diary (SED). RESULTS: In all, 42 of 45 patients completed the study and were evaluable. The median times to peak rash, skin redness, peeling, and skin swelling were weeks 6, 6, 7, and 7, respectively as measured by the SED. The Skindex AUC scores tended to be lower in emu oil patients than in placebo patients (mean total AUC 7.2 vs 10.4, respectively). This trend was also seen in all the Skindex subdomains. The overall QOL was slightly better in the emu oil group but remained stable throughout the study for both arms. Peak CTC toxicity occurred at week 6. Patients using emu oil appeared slightly worse on maximum CTC grade, but the difference was not significant. CONCLUSIONS: This pilot study confirmed the safety of oil-based skin treatments during radiation therapy and suggests a trend for reduced skin toxicity for patients receiving emu oil. A larger study is needed to evaluate the efficacy of emu oil in reducing radiation dermatitis in patients receiving breast radiation.

Evaluation of immune response following one dose of an AS03A-adjuvanted H1N1 2009 pandemic influenza vaccine in Japanese adults 65 years of age or older.

OBJECTIVE: This study assessed the immunogenicity, long-term persistence of immune response and safety of a single dose of an A/California/07/2009 H1N1 pandemic influenza vaccine adjuvanted with AS03 (α-tocopherol and squalene based oil-in-water emulsion Adjuvant System) in subjects ≥ 65 y of age (NCT01114620). RESULTS: At Day 21, the HI immune response met all three European guidance criteria [seroconversion rate (SCR): 60.0%; seroprotection rate (SPR): 64.0%; geometric mean fold rise (GMFR): 10.2] and the US guidance criterion for SCR. At month 6, the HI immune response against the A/California/07/2009 H1N1 strain persisted but at levels lower than that observed at Day 21 (SCR: 38.8%; SPR: 42.9%; HI antibody geometric mean titer: 27.6); the European regulatory guidance criteria for SCR and GMFR were still met. Overall, the vaccine was well-tolerated. METHODS: In this open-label, single group study, 50 subjects received one dose of the 3.75 µg hemagglutinin (HA) AS03-adjuvanted H1N1 2009 vaccine. Immunogenicity assessments were made before vaccination, 21 days and six months after vaccination using hemagglutination inhibition (HI) and microneutralization assays. Immunogenicity end points were based on US and European regulatory criteria. CONCLUSION: A single dose of the 3.75 µg HA AS03-adjuvanted H1N1 2009 pandemic vaccine induced immune responses against the vaccine strain that met the European regulatory guidance criteria at day 21 in the elderly Japanese population; the immune response persisted at lower levels at month 6. No safety concerns were identified. These results suggest that two vaccine doses might be useful for the elderly population to improve antibody induction and persistence.

Immunomodulatory and physical effects of oil composition in vaccine adjuvant emulsions.

Squalene-based oil-in-water emulsions have been used for years in some seasonal and pandemic influenza vaccines. However, concerns have been expressed regarding squalene source and potential biological activities. Little information is available regarding the immunomodulatory activity of squalene in comparison with other metabolizable oils in the context of oil-in-water emulsions formulated with vaccines. The present work describes the manufacture and physical characterization of emulsions composed of different classes of oils, including squalene, long chain triglycerides, a medium chain triglyceride, and a perfluorocarbon, all emulsified with egg phosphatidylcholine. Some differences were apparent among the non-squalene oils in terms of emulsion stability, including higher size polydispersity in the perfluorocarbon emulsion, more rapid visual instability at 60°C for the long-chain triglyceride and perfluorocarbon emulsions, and an increased creaming rate in the medium-chain triglyceride emulsion at 60°C as detected by laser scattering optical profiling. The biological activity of each of these emulsions was compared when formulated with either a recombinant malaria antigen or a split-virus inactivated influenza vaccine. Overall, vaccines containing the squalene emulsion elicited higher antibody titers and more abundant long-lived plasma cells than vaccines containing emulsions based on other oils. Since squalene-based emulsions show higher adjuvant potency compared to the other oils tested, non-squalene oils may be more suitable as carriers of amphiphilic or hydrophobic immunostimulatory molecules (such as TLR agonists) rather than as stand-alone adjuvants.

Mangrove bacterial diversity and the impact of oil contamination revealed by pyrosequencing: bacterial proxies for oil pollution.

BACKGROUND: Mangroves are transitional coastal ecosystems in tropical and sub-tropical regions and represent biologically important and productive ecosystems. Despite their great ecological and economic importance, mangroves are often situated in areas of high anthropogenic influence, being exposed to pollutants, such as those released by oil spills. METHODOLOGY/PRINCIPAL FINDINGS: A microcosm experiment was conducted, which simulated an oil spill in previously pristine mangrove sediment. The effect of the oil spill on the extant microbial community was studied using direct pyrosequencing. Extensive bacterial diversity was observed in the pristine mangrove sediment, even after oil contamination. The number of different OTUs only detected in contaminated samples was significantly higher than the number of OTUs only detected in non-contaminated samples. The phylum Proteobacteria, in particular the classes Gammaproteobacteria and Deltaproteobacteria, were prevalent before and after the simulated oil spill. On the other hand, the order Chromatiales and the genus Haliea decreased upon exposure to 2 and 5% oil, these are proposed as sensitive indicators of oil contamination. Three other genera, Marinobacterium, Marinobacter and Cycloclasticus increased their prevalence when confronted with oil. These groups are possible targets for the biomonitoring of the impact of oil in mangrove settings. CONCLUSIONS/SIGNIFICANCE: We suggest the use of sequences of the selected genera as proxies for oil pollution, using qPCR assessments. The quantification of these genera in distinct mangrove systems in relation to the local oil levels would permit the evaluation of the level of perturbance of mangroves, being useful in field monitoring. Considering the importance of mangroves to many other environments and the susceptibility of such areas to oil spills this manuscript will be of broad interest.

Supplementary catechins attenuate cooking-oil-fumes-induced oxidative stress in rat lung.

Cooking-oil-fumes containing toxic components may induce reactive oxygen species (ROS) to oxidize macromolecules and lead to acute lung injury. Our previous study showed that a decaffineated green tea extract containing (+)-catechin, (-)-epicatechin, (+)-gallocatechin, (-)-epigallocatechin, (-)-epicatechin gallate, and (-)-epigallocatechin gallate can inhibit oxidation, inflammation, and apoptosis. We determined whether the catechins supplement may reduce cooking-oil-fumes-induced acute lung injury in rat. In the urethane-anesthetized Wistar rat subjected to 30-120 min of cooking-oil-fumes exposure, blood ROS significantly increased in the recovery stage. After 30-min cooking-oil-fumes exposure, the enhanced blood ROS level further increased in a time-dependent manner during the recovery stage (321 +/- 69 counts/10 s after 1 h, 540 +/- 89 counts/10 s after 2 h, and 873 +/- 112 counts/10 s after 4 h). Four hours after 30-min cooking-oil-fumes exposure, lung lavage neutrophils and ROS as well as lung tissue dityrosine and 4-hydroxy-2-nonenal increased significantly. Two weeks of catechins supplememnt significantly reduced the enhanced lavage ROS, lung dityrosine and 4-hydroxy-2-nonenal level. Cooking-oil-fumes-induced oxidative stress decreased lung Bcl-2/Bax ratio and HSP70 expression, but catechins treatment preserved the downregulation of Bcl-2/Bax ratio and HSP70 expression. We conclude that catechins supplement attenuates cooking-oil-fumes-induced acute lung injury via the preservation of oil-smoke induced downregulation of antioxidant, antiapoptosis, and chaperone protein expression.

The use of oil adjuvants in therapeutic vaccines.

Water in oil emulsions represents one of the new promising generations of adjuvants for immunotherapy. Fifty years ago, incomplete freund adjuvant (IFA) has been used in clinical trials for prophylactic vaccines like poliomyelitis or flu vaccine because of its strong potency. However, even if the quality of the raw materials has been improved in order to avoid secondary reactions, the risk benefit ratio was not favorable to its use for prophylactic vaccines. Moreover, emulsions were highly viscous with a weak stability. The development of new adjuvants concepts like liposomes, oil in water emulsions, bacterial immunostimulating compounds has induced a loss of interest for such formulations. The emergence of immunotherapy treatments for cancer, AIDS or other diseases leads to the re-emergence of these adjuvants, as the risk benefit ratio is more favorable. Then, safety of these adjuvants has been improved by the use of more specific surfactants and refined oils but also by improving their manufacturing process, allowing even sometimes their use in clinical trials for prophylactic vaccines.

Traditional practice of oil massage of neonates in Bangladesh.

Topical application of natural oils is practised routinely in many countries and may either improve skin barrier function and health or have detrimental cutaneous and systemic effects, depending on the composition of the oil. Little literature on the epidemiology, practice, and perceptions of traditional neonatal oil massage is available. This study was undertaken to gain insights into the epidemiology, practice, and perceptions regarding traditional oil massage of Bangladeshi neonates. A questionnaire was administered verbally to the primary caretaker of 332 outpatients at the Dhaka Shishu Hospital, and to 20 women with children encountered at the Matlab Health Complex in Bangladesh. More than 96% (340/352) of the caregivers practised oil massage, irrespective of socioeconomic status and place of residence. Among those at the Dhaka Shishu Hospital who practised oil massage, mustard oil was used alone or in combination by 95% (303/320) over the entire body, 1-3 time(s) daily (96%), starting in the first three days of life (72%) in both term and preterm neonates. Perceived benefits included prevention of infections (69%) and hypothermia (2%). Oil massage is an important traditional domiciliary practice used annually on more than three million newborns in Bangladesh. Given its potential for beneficial and harmful effects, further research is needed on the value of this practice, and ways to optimize its beneficial effects.

GM-144, a novel lipophilic vaginal contraceptive gel-microemulsion.

In a systematic effort to develop a dual-function intravaginal spermicide as well as a drug delivery vehicle against sexually transmitted pathogens, a submicron particle size (30-80 nm), lipophilic and spermicidal gel-microemulsion (viz GM-144) containing the pharmaceutical excipients propylene glycol, Captex 300, Cremophor EL, Phospholipon 90G, Rhodigel, Pluronic F-68, and sodium benzoate was formulated. GM-144 completely immobilized sperm in human or rabbit semen in less than 30 seconds. Therefore, the in vivo contraceptive potency of intravaginally applied GM-144 was compared in the standard rabbit model to those of the detergent spermicide, nonoxynol-9 (N-9)-containing formulation. Eighty-four ovulated New Zealand White rabbits in subgroups of 28 were artificially inseminated with and without intravaginal administration of GM-144 or 2% N-9 (Gynol II) formulation and allowed to complete term pregnancy. GM-144 showed remarkable contraceptive activity in the rigorous rabbit model. When compared with control, intravaginal administration of GM-144 and Gynol II resulted in 75% and 70.8% inhibition of fertility (P <.0001 versus control, Fisher's exact test), respectively. Thus, GM-144 as a vaginal contraceptive was as effective as the commercially available N-9 gel. In the rabbit vaginal irritation test, none of the 6 rabbits given daily intravaginal application of spermicidal GM-144 for 10 days developed epithelial ulceration, edema, leukocyte influx, or vascular congestion characteristic of inflammation (total score = 5). Therefore, GM-144 has the potential to become a clinically useful safe vaginal contraceptive and a vehicle for formulating lipophilic drugs used in reducing the risk of heterosexual transmission of sexually transmitted diseases.

An aqueous concentration model for riverine spills.

A numerical model is developed to predict the aqueous concentrations of sparingly soluble compounds resulting from oil, fuel, or chemical spills onto rivers. The model computes the concentration of compounds both in the slick phase and in the aqueous phase by simulating the processes that affect the fate of the spilled compound. Processes simulated by the model include spreading and drifting of the surface slick, evaporation from the slick, dissolution from the slick into the water, volatilization from the water, and longitudinal dispersion in the river. The model is used to simulate a hypothetical spill of jet fuel, demonstrating that the concentration of a compound in the aqueous phase is strongly linked to its concentration in the slick phase. The most soluble and most volatile compounds exhibit the highest aqueous concentrations in the early stages of the spill, but ultimately the less soluble and less volatile compounds reach the highest aqueous concentrations. Streamwise concentration gradients in the slick due to the rapid evaporation of the more volatile compounds are shown to have an effect on the aqueous concentration.

Processes controlling aqueous concentrations for riverine spills.

The aqueous concentrations of sparingly soluble compounds resulting from oil, fuel, or chemical spills onto rivers predicted by numerical spill models contain an inherent degree of uncertainty due to the inaccuracies, or bias, of the user supplied rate coefficients. Methods for estimating the values of spreading, evaporation, dissolution, volatilization, and longitudinal dispersion coefficients for a small sheltered river are reviewed, and the uncertainties associated with each coefficient are estimated. The uncertainties in the predicted aqueous concentrations are then computed using a concurrently developed riverine spill model for a simulated spill of 10,000 kg of jet fuel. The resulting aqueous concentrations were found to be most sensitive to the saturation concentrations and the dissolution rates, moderately sensitive to the evaporation rates and longitudinal dispersion coefficient, and nearly completely insensitive to the volatilization coefficient.