Zebrafish heart regenerates after chemoptogenetic cardiomyocyte depletion.

BACKGROUND: Zebrafish can regenerate adult cardiac tissue following injuries from ventricular apex amputation, cryoinjury, and cardiomyocyte genetic ablation. Here, we characterize cardiac regeneration from cardiomyocyte chemoptogenetic ablation caused by localized near-infrared excited photosensitizer-mediated reactive oxygen species (ROS) generation. RESULTS: Exposure of transgenic adult zebrafish, Tg(myl7:fapdl5-cerulean), to di-iodinated derivative of the cell- permeable Malachite Green ester fluorogen (MG-2I) and whole-body illumination with 660 nm light resulted in cytotoxic damage to about 30% of cardiac tissue. After chemoptogenetic cardiomyocyte ablation, heart function was compromised, and macrophage infiltration was detected, but epicardial and endocardial activation response was much muted when compared to ventricular amputation. The spared cardiomyocytes underwent proliferation and restored the heart structure and function in 45-60 days after ablation. CONCLUSIONS: This cardiomyocyte ablation system did not appear to activate the epicardium and endocardium as is noted in other cardiac injury models. This approach represents a useful model to study specifically cardiomyocyte injury, proliferation and regeneration in the absence of whole organ activation. Moreover, this system can be adapted to ablate distinct cell populations in any organ system to study their function in regeneration.

Computed tomography-guided dye localization prior to uniportal thoracoscopic surgery for lung nodules: A propensity score matching analysis.

PURPOSE: Uniportal video-assisted thoracoscopic surgery (VATS) has recently been reported as an alternative to conventional VATS. However, preoperative image-guided localization is usually required for small nodules. The present study evaluated the efficacy of preoperative computed tomography-guided dye localization prior to uniportal VATS for small undetermined pulmonary nodules. METHODS: We retrospectively reviewed 298 consecutive patients who underwent uniportal VATS to treat undetermined pulmonary nodules (diameter ≤ 1.5 cm). Propensity score matching incorporating preoperative parameters was used to reduce the selection bias in a 1:1 manner. Comprehensive data including clinical features and perioperative variables were compared to evaluate the efficacy of preoperative computed tomography (CT)-guided dye localization prior to uniportal VATS. RESULTS: A total of 232 patients received preoperative CT-guided dye localization (localization group) and 66 did not (direct surgery group), and the propensity score matching analysis generated 55 pairs of patients in both groups. The demographics and operative outcomes, including clinical nodule size, depths of the nodule, were comparable for both groups. The complication rates were low in both groups (3.6% and 1.8%, respectively). The uniportal to multi-portal VATS conversion rate was significantly higher in the direct surgery group than in the localization group (12.7% vs 1.8%, P = 0.030). 5 cases were converted due to failure in tumor identification (7.3% vs 1.8%, P = 0.182). CONCLUSION: Uniportal VATS is a feasible, effective, and safe procedure for the treatment of undetermined pulmonary nodules. The use of preoperative computed tomography-guided dye localization may be associated with a lower risk of conversion of uniportal VATS.

The Bio-Safety Concerns of Three Domestic Temporary Hair Dye Molecules: Fuchsin Basic, Victoria Blue B and Basic Red 2.

Hair-coloring products include permanent, semi-permanent and temporary dyes that vary by chemical formulation and are distinguished mainly by how long they last. Domestic temporary hair dyes, such as fuchsin basic, basic red 2 and Victoria blue B, are especially popular because of their cheapness and facile applications. Despite numerous studies on the relationship between permanent hair dyes and disease, there are few studies addressing whether these domestic temporary hair dyes are associated with an increased cancer risk. Herein, to ascertain the bio-safety of these temporary hair dyes, we comparatively studied their percutaneous absorption, hemolytic effect and cytotoxic effects in this paper. Furthermore, to better understand the risk of these dyes after penetrating the skin, experimental and theoretical studies were carried out examining the interactions between the dyes and serum albumins as well as calf thymus (CT)-DNA. The results showed that these domestic temporary hair dyes are cytotoxic with regard to human red blood cells and NIH/3T3 cell lines, due to intense interactions with bovine serum albumin (BSA)/DNA. We conclude that the temporary hair dyes may have risk to human health, and those who use them should be aware of their potential toxic effects.

[Investigation on contamination situation of malachite green in freshwater fish and its dietary exposure assessment of Shaanxi Province].

OBJECTIVE: To investigate the residue levels of malachite green (MG) in freshwater fish and assess the dietary MG exposure of Shaanxi residents. The second aim was to assess the health risk of intaking MG from freshwater fish for Shaanxi residents. METHODS: The samples were determined by UPLC-MS/MS after purified by neutral alumina SPE cartridges and separated by waters-BEH C18 column (2.1 mm x 100 mm, 2.5 µm). The MOE method was used to assess the risk of intaking MG from freshwater fish for Shaanxi residents. RESULTS: The average detection rate of MG in freshwater fish in Shaanxi province was 7.32% and the highest residue level was 428 µg/kg. The detection rate was quite different in different fish species. The catfish devoted the highest detection rate which was 28.57%. In ten cities of Shaanxi, the highest detection rate was obtained from Yulin which was 33.33%. CONCLUSION: The health risk of intaking MG from freshwater fish is quite low for Shaanxi residents, however the contamination of illegal use of MG in freshwater fish was severe in Shaanxi Province. Supervision and inspection of MG should be strengthened in fish farming.

Fungal endophthalmitis associated with compounded products.

Fungal endophthalmitis is a rare but serious infection. In March 2012, several cases of probable and laboratory-confirmed fungal endophthalmitis occurring after invasive ocular procedures were reported nationwide. We identified 47 cases in 9 states: 21 patients had been exposed to the intraocular dye Brilliant Blue G (BBG) during retinal surgery, and the other 26 had received an intravitreal injection containing triamcinolone acetonide. Both drugs were produced by Franck's Compounding Lab (Ocala, FL, USA). Fusarium incarnatum-equiseti species complex mold was identified in specimens from BBG-exposed case-patients and an unopened BBG vial. Bipolaris hawaiiensis mold was identified in specimens from triamcinolone-exposed case-patients. Exposure to either product was the only factor associated with case status. Of 40 case-patients for whom data were available, 39 (98%) lost vision. These concurrent outbreaks, associated with 1 compounding pharmacy, resulted in a product recall. Ensuring safety and integrity of compounded medications is critical for preventing further outbreaks associated with compounded products.

Blue dye is sufficient for sentinel lymph node biopsy in breast cancer.

BACKGROUND: Most previous studies have reported superior results when blue dye and radiocolloids were used together for sentinel lymph node (SLN) biopsy in early breast cancer. Blue dye was reported to perform poorly when used alone, although more recent studies have found otherwise. This study reviewed the authors' practice of performing SLN biopsy with blue dye alone. METHODS: This was a retrospective review of patients who underwent SLN biopsy using blue dye alone from 2001 to 2005, when SLN biopsy was performed selectively and always followed by axillary lymph node dissection (ALND), and from 2006 to 2010, when SLN biopsy was offered to all suitable patients and ALND done only when the SLN was not identified or positive for metastasis. RESULTS: Between 2001 and 2005, 170 patients underwent SLN biopsy with blue dye alone. The overall SLN non-identification rate was 8·4 per cent. The overall false-negative rate was 34 per cent, but decreased with each subsequent year to 13 per cent in 2005. From 2006 to 2010, 610 patients underwent SLN biopsy with blue dye alone. The SLN was not identified in 12 patients (2·0 per cent) and no significant contributing factor was identified. A median of 2 (range 1-11) SLNs were identified. A non-SLN was found to be positive for metastasis in two patients with negative SLNs. Axillary nodal recurrence developed in one patient; none developed internal mammary nodal recurrence. Anaphylaxis occurred in one patient. CONCLUSION: Blue dye performed well as a single modality for SLN biopsy. Non-identification, axillary nodal recurrence and serious allergic reactions were uncommon.

Soluble lutein in combination with brilliant blue as a new dye for chromovitrectomy.

UNLABELLED: A new dye for vitreoretinal surgery comprised of soluble lutein/zeaxanthin 1 % and brilliant blue 0.025 % is advantageous compared with other dyes currently used for chromovitrectomy, and showed no signs of toxicity at 1 month of follow-up. PURPOSE: To evaluate the feasibility and safety of a dye [soluble lutein/zeaxanthin (LZ) 1 % and brilliant blue (BB) 0.025 %] for improving removal of vitreous, epiretinal membranes (ERM), and internal limiting membranes (ILM) in humans. METHODS: We prospectively evaluated 18 eyes treated surgically for a macular hole or ERM. Eighteen surgeons performed chromovitrectomy using the dye, and completed a questionnaire to evaluate the efficacy and safety of the dye. . Examinations included best-corrected visual acuity and intraocular pressure measurements and optical coherence tomography, fluorescein angiography, and autofluorescence performed at baseline and days 1, 7, and 30 postoperatively. RESULTS: The green dye was deposited on the posterior pole; vigorous dye flushing into the vitreous cavity was unnecessary. All surgeons reported that the ILM stained greenish-blue; 94.4 % reported ILM peeling adequate; the ERM stained poorly. No evidence of toxicity was observed. CONCLUSION: The new dye deposited on the posterior pole due to its higher density. The ability to stain the ILM was similar to BB. The new dye has ability to stain the vitreous, hyaloid, and especially the ILM satisfactorily. The new dye may be useful during chromovitrectomy.

[Anaphylaxis to blue dyes]. / Anaphylaxie aux colorants bleus.

In medicine, vital blue dyes are mainly used for the evaluation of sentinel lymph nodes in oncologic surgery. Perioperative anaphylaxis to blue dyes is a rare but significant complication. Allergic reactions to blue dyes are supposedly IgE-mediated and mainly caused by triarylmethanes (patent blue and isosulfane blue) and less frequently by methylene blue. These substances usually do not feature on the anesthesia record and should not be omitted from the list of suspects having caused the perioperative reaction, in the same manner as latex and chlorhexidine. The diagnosis of hypersensitivity to vital blue dyes can be established by skin test. We illustrate this topic with three clinical cases.

Hypersensitivity reactions to Patent Blue V in breast cancer surgery: a prospective multicentre study.

BACKGROUND: An increasing number of immediate hypersensitivity reactions (HSR) have been reported after the use of Patent Blue V (PBV) for breast cancer surgery. This is the first study to publish prospective data with systematic allergological assessment. METHODS: We conducted a multicentre study in 10 French cancer centres for over 6 months. All patients scheduled for breast surgery with injection of PBV were included in the study. Patients were screened for past medical history, atopy, and known food and drug allergies. When suspected HSR or unexplained reactions occurred after injection of PBV, blood samples were taken, and plasma histamine and serum tryptase concentrations were measured. HSR to PBV was suggested if skin tests performed 6 weeks later were positive. RESULTS: Nine suspected HSR to PBV were observed in 1742 patients. Skin tests were positive in six patients, giving an incidence of 0.34%. Four grade I and two grade III HSR were observed, both requiring intensive care unit treatment. Mean onset time of the reaction was 55 ± 37 min. Plasma histamine was elevated in four patients, while serum tryptase was normal. We found no risk factors associated with HSR to PBV. CONCLUSION: An incidence rate of one in 300 HSR to PBV was observed for patients exposed to PBV during sentinel lymph node detection. This rate is higher than rates reported after the use of neuromuscular blocking agents, latex or antibiotics.

Diphenylmethyl selenocyanate attenuates malachite green induced oxidative injury through antioxidation & inhibition of DNA damage in mice.

BACKGROUND & OBJECTIVES: Malachite green (MG), an environmentally hazardous material, is used as a non permitted food colouring agent, especially in India. Selenium (Se) is an essential nutritional trace element required for animals and humans to guard against oxidative stress induced by xenobiotic compounds of diverse nature. In the present study, the role of the selenium compound diphenylmethyl selenocyanate (DMSE) was assessed on the oxidative stress (OS) induced by a food colouring agent, malachite green (MG) in vivo in mice. METHODS: Swiss albino mice (Mus musculus) were intraperitoneally injected with MG at a standardized dose of 100 µg/ mouse for 30 days. DMSE was given orally at an optimum dose of 3 mg/kg b.w. in pre (15 days) and concomitant treatment schedule throughout the experimental period. The parameters viz. ALT, AST, LPO, GSH, GST, SOD, CAT, GPx, TrxR, CA, MN, MI and DNA damage have been evaluated. RESULTS: The DMSE showed its potential to protect against MG induced hepatotoxicity by controlling the serum alanine aminotransferase and aspartate amino transferase (ALT and AST) levels and also ameliorated oxidative stress by modulating hepatic lipid peroxidation and different detoxifying and antioxidative enzymes such as glutathione-S-transferase (GST), superoxide dismutase (SOD), catalase (CAT), and also the selenoenzymes such as glutathione peroxidase (GPx) and thioredoxin reductase (TrxR) and reduced glutathione level which in turn reduced DNA damage. INTERPRETATION & CONCLUSIONS: The organo-selenium compound DMSE showed significant protection against MG induced heptotoxicity and DNA damage in murine model. Better protection was observed in pretreatment group than in the concomitant group. Further studies need to be done to understand the mechanism of action.

Notes from the field: Multistate outbreak of postprocedural fungal endophthalmitis associated with a single compounding pharmacy - United States, March-April 2012.

On March 5, 2012, the California Department of Public Health was notified of nine cases of clinically diagnosed fungal endophthalmitis at a single California ambulatory surgical center. The initial investigation, led by the Los Angeles County Department of Public Health, determined that in all cases patients had undergone vitrectomy with epiretinal membrane peeling using a dye called Brilliant Blue-G (BBG) from Franck's Compounding Lab, Ocala, Florida. This investigation has since expanded to involve intravitreal injection of triamcinolone-containing products from Franck's, an overall total of 33 cases in seven states, and collaboration between state and local health departments, CDC, and the Food and Drug Administration (FDA). This report describes the current investigative findings. Clinicians should be aware of the ongoing investigation and should avoid use of compounded products labeled as sterile from Franck's during this ongoing investigation.

A retrospective analysis of rates of allergic reaction to Patent V blue dye used in sentinel lymph node biopsies for melanoma.

Sentinel lymph node biopsies are a well-established component of the assessment and treatment pathway for patients with cutaneous melanoma in the UK. Commonly utilised techniques involve the use of blue dye which has an established risk of inducing allergic reactions in patients. Such reactions can be life-threatening, and this risk is important to highlight to patients. We conducted a retrospective review of all patients who had undergone this procedure at our melanoma centre in Cambridge, UK. From a group of 715 patients who received blue dye as part of the procedure, six patients suffered an allergic reaction (0.84%) with one of these treated as anaphylaxis. Our incidence of anaphylaxis is almost ten times greater than that reported in the NAP6 report led by the National Institute of Academic Anaesthesia and significantly higher than reported by others. We propose several reasons why our results differ from previous estimates. This study has focused only on patients undergoing a sentinel node procedure for melanoma, others have focused on such procedures performed on patients with breast cancer and some have combined the two. The administration technique, volume and anatomical distribution of disease all differ significantly from melanoma, possibly influencing rates and severity of allergic reactions.

Anaphylaxis to Patent Blue V. II. A unique IgE-mediated reaction.

BACKGROUND: Patent Blue V (PBV) is injected in order to map sentinel nodes during cancer staging procedures. Anaphylactic reactions, allegedly IgE antibody mediated, have been reported. The aim of the study was to explore the immunological mechanism of anaphylaxis to PBV. METHODS: PBV allergen threshold basophil sensitivity, CD-sens, was performed on cells from nine patients diagnosed as having had adverse reactions to PBV. The mechanisms of the CD-sens were studied by immunological and immuno-chemical methods. RESULTS: Five of the nine patients had a positive CD-sens to PBV which was completely eliminated by washing the cells in phosphate buffered saline before allergen challenge. However, the positive CD-sens was completely reconstituted by incubating the cells in plasma or serum of that patient or the other PBV-anaphylactic patients for 15 min at room temperature. In some patients the factor mediating CD-sens was completely or partially destroyed by heating at +56 degrees C for 30 min or being exposed to the low pH used for elution from anti-Ig columns. A 1000-fold excess of monoclonal IgE blocked the reconstitution by approximately 50%. CONCLUSION: Anaphylactic reactions to PBV are mediated by IgE antibodies giving a classical CD-sens reaction. However, the allergenic configuration seems to constitute a structure completely dependent on PBV, as a hapten, linked to a, so far, unknown carrier that seems to be unique for patients having experienced a PBV-induced reaction. Further studies are needed to characterize the postulated carrier.

Anaphylaxis to Patent Blue V. I. Clinical aspects.

BACKGROUND: The dye Patent Blue V (PBV) is increasingly used for staging procedures in operable breast cancer, but is reported to cause adverse reactions. The aim of this study was to present the clinical features and the results of follow-up examinations in patients with such reactions. METHODS: We studied nine patients with hypersensitivity reactions to PBV between 1999 and 2006 who were identified through the Norwegian network for reporting and investigating allergic reactions during anesthesia. RESULTS: We observed incidences of 0.5% (7/1418) for all kinds of PBV reactions and 0.4% (5/1418) for anaphylaxis. Typical clinical features included: (i) cardiovascular and/or cutaneous symptoms, (ii) a delay in symptoms, compared to the time of dye injection, (iii) poor response to ephedrine and intravenous fluid, and (iv) need for adrenaline administration, sometimes prolonged, for circulatory stabilization. Cutaneous manifestations were noted in five of the seven patients with anaphylaxis and two additional patients without circulatory instability. During anaphylactic reactions, serum tryptase was increased in six patients and normal in one. Serum tryptase was normal in one patient with skin symptoms only. Skin prick tests to PBV were positive in all eight patients tested, including the two with skin manifestations only. CONCLUSION: The clinical features and the results of follow-up studies strongly suggest that these reactions are IgE mediated.